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THE REGIONAL MUNICIPALITY OF PEEL

COMMUNITY WATER FLUORIDATION COMMITTEE AGENDA CWFC - 4/2016 DATE: Thursday, June 9, 2016 TIME: 8:30 AM – 9:30 AM LOCATION: Regional Council Chamber, 5th Floor Regional Administrative Headquarters 10 Peel Centre Drive, Suite A Brampton, Ontario MEMBERS: F. Dale; J. Downey; A. Groves; M. Palleschi; C. Parrish; K. Ras;

J. Sprovieri; J. Tovey 1.

DECLARATIONS OF CONFLICTS OF INTEREST

2.

APPROVAL OF AGENDA

3.

DELEGATIONS

4.

REPORTS

4.1. Report on the Legislative Framework for the Authorization and Regulation of Community Water Fluoridation (For information)

Presentation by Patrick O'Connor, Regional Solicitor and Director of Legal Services and Jeff Hennings, Acting Director, Water Division

4.2. Fluoridation of Drinking Water in the Region of Peel (For information)

5.

COMMUNICATIONS

5.1. The Lancet Neurology, Two Articles Published in 2014, Regarding Water Fluoridation (Receipt recommended)

5.2. Dr. G. Richard Dundas, Bennington Oral Health Coalition (BOHC), Letter to the Editor of the Bennington Banner posted April 4, 2016, Regarding the Accomplishments of the BOHC (Receipt recommended)

CWFC-4/2016 -2- Thursday, June 9, 2016 5.3. Maurice W. Smith, Resident, Letter forwarded by the Town of Caledon, Regarding

Water Fluoridation (Receipt recommendation)

5.4. Kallie Miller, Registered Nurse, Letter dated May 18, 2016, Regarding the Safety of Artificial Water Fluoridation Chemical (Receipt recommended)

5.5. Richard L. Shames, Doctor of Medicine (MD), Email dated May 25, 2016, Regarding Artificial Water Fluoridation (Receipt recommended)

5.6. Frank Dale, Regional Chair, Letter dated May 28, 2016, to Eric Hoskins, Minister of Health and Long-Term Care, Regarding Provincial Policy on Water Fluoridation (Receipt recommended)

6.

IN CAMERA MATTERS

7.

OTHER BUSINESS

8.

NEXT MEETING To be determined.

9.

ADJOURNMENT

REPORT Meeting Date: 2016-06-09

Community Water Fluoridation Committee

For Information

DATE: May 24, 2016

REPORT TITLE: REPORT ON THE LEGISLATIVE FRAMEWORK FOR THE

AUTHORIZATION AND REGULATION OF COMMUNITY WATER FLUORIDATION

FROM: Patrick O'Connor, Regional Solicitor

OBJECTIVE

The objective of this report is to provide an overview of the legislative framework that regulates the practice of community water fluoridation in the Province of Ontario.

REPORT HIGHLIGHTS

The responsibility of providing safe drinking water and community water fluoridation is a shared responsibility between all levels of government.

The Province of Ontario provides the principal legislation for community water fluoridation that both delegates responsibility to municipalities as well as regulates safe drinking water.

The Fluoridation Act, R.S.O. 1990, c. F.22 provides the authority for municipalities to fluoridate the water supply, and delegates all decision making regarding community water fluoridation to municipalities.

The Safe Drinking Water Act, 2002, S.O. 2002. c. 32 regulates municipal drinking water systems by ensuring water quality meets prescribed standards, operating systems comply with the Act and are kept in good state of repair, and regular water sampling, testing and monitoring requirements are completed and reported.

Specific guidelines for the operation of drinking water systems are detailed for municipalities in several technical documents to ensure municipalities meet safety and quality drinking water standards.

Health Canada provides the scientific rationale and technical expertise to establish the guideline for fluoride in drinking water.

The Region of Peel is working under statutory authority as well as the provisions and guidelines of quality and technical standards to support oral health benefits while maintaining a safe municipal drinking water supply.

DISCUSSION 1. Background

In general, the responsibility of providing safe drinking water and community water fluoridation is shared between the federal, provincial/territorial, and municipal governments. However, the primary enabling legislation for community water fluoridation is provided at the Provincial level.

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REPORT ON THE LEGISLATIVE FRAMEWORK FOR THE AUTHORIZATION AND REGULATION OF COMMUNITY WATER FLUORIDATION

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a) Provincial Level: Authority to Fluoridate and Ensuring Safety of the Water

The Province of Ontario has delegated the power to make a decision regarding community water fluoridation to municipalities through the Fluoridation Act, R.S.O. 1990, c. F.22. The Act provides municipalities with the necessary authority to establish, continue, maintain and operate or discontinue a fluoridation system. The Fluoridation Act and its predecessor legislation to provide the authority for municipalities to fluoridate the water supply dates back to 1957. Community water fluoridation had occurred before that time in some municipalities, however the express authority was granted by the Province following a 1957 court challenge brought to the Supreme Court of Canada (Toronto v. Forest Hill, [1957] S.C.R. 569) in which the City of Toronto was found to be lacking in legal authority to fluoridate the water system. The Fluoridation Act now provides the lack necessary authority. Further regulation of fluoride in the water system is provided by the Safe Drinking Water Act, 2002, S.O. 2002. c. 32 (“SDWA”). One of the purposes of the SDWA is “to provide for the protection of human health and the prevention of drinking water health hazards through the control and regulation of drinking water systems and drinking water testing”. Accordingly, the Ministry of the Environment and Climate Change (“the Ministry”) is responsible for overseeing the regulation of safe drinking water in Ontario. Among other things, the SDWA requires that:

All water provided by a municipal drinking water system must meet prescribed drinking water quality standards;

The drinking water system be operated in accordance with the Act and regulations and be kept in a good state of repair;

All sampling, testing and monitoring requirements be complied with; and All reporting requirements be complied with.

In accordance with the statutory scheme, Ontario Drinking Water Quality Standards have been established within Ontario Regulation 169/03. Schedule 2 of the Ontario Regulation 169/03 establishes a drinking water quality standard for fluoride expressed as a maximum concentration of 1.5 mg/L. Drinking water that contains fluoride at, or below, this maximum acceptable concentration does not pose a risk to human health according to Health Canada. Where fluoride is added to drinking water the Ministry, in its publication entitled “Technical Support Document for Ontario Drinking Water Standards, Objectives and Guidelines”, recommends that the concentration be adjusted to 0.5 to 0.8 mg/L. This is the range of concentrations that the Ministry has adopted as the optimum level for the prevention and control of tooth decay. Accordingly, the level of naturally-occurring fluoride in Peel’s lake based municipal water supply is adjusted to the optimal concentration range to protect against tooth decay. This process is dealt with in detail in the accompanying report of the Commissioner of Public Works dated May 17, 2016 titled “Fluoridation of Drinking Water in the Region of Peel”. Tests for fluoride concentration are performed regularly and in accordance with the regulations for drinking water systems provided for in Ontario Regulation 170/03. The Region’s drinking water system is also operated in a manner consistent with Ministry guidelines as articulated in the

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Ministry’s publication entitled “Design Guidelines for Drinking-Water Systems 2008”. In particular, these guidelines specifically identify hydrofluosilicic acid as an acceptable source of fluoride for community water fluoridation.

b) Federal Level: Providing Scientific and Technical Expertise to Determine Safe Levels of Fluoride in Drinking Water

There is no direct federal regulation of community water fluoridation. However, Health Canada plays a major role in providing the scientific and technical basis for the drinking water standards that are implemented by the provinces and territories. Health Canada's Federal-Provincial-Territorial Committee on Drinking Water (the “Committee”) has undertaken responsibility for the development of scientifically informed Guidelines for Canadian Drinking Water Quality and the protection of drinking water quality in collaboration with the Canadian Council of Ministers of the Environment. The Province of Ontario is represented on the Committee by a representative from the Ontario Ministry of the Environment and Climate Change. With input from the Committee, Health Canada produces the publication entitled “Guidelines for Canadian Drinking Water Quality” and the related Guideline Technical Documents. Among these Guideline Technical Documents is a document concerning fluoride, the most recent version of which was published in 2010. The guidelines are based on current, published scientific research related to health effects, aesthetics (taste and odour), and operational considerations associated with drinking water supplies. The process of formulating these guidelines includes internal reviews, external peer reviews, and public consultation through the Health Canada website. Following the period of public consultation, Health Canada convenes a panel of experts to provide advice and recommendations on the scientific studies and approaches that should be incorporated into the guidelines and technical documents. These Health Canada publications provide the scientific rationale for the Ontario Drinking Water Quality Standards, and in particular the identification of the maximum acceptable concentration of fluoride as 1.5 mg/L. Drinking water that contains fluoride at, or below, this maximum acceptable concentration does not pose a risk to human health according to Health Canada. This maximum acceptable concentration has been established based on the segment of the population most at risk of developing dental fluorosis (i.e. children from 1-4 years of age). The optimal concentration of fluoride in drinking water to promote dental health has been determined by Health Canada to be 0.7 mg/L. This concentration provides optimal dental health benefits and is well below the maximum acceptable concentration to ensure protection against potential adverse effects. This recommended level also takes into account the other sources of fluoride to which Canadian consumers are commonly exposed such as food and drinks prepared or processed with fluoridated water, and toothpaste.

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CONCLUSION

Within the legislative framework there is statutory authority for fluoridation of the municipal water supply by the Region. The Region monitors water quality to ensure drinking water is safe for consumption based on all regulatory standards under the SDWA, while providing optimal dental health benefits.

Patrick O'Connor, Regional Solicitor Approved for Submission:

D. Szwarc, Chief Administrative Officer

For further information regarding this report, please contact Patrick O'Connor, Regional Solicitor and Director, Legal Services, extension 4319, patrick.o’[email protected].

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Fluoridation of Drinking Water in Peel

Community Water Fluoridation Committee June 9, 2016

Patrick O’Connor, Regional Solicitor & Director, Legal Services

Jeff Hennings, Acting Director, Water Division Justyna Burkiewicz, Supervisor, Water Quality & Compliance

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Provincial Role

• Fluoridation Act

Fluoridation systems

2.1 (1) The council of a regional

municipality may by by-law

establish, maintain and operate or

discontinue fluoridation systems.

2001, c. 25, s. 476 (3).

2

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http://www.ontario.ca/laws/statute/90f22

Provincial Role

• Safe Drinking Water Act, 2002

Purposes

1. The purposes of this Act are as follows:

1.To recognize that the people of Ontario are

entitled to expect their drinking water to be

safe.

2.To provide for the protection of human

health and the prevention of drinking water

health hazards through the control and

regulation of drinking water systems and

drinking water testing. 2002, c. 32, s. 1.

3

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Provincial Role

• O. Reg. 169/03: Ontario Drinking Water Quality Standards

• O. Reg. 170/03: Drinking Water Systems

4

4.1-8


Federal Role

• Guidelines for Canadian Drinking

Water Quality: Guideline Technical

Document – Fluoride

5

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Certification of Water Additives

• NSF/ ANSI 60

• Third party certification process

• Plant audit

6

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Fluoride

• Meets MOECC regulatory standards

• Continuously monitored to maintain the optimal range as recommended within MOECC guidelines

• MOECC regulates and enforces drinking water products

• Legislative and operationally fluoride administered same as chlorine

7

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Drinking Water Fluoride Additives

• Hydrofluorosilicic Acid (HFSA)

– Phosphorite Rock

– Calcium Fluoride

• Powder Forms

– Sodium Fluorosilicate

– Sodium Fluoride

• Pharmaceutical Grade Fluoride

8

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Hydrofluorosilicic Acid

• Produced from Phosphorite Rock

• Most commonly used additive in North America

• Alternatively produced from Calcium Fluoride

• Others using Calcium Fluoride additive

9

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Residual Components

Residual

Components

(mg/L)

Concentration in HFSA

(from Phosphorite Rock)

Concentration in HFSA

(from Calcium Fluoride)

Arsenic

12.10 3.00

Lead

1.70 0.18

• Concentration in treated water is below detection limit.

10

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Dry Powders

• Sodium Fluorosilicate and Sodium Fluoride

• NSF 60 approved

• Produced by further reacting HFSA, likely from phosphorite rock

11

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Cost of Fluoride Additives

Annual

Additive

Costs

Annual

Operating &

Maintenance Costs

Retrofit

Capital

Costs

HFSA (Phosphorite Rock)

$ 321,000 $ 130,000 N/A

HFSA (Calcium Fluoride)

$ 364,000 $ 130,000 N/A

Sodium Fluorosilicate or Sodium Fluoride

$ 200,000 $ 250,000 $ 2,000,000

12

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Pharmaceutical Grade Fluoride

• Not subject to NSF 60 standards; therefore would not be approved by MOECC for use in drinking water

• Difficult to obtain cost and quality data

13

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Lakeview WTP Delivery

14

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Lakeview Tanks and Pumps

15

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Storage and Supply

16

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Safe Work Environment

17

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Monitor and Control

18

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Thank you

4.1-23

REPORT Meeting Date: 2016-06-09

Community Water Fluoridation Committee

For Information

DATE: May 26, 2016

REPORT TITLE: FLUORIDATION OF DRINKING WATER IN THE REGION OF PEEL

FROM: Dan Labrecque, Commissioner of Public Works

OBJECTIVE

To provide information on the Region of Peel's current fluoridation practices of the lake based drinking water system and to highlight alternative additives for use in the municipal water supply. REPORT HIGHLIGHTS

The level of naturally-occurring fluoride in Peel’s lake based municipal water supply is adjusted to an optimal concentration range to protect against tooth decay: 0.5 to 0.8 mg/L, as recommended by the Ministry of the Environment and Climate Change (MOECC)’s Technical Support Document for Ontario Drinking Water Standards, Objectives and Guidelines.

For the 2015 reporting year, average fluoride levels at the Lakeview and Lorne Park Water Treatment Plants were 0.64 mg/L and 0.65 mg/L, respectively.

The Region of Peel’s current fluoride additive, hydrofluorosilicic acid (HFSA), is a co-product collected during the refinement process following phosphate extraction from rocks and is subject to stringent standards, testing and certification for use in drinking water. Hydrofluorosilicic acid can also be manufactured from calcium fluoride mineral in the production of hydrogen fluoride.

HFSA from both sources (calcium fluoride and calcium phosphate rock) is NSF certified and contains residual component (arsenic and lead) levels well below established guidelines. Fluoride derived from calcium fluoride, however, contains a lower level of residual components when in concentrated form than our current product.

Dry product forms of fluoride additive are also available but would require a four to six month fluoridation disruption and an expensive retrofit to both water treatment plants.

Pharmaceutical grade additives are available but are not NSF certified for drinking water, and therefore not permitted by the MOECC.

DISCUSSION 1. Background

The Region of Peel’s (the Region) lake based drinking water supply has been fluoridated for over 40 years, as part of the Region’s comprehensive strategy to protect oral health of Peel residents. Over the years, the process of fluoridation in the Region has been diligently

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FLUORIDATION OF DRINKING WATER IN THE REGION OF PEEL

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monitored and carried out in accordance with the regulatory framework for water fluoridation in Canada and Ontario. Fluoride is an abundant naturally occurring ion of the element fluorine. Fluoride can be found in drinking water sources throughout the world. When naturally occurring fluoride in the source water is below the optimal level of 0.7 mg/L, as recommended by Health Canada, the fluoride level can be adjusted in drinking water supplies to provide optimal oral health benefits. Based on long-term routine tests conducted at the Region, the naturally occurring levels of fluoride in Lake Ontario range from 0.07 to 0.22 mg/L and to attain the optimal level, the fluoride level is adjusted in the lake based drinking water supply. To date, the fluoridation additive used at the Region has been hydrofluorosilicic acid (HFSA). This product is also known by other names, including hydrofluosilicic acid, fluorosilicic acid and fluosilicic acid. HFSA is the most commonly used additive in communal water fluoridation. The fluoridation process consists of using HFSA to adjust the water’s fluoride content to the recommended level for the promotion of oral health. The concentration of fluoride in the Region’s drinking water is targeted at the operational range between 0.5 – 0.8 mg/L as recommended by the Ministry of the Environment and Climate Change (MOECC) Technical Support Document for Ontario Drinking Water Standards, Objectives and Guidelines. The optimal concentration of fluoride in drinking water, recommended by Health Canada, is 0.7 mg/L. The average level of fluoride in the South Peel drinking water system tested over the past few years has ranged from 0.53 to 0.68 mg/L. HFSA, formula H2SiF6, achieves complete dissolution and ionic disassociation when added to water. Upon contact with water, it immediately breaks up into silicon (Si), hydrogen (H) and fluoride (F) ions, with no HFSA remaining at the end of the treatment process in the water leaving the treatment plant: H2SiF6 + 4H2O → 6H+ + 6F- + Si(OH)4 (HFSA) (water) (hydrogen) (fluoride) (silicic acid) Fluoride ions that are the product of the HFSA dissolution are comparable to the ions found in the natural source water. The operation and testing of water treatment systems in Ontario and fluoride levels in water are regulated by the MOECC under the Safe Drinking Water Act, 2002 (SDWA) and its regulations. The current guideline by Health Canada and the Ontario Drinking Water Quality Standards (Ontario Regulation 169/03) sets the maximum acceptable concentration for fluoride in drinking water at 1.5 mg/L. Through continuous monitoring of fluoride levels at the Region’s Lakeview and Lorne Park Water Treatment Plants to maintain the optimal target range, the fluoride concentration is found at levels within the operational target range, well below the maximum limit. For the 2015 reporting year, average fluoride levels were 0.64 mg/L and 0.65 mg/L at the Lakeview and Lorne Park Water Treatment Plants respectively. The Region’s fluoridation process complies with the federal and provincial standards for safe drinking water.

2. Findings

The Region currently fluoridates its lake based water supply using HFSA, which is an aqueous (water based) liquid additive obtained from Minchem, a reputable North American distributor, and manufactured by Solvay. Procurement of HFSA through our contracted

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https://www.ontario.ca/document/technical-support-document-ontario-drinking-water-standards-objectives-and-guidelines


https://www.ontario.ca/laws/statute/02s32


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operator, the Ontario Clean Water Agency (OCWA) is under a three year contract that is scheduled to expire in 2018. Fluoride is often found in the same rocks and minerals as phosphate and during the phosphate production process, separate collection of fluoride takes place. HFSA, our current fluoride additive, is a co-product collected during the refinement process following phosphate extraction from rocks and is subject to stringent standards, testing and certification for use in drinking water. The same rigorous standards apply to all drinking water additives, regardless of their source. It is not uncommon for co-products or by-products of one industry to be used in products manufactured by a different industry. An example of this is the wide use of by-products of the oil industry in products such as personal care and beauty products, capsules for health supplements, toothpaste or food preservatives. Regulatory Regimen Through the SDWA, the MOECC regulates and enforces how additives used in drinking water systems in Ontario are handled, stored, added, monitored, controlled and reported. Through annual inspections, the MOECC ensures that drinking water systems that fluoridate do so in accordance with the Technical Support Document for Ontario Drinking Water Standards, Objectives and Guidelines, that the systems are designed in conformance to the Design Guidelines for Drinking Water Systems and that all additives that come in contact with drinking water meet the applicable standards set by the American Water Works Association (AWWA) and safety criteria standard NSF 60. The same standards apply for mandatory chemicals such as chlorine as for discretionary additives such as fluorides. AWWA, a well-respected water supply industry association, sets standards for all additives used in the water treatment process. NSF International, an independent accredited global organization, tests, certifies products, and develops public health standards that help protect food, drinking water, consumer products and the environment. The NSF certification program includes unannounced audits of production and distribution facilities to certify that the products are properly formulated, packaged, and transported with appropriate safe guards in place to protect against potential contamination and to confirm they meet the requirements of the standards. It also includes testing and evaluation of each NSF certified product to confirm the absence of residual components at concentrations of concern; not to exceed 10 per cent of the allowable maximum contaminant level for the substance. For example, if the Maximum Acceptable Concentration of a residual component in drinking water is 10 mg/L, then the additive can’t increase the level by more than 1 mg/L. The Region is mandated through its Municipal Drinking Water License, issued by the MOECC under the SDWA, to have all drinking water additives used at the Region’s water treatment plants, including fluoride, chlorine and coagulants meet the industry accepted quality standards: the AWWA standards, and the American National Standards Institute safety criteria standard NSF 60. In situations where the NSF approval of additives is difficult to obtain, food grade products, approved by the MOECC for use in the municipal drinking water systems may be used. Subject to NSF 60 certification, HFSA supplied to the Region is tested for regulated metal compounds and other substances with an established maximum contaminant level. Each shipment of HFSA requires a NSF certification assuring compliance with the standard. With every HFSA delivery, a Certificate of Analysis is provided, which presents the breakdown of

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https://www.ontario.ca/document/design-guidelines-drinking-water-systems


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the residual components found within, reflective of the pure product. The lead and arsenic residuals sometimes found in HFSA are routinely tested for in the Region’s treated drinking water supply and found to consistently measure at concentrations below the legislated maximum acceptable concentrations, 0.010mg/L for lead and 0.025 mg/L for arsenic, in drinking water (Ontario Regulation 169/03).

Residual Component

Concentration in HFSA (delivered)

(mg/L)

Concentration added to Drinking

Water when HFSA is 0.7

mg/L (mg/L)

Concentration in Treated Water

(mg/L)

SDWA Limit (mg/L)

Arsenic 12.10 0.000042 < 0.0010 0.025

Lead 1.70 0.000006 0.0059 0.010 Table 1. Comparing concentrations of residuals in HFSA and in drinking water in Peel. All types of fluoride additives, regardless of their source or production process, contain trace levels of residual components in varying degrees. Fluoride addition to drinking water to achieve the target range of 0.5-0.8 mg/L, does not result in any significant increase in residual components in drinking water, which testing demonstrates remain at levels below method detection limit and well under the maximum acceptable concentration. Health and Safety Procedures are established specific to HFSA delivery to ensure product acceptability and to minimize possible hazards. HFSA deliveries are always supervised by qualified, MOECC certified water operators, who verify that the product is NSF 60 certified before accepting the shipment. Procedures on safe handling and storage of the product are also in place to ensure employee safety. The management of potential hazards includes review of HFSA Material Safety Data Sheets, familiarity with the Liquid Spill Contingency Plan, the Region’s Sewer Use By-law and other procedures for the safe handling of fluoride and other substances, as well as use of appropriate personal protective equipment. Standard health and safety protocols are carefully followed by trained operators throughout the entire water treatment process. Appropriate equipment is in place to aid the operators in the safe handling of each product used in the Region’s water treatment facilities. The chemical storage tanks are lined with a corrosion-resistant material, and fluoride feed pumps and piping made of appropriate materials for the safe storage, containment and application of fluoride comply with the MOECC’s Design Guidelines for Drinking Water Systems. The design and maintenance of our drinking water systems, well documented procedures and highly skilled and trained staff help us maintain a good safety record with no lost time incidents in the last ten years related to fluoride handling. Process Automation To achieve the optimal fluoride levels with the use of HFSA, the Region utilizes a liquid fluoride feed system that is controlled through a computerized system overseen by water operators. The system is designed with several safeguards for the accurate control of

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https://www.ontario.ca/document/design-guidelines-drinking-water-systems


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fluoride addition and is monitored around the clock, 365 days per year. It automatically adjusts HFSA flow to achieve the correct fluoride concentration and maintain the desired levels. Fluoride concentration is monitored and measured by continuous analyzers and also sampled and tested manually twice daily. Testing equipment is maintained and calibrated regularly by qualified technicians. In addition to fluoridation compounds, many other chemicals are routinely added to water throughout various stages of the treatment process. From the operational and legislative standpoint, fluoride is administered and monitored in the same way as chlorine, which is used at the treatment plants for primary and secondary disinfection of our water supplies. These two additives are governed by the same drinking water legislation and treated with the same due diligence.

3. Alternate Fluoride Additives

As mentioned above, our current source of HFSA is manufactured during the extraction of phosphate from calcium phosphate rock. Alternatives to our current source of HFSA and other additives are listed below. Hydrofluorosilicic Acid (from Calcium Fluoride) HFSA can also be manufactured from calcium fluoride mineral in the production of hydrogen fluoride. Like the HFSA made from phosphorite rock it is a commonly used additive to fluoridate water supplies, especially in large water plants, due to the ease of its use, transportation, the minimum need for different equipment and its cost effectiveness. Similar to the current product, this alternate product is liquid and hence easy to handle and to measure accurately when it is added to water. In addition, as noted in Table 2, HFSA derived from calcium fluoride presents a concentration of residual components at a lower level than the HFSA additive currently used in Peel.

Residual Component

Concentration in HFSA (from Phosphorite Rock)

(mg/L)

Concentration in HFSA (from Calcium Fluoride)

(mg/L)

Arsenic 12.10 3.00

Lead 1.70 0.18 Table 2. Concentrations of residuals in the two different sources of HFSA. A number of local municipalities have recently started using HFSA manufactured from calcium fluoride, including the cities of Toronto and Hamilton, as well as the Region of Durham. Sodium Fluorosilicate and Sodium Fluoride Two less frequently used additives are sodium fluorosilicate (NaSF) and sodium fluoride (NaF), both produced by neutralizing HFSA using sodium chloride (table salt) or caustic soda. Smaller water treatment plants tend to use these fluorides, which are transported and stored as a solid, dry product. The quality standards for these fluorides, as with all products used in drinking water treatment processes, are set by NSF 60, which, as mentioned earlier, addresses the health

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effects of treatment additives and sets a criterion that determines that fluorides are safe at their maximum use level with respect to potential residual components. The use of powder additives introduces the need for specific health and safety protocols to protect water operators from exposure to fine powders of the dry product during its delivery, storage and handling. Since both the Lakeview and Lorne Park Water Treatment Plants currently use liquid HFSA, switching to a dry powder would require the retrofit of both plants to replace the large liquid storage tanks with storage silos, dust collectors, feed hoppers, mixing tanks, and a different fire protection system. Further investigation would be required to determine if a switch to a dry feed system could be achieved without a four to six month disruption to the fluoridation program. The estimated cost to retrofit the two plants is approximately $ 2,000,000, including engineering fees.

Fluoride Additive

Annual Chemical Costs

Annual Operating & Maintenance Costs

Retrofit Capital Costs

HFSA (current source)

$ 321,000 $ 130,000 N/A

HFSA (alternate source)

$ 364,000 $ 130,000 N/A

Either Dry Powder

$ 200,000 $ 250,000 $ 2,000,000

Table 3. Cost comparison of the different fluoride additives. Pharmaceutical Grade Fluoride Pharmaceutical grade fluoride compounds fall under the Food and Drug Administration and are used in the formulation of prescription medications, not for use in water treatment. Unlike the fluoride additives described above, they are not subjected to the stringent NSF and AWWA standards and diligent testing for lead and arsenic. It is therefore not certain that pharmaceutical grade fluoride is a higher quality product with fewer residual components. The NSF certification has been relied on by the drinking water industry and recognized by the MOECC for additives that are deemed safe for use in drinking water applications. The MOECC’s position is fixed regarding non-NSF certified fluoride additive being unsuitable for use in the drinking water systems in Ontario, which is supported by the regulatory approvals under the SDWA. A comparison of the three types of industrial grade fluoride additives as well as information on the pharmaceutical grade of fluoride are included in Appendix I.

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CONCLUSION

The Region’s current fluoridation practice meets all the legislated requirements mandated by the MOECC regulations and standards, and is managed in keeping with Health Canada’s guidelines. The additive used is tested and approved for use under this same regulatory

framework.

Alternatives do exist, which range from the use of liquid form calcium fluoride-based HFSA to powder form Sodium based fluoride product. At the scale of the Region’s water treatment facilities, which are some of the largest in Canada, liquid additive is typically used for health and safety purposes, ease of handling and shipment, and cost.

Dan Labrecque, Commissioner of Public Works Approved for Submission:

D. Szwarc, Chief Administrative Officer APPENDICES:

Appendix I – Fluoride Additives For further information regarding this report, please contact Andrew Farr, Executive Director Water and Wastewater Division at ext. 4761 or via email at [email protected]. Authored By: Jeff Hennings

Reviewed in workflow by:

Public Health

Legal Services

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FLUORIDATION OF DRINKING WATER IN THE REGION OF PEEL Appendix I

1

Fluoride Additives

Additive Source Mineral/Rock

Description NSF 60 Certification

Annual Cost Jurisdictions using the Product

Hydrofluorosilicic Acid (HFSA) – water based Chemical Formula: H2SiF6

Phosphorite Rock

Most fluoride additives used in North America are produced from phosphorite rock.

Phosphorite contains calcium phosphate mixed with limestone (calcium carbonates) minerals and apatite - a mineral with high phosphate and fluoride content. It is refluxed (heated) with sulfuric acid to produce a phosphoric acid-gypsum slurry (calcium sulfate-CaSO4).

The heating process releases hydrogen fluoride (HF) and silicon tetrafluoride (SiF4) gases, which are captured by vacuum evaporators. These gases are then condensed to a water-based solution of approximately 23% FSA.

Yes

$321,000

$213,000 at Lakeview $108,000 at Lorne Park

Peel Cornwall London Ottawa

Hydrofluorosilicic Acid (HFSA) - water based Chemical Formula: H2SiF6

Calcium Fluoride

Hydrogen fluoride is produced from fluorspar, the commercial name for the mineral fluorite (CaF2).

The gases, mainly hydrogen fluoride, emerge from the end of a horizontal kiln, and are fractionally distilled in a column, termed the pre-scrubber. Solids and sulfuric acid are removed and the hydrogen fluoride vapour is purified to >99.9% purity by distillation in copper or steel vessels, condensed and stored in steel containers.

Yes

$364,000


Durham Hamilton Toronto

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FLUORIDATION OF DRINKING WATER IN THE REGION OF PEEL Appendix I

2

Additive Source Mineral/Rock

Description NSF 60 Certification

Annual Cost Jurisdictions using the Product

Sodium Fluorosilicate - dry additive Chemical Formula: Na2SiF6

Most likely from Phosphorite Rock HFSA

Made by neutralizing HFSA with sodium chloride or sodium sulfate.

Similar in application to sodium fluoride.

Yes

$200,000


Denver Water Foothills WTP - a 300 million gallons / day facility.

Sodium Fluoride - dry additive Chemical Formula: NaF

Most likely from Phosphorite Rock HFSA

Sodium fluoride is either produced by neutralizing hydrofluoric acid with soda ash, or reacting sodium fluorosilicate with caustic soda or soda ash.

Sodium fluoride is manufactured by the reaction of hydrofluoric acid with sodium carbonate or sodium hydroxide. The salt (NaF) is centrifuged and dried.

Yes

$200,000

$130,000 at Lakeview $ 70,000 at Lorne Park

City of Merced, California. Population 80,000. 22 groundwater wells.

Pharmaceutical Grade Fluoride (usually comes in a powder form)

Most likely from Calcium Fluoride

Generally, this type of fluoride containing powder is produced by the same method as exposing calcium fluoride to sulphuric acid, making hydrogen fluoride.

Subject to U.S. Pharmacopeia-National Formulary (USP 29 NF–24) acceptance criteria which do not include specific protection levels for individual contaminants such as arsenic and lead.

NA

Unknown Could not locate municipalities that use it, likely due to lack of NSF 60 certification.

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330 www.thelancet.com/neurology Vol 13 March 2014

Review

Neurobehavioural eff ects of developmental toxicity

Philippe Grandjean, Philip J Landrigan

Neurodevelopmental disabilities, including autism, attention-defi cit hyperactivity disorder, dyslexia, and other cognitive impairments, aff ect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identifi ed fi ve industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants—manganese, fl uoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these eff orts and to accelerate translation of science into prevention, we propose the urgent formation of a new international clearinghouse.

IntroductionDisorders of neurobehavioural development aff ect 10–15% of all births,1 and prevalence rates of autism spectrum disorder and attention-defi cit hyperactivity disorder seem to be increasing worldwide.2 Subclinical decrements in brain function are even more common than these neurobehavioural developmental disorders. All these disabilities can have severe consequences3—they diminish quality of life, reduce academic achievement, and disturb behaviour, with profound consequences for the welfare and productivity of entire societies.4

The root causes of the present global pandemic of neurodevelopmental disorders are only partly understood. Although genetic factors have a role,5 they cannot explain recent increases in reported prevalence, and none of the genes discovered so far seem to be responsible for more than a small proportion of cases.5 Overall, genetic factors seem to account for no more than perhaps 30–40% of all cases of neurodevelopmental disorders. Thus, non-genetic, environmental exposures are involved in causation, in some cases probably by interacting with genetically inherited predispositions.

Strong evidence exists that industrial chemicals widely disseminated in the environment are important contributors to what we have called the global, silent pandemic of neurodevelopmental toxicity.6,7 The developing human brain is uniquely vulnerable to toxic chemical exposures, and major windows of developmental vulnerability occur in utero and during infancy and early childhood.8 During these sensitive life stages, chemicals can cause permanent brain injury at low levels of exposure that would have little or no adverse eff ect in an adult.

In 2006, we did a systematic review of the published clinical and epidemiological studies into the neurotoxicity of industrial chemicals, with a focus on developmental neurotoxicity.6 We identifi ed fi ve industrial chemicals that could be reliably classifi ed as developmental neurotoxicants: lead, methylmercury, arsenic, poly-chlorinated biphenyls, and toluene. We also noted 201 chemicals that had been reported to cause injury

to the nervous system in adults, mostly in connection with occupational exposures, poisoning incidents, or suicide attempts. Additionally, more than 1000 chemicals have been reported to be neurotoxic in animals in laboratory studies.

We noted that recognition of the risks of industrial chemicals to brain development has historically needed decades of research and scrutiny, as shown in the cases of lead and methylmercury.9,10 In most cases, discovery began with clinical diagnosis of poisoning in workers and episodes of high-dose exposure. More sophisticated epidemiological studies typically began only much later. Results from such studies documented developmental neurotoxicity at much lower exposure levels than had previously been thought to be safe. Thus, recognition of widespread subclinical toxicity often did not occur until decades after the initial evidence of neurotoxicity. A recurring theme was that early warnings of subclinical neurotoxicity were often ignored or even dismissed.11 David P Rall, former Director of the US National Institute of Environmental Health Sciences, once noted that “if thalidomide had caused a ten-point loss of intelligence quotient (IQ) instead of obvious birth defects of the limbs, it would probably still be on the market”.12 Many industrial chemicals marketed at present probably cause IQ defi cits of far fewer than ten points and have therefore eluded detection so far, but their combined eff ects could have enormous consequences.

In our 2006 review,6 we expressed concern that additional developmental neurotoxicants might lurk undiscovered among the 201 chemicals then known to be neurotoxic to adult human beings and among the many thousands of pesticides, solvents, and other industrial chemicals in widespread use that had never been tested for neurodevelopmental toxicity. Since our previous review, new data have emerged about the vulnerability of the developing brain and the neurotoxicity of industrial chemicals. Particularly important new evidence derives from prospective epidemiological birth cohort studies.

In this Review, we consider recent information about the developmental neurotoxicity of industrial chemicals

Lancet Neurol 2014; 13: 330–38

Published Online

February 15, 2014

http://dx.doi.org/10.1016/

S1474-4422(13)70278-3

Department of Environmental

Medicine, University of

Southern Denmark, Odense,

Denmark (P Grandjean MD);

Department of Environmental

Health, Harvard School of

Public Health, Boston, MA, USA

(P Grandjean); and Icahn School

of Medicine at Mount Sinai,

New York, NY, USA

(P J Landrigan MD)

Correspondence to:

Dr Philippe Grandjean,

Environmental and Occupational

Medicine and Epidemiology,

Harvard School of Public Health,

401 Park Drive E-110, Boston,

MA 02215, USA

[email protected]

REFERRAL TO ______________________________

RECOMMENDED

DIRECTION REQUIRED _______________________

RECEIPT RECOMMENDED ____________________P

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68493

Stamp - Clerks Received

68493

Typewritten Text

MAY 25 16

www.thelancet.com/neurology Vol 13 March 2014 331

Review

to update our previous report.6 Additionally, we propose strategies to counter this pandemic and to prevent the spread of neurological disease and disability in children worldwide.

Unique vulnerability of the developing brainThe fetus is not well protected against industrial chemicals. The placenta does not block the passage of many environmental toxicants from the maternal to the fetal circulation,13 and more than 200 foreign chemicals have been detected in umbilical cord blood.14 Additionally, many environmental chemicals are transferred to the infant through human breastmilk.13 During fetal life and early infancy, the blood–brain barrier provides only partial protection against the entry of chemicals into the CNS.15

Moreover, the developing human brain is exceptionally sensitive to injury caused by toxic chemicals,6 and several developmental processes have been shown to be highly vulnerable to chemical toxicity. For example, in-vitro studies suggest that neural stem cells are very sensitive to neurotoxic substances such as methylmercury.16 Some pesticides inhibit cholinesterase function in the developing brain,17 thereby aff ecting the crucial regulatory role of acetylcholine before synapse formation.18 Early-life epigenetic changes are also known to aff ect subsequent gene expression in the brain.19 In summary, industrial chemicals known or suspected to be neurotoxic to adults are also likely to present risks to the developing brain.

Figure 1 shows the unique vulnerability of the brain during early life and indicates how developmental exposures to toxic chemicals are particularly likely to lead to functional defi cits and disease later in life.

New fi ndings about known hazardsRecent research on well-documented neurotoxicants has generated important new insights into the neuro-developmental consequences of early exposures to these industrial chemicals.

Joint analyses that gathered data for lead-associated IQ defi cits from seven international studies20,21 support the conclusion that no safe level of exposure to lead exists.22 Cognitive defi cits in adults who had previously shown lead-associated developmental delays at school age suggest that the eff ects of lead neurotoxicity are probably permanent.23 Brain imaging of young adults who had raised lead concentrations in their blood during childhood showed exposure-related decreases in brain volume.24 Lead exposure in early childhood is associated with reduced school performance25 and with delinquent behaviour later in life.26,27

Developmental neurotoxicity due to methylmercury occurs at much lower exposures than the concentrations that aff ect adult brain function.28 Defi cits at 7 years of age that were linked to low-level prenatal exposures to methylmercury were still detectable at the age of 14 years.29 Some common genetic polymorphisms seem to increase the vulnerability of the developing brain to

methylmercury toxicity.30 Functional MRI scans of people exposed prenatally to excess amounts of methylmercury showed abnormally expanded activation of brain regions in response to sensory stimulation and motor tasks (fi gure 2).31 Because some adverse eff ects might be counterbalanced by essential fatty acids from seafood, statistical adjustment for maternal diet during pregnancy results in stronger methylmercury eff ects.32,33

Prenatal and early postnatal exposures to inorganic arsenic from drinking water are associated with cognitive defi cits that are apparent at school age.34,35 Infants who survived the Morinaga milk arsenic poisoning incident had highly raised risks of neurological disease during adult life.36

The developmental neurotoxicity of polychlorinated biphenyls has been consolidated and strengthened by recent fi ndings.37 Although little new information has been published about the developmental neurotoxicity of toluene, much has been learned about the developmental neurotoxicity of another common solvent, ethanol, through research on fetal alcohol exposure. Maternal consumption of alcohol during pregnancy, even in very small quantities, has been linked to a range of neurobehavioural adverse eff ects in off spring, including reduced IQ, impaired executive function and social judgment, delinquent behaviour, seizures, other neurological signs, and sensory problems.38

Newly recognised developmental neurotoxicantsProspective epidemiological birth cohort studies make it possible to measure maternal or fetal exposures in real time during pregnancy as these exposures actually occur, thus generating unbiased information about the degree and timing of prenatal exposures. Children in these prospective studies are followed longitudinally and assessed with age-appropriate tests to show delayed or deranged neurobehavioural development. These powerful epidemiological methods have enabled the discovery of additional developmental neurotoxicants.

Figure 1: Eff ect of neurotoxicants during early brain development

Exposures in early life to neurotoxic chemicals can cause a wide range of adverse

eff ects on brain development and maturation that can manifest as functional

impairments or disease at any point in the human lifespan, from early infancy to

very old age.

Early-life exposures to neurotoxic chemicals

Development/programming

Functional maturation

Neurological disease and degenerative changes

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Review

Cross-sectional data from Bangladesh show that exposure to manganese from drinking water is associated with reduced mathematics achievement scores in school children.39 A study in Quebec, Canada, showed a strong correlation between manganese concentrations in hair and hyperactivity.40 School-aged children living near manganese mining and processing facilities have shown associations between airborne manganese concentrations and diminished intellectual function41 and with impaired motor skills and reduced olfactory function.42 These results are supported by experimental fi ndings in mice.43

A meta-analysis of 27 cross-sectional studies of children exposed to fl uoride in drinking water, mainly from China, suggests an average IQ decrement of about seven points in children exposed to raised fl uoride concentrations.44 Confounding from other substances seemed unlikely in most of these studies. Further characterisation of the dose–response association would be desirable.

The occupational health literature45 suggests that solvents can act as neurotoxicants, but the identifi cation of individual responsible compounds is hampered by the complexity of exposures. In a French cohort study of 3000 children, investigators linked maternal occupational solvent exposure during pregnancy to defi cits in behavioural assessment at 2 years of age.46 The data showed dose-related increased risks for hyperactivity and aggressive behaviour. One in every fi ve mothers in this cohort reported solvent exposures in common jobs, such as nurse or other hospital employee, chemist, cleaner, hairdresser, and beautician. In Massachusetts, USA, follow-up of a well-defi ned population with prenatal and early childhood exposure to the solvent tetrachloroethylene (also called perchlor ethylene) in drinking water showed a tendency towards defi cient neurological function and increased risk of psychiatric diagnoses.47

Acute pesticide poisoning occurs frequently in children worldwide, and subclinical pesticide toxicity is also widespread. Clinical data suggest that acute pesticide poisoning during childhood might lead to lasting neurobehavioural defi cits.48,49 Highly toxic and bio-accumulative pesticides are now banned in high-income nations, but are still used in many low-income and middle-income countries. In particular, the organochlorine compounds dichlorodiphenyltrichloroethane (DDT), its metabolite dichlorodiphenyldichloroethylene (DDE), and chlordecone (Kepone), tend to be highly persistent and remain widespread in the environment and in people’s bodies in high-use regions. Recent studies have shown inverse correlations between serum concentrations of DDT or DDE (which indicate accumulated exposures), and neurodevelopmental performance.50,51

Organophosphate pesticides are eliminated from the human body much more rapidly than are organochlorines, and exposure assessment is therefore inherently less precise. Nonetheless, three prospective epidemiological birth cohort studies provide new evidence that prenatal exposure to organophosphate pesticides can cause developmental neurotoxicity. In these studies, prenatal organophosphate exposure was assessed by measurement of maternal urinary excretion of pesticide metabolites during pregnancy. Dose-related correlations were recorded between maternal exposures to chlorpyrifos or other organophosphates and small head circumference at birth—which is an indication of slowed brain growth in utero—and with neurobehavioural defi cits that have persisted to at least 7 years of age.52–54 In a subgroup study, MRI of the brain showed that prenatal chlorpyrifos exposure was associated with structural abnormalities that included thinning of the cerebral cortex.55

Herbicides and fungicides might also have neurotoxic potential.56 Propoxur,57 a carbamate pesticide, and permethrine,58 a member of the pyrethroid class of pesticides, have recently been linked to neuro develop-mental defi cits in children.

The group of compounds known as polybrominated diphenyl ethers (PBDEs) are widely used as fl ame retardants and are structurally very similar to the polychlorinated biphenyls. Experimental evidence now suggests that the PBDEs might also be neurotoxic.59 Epidemiological studies in Europe and the USA have shown neurodevelopmental defi cits in children with increased prenatal exposures to these compounds.60–62 Thus, the PBDEs should be regarded as hazards to human neurobehavioural development, although attribution of relative toxic potentials to individual PBDE congeners is not yet possible.

Other suspected developmental neurotoxicants A serious diffi culty that complicates many epidemiological studies of neurodevelopmental toxicity in children is the problem of mixed exposures. Most populations are exposed to more than one neurotoxicant at a time, and yet

Figure 2: Functional MRI scans show abnormal activation in the brain

Average activation during fi nger tapping with the left hand in three adolescents with increased prenatal

methylmercury exposure (A) and three control adolescents (B). The control participants activate the premotor and

motor cortices on the right, whereas participants exposed to methylmercury activate these areas bilaterally.31

A

B

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most studies have only a fi nite amount of power and precision in exposure assessment to discern the possible eff ects of even single neurotoxicants. A further problem in many epi demiological studies of non-persistent toxicants is that imprecise assessment of exposure tends to obscure associations that might actually be present.63 Guidance from experimental neurotoxicity studies is therefore crucial. In the assessment of potential developmental neurotoxicants, we have used a strength of evidence approach similar to that used by the International Agency for Research on Cancer for assessing epidemiological and experimental studies.

Phthalates and bisphenol A are added to many diff erent types of plastics, cosmetics, and other consumer products. Since they are eliminated rapidly in urine, exposure assessment is complicated, and such imprecision might lead to underestimation of the true risk of neurotoxicity. The best-documented eff ects of early-life exposure to phthalates are the consequence of disruption of endocrine signalling.64 Thus, prenatal exposures to phthalates have been linked to both neurodevelopmental defi cits and to behavioural ab-normalities characterised by shortened attention span and impaired social interactions.65 The neurobehavioural toxicity of these compounds seems to aff ect mainly boys and could therefore relate to endocrine disruption in the developing brain.66 In regard to bisphenol A, a prospective study showed that point estimates of exposure during gestation were linked to abnormalities in behaviour and executive function in children at 3 years of age.67

Exposure to air pollution can cause neuro developmental delays and disorders of behavioural functions.68,69 Of the individual components of air pollution, carbon monoxide is a well-documented neurotoxicant, and indoor exposure to this substance has now been linked to defi cient neurobehavioural performance in children.70 Less clear is the reported contribution of nitrogen oxides to neurodevelopmental defi cits,71 since these compounds often co-occur with carbon monoxide as part of complex emissions. Tobacco smoke is a complex mixture of hundreds of chemical compounds and is now a well-documented cause of developmental neurotoxicity.72 Infants exposed pre natally to polycyclic aromatic hydrocarbons from traffi c exhausts at 5 years of age showed greater cognitive impairment and lower IQ than those exposed to lower levels of these compounds.68

Perfl uorinated compounds, such as perfl uorooctanoic acid and perfl uorooctane sulphonate, are highly persistent in the environment and in the human body, and seem to be neurotoxic.73 Emerging epidemiological evidence suggests that these compounds might indeed impede neurobehavioural development.74

Developmental neurotoxicity and clinical neurologyExposures in early life to developmental neurotoxicants are now being linked to specifi c clinical syndromes in

children. For example, an increased risk of attention-defi cit hyperactivity disorder has been linked to prenatal exposures to manganese, organophosphates,75 and phthalates.76 Phthalates have also been linked to behaviours that resemble components of autism spectrum disorder.77 Prenatal exposure to automotive air pollution in California, USA, has been linked to an increased risk for autism spectrum disorder.78

The persistent decrements in intelligence documented in children, adolescents, and young adults exposed in early life to neurotoxicants could presage the development of neurodegenerative disease later in life. Thus, accumulated exposure to lead is associated with cognitive decline in the elderly.79 Manganese exposure may lead to parkinsonism, and experimental studies have reported Parkinson’s disease as a result of developmental exposures to the insecticide rotenone, the herbicides paraquat and maneb, and the solvent trichloroethylene.80 Any environmental exposure that increases the risk of neurodegenerative disorders in later life (fi gure 1) requires urgent investigation as the world’s population continues to age.81

The expanding complement of neurotoxicantsIn our 2006 review,6 we expressed concern that additional developmental neurotoxicants might lie undiscovered in the 201 chemicals that were then known to be neurotoxic to human adults, in the roughly 1000 chemicals known to be neurotoxic in animal species, and in the many thousands of industrial chemicals and pesticides that have never been tested for neurotoxicity. Exposure to neurotoxic chemicals is not rare, since almost half of the 201 known human neurotoxicants are regarded as high production volume chemicals.

Our updated literature review shows that since 2006 the list of recognised human neurotoxicants has expanded by 12 chemicals, from 202 (including ethanol) to 214 (table 1 and appendix)—that is, by about two substances per year. Many of these chemicals are widely used and disseminated extensively in the global environment. Of the newly identifi ed neuro developmental toxicants, pesticides constitute the largest group, as was already the case in

Number

known in

2006

Number

known in

2013

Identifi ed since 2006

Metals and inorganic

compounds

25 26 Hydrogen phosphide82

Organic solvents 39* 40 Ethyl chloride83

Pesticides 92 101 Acetamiprid,84 amitraz,85 avermectin,86 emamectin,87

fi pronil (Termidor),88 glyphosate,89 hexaconazole,90

imidacloprid,91 tetramethylenedisulfotetramine92

Other organic compounds 46 47 1,3-butadiene93

Total 202* 214 12 new substances

*Including ethanol.

Table 1: Industrial chemicals known to be toxic to the human nervous system in 2006 and 2013,

according to chemical group

See Online for appendix

5.1-4


Review

2006. In the same 7-year period, the number of known developmental neurotoxicants has doubled from six to 12 (table 2). Although the pace of scientifi c discovery of new neurodevelopmental hazards is more rapid today than in the past, it is still slower than the identifi cation of adult neurotoxicants.

The gap that exists between the number of substances known to be toxic to the adult brain and the smaller number known to be toxic to the much more vulnerable developing brain is unlikely to close in the near future. This discrepancy is attributable to the fact that toxicity to the adult brain is usually discovered as a result of acute poisoning incidents, typically with a clear and immediate association between causative exposure and adverse eff ects, as occurs for workplace exposures or suicide attempts. By contrast, the recognition of developmental neurotoxicity relies on two sets of evidence collected at two diff erent points in time: exposure data (often obtained from the mother during pregnancy), and data for the child’s postnatal neurobehavioural development (often obtained 5–10 years later). Because brain functions develop sequentially, the full eff ects of early neurotoxic damage might not become apparent until school age or beyond. The most reliable evidence of developmental neurotoxicity is obtained through prospective studies that include

real-time recording of information about exposure in early life followed by serial clinical assessments of the child. Such research is inherently slow and is hampered by the diffi culty of reliable assessment of exposures to individual toxicants in complex mixtures.

Consequences of developmental neurotoxicityDevelopmental neurotoxicity causes brain damage that is too often untreatable and frequently permanent. The consequence of such brain damage is impaired CNS function that lasts a lifetime and might result in reduced intelligence, as expressed in terms of lost IQ points, or disruption in behaviour. A recent study compared the estimated total IQ losses from major paediatric causes and showed that the magnitude of losses attributable to lead, pesticides, and other neurotoxicants was in the same range as, or even greater than, the losses associated with medical events such as preterm birth, traumatic brain injury, brain tumours, and congenital heart disease (table 3).94

Loss of cognitive skills reduces children’s academic and economic attainments and has substantial long-term economic eff ects on societies.4 Thus, each loss of one IQ point has been estimated to decrease average lifetime earnings capacity by about €12 000 or US$18 000 in 2008 currencies.96 The most recent estimates from the USA indicate that the annual costs of childhood lead poisoning are about US$50 billion and that the annual costs of methylmercury toxicity are roughly US$5 billion.97 In the European Union, methylmercury exposure is estimated to cause a loss of about 600 000 IQ points every year, corresponding to an annual economic loss of close to €10 billion. In France alone, lead exposure is associated with IQ losses that correspond to annual costs that might exceed €20 billion.98 Since IQ losses represent only one aspect of developmental neurotoxicity, the total costs are surely even higher.

Evidence from worldwide sources indicates that average national IQ scores are associated with gross domestic product (GDP)—a correlation that might be causal in both directions.99 Thus, poverty can cause low IQ, but the opposite is also true. In view of the widespread exposures to lead, pesticides, and other neurotoxicants in developing countries, where chemical controls might be ineff ective compared with those in more developed countries,100,101 developmental exposures to industrial chemicals could contribute substantially to the recorded correlation between IQ and GDP. If this theory is true, developing countries could take decades to emerge from poverty. Consequently, pollution abatement might then be delayed, and a vicious circle can result.

The antisocial behaviour, criminal behaviour, violence, and substance abuse that seem to result from early-life exposures to some neurotoxic chemicals result in increased needs for special educational services, institutionalisation, and even incarceration. In the USA, the murder rate fell sharply 20 years after the removal of lead from petrol,102 a fi nding consistent with the idea that

Known in 2006 Newly identifi ed

Metals and inorganic compounds Arsenic and arsenic compounds,

lead, and methylmercury

Fluoride and manganese

Organic solvents (Ethanol) toluene Tetrachloroethylene

Pesticides None Chlorpyrifos and DDT/DDE

Other organic compounds Polychlorinated biphenyls Brominated diphenyl ethers

Total 6* 6

DDT=dichlorodiphenyltrichloroethane. DDE=dichlorodiphenyldichloroethylene. *Including ethanol.

Table 2: Industrial chemicals known to cause developmental neurotoxicity in human beings in 2006 and

2013, according to chemical group

Number of IQ points lost

Major medical and neurodevelopmental disorders

Preterm birth 34 031 025

Autism spectrum disorders 7 109 899

Paediatric bipolar disorder 8 164 080

Attention-defi cit hyperactivity disorder 16 799 400

Postnatal traumatic brain injury 5 827 300

Environmental chemical exposures

Lead 22 947 450

Methylmercury 1 590 000*

Organophosphate pesticides 16 899 488

Other neurotoxicants Unknown

IQ=intelligence quotient. Data from from Bellinger.94 *From Grandjean and

colleagues.95

Table 3: Total losses of IQ points in US children 0–5 years of age

associated with major risk factors, including developmental exposure

to industrial chemicals that cause neurotoxicity

5.1-5


Review

exposure to lead in early life is a powerful determinant of behaviour decades later. Although poorly quantifi ed, such behavioural and social consequences of neuro-developmental toxicity are potentially very costly.76

Prevention of developmental neurotoxicity caused by industrial chemicals is highly cost eff ective. A study that quantifi ed the gains resulting from the phase-out of lead additives from petrol reported that in the USA alone, the introduction of lead-free petrol has generated an economic benefi t of $200 billion in each annual birth cohort since 1980,103 an aggregate benefi t in the past 30 years of over $3 trillion. This success has since been repeated in more than 150 countries, resulting in vast additional savings. Every US$1 spent to reduce lead hazards is estimated to produce a benefi t of US$17–220, which represents a cost-benefi t ratio that is even better than that for vaccines.4 Furthermore, the costs associated with the late-life consequences of developmental neurotoxicity are enormous, and the benefi ts from prevention of degenerative brain disorders could be very substantial.

New methods to identify developmental neurotoxicantsNew toxicological methods now allow a rational strategy for the identifi cation of developmental neurotoxicants based on a multidisciplinary approach.104 A new guideline has been approved as a standardised approach for the identifi cation of developmental neurotoxicants.105 However, completion of such tests is expensive and requires the use of many laboratory animals, and reliance on mammals for chemicals testing purposes needs to be reduced.106 US governmental agencies have established the National Center for Computational Toxicology and an initiative—the Tox 21 Program—to promote the evolution of toxicology from a mainly observational science to a predominantly predictive science.107

In-vitro methods have now reached a level of predictive validity that means they can be applied to neurotoxicity testing.108 Some of these tests are based on neural stem cells. Although these cell systems do not have a blood–brain barrier and particular metabolising enzymes, these approaches are highly promising. As a further option, data for protein links and protein–protein interactions can now be used to explore potential neurotoxicity in silico,109 thus showing that existing computational methods might predict potential toxic eff ects.110

In summary, use of the whole range of approaches along with clinical and epidemiological evidence, when available, should enable the integration of information for use in at least a tentative risk assessment. With these methods, we anticipate that the pace of scientifi c discovery in developmental neurotoxicology will accelerate further in the years ahead.

Conclusions and recommendationsThe updated fi ndings presented in this Review confi rm and extend our 2006 conclusions.6 During the 7 years

since our previous report, the number of industrial chemicals recognised to be developmental neurotoxicants has doubled. Exposures to these industrial chemicals in the environment contribute to the pandemic of developmental neurotoxicity.

Two major obstacles impede eff orts to control the global pandemic of developmental neurotoxicity. These barriers, which we noted in our previous review6 and were recently underlined by the US National Research Council,111 are: large gaps in the testing of chemicals for developmental neurotoxicity, which results in a paucity of systematic data to guide prevention; and the huge amount of proof needed for regulation. Thus, very few chemicals have been regulated as a result of developmental neurotoxicity.

The presumption that new chemicals and technologies are safe until proven otherwise is a fundamental problem.111 Classic examples of new chemicals that were introduced because they conveyed certain benefi ts, but were later shown to cause great harm, include several neurotoxicants, asbestos, thalidomide, diethylstilboestrol, and the chlorofl uorocarbons.112 A recurring theme in each of these cases was that commercial introduction and wide dissemination of the chemicals preceded any systematic eff ort to assess potential toxicity. Particularly absent were advance eff orts to study possible eff ects on children’s health or the potential of exposures in early life to disrupt early development. Similar challenges have been confronted in other public health disasters, such as those caused by tobacco smoking, alcohol use, and refi ned foods. These problems have been recently termed industrial epidemics.113

To control the pandemic of developmental neurotoxicity, we propose a coordinated international strategy (panel). Mandatory and transparent assessment of evidence for neurotoxicity is the foundation of this strategy. Assessment of toxicity must be followed by governmental regulation and market intervention. Voluntary controls seem to be of little value.11

Panel: Recommendations for an international clearinghouse on neurotoxicity

The main purpose of this agency would be to promote optimum brain health, not just

avoidance of neurological disease, by inspiring, facilitating, and coordinating research and

public policies that aim to protect brain development during the most sensitive life stages.

The main eff orts would aim to:

• Screen industrial chemicals present in human exposures for neurotoxic eff ects so that

hazardous substances can be identifi ed for tighter control

• Stimulate and coordinate new research to understand how toxic chemicals interfere

with brain development and how best to prevent long-term dysfunctions and defi cits

• Function as a clearinghouse for research data and strategies by gathering and assessing

documentation about brain toxicity and stimulating international collaboration on

research and prevention

• Promote policy development aimed at protecting vulnerable populations against

chemicals that are toxic to the brain without needing unrealistic amounts of scientifi c

proof

5.1-6


Review

The three pillars of our proposed strategy are: legally mandated testing of existing industrial chemicals and pesticides already in commerce, with prioritisation of those with the most widespread use, and incorporation of new assessment technologies; legally mandated premarket evaluation of new chemicals before they enter markets, with use of precautionary approaches for chemical testing that recognise the unique vulnerability of the developing brain; and the formation of a new clearinghouse for neurotoxicity as a parallel to the International Agency for Research on Cancer. This new agency will assess industrial chemicals for developmental neurotoxicity with a precautionary approach that emphasises prevention and does not require absolute proof of toxicity. It will facilitate and coordinate epidemiological and toxicological studies and will lead the urgently needed global programmes for prevention.

These new approaches must reverse the dangerous presumption that new chemicals and technologies are safe until proven otherwise. They must also overcome the existing requirement to produce absolute proof of toxicity before action can be started to protect children against neurotoxic substances. Precautionary interpretation of data about developmental neurotoxicity should take into account the very large individual and societal costs that result from failure to act on available documentation to prevent disease in children.114 Academic research has often favoured scepticism and required extensive replication before acceptance of a hypothesis,114 thereby adding to the inertia in toxicology and environmental health research and the consequent disregard of many other potential neurotoxicants.115 Additionally, the strength of evidence that is needed to constitute “proof” should be analysed in a societal perspective, so that the implications of ignoring a developmental neurotoxicant and of failing to act on the basis of available data are also taken into account.

Finally, we emphasise that the total number of neurotoxic substances now recognised almost certainly represents an underestimate of the true number of developmental neurotoxicants that have been released into the global environment. Our very great concern is that children

worldwide are being exposed to unrecognised toxic chemicals that are silently eroding intelligence, disrupting behaviours, truncating future achievements, and damaging societies, perhaps most seriously in developing countries. A new framework of action is needed.

Contributors

Both authors did the literature review, wrote and revised the report, and

approved the fi nal version.

Confl icts of interest

PG has provided paid expert testimony about mercury toxicology for the

US Department of Justice. PJL has provided paid expert testimony in

cases of childhood lead poisoning. We declare that we have no other

confl icts of interest.

Acknowledgments

This work was supported by the National Institutes of Health, National

Institute for Environmental Health Sciences (ES09584, ES09797, and

ES11687). The funding source had no role in the literature review,

interpretation of data, writing of this Review, or in the decision to submit

for publication. The contents of this paper are solely the responsibility of

the authors and do not represent the offi cial views of the National

Institutes of Health. We thank Mary S Wolff (Icahn School of Medicine

at Mount Sinai, New York, NY, USA) and Linda S Birnbaum (US

National Institute of Environmental Health Sciences, Research Triangle

Park, NC, USA) for their critical reading of the report.

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for U.S. children: National Health Interview Survey, 2009. Vital Health Stat 2010; 10: 1–82.

2 Landrigan PJ, Lambertini L, Birnbaum LS. A research strategy to discover the environmental causes of autism and neurodevelopmental disabilities. Environ Health Perspect 2012; 120: a258–60.

3 Bellinger DC. Interpreting epidemiologic studies of developmental neurotoxicity: conceptual and analytic issues. Neurotoxicol Teratol 2009; 31: 267–74.

4 Gould E. Childhood lead poisoning: conservative estimates of the social and economic benefi ts of lead hazard control. Environ Health Perspect 2009; 117: 1162–67.

5 National Research Council. Scientifi c frontiers in developmental toxicology and risk assessment. Washington, DC: National Academies Press, 2000.

6 Grandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet 2006; 368: 2167–78.

7 Grandjean P. Only one chance. How environmental pollution impairs brain development – and how to protect the brains of the next generation. New York: Oxford University Press, 2013.

8 Rice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 2000; 108 (suppl 3): 511–33.

9 Needleman HL. The removal of lead from gasoline: historical and personal refl ections. Environ Res 2000; 84: 20–35.

10 Grandjean P, Satoh H, Murata K, Eto K. Adverse eff ects of methylmercury: environmental health research implications. Environ Health Perspect 2010; 118: 1137–45.

11 Landrigan PJ, Goldman LR. Children’s vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy. Health Aff 2011; 30: 842–50.

12 Weiss B. Food additives and environmental chemicals as sources of childhood behavior disorders. J Am Acad Child Psychiatry 1982; 21: 144–52.

13 Needham LL, Grandjean P, Heinzow B, et al. Partition of environmental chemicals between maternal and fetal blood and tissues. Environ Sci Technol 2011; 45: 1121–26.

14 Environmental Working Group. Body burden—the pollution in newborns. Washington, DC: Environmental Working Group, 2005.

15 Zheng W, Aschner M, Ghersi-Egea JF. Brain barrier systems: a new frontier in metal neurotoxicological research. Toxicol Appl Pharmacol 2003; 192: 1–11.

16 Bose R, Onishchenko N, Edoff K, Janson Lang AM, Ceccatelli S. Inherited eff ects of low-dose exposure to methylmercury in neural stem cells. Toxicol Sci 2012; 130: 383–90.

Search strategy and selection criteria

We identifi ed studies published since 2006 on the neurotoxic

eff ects of industrial chemicals in human beings by using the

search terms “neurotoxicity syndromes”[MeSH], “neurotoxic”,

“neurologic”, or “neuro*”, combined with “exposure” and

“poisoning” in PubMed, from 2006 to the end of 2012. For

developmental neurotoxicity, the search terms were “prenatal

exposure delayed eff ects”[MeSH], “maternal exposure” or

“maternal fetal exchange”, “developmental disabilities/

chemically induced” and “neurotoxins”, all of which were

searched for with the limiters “All Child: 0–18 years, Human”.

We also used references cited in the publications retrieved.

5.1-7


Review

17 Costa LG. Current issues in organophosphate toxicology. Clin Chim Acta 2006; 366: 1–13.

18 Augusti-Tocco G, Biagioni S, Tata AM. Acetylcholine and regulation of gene expression in developing systems. J Mol Neurosci 2006; 30: 45–48.

19 Roth TL. Epigenetics of neurobiology and behavior during development and adulthood. Dev Psychobiol 2012; 54: 590–97.

20 Lanphear BP, Hornung R, Khoury J, et al. Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ Health Perspect 2005; 113: 894–99.

21 Budtz-Jorgensen E, Bellinger D, Lanphear B, Grandjean P. An international pooled analysis for obtaining a benchmark dose for environmental lead exposure in children. Risk Anal 2013; 33: 450–61.

22 Grandjean P. Even low-dose lead exposure is hazardous. Lancet 2010; 376: 855–56.

23 Mazumdar M, Bellinger DC, Gregas M, Abanilla K, Bacic J, Needleman HL. Low-level environmental lead exposure in childhood and adult intellectual function: a follow-up study. Environ Health 2011; 10: 24.

24 Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008; 5: e112.

25 Zhang N, Baker HW, Tufts M, Raymond RE, Salihu H, Elliott MR. Early childhood lead exposure and academic achievement: evidence from Detroit public schools, 2008–2010. Am J Public Health 2013; 103: e72–77.

26 Fergusson DM, Boden JM, Horwood LJ. Dentine lead levels in childhood and criminal behaviour in late adolescence and early adulthood. J Epidemiol Community Health 2008; 62: 1045–50.

27 Wright JP, Dietrich KN, Ris MD, et al. Association of prenatal and childhood blood lead concentrations with criminal arrests in early adulthood. PLoS Med 2008; 5: e101.

28 Oken E, Bellinger DC. Fish consumption, methylmercury and child neurodevelopment. Curr Opin Pediatr 2008; 20: 178–83.

29 Debes F, Budtz-Jorgensen E, Weihe P, White RF, Grandjean P. Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years. Neurotoxicol Teratol 2006; 28: 536–47.

30 Julvez J, Smith GD, Golding J, et al. Genetic predisposition to cognitive defi cit at age 8 years associated with prenatal methylmercury exposure. Epidemiology 2013; 24: 643–50.

31 White RF, Palumbo CL, Yurgelun-Todd DA, et al. Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity. Neurotoxicology 2011; 32: 975–80.

32 Budtz-Jorgensen E, Grandjean P, Weihe P. Separation of risks and benefi ts of seafood intake. Environ Health Perspect 2007; 115: 323–27.

33 Strain JJ, Davidson PW, Bonham MP, et al. Associations of maternal long-chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study. Neurotoxicology 2008; 29: 776–82.

34 Wasserman GA, Liu X, Parvez F, et al. Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh. Environ Health Perspect 2007; 115: 285–89.

35 Hamadani JD, Tofail F, Nermell B, et al. Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study. Int J Epidemiol 2011; 40: 1593–604.

36 Tanaka H, Tsukuma H, Oshima A. Long-term prospective study of 6104 survivors of arsenic poisoning during infancy due to contaminated milk powder in 1955. J Epidemiol 2010; 20: 439–45.

37 Engel SM, Wolff MS. Causal inference considerations for endocrine disruptor research in children’s health. Annu Rev Public Health 2013; 34: 139–58.

38 Mattson SN, Crocker N, Nguyen TT. Fetal alcohol spectrum disorders: neuropsychological and behavioral features. Neurospychol Rev 2011; 21: 81–101.

39 Khan K, Wasserman GA, Liu X, et al. Manganese exposure from drinking water and children’s academic achievement. Neurotoxicology 2012; 33: 91–97.

40 Bouchard M, Laforest F, Vandelac L, Bellinger D, Mergler D. Hair manganese and hyperactive behaviors: pilot study of school-age children exposed through tap water. Environ Health Perspect 2007; 115: 122–27.

41 Riojas-Rodriguez H, Solis-Vivanco R, Schilmann A, et al. Intellectual function in Mexican children living in a mining area and environmentally exposed to manganese. Environ Health Perspect 2010; 118: 1465–70.

42 Lucchini RG, Guazzetti S, Zoni S, et al. Tremor, olfactory and motor changes in Italian adolescents exposed to historical ferro-manganese emission. Neurotoxicology 2012; 33: 687–96.

43 Moreno JA, Yeomans EC, Streifel KM, Brattin BL, Taylor RJ, Tjalkens RB. Age-dependent susceptibility to manganese-induced neurological dysfunction. Toxicol Sci 2009; 112: 394–404.

44 Choi AL, Sun G, Zhang Y, Grandjean P. Developmental fl uoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect 2012; 120: 1362–68.

45 Julvez J, Grandjean P. Neurodevelopmental toxicity risks due to occupational exposure to industrial chemicals during pregnancy. Ind Health 2009; 47: 459–68.

46 Pele F, Muckle G, Costet N, et al. Occupational solvent exposure during pregnancy and child behaviour at age 2. Occup Environ Med 2013; 70: 114–19.

47 Janulewicz PA, White RF, Martin BM, et al. Adult neuropsychological performance following prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water. Neurotoxicol Teratol 2012; 34: 350–59.

48 Kofman O, Berger A, Massarwa A, Friedman A, Jaff ar AA. Motor inhibition and learning impairments in school-aged children following exposure to organophosphate pesticides in infancy. Pediatr Res 2006; 60: 88–92.

49 London L, Beseler C, Bouchard MF, et al. Neurobehavioral and neurodevelopmental eff ects of pesticide exposures. Neurotoxicology 2012; 33: 887–96.

50 Torres-Sanchez L, Schnaas L, Rothenberg SJ, et al. Prenatal p,p’-DDE exposure and neurodevelopment among children 3.5–5 years of age. Environ Health Perspect 2013; 121: 263–68.

51 Boucher O, Simard MN, Muckle G, et al. Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants. Neurotoxicology 2013; 35: 162–68.

52 Rauh V, Arunajadai S, Horton M, et al. 7-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect 2011; 119: 1196–201.

53 Bouchard MF, Chevrier J, Harley KG, et al. Prenatal exposure to organophosphate pesticides and IQ in 7-year old children. Environ Health Perspect 2011; 119: 1189–95.

54 Engel SM, Wetmur J, Chen J, et al. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ Health Perspect 2011; 119: 1182–88.

55 Rauh VA, Perera FP, Horton MK, et al. Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci USA 2012; 109: 7871–76.

56 Bjorling-Poulsen M, Andersen HR, Grandjean P. Potential developmental neurotoxicity of pesticides used in Europe. Environ Health 2008; 7: 50.

57 Ostrea EM Jr, Reyes A, Villanueva-Uy E, et al. Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age. Neurotoxicology 2012; 33: 669–75.

58 Horton MK, Rundle A, Camann DE, Boyd Barr D, Rauh VA, Whyatt RM. Impact of prenatal exposure to piperonyl butoxide and permethrin on 36-month neurodevelopment. Pediatrics 2011; 127: e699–706.

59 Dingemans MM, van den Berg M, Westerink RH. Neurotoxicity of brominated fl ame retardants: (in)direct eff ects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system. Environ Health Perspect 2011; 119: 900–07.

60 Roze E, Meijer L, Bakker A, Van Braeckel KN, Sauer PJ, Bos AF. Prenatal exposure to organohalogens, including brominated fl ame retardants, infl uences motor, cognitive, and behavioral performance at school age. Environ Health Perspect 2009; 117: 1953–58.

61 Herbstman JB, Sjodin A, Kurzon M, et al. Prenatal exposure to PBDEs and neurodevelopment. Environ Health Perspect 2010; 118: 712–19.

62 Eskenazi B, Chevrier J, Rauch SA, et al. In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study. Environ Health Perspect 2013; 121: 257–62.

63 Grandjean P, Budtz-Jorgensen E. An ignored risk factor in toxicology: the total imprecision of exposure assessment. Pure Appl Chem 2010; 82: 383–91.

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Review

64 Vandenberg LN, Colborn T, Hayes TB, et al. Hormones and endocrine-disrupting chemicals: low-dose eff ects and nonmonotonic dose responses. Endocr Rev 2012; 33: 378–455.

65 Engel SM, Miodovnik A, Canfi eld RL, et al. Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ Health Perspect 2010; 118: 565–71.

66 Swan SH, Liu F, Hines M, et al. Prenatal phthalate exposure and reduced masculine play in boys. Int J Androl 2010; 33: 259–69.

67 Braun JM, Kalkbrenner AE, Calafat AM, et al. Impact of early-life bisphenol A exposure on behavior and executive function in children. Pediatrics 2011; 128: 873–82.

68 Perera FP, Li Z, Whyatt R, et al. Prenatal airborne polycyclic aromatic hydrocarbon exposure and child IQ at age 5 years. Pediatrics 2009; 124: e195–202.

69 Calderon-Garciduenas L, Mora-Tiscareno A, Ontiveros E, et al. Air pollution, cognitive defi cits and brain abnormalities: a pilot study with children and dogs. Brain Cogn 2008; 68: 117–27.

70 Dix-Cooper L, Eskenazi B, Romero C, Balmes J, Smith KR. Neurodevelopmental performance among school age children in rural Guatemala is associated with prenatal and postnatal exposure to carbon monoxide, a marker for exposure to woodsmoke. Neurotoxicology 2012; 33: 246–54.

71 Vrijheid M, Martinez D, Aguilera I, et al. Indoor air pollution from gas cooking and infant neurodevelopment. Epidemiology 2012; 23: 23–32.

72 Hernandez-Martinez C, Arija Val V, Escribano Subias J, Canals Sans J. A longitudinal study on the eff ects of maternal smoking and secondhand smoke exposure during pregnancy on neonatal neurobehavior. Early Hum Dev 2012; 88: 403–08.

73 Mariussen E. Neurotoxic eff ects of perfl uoroalkylated compounds: mechanisms of action and environmental relevance. Arch Toxicol 2012; 86: 1349–67.

74 Gump BB, Wu Q, Dumas AK, Kannan K. Perfl uorochemical (PFC) exposure in children: associations with impaired response inhibition. Environ Sci Technol 2011; 45: 8151–59.

75 Froehlich TE, Anixt JS, Loe IM, Chirdkiatgumchai V, Kuan L, Gilman RC. Update on environmental risk factors for attention-defi cit/hyperactivity disorder. Curr Psychiatry Rep 2011; 13: 333–44.

76 Carpenter DO, Nevin R. Environmental causes of violence. Physiol Behav 2010; 99: 260–68.

77 Miodovnik A, Engel SM, Zhu C, et al. Endocrine disruptors and childhood social impairment. Neurotoxicology 2011; 32: 261–67.

78 Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffi c-related air pollution, particulate matter, and autism. JAMA Psychiatry 2013; 70: 71–77.

79 Bandeen-Roche K, Glass TA, Bolla KI, Todd AC, Schwartz BS. Cumulative lead dose and cognitive function in older adults. Epidemiology 2009; 20: 831–39.

80 Lock EA, Zhang J, Checkoway H. Solvents and Parkinson disease: a systematic review of toxicological and epidemiological evidence. Toxicol Appl Pharmacol 2013; 266: 345–55.

81 Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D. Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect 2005; 113: 1230–33.

82 Lauterbach M, Solak E, Kaes J, Wiechelt J, Von Mach MA, Weilemann LS. Epidemiology of hydrogen phosphide exposures in humans reported to the poison center in Mainz, Germany, 1983–2003. Clin Toxicol 2005; 43: 575–81.

83 Demarest C, Torgovnick J, Sethi NK, Arsura E, Sethi PK. Acute reversible neurotoxicity associated with inhalation of ethyl chloride: a case report. Clin Neurol Neurosurg 2011; 113: 909–10.

84 Imamura T, Yanagawa Y, Nishikawa K, Matsumoto N, Sakamoto T. Two cases of acute poisoning with acetamiprid in humans. Clin Toxicol 2010; 48: 851–53.

85 Veale DJ, Wium CA, Muller GJ. Amitraz poisoning in South Africa: a two year survey (2008–2009). Clin Toxicol 2011; 49: 40–44.

86 Sung YF, Huang CT, Fan CK, Lin CH, Lin SP. Avermectin intoxication with coma, myoclonus, and polyneuropathy. Clin Toxicol 2009; 47: 686–88.

87 Yang CC. Acute human toxicity of macrocyclic lactones. Curr Pharm Biotechnol 2012; 13: 999–1003.

88 Lee SJ, Mulay P, Diebolt-Brown B, et al. Acute illnesses associated with exposure to fi pronil—surveillance data from 11 states in the United States, 2001–2007. Clin Toxicol 2010; 48: 737–44.

89 Malhotra RC, Ghia DK, Cordato DJ, Beran RG. Glyphosate-surfactant herbicide-induced reversible encephalopathy. J Clin Neurosci 2010; 17: 1472–73.

90 David D, Prabhakar A, Peter JV, Pichamuthu K. Human poisoning with hexastar: a hexaconazole-containing agrochemical fungicide. Clin Toxicol 2008; 46: 692–93.

91 Shadnia S, Moghaddam HH. Fatal intoxication with imidacloprid insecticide. Am J Emerg Med 2008; 26: 634.e1–4.

92 Deng X, Li G, Mei R, Sun S. Long term eff ects of tetramine poisoning: an observational study. Clin Toxicol 2012; 50: 172–75.

93 Khalil M, Abudiab M, Ahmed AE. Clinical evaluation of 1,3-butadiene neurotoxicity in humans. Toxicol Ind Health 2007; 23: 141–46.

94 Bellinger DC. A strategy for comparing the contributions of environmental chemicals and other risk factors to neurodevelopment of children. Environ Health Perspect 2012; 120: 501–07.

95 Grandjean P, Pichery C, Bellanger M, Budtz-Jorgensen E. Calculation of mercury’s eff ects on neurodevelopment. Environ Health Perspect 2012; 120: A452.

96 Bellanger M, Pichery C, Aerts D, et al. Economic benefi ts of methylmercury exposure control in Europe: monetary value of neurotoxicity prevention. Environ Health 2013; 12: 3.

97 Trasande L, Liu Y. Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008. Health Aff 2011; 30: 863–70.

98 Pichery C, Bellanger M, Zmirou-Navier D, Glorennec P, Hartemann P, Grandjean P. Childhood lead exposure in France: benefi t estimation and partial cost-benefi t analysis of lead hazard control. Environ Health 2011; 10: 44.

99 Lynn R, Vanhanen T. IQ and the wealth of nations. Westport: Praeger, 2002.

100 Blacksmith Institute. The world’s worst pollution problems: assessing health risks at hazardous waste sites. New York: Blacksmith Institute, 2012.

101 Trasande L, Massey RI, DiGangi J, Geiser K, Olanipekun AI, Gallagher L. How developing nations can protect children from hazardous chemical exposures while sustaining economic growth. Health Aff 2011; 30: 2400–09.

102 Nevin R. Understanding international crime trends: the legacy of preschool lead exposure. Environ Res 2007; 104: 315–36.

103 Schwartz J. Societal benefi ts of reducing lead exposure. Environ Res 1994; 66: 105–24.

104 National Research Council. Toxicity testing in the 21st century: a vision and a strategy. Washington, DC: National Academies Press, 2007.

105 Makris SL, Raff aele K, Allen S, et al. A retrospective performance assessment of the developmental neurotoxicity study in support of OECD test guideline 426. Environ Health Perspect 2009; 117: 17–25.

106 Rovida C, Longo F, Rabbit RR. How are reproductive toxicity and developmental toxicity addressed in REACH dossiers? Altex 2011; 28: 273–94.

107 Collins FS, Gray GM, Bucher JR. Toxicology. Transforming environmental health protection. Science 2008; 319: 906–07.

108 Crofton KM, Mundy WR, Lein PJ, et al. Developmental neurotoxicity testing: recommendations for developing alternative methods for the screening and prioritization of chemicals. Altex 2011; 28: 9–15.

109 Audouze K, Grandjean P. Application of computational systems biology to explore environmental toxicity hazards. Environ Health Perspect 2011; 119: 1754–59.

110 Willighagen EL, Jeliazkova N, Hardy B, Grafstrom RC, Spjuth O. Computational toxicology using the OpenTox application programming interface and Bioclipse. BMC Res Notes 2011; 4: 487.

111 National Research Council. Science and decisions: advancing risk assessment. Washington, DC: National Academies Press, 2009.

112 Late lessons from early warnings: science, precaution, innovation. Copenhagen: European Environment Agency, 2013.

113 Moodie R, Stuckler D, Monteiro C, et al. Profi ts and pandemics: prevention of harmful eff ects of tobacco, alcohol, and ultra-processed food and drink industries. Lancet 2013; 381: 670–79.

114 Grandjean P. Seven deadly sins of environmental epidemiology and the virtues of precaution. Epidemiology 2008; 19: 158–62.

115 Grandjean P, Eriksen ML, Ellegaard O, Wallin JA. The Matthew eff ect in environmental science publication: a bibliometric analysis of chemical substances in journal articles. Environ Health 2011; 10: 96.

5.1-9

Neurodevelopmental toxicity: still more questions than answers

Volume 13, No. 7, p647–648, July 2014

Julianna Gelinas , Myron Allukian Jr

The American Association for Community Dental Programs' primary goal is to support the

efforts of those serving the oral health needs of vulnerable populations at the community level.

In view of our commitment to preventing oral diseases and improving access to services for the

public, we read with interest Grandjean and Landrigan's Review on neurobehavioral effects of

developmental toxicity.1

In their Review, Grandjean and Landrigan claim that fluoride might cause neurodevelopmental

harm, a claim based on only one paper,2 of which Grandjean is a coauthor. The study

methodology contains several flaws that undermine its credibility and calls into question its

applicability to the community water fluoridation programme in the USA.

The study2 is a meta-analysis of 27 cross-sectional studies done in poor, rural communities in

China, Mongolia, and Iran, countries where the drinking water contains high levels of naturally

occurring fluoride. The 27 original studies did not adequately control for a variety of intervening

and confounding variables that could have affected intelligence quotient (IQ) scores, such as

parents' education and socioeconomic status and air and water pollution. It is unfortunate that

Grandjean and Landrigan did not mention these limitations.

Additionally, they did not clearly state that the reference groups in their article2 use water

fluoridated at about the recommended level. Thus, another interpretation of their analysis could

be that communities fluoridated at the recommended level have a higher IQ.

No credible scientific studies show a relation between fluoride consumption and IQ levels;

however, several have shown that fluoride ingested at recommended levels is not harmful.

Grandjean and Landrigan did not acknowledge the animal study3 that showed no evidence of a

neurotoxic effect of fluoride, even at levels up to 230 times the recommended concentration; an

earlier study showing that fluoride causes no harm to children;4 two formal reviews that

delineate weaknesses in the Chinese fluoride and IQ studies;5, 6 and the conclusion by one of

these sets of investigators6 that biological plausibility for a link between fluoridated water and IQ

has not been established.

5.1-10

http://www.thelancet.com/journals/laneur/issue/vol13no7/PIIS1474-4422(14)X7044-4

Unfortunately, Grandjean and Landrigan's Review has been aggressively and improperly used

by antifluoridationists to frighten the public about the effects of fluoridation, a well-established

public health measure that has been shown to be cost-effective and safe. As a result, the

public's oral health, especially that of the most vulnerable people, is put in jeopardy.

As advocates for better oral health and for serving the public's best interest, we are pleased

that The Lancet Neurology is providing a forum for credible experts and organisations to reaffirm

the safety and cost-effectiveness of fluoridation—a proven public health measure.

A statement from Grandjean and Landrigan clearly stating that their addition of fluoride to their

list of neurotoxins does not apply to fluoridation at the recommended levels of 0·7–1·2 ppm

would clarify our concerns on the misuse and misinterpretation of their paper.

We declare no no competing interests.

References

1. Grandjean, P and Landrigan, PJ. Neurobehavioral effects of developmental

toxicity. Lancet Neurol.2014; 13: 330–338

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2. Choi, AL, Sun, G, Zhang, Y, and Grandjean, P. Developmental fluoride neurotoxicity: a

systematic review and meta-analysis. Environ Health Perspect. 2012; 120: 1362–1368

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3. Whitford, GM, Whitford, JL, and Hobbs, SH. Appetitive-based learning in rats: Lack of

effect of chronic exposure to fluoride. Neurotoxicol Teratol. 2009; 31: 210–215

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http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70119-X/fulltext?hc_location=ufi#back-bib1

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http://www.thelancet.com/servlet/linkout?suffix=e_1_4_1_2_1_2&dbid=4&doi=10.1016/S1474-4422(14)70119-X&key=10.1016%2FS1474-4422%2813%2970278-3&cf=pdf&site=lancet-site

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4. Shannon, FT, Fergusson, DM, and Horwood, LJ. Exposure to fluoridated public water

supplies and child health and behaviour. N Z Med J. 1986; 99: 416–418

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5. Bazian Ltd. Independent critical appraisal of selected studies reporting an association

between fluoride in drinking water and IQ: a report for South Central Strategic Health

Authority. London, UK.http://www.fairbanksalaska.us/wp-

content/uploads/2011/07/20090211Bazian-Review-IQ-Studies.pdf. ((accessed March 18,

2014).)

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6. European Union Scientific Committee on Health and Environmental Risks

(SCHER). Opinion on critical review of any new evidence on the hazard profile, health

effects, and human exposure to fluoride and the fluoridating agents of drinking

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_122.pdf; May 16, 2011. ((accessed March 18, 2014).)

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http://www.fairbanksalaska.us/wp-content/uploads/2011/07/20090211Bazian-Review-IQ-Studies.pdf


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http://ec.europa.eu/health/scientific_committees/environmental_risks/docs/scher_o_122.pdf


Letter to the editor: Help sought to do more for teeth

Bennington Banner

POSTED: 04/04/2016 02:53:03 PM EDT

Help sought to do more for teeth

I enjoyed reading Makayla McGeeney's fine article about primary care doctors and nurses promoting oral health by applying Fluoride Varnish. This is yet another program initiated and sponsored by the Bennington Oral Health Coalition, an organization of volunteers working to improve public health. The situation is as follows. Fluoride is good for teeth. Bennington's community water is not fluoridated. Bennington's citizens have some of the worst dental problems in the entire state. Children's teeth need attention when they first erupt. Most local dentists don't see children until the child reaches age 3. Our local primary care physicians and pediatricians could fill the gap between the first tooth and age 3. If they apply Fluoride Varnish to these younger kids then the amount of childhood tooth decay might be reduced. We hope that the doctors can establish a Fluoride Varnish program in their offices. This is not the only accomplishment of the BOHC. Over the last year we have held three community-wide forums to consider tactics to improve oral health. We worked with doctors and nurses to provide better education to pregnant women. We developed educational programs for schools and so far have presented in over 50 classrooms. We helped to start classroom toothbrushing programs at Bennington Elementary School. We sponsored classroom essay contests about the importance of teeth, with winners choosing a book from the Bennington Bookstore. We have given out thousands of Dental Goody Bags (toothbrush, floss, and toothpaste). We screened 520 kids at MAUMS for tooth decay (we found a lot of it). We reestablished the long-unused dental chair at MAUMS and arranged to staff it with a dental hygienist and a supervising dentist. We have worked with the Select Board to establish the Oral Health Commission and with the SVSU Administration to look for a Tooth Tutor. We are proud of our accomplishments but we are stretched thin. If you can help us financially or can volunteer, please call 447-3700. You could get more information about us on our Facebook page Bennington Oral Health.

— G. Richard Dundas, MD Bennington

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May 18, 2016 Re: Inquiry regarding safety of artificial water fluoridation chemical Dear Dr. de Villa Medical Officer of Health, I draw your attention to a recent article in the Brampton Guardian where you made the following statement. “Peel health staff will not ‘cherry-pick’ studies to support water fluoridation: Medical Officer of Health” and then I heard about this tweet. “From Dr. de Villa's twitter feed: "Eileen de Villa Retweeted David Juurlink @DavidJuurlink Feb 19 @picardonhealth I recently reviewed safety of fluoridation for a city council. 0.7 ppm is safe, full stop. Same for fluoridation agent HFSA" I'm a retired Registered Nurse and have been researching the practice of artificial water fluoridation for a number of years and am shocked to learn that the practice continues without toxicology studies showing that the chemical in question, Hydrofluorosilicic Acid is safe for human consumption for short and long term use particularly for the sub groups who are at greater risk of harm such as unborn children, infants, renal and cancer patients, people with autoimmune disorders, hypothyroidism, diabetics, etc. My neighbor is a Registered Nurse with a university degree and she works at a local Health Unit. She told me that it's the Health Unit's policy to tell new mothers to mix baby formula with fluoridated tap water as long as it's boiled for five minutes prior to use. I'm afraid she is terribly ill informed, because by boiling the water, it increases the concentration of fluoride and is extremely harmful to the infants developing brain according to a recent Harvard study which shows that fluoride lowers the IQ of infants up to 7 points. http://fluoridealert.org/studies/brain01 Why are citizens not being warned of this? Unfortunately, I've only been able to locate many scientific studies showing harmful effects regarding the consumption of Hydrofluorosilicic Acid on human health. Dr. de Villa, you said that you recently researched the issue of 'safety' yourself. For that, I'm very grateful as it will relieve my worry somewhat. Please refer me to the toxicology/scientific peer-reviewed studies showing that the toxic waste by-product, Hydrofluorosilicic Acid which is a known neurotoxin used to mass medicate the public is safe, for human consumption. I've been searching this issue for a long time and haven't been able to locate the studies and when I asked my City Councillor for them - they are nowhere to be found. I draw your attention to a letter from Health Canada stating they do not have any such studies. I understand the

REFERRAL TO ______________________________

RECOMMENDED



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http://fluoridealert.org/studies/brain01

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Concerned Citizens of Peel to End Fluoridation have provided the letter to the Region and to refresh your memory, I have attached a copy for you. Please find attached, an extensive bibliography from a retired Professor, Dr. Roger Masters. Dr. Masters many studies on the chemical in question, shows beyond a doubt that there are many adverse harmful effects on human health when exposed to this toxic chemical. I understand that Consumer Advocate, Erin Brockovich's signed letter to the Institute of Medicine, Environmentalist Lois Gibbs, a Nobel Prize Nominee and Civil Rights Leader Henry Rodriques have all sent important information in order to inform the Water Fluoridation Committee, Regional Councillors and all staff which would include you; of the many dangers in using Hydrofluorosilicic Acid to fluoridate the municipal drinking water in Peel Region. Most recently, Dr. Mark Hyman, a prestigious well known specialist in Functional Medicine has publicly announced his opposition to fluoridation and has asked the US government to undergo an investigation on this issue. Many community safe water advocates like myself are supporting the pending lawsuit against Peel Region and the Province of Ontario as we trust the judicial system will call upon the required experts in the fields necessary to determine the legality, safety and efficacy of the chemical in question. Thank you in advance for your consideration and I look forward to receiving the links to the toxicological studies showing that Hydrofluorosilic Acid used in the municipal drinking water is safe for human consumption. Regards, Kallie Miller, RN

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Publications on Silicofluorides, Neurotoxicity, and Behavior Roger D. Masters & Myron J. Coplan

This bibliography was the collective work of the late Myron J.

Coplan and Roger D. Masters, and is distributed in memory of Mike Coplan's pioneering work in the study of the harmful

effects of water treated with either fluorosilicic acid or sodium silicofluoride.

I. Early Work by Other Authors

Kick C H, et al. (1935). Fluorine in Animal Nutrition, Bulletin 558

Wooster, OH: Ohio Experiment Station.

Bibby, B. G. (1946). "Topical Application of Fluorides as a Method of

Combating Dental Caries," in Moulton FR, ed; Symposium on Dental Caries and Fluorine, Amer. Assn. for the Advancement of Science.

McClure, F. J., “Availability of Fluorine in Sodium Fluoride vs. Sodium

Fluosilicate.” U.S. Public Health Service Report 65 (1950), pp. 1175-1186; reprinted in Fluoride Drinking Waters (Washington: US Public

Health Service, 1962), 825: 527-532. “In dilute aqueous solutions the hydrolysis of these two fluorine

salts yielding fluoride ions is comparatively simple in the case of sodium fluoride, which is practically completely ionized, but quite

complex and somewhat obscure in the case of sodium fluosilicate.”i Following the specific chemical reactions

“postulated” or suggested by chemists, McClure considers “the

rate of retention and paths of excretion of fluorine” when ingested from these compounds, beginning by summarizing data in a 1935

study by Kick et al., who found that “there was no difference between sodium fluosilicate and sodium fluoride as regards the

ultimate percent of fluorine retained in the rat’s body, i.e., the percent fluorine balance in the above data. There were some

differences, however, in the paths of excretion, i.e., in urine or feces.” McClure’s replication confirms data on percentage of

fluorine retained but does not challenge Kick’s finding of a difference in pathways of excretion (which is consistent with

hypothesis of different biochemical side-effects from “residual species of silicate found by Westendorf).

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Zipkin, I and McClure, F.J. (1950). "Complex Fluorides, Caries

Reduction and Fluorine Retention in the Bones and Teeth of White Rats," Public Health Reports

#66: 1523-1532.

Zipkin, I. and McClure, F.J., (1952). "Deposition of Fluorine in the Bones and Teeth of the Growing Rat," J. Nutr. 47: 611-620.

Weddle, D.A. and Muhler, J.C. (1957). The Metabolism of Different

Fluorides in the Rat, Journal of Dental Research., 36: 386-390.

Feldman, I, Morkin, D, and Hodge, HC. (1957) “The State of Fluoride in Drinking Water,” Journal of Dental Research, 36 (2): 192-202.

The first sentence of this article confirms that, at the time of their approval in 1950, the extent of dissociation of silicofluorides

injected in a water supply was unknown: “The widespread use of

sodium silicofluoride in fluoridating drinking water has made it important to determine the state of the fluoride in such water,

specifically, how much is fluoride ion, how much, if any, is unchanged silicofluoride, how much is fluoride bound to other

ions. If all or nearly all of the fluoride is the ion F-, the great body of information about the biologic effects of fluorides can be

brought forward as a guarantee of safety. If considerable amounts of silicofluoride remain, a question can legitimately be

raised since comparatively little work has been done on the biologic effects of silicofluorides.” (p.192). Despite the authors’

claim to present (in 1957) “experimental results,” their analysis is essentially a theoretical extrapolation which does not provide a

direct test of chemical and biochemical effects under conditions approximating actual usage. Moreover, the claim of safety is

limited to the extent of dissociation of fluoride, ignoring issues of

biological effects of “residual species” of silicates such as those found by Westendorf.

Colton, E.. (1958). "Fluosilicic Acid." Jour. of Chem. Educ. 35:562-

563.

Frant, M. and Ross, J.W. (1966). "Electrode for Sensing Fluoride Ion Activity in Solution," Science. 154:1553-55.

Crosby, N.T. (1969). “”Equilibria of Fluosilicate Solutions with Special

Reference to the Fluoridation of Public Water Supplies,” J. Appl. Chem 19: 100-102.

Silicofluorides are unlikely to dissociate completely under water plant conditions, producing only free fluoride and silicic acid

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without side reactions because the silicofluoride moiety [SiF6]2-

can react with Al(OH)3 to produce a number of derivative compounds. Moreover, silicofluoride residues may reassociate

either within the stomach or in food preparation.

Knappwost A, Westendorf J, (1974) “Hemmung von Cholinesterasen durch Fluorokomplexe des Siliciums und des Eisens [Inhibition of

cholinesterasse by fluorocomplexes of silicon and iron]” Naturwiswsenschaften 61: 275.

First publication on research more fully reported in Westendorf, 1975.

Westendorf, Johannes (1975) . Die Kinetik der Acetylcholinesterase

Himmung und Die Beeinflussung der Permeabilitat von Erythrozytenmembranen durch Fluorid und Flurocomplex-Jonen;

Doctoral Dissertation, Hamburg: Universität Hamburg Fachbereich

Chemie; available in English translation at: http//www.dartmouth.edu/~rmasters/ahabs.

Experimental evidence showing that the extent of SiF dissociation into its component elements is at odds with the

assumption that SiF and NaF are equivalent sources of free fluoride when used for water fluoridation. While the “residual

species” of silicate remaining in water is not precise identified, the thesis confirms potentially harmful biological effects

(acetylcholinesterase inhibition). These demonstrations of biochemical differences between silicofluorides and sodium

fluoride have never been challenged with experimental data.

Manocha, S.L et al, (1975). "Cytochemical Response of Kidney, Liver and Nervous System to Fluoride Ions in Drinking Water," Histochemical

Journal, 5: 343-355.

Busey, R. HJ. (1980) “Fluosilicate Equilibria in Sodium Chloride

Soluitons from 0 to 60o C” Inorg. Chem 19: 758-761.

Edelman, N. and Chow, L.C. (1991). "Effects of pH and Calcium on Hydrolysis of Na2SiF6 and Na2SnF6," Caries Research. 25: 101-107.

Whitford, G.M., Biles, E.D., Birdsong-Whitford. N.L. (1991). "A

comparative study of fluoride pharmacokinetics in five species," Journal of Dental Research, 70: 948-51.

Whitford, G.M. (1994a). "Intake and metabolism of fluoride, "

Advances in Dental Reearch; 8:5-14.

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Whitford, G. M.. (1994). "Effects of plasma fluoride and dietary

calcium concentrations on GI absorption and secretion of fluoride in the rat," Calcif Tissue Int 54:421-5.

Reeves, T.G. (1994). Water Fluoridation; A Manual for Water Plant

Operators. Washington, DC: U.S. Public Health Service, Division of Oral Health.

Cory-Schlechta, D. A. (1995). "Relationships between Lead Induced

Learning Impairments and Changes in Dopaminergic, Cholinergic, and Glutamatergic Neurotransmitter System Functioning." Annual Review

of Pharmacology and Toxicology 35: 391-454.,

Skoog, West, and Holler . (1996). The Direct Potentiometric Determination of Fluoride Ion, Fundamentals of Analytical Chemistry,

Saunders, 7th Ed., pp. 850-852

Colquhoun, J. (1997). "Why I changed my mind about water

fluoridation," Perspectives in Biology and Medicine. 41:29-44.

He H., Ganapathy V., Isales C.M., Whitford G.M. (1998). "pH-dependent fluoride transport in intestinal brush border membrane

vesicles," Biochem Biophys Acta 1372: 244-254.

Whitford, G.M.. (1999). "Fluoride metabolism and excretion in children;" Journal of Public Health Dentistry, 593:224-228.

Featherstone, J.D.B. (2000). "The Science and Practice of Caries

Prevention." Journal of the American Dental Associaton, 131: 887-100.

Burt B.A., Keels M.A, Heller K.E. (2000). "The effects of a break in

water fluoridation on the development of dental caries and fluorosis," J Dent Res.79:761-769.

Ballabriga, A. (2000). "Morphological and physiological changes during

growth: an update," British Journal of Clinical Nutrition, 54:S1-6.

Kunzel, W. and Fischer, T. (2000). "Caries prevalence after cessation

of water fluoridation in La Salud, Cuba," Caries Research, 34:20-5.

Letter from Sally C. Gutierrez, Director, Water Supply and Water Resources Division, Office of Research and Development, National Risk

Management Research Laboratory, U.S. EPA, Cincinnati to Roger Masters, March 15, 2001.

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At a meeting in January 2001: “Several fluoride chemistry

related research needs were identified including; (1) accurate and precise values for the stability constants of mixed

fluorohydroxo complexes with aluminum (III), iron (III) and other metal cations likely to be found under drinking water

conditions and (2) a kinetic model for the dissociation and hydroloysis (sic) of fluosilicates and stepwise equilibrium

constants for the partial hydrolyisis products. As a result of these discussions, ORD is exploring options to initiate research

in the identified research areas.” (OFFICIAL CONFIRMATION THAT, WHEN APPROVED IN 1950, PRECISE CHEMISTRY AND

BIOLOGICAL EFFECTS OF SILICOFLUORIDES WERE NOT FULLY KNOWN.)

Burgstahler, A.W., Freeman, R.F., Jacobs, P.N. (2002). "Early And

Prolonged Toxic Effects of Silicofluoridated Water on Chinchillas,

Caimans, Alligators, and Rats in Captivity," Fluoride. 35:259-260.

National Toxicology Program (2002), “NTP Nomination Of Silicofluorides For Study,” Federal Register (June 12, 2002; Vol. 67,

No. 113, p. 40329-33). “Substances Nominated to the NTP for Toxicological Studies

and Recommendations Made by the ICCEC on April 17, 2002. “Table 1. -- Substances Recommended for Study

Substance [CAS No.] … Hexafluorosilicic acid [16961-83-4] and Sodium hexafluorosilicate [16893-85-9]. Nominated by:

Private Individuals (multiple nominations). Nominated for: -Chemical characterization Toxicological characterization

including chronic toxicity, carcinogenicity, neurotoxicity, and toxicokinetics. -Mechanistic studies related to cholinesterase

inhibition and lead bioavailability. Rationale for Nomination:

Primary agents used to fluoridate public drinking water systems; lack of toxicity information; assumed complete

dissociation to free fluoride under normal conditions of use not supported by experimental evidence. ICCEC

Recommendations: - Chemical characterization studies to assess chemical fate under aqueous conditions -Toxicological

studies may be considered when results of chemical characterization studies are available for review.” Source:

Above “information about substances nominated to the NTP for toxicology and carcinogenesis studies and the ICCEC's

recommendations was published in This notice is available on the web (http://ntp-

server.niehs.nih.gov/htdocs/Liason/ICCECFinal02JuneFR.html) along with

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supporting documents for each nomination:(http://ntp-

server.niehs.nih.gov/htdocs/liason/BkgrSum02June.html)…” TO OUR KNOWLEDGE, NO RESULTS FROM A STUDY

IMPLEMENTING THIS NOMINATION HAVE BEEN PUBLISHED. NOTE ALSO: THE POSSIBILITY THAT SILICIC ACID RESIDUES

MIGHT BOND TO ALUMINUM COULD RELATE TO CONDITIONS LIKE AUTISM AND ALZHEIMER’S DISEASE (WHOSE APPARENT

INCREASE IN FREQUENCY MIGHT BE DUE TO ALUMINUM NEUROTOXICITY).

Machalinski B, et al. (2003). "The influence of sodium fluoride and

sodium hexafluorosilicate on human leukemic cell lines," Fluoride, 36: 231-40.

Seavey J. (2005). "Water fluoridation and crime in America," Fluoride:

38:11-22; & 38:174.

Cites work of Roger Masters and Myron Coplan, 1999a & 1999b.

Luo G., Niu R., Sun Z., Zhang J., Wang Jinming, Wang Jundong

(2011), "Fluoride and Lead Combined Exposure Alters CaMKII Expression in Hippocampus of

Rats," (Shanzi Agricultural University; in preparation) Experimental demonstration that when rats are simultaneously

exposed to both fluoride (from 150mg/L sodium fluoride in drinking water) and lead (from lead acitate), expression of

Calcium/calmodulin-dependent protein kinase II (CaMKII) in hippocampus is significantly decreased. Since CaMKII is "a

leading candidate in the search for the molecular basis of learning and memory," this effect is a plausible mechanism for

harmful effects on educational performance associated with the

combination of environmental exposures to lead and fluoride. Moreover, the hypothesized effects should be at least as great in

communities with sources of exposure to lead (whether from industrial lead pollution, old housing with lead paint, or other

sources of high lead in tapwater) and water treatment with silicofluorides (from which quantities of free fluoride are

released). As a result, this study can be viewed as a model of a laboratory study of the effects of silicofluoride water treatment

in American communities. While all behavioral findings are reinforced by this study, it is especially striking as an explanation

for the Massachusetts data showing behavioral effects congruent with prediction of authors both in community frequencies of

learning disabled students ["Neurotoxins, Disease, and Behavior," Fig. 12] and for scores on standardized MCAS tests in

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seven different subjects and grades ["Lead, Brain Chemistry, and

Educational Faillure," Fig. 1]).

Schneider, J.S. Williams, C.; Ault, M; Guilarte, T.R. (2015) "Effects of chronic manganese exposure on attention and working memory in

non-human primates," Neurotoxicology, 48:217-222. Manganese (Mn) is essential for a variety of physiological

processes, but at elevated levels, can be neurotoxic. While cognitive dysfunction has been recently appreciated to occur as

a result of chronic Mn exposures, it is still unclear as to which cognitive domains are most susceptible to disruption by Mn

exposure. We previously decried early appearing Mn-induced changes in performance on a paired associate learning task in

monkeys chronically exposed to Mn and suggested that performance of this task might be a sensitive too for detecting

cognitive dysfunction resulting from Mn exposure. As chronic

Mn exposure has been suggested to be associated with attention, working memory and executive function deficits, the

present study was conducted to assess the extent to which detrimental effects of chronic Mn exposure could be detected

using tasks specifically designed to preferentially assess attention, working memory and executive function ..... These

data suggest that in addition to the paired associate learning task, cognitive processing speed (as measured by the 5-CSRT)

may be a sensitive measure of Mn toxicity and the brain circuits involved in performance of the SOSS task ['perform a self-

ordered spatial search...task'] may be somewhat less sensitive to disruption by chronic Mn exposure.

Ellingsen, Dag G; Chashchin, Maxim; Bast-Pettersen, Rita; Zibarev,

Evgenij; Thomassen, Yngvar; Chashhin, Valery (2015), "A follow-up study of neurobehavioral functions in welders exposed to

manganese,," NeuroToxicology 47: 8-15. Welders may be exposed to high amounts of manganese (Mn).

In this study 63 welders and 65 referents were followed up with neurobehavioral tests approximately 6 years after the initial

examination at baseline.... When subjects with sCDT above the upper reference limit of the laboratory (>/=1/7%) were

excluded from the analyses, no difference in the decline in performance was observed between welders and referents for

any of the applied neurobehavioral tests... Three welders had developed bradykinesia at follow-up, as assessed by a

substantial decline in their Finger Tapping Test performance. They had also experienced a severe decline in Foot Tapping,

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Grooved Pegboard and Postural Sway Test Scores (while

blindfolded), while postural tremor as assessed with the CATSYS Tremor 7.0 was normal."

II. Publications co-authored by Roger Masters & Myron Coplan

et al.

Masters, Roger D., with Baldwin Way, Brian T. Hone, David J. Grelotti, David Gonzalez, and David Jones (1997) "Neurotoxicity and Violence,"

Vermont Law Review, 22:358-382. Legal implications of the evidence linking neurotoxicity and crime

(including data from Toxic Release Inventory and crime for partial sample of US counties)

Masters, R, Hone, B, and Doshi, A. (1998). “Environmental Pollution, Neurotoxicity, and Criminal Violence,” in J. Rose, ed.,

Environmental Toxicology: Current Developments (London: Gordon and Breach, 1998), pp. 13-48.

Survey of evidence linking lead and manganese neurotoxicity to aggressive behavior and crime, presenting multivariate analysis

correlating Toxic Release Inventory for lead and manganese with crime data for 1991 from all 3141 US counties Emphasizes

effects of heavy metals on neurotransmitter function and behavior.

Masters, R. and Coplan, M. (1999a) “Water Treatment with

Silicofluorides and Lead Toxicity,” International Journal of Environmental Studies, 56: 435-49

First published analysis of data linking silicofluoride treatment of

public water supplies with higher uptake of lead, using survey of children’s blood lead in Massachusetts (by town).

Masters, R. and Coplan, M. (1999b) “A Dynamic, Multifactorial Model

of Alcohol, Drug Abuse, and Crime: Linking Neuroscience and Behavior to Toxicology,” Social Science Information, 38:591-624.

Articulation of the linkages between neurotoxicity, brain chemistry, environmental pollution, and behavior (with focus on

substance abuse and crime), using data from National Institute of Justice study of drug use in over 30,000 criminal offenders at time

of arrest). Data show that where silicofluorides are in use, criminals are more likely to consume alcohol, more likely to have

used cocaine at time of arrest – and that communities have significantly higher crime rates.

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Coplan, M.J. and Masters, R.D. (1999). "Is Silicofluoride Safe?

Comments Re EPA Response to Rep. Calvert's Inquiry" Submission to Representative Kenneth Calvert, Subcommittee on Energy and

Science, Committee on Science, U. S. House of Representatives (August 12, 1999).

Analysis and rejoinder to letter dated 12 June 1999 from J. Charles Fox, Assistant Administrator, EPA, to Hon.Kenneth

Calvert, U. S. House of Representative, commenting on errors and omissions in a "Question and Answer" statement and

"Fluorosilicate Fact Sheet" enclosed by Mr. Fox. This document contains a preliminary review of scientific data on the differences

between sodium fluoride (NaF) and the silicofluorides (H2SiF6 and Na2SiF6), with an emphasis on the complex production

process and chemical interactions of the latter compounds.

Masters, R. D. and Coplan, M. J., with Hone, B.T., Grelotti, D. J., Gonzalez,

D. and Jones, D. (1999). “Brain Biochemistry and the Violence Epidemic: Toward a ‘Win-Win’ Strategy for Reducing Crime,” in Stuart Nagel, ed.,

Super-Optimizing Examples Across Public Policy Problems (NOVA Science Publishers)

Review of the evidence linking neurotoxicity and crime, using data from both county-level study (correlating EPA Toxic

Release Inventory with FBI crime reports ) and Massachusetts data on silicofluorides and lead uptake.

Wilson, Jim (1999). “The Chemistry of Violence,” Popular Mechanics,

(April), pp. 42-43. Summary of findings from our project

Masters, R.D., Coplan, M. J., Hone, B.T., and Dykes, J.E. (2000)."Association of Silicofluoride Treated Water with Elevated Blood

Lead," Neurotoxicology 21: 1091-1100. Follow-up epidemiological study of the association between

silicofluoride treated community water and enhanced child blood lead parameters. This statistical study of 151,225 venous blood

lead (VBL) tests taken from children ages 0-6 inclusive, living in 105 communities with populations from 15,000 to 75,000 in New

York state, shows for every age and racial group a significant association between silicofluoride treated community water and

elevated blood lead.

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Roger D. Masters (2001), “Biology and Politics: Linking Nature and

Nurture” in Nelson W. Polsby, ed., Annual Review of Political Science, vol. 4, pp. 345-369.

A survey of the scope of the emerging subfield called “biopolitics,” reflecting the activities of the membership of the Association for

Politics and the Life Sciences. Four areas are discussed in some detail: 1). genetics and health; 2), toxins and behavior (including

hyperactivity, depression, and violent crime), 3) the specific case of silicofluorides in water treatment and their effect in enhancing

lead uptake; and 4) biopolitics and political theory. Note: one-time e-print available at following URL:

http://polisci.annualreviews.org/cgi/content/full/4/1/345?ijkey=0K1GnNcUKf2Gg&keytype=ref&siteid=arjournals

Myron J. Coplan and Roger Masters. (2001). “Guest Editorial:

Silicofluorides and fluoridation,” Fluoride: Quarterly Journal of the

International Society for Fluoride Research, 34: 161-220. Given data showing harmful side-effects of water treated with

hydrofluorosilicic acid or sodium silicofluoride, a moratorium is desireable on continued use of silicofluorides until such time as

they are shown to be safe (and contrary findings explained). Masters, R.D. (2002). “MacLean’s Evolutionary Neuroethology:

Environmental Pollution, Brain Chemistry, and Violent Crime," Gerald A. Corey Jr. & Russell Gardner Jr., eds. The Evolutionary

Neuroethology of Paul MacLean (Westport: Praeger), pp. 275-296 (Ch. 15).

Survey of research on neurotoxicity, brain chemistry and behavior, including evidence of the role of lead and other heavy

metal pollution and crime (as demonstrated by individual data, neurochemistry, and both geographic and longitudinal data} as

well as survey of data linking silicofluorides to enhanced lead

uptake. First presentation of findings on the extremely high correlation (r = .90) between gallons of leaded gasoline sold and

the crime rates sixteen years later, confirming special vulnerability of pregnant mothers and newborns to lead toxicity.

Masters, Roger D. (2003). “The Social Implications of Evolutionary

Psychology: Linking Brain Biochemistry, Toxins, and Violent Crime,” in Richard W. Bloom and Nancy K. Dess, eds., Evolutionary

Psychology and Violence: A Primer for Policymakers and Public Policy Advocates (Westwood: Praeger), Ch. 2, pp. 23-56.

Analysis of evidence of neurotransmitter dysfunction due to toxins associated with increased rates of violent crime, with

extensive discussion of silicofluoride neurotoxicity as an important instance.

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Masters Roger D. (2005). “A Moritorium on Silicofluoride Usage will Save

$$millions,” Fluoride, 38(1):1-5; crn 38(2):174. Estimation of rates of harmful effects of water treated with

silicofluorides, based on national county-level data for violent crime and other statistics, and corresponding costs to taxpayers.

Total financial benefits to taxpayers are in the Millions – and probably Billions – of dollars, with virtually no costs to the public.

Masters, Roger D. (2006). “Science, Bureaucracy, and Public Policy:

Can Scientific Inquiry Prevail Over Entrenched Institutional Self-Interest?” New England Journal of Political Science, 1: 58-140.

Richard P. Maas, Steven C. Patch, Anna-Marie Christian, Myron J.

Coplan, “Effects of fluoridation and disinfection agent combinations on

lead leaching from leaded-brass parts,” Neurotoxicology (September 2007), 38: 1023-31.

Disinfection agents (chloramines as well as chlorine) have the effect of leaching lead from leaded-brass water fixtures, and

this effect is significantly enhanced where fluoride compounds are also used to treat the water supply (with higher effects from

long term combinations including fluorosilicic acid).

Myron J. Coplan, Steven C. Patch, Roger D. Masters, Marcia S.

Bachman, “Confirmation of and Explanations for Elevated Blood Lead and Other Disorders in Children Exposed to Water Disinfection and

Fluoridation Chemicals,” Neurotoxicology (September, 2007), 38: 1032-1041.

Confirmation of association between silicofluoride use in local

water supplies and significant increase in absorption of lead from environmental sources, using new children's blood lead data from

National Health and Nutrition Evaluation Survey III, counties of over 150,000 population. Review of important new findings, including lead

leaching from brass water fixtures where systems combine use of silicofluorides with chloramine for disinfection; evidence confirming

incomplete dissociation of silicofluorides (contradicting original "assumption" when silicofluorides were approved without testing

by the Public Health Service in 1950); Westendorf's finding of acetylcholinesterase inhibition, interference with cholinergic function;

and other evidence confirming research hypotheses and data explanations in our previous published research.

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Masters, Roger D. (July-Sept. 2009), "Cost and Effectiveness in

American Health Care," Special Article, International Journal of Health Science, II, 221-226.

Analysis of high cost and disappointing outcomes of American health care system when compared to other industrialized countries.

The U.S. has average per capita health costs over twice the OECD average, but a year less of life expectancy and over 1 additional infant

death per 1,000 live births. This paradox is explained by the great expense of health care for the uninsured, which is a hidden cost

associated with the low prercent of American health costs that's supported by public funding (only 45.8%), compared to the average of

73% public health financing for all OECD countries. Preventive care (epitomized by reducing toxic exposure and uptake) has the potential

to improve outomes at low cost.

Masters, Roger D., "Toxins, and Violent Crime," Biopolicy: the Life

Sciences and Public Policy: Research in Biopolitics (2012), 10, 119-156.

A study testing the hypothesis that a neuroscientific analysis of brain and behavior can explain hitherto unexplained local

differences in rates of violent crime, to explore whether these behavior are significantly influenced both by local exposure to

either fluorosilicic acid or sodium silicofluoride (together "SiF") -- toxic compounds used in place of sodium fluoride (NaF) in over

90% of fluoridated water in the U.S. Multivariate statistical analysis confirms the predicted association between SiF and

violent crime as well as the hypothesis that "children in communities using SiF should have increased uptake of lead

from environmental sources and higher rates of behavioral dysfunctions known to be caused by lead neurotoxicity."

Masters, Roger, "On the Relationship between Liberalism and

Darwinism," in Stephen Dilley, ed., Darwinian Evolution and Classical Liberalism (Lanham, Boulder & N.Y.: Lexington Books, 2013), ch. 10,

pp. 217-236. Contrary to the prevailing gulf separating the social sciences

from contemporary biology, this essay explores parallels between the Darwinian theoretical approach to human social

behavior as a product of evolutionary biology and the tradition of "classical liberalism" from Locke to the present, based on "the

core concept" of "freedom from the restraints of political, social and theological practices and power structures that block

innovation in social behavior."

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Kennedy, David; Seneff, Stephenie; Davidson, Robert M.; Haley, Boyd

E.; & Masters, Roger D., "Environmental Toxicants and Infant Mortality," accepted pending acceptance of revision by ENTROPY

(ISSN 2099-4300). This article presents a highly innovative exploration of the

relationship between "environmental toxicants" (i.e., toxins intentionally added to the environment) and the public policies of

"water fluoridation" as factors contributing the relatively high rates of infant mortality in the U.S. My contribution explained

the role of silicofluorides in the chemical process by which the aluminum adjuvants added to vaccines to increase their

effectiveness bonds to fluoride (from water treatment) to form highly toxic aluminum fluoride (Al2F3 ). Given the relationship

between aluminum fluoride and higher rates of many diseases (explored elsewhere in this volume), the ability to end the use of

silicofluorides by listing these compounds under the Toxic

Substances Control Act, §5-6 might make it possible to end this source of disease without a highly controversial attempt to end

the use of aluminum adjuvants in vaccines.

Articles in Preparation

Masters, Roger D., "Neurotoxins, Disease, and Behavior," (in manuscript), Poster proposal for First Annual Neuroscience, Behavior

and Health Research Forum, University of Vermont Medical School ( Jan. 21-22, 2011).

Survey of wide variety of outcomes for which data provide evidence of harmful effects of toxins and their exacerbation by

presence of water treated with silicofluorides.

Masters, Roger D. & Coplan, Myron J., (in manuscript), "Behavioral

Effects of Water Toxicity: An Unexpected Problem in Experimental Methodology" (UNPUBLISHED)

John Crabbe, Jr.'s ambitious attempt to demonstrate the importance of the principle of replication in experimental

behavioral neuroscience had an unintended consequence, which was viewed in as evidence that such scientific studies are in

principle impossible to replicate. Crabbe conducted a series of behavioral experiments with 16 different strains of rats, taking

great pains to insure that handling of animals and all experimental protocols were as identical as possible in three different Canadian

cities. To his disappointment, rats in one of the three cities did not exhibit an aversion to entry in the dark arm of a "Y maze" --

which seemingly meant that the experiment failed to have reproducible effects. In fact, however, one of the "controls" was

5.4-19

14

the use of "tap water" for all animals. Of the three cities, only one

-- Edmunton, Alberta -- treats its public water supplies with silicofluoride, and it was in that city that the rats failed to learn

reliably and impulsively entered the dark arm of the maze more often than expected. Far from being a demonstration of non-

reproducibility, therefore, Crabbe and his colleagues provided experimental evidence confirming our hypotheses on the

neurotoxic effects of silicofluoride treated water. As a result, this study not only strengthens our findings; it also suggests a

possible danger in reproducibility for laboratory studies if water treatment systems differ from one test to another.

Masters, Roger D. (UNPUBLISHED). "Lead, Brain Chemistry, and

Educational Failure" Multivariate statistical analyses of outcome variables related to

learning and educational systems are considered in the light of the

established hypotheses in cognitive neuroscience and neurotoxicology. As a result, many negative outcomes attributed

to poor teaching staff or racial inferiority illustrate the gene-environment interactions associated with impulse control and

learning.

Roger D. Masters* & Myron J. Coplan**

Presentations to Scientific Conferences: Masters, R.D. and Coplan, M.J. "Silicofluoride Usage and Lead

Uptake," Presentation to XXIInd Conference of the International

Society for Fluoride Research, Bellingham, Washington, August 24-27, 1998.

Report on findings of elevated blood lead associated with communities using silicofluoride, based on sample of over

250,000 children in Massachusetts (see Masters and Coplan, 1999a)

Masters, R. D. . "Poisoning the Well: Neurotoxic Metals, Water

Treatment and Human Behavior," Plenary address to Annual Conference of the Association for Politics and the Life Sciences," Four

Seasons Hotel, Atlanta, GA (September 2, 1999). Review of evidence linking heavy metal pollution with substance

abuse and crime, including presentation of data linking ban on sales of leaded gasoline with decline in crime 16 years later.

5.4-20

15

Summary of geographical data analyses contradicting the "null

hypothesis" that there is no difference in the effects of sodium fluoride and the silicofluorides.

Coplan, M. J., Masters, R. D., and Hone, B. (1999a) “Silicofluoride Usage, Tooth Decay and Children’s Blood Lead,” Poster presentation to

Conference on “Environmental Influences on Children: Brain, Development and Behavior, New York Academy of Medicine, Mt. Sinai

Hospital, New York, May 24-25, 1999. Preliminary report on data from analysis of national sample of

over 4,000 children in NHANES III, showing that while water fluoridation is associated with a significant increase in children's

blood lead (with especially strong effects among minority children), data on tooth decay from the same survey show

limited benefits that are no longer evident among those aged

15-17.

Coplan, M.J., Masters, R.D., and Hone, B. (1999b) "Association of Silicofluoride Treated Water with Elevated Blood Lead," Poster

presentation to 17th International Nerotoxicology Conference, Little Rock, AR, October 17

Preliminary report on data from analysis of sample of blood lead testing of over 150,000 children in New York State communities

of 15,000 to 75,000 population. Once again, average blood lead levels were significantly higher (p < .0001) in communities

using silicofluorides in water treatment than in those with unfluoridated water. The effect was found independently in

every age group for three ethnic subsamples

Roger D. Masters (2002) “Science, Bureaucracy, and Public Policy:

Can Scientific Inquiry Prevail Over Entrenched Institutional Self-Interest?” presentation at the annual meeting of the Association for

Politics and the Life Sciences, Montreal, Que. (August 19-23, 2002). Analysis of bureaucratic opposition to reconsideration of public

policy decisions challenged by new data on silicofluoride chemistry and its effects on human biology and behavior.

Roger D. Masters (2002). “Toxins and Behavior: Implications of

‘Toxicogenomics’ for Public Policy,” Paper presented to XXth International Neurotoxicology Conference, Little Rock, ARK, Nov. 19,

2002.

Roger D. Masters (2004), “The Hidden Handicap: Lead, Brain Chemistry, and Educational Failure,” Paper presented to 2004 Annual

5.4-21

16

Meeting of the American Political Science Association, Chicago, IL.,

Sept. 3, 2004.

Roger D. Masters (2010), "Toxins, Health, & Behavior: Gene-Environment Interaction & Public Policy," Paper presented to 2010

Annual Meeting of the Association for Politics and the Life Sciences, Bloomington, IL, October 15, 2010.

Myron J. Coplan & Roger D. Masters (2011), "Silicofluoride

Neurotoxicity, Higher Blood Lead, and Impulsive Behaviors," Paper presented to 27th International Neurotoxicology Conference,"

Research TrianglePark, NC, Oct. 30-Nov. 2, 2011.

Symposium on Aluminium in Biology and Medicine, Derek Chadwick, and Julie

Whelan. 1992. Aluminium in biology and medicine. Chichester [England]: Wiley.

Design manual, removal of fluoride from drinking water supplies by activated

alumina / by Frederick Rubel, Frederick, 1931-2010.

Location

(link to map) Call Number Status ? Note

Jones Media

Center EP 1.23/2:600/2-84-134

The equilibrium fluoride capacity of activated alumina / Gurinderjit Singh and Dennis A.

Clifford. Singh, Gurinderjit.

Location


Baker Berry US

Gov Docs

EP 1.89/2:F 68

Show Similar Items AVAILABLE

Removal of fluorides from industrial wastewaters using activated alumina / by Irwin

Frankel and Eric Frankel, I. F.

Location


Baker Berry US

Gov Docs

EP 1.23/2:600/2-80-058


Recovery of plutonium from sodium fluoride and alumina traps loaded with plutonium

tetrafluoride by Gray, L. W.

Location


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http://libcat.dartmouth.edu/search~S1?/X%22alumina%22&searchscope=1&SORT=D&Da=&Db=&p=/X%22alumina%22&searchscope=1&SORT=D&Da=&Db=&p=&SUBKEY=%22alumina%22/1%2C47%2C47%2CB/frameset&FF=X%22alumina%22&searchscope=1&SORT=D&Da=&Db=&p=&21%2C21%2C


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17

Jones Media

Center

E 1.28:DP-1502


Masters, Roger D Dept. of Government

Dartmouth College

23311001226764 53 Lyme Rd, Hanover, NH 03755

[email protected]

RETIRED PROFESSOR

5.4-23



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From: Richard Shames [ ]

Sent: May 25, 2016 10:52 AM

To: Lockyer, Kathryn; ZZT-Members of Regional Council

Cc:

Subject: Why We Oppose Artificial Water Fluoridation

Dear Regional Councilors, Water Fluoridation Committee Members, City Solicitors and City

Staff - -

I am a Harvard graduate, former researcher at the U.S. National Institutes of Health (NIH), and

now a practicing physician specializing in thyroid. Together with my wife, Karilee Halo Shames,

R.N., Ph.D., I have authored several well-received books on thyroid health. Most recently, I

helped put together a well-documented letter to the American Thyroid Association (ATA), urging

them to oppose artificial community water fluoridation.

This letter briefly summarizes the extensive science of low-level fluoride's harmful impact on

thyroid hormones, its interference with glucose and calcium metabolism in

susceptible populations, and its general capacity for endocrine disruption. (One of the stated

reasons why the entire country of Israel recently suspended all water fluoridation.)

Given your region’s current conflict regarding fluoridation, I would like to submit that ATA letter

for your review. I trust after reading it, you will agree with me that regardless of what little dental

benefit fluoridation may or may not provide, the damage caused by this outdated practice can

no longer be ignored. See: http://www.ehcd.com/wp-

content/uploads/2016/02/2016_02_11_ATALtrCWF.pdf

Sincerely,

Richard L. Shames, MD

www.ThyroidPower.com

5.5-1

http://www.ehcd.com/wp-content/uploads/2016/02/2016_02_11_ATALtrCWF.pdf

http://www.ehcd.com/wp-content/uploads/2016/02/2016_02_11_ATALtrCWF.pdf

http://www.thyroidpower.com/

68493

Stamp2 - Receipt

To: American Thyroid Association 6066 Leesburg Pike Suite 550Falls Church, VA 22041

From:

February 11, 2016

Dear Vivian Cody and Warren Oliveri as Registered Agents and ATA Leadership,

We recognize the American Thyroid Association (ATA) as the world’s leading organization ‘devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health.’ We appreciate the ATA values that include, ‘scientific inquiry, public service patient advocacy, education, and ethical conduct.’ We are writing because it is time for the ATA, in keeping with its mission and values, to openly advise the American public of what many physicians have been privately advising patients behind closed doors for decades, that drinking fluoridated water is harmful to thyroid health.

We suggest that February 2016 is the time to step forward for several reasons:

1. We believe it is unconscionable for this professional association to stand by silently while fluoridation advocates in the American Dental Association, American Medical Association and the American Academy of Pediatrics continue to aggressively market fluoridation as a dental panacea by distorting medical facts and denying recent scientific studies regarding endocrine disruption.

2. We believe that the political lobbying of fluoridationists who are increasingly attempting to mandate fluoridation at the state level, as they have done successfully in over a dozen states already, including California, Connecticut and Arkansas, will invariably increase the burden on those already ill with thyroid and other endocrine disorders, as well as increase their numbers substantially.

Antonio C. Bianco, PresidentVictor J. Bernet, COODavid H. Sarne, TreasurerJohn C. Morris, III, President ElectBarbara R. Smith, Exec Director

Andrew J. Bauer Sally E. CartyM. Regina CastroJames V. HennesseyAnthony N. Hollenberg

Jacqueline JonklaasRebecca E. Schweppe Susan A. ShermanJulie Ann SosaChristine Spitzweg

Registered Agents of American Thyroid Association

Vivian CodyHauptman-Woodward Medical Research Institute700 Ellicott StreetBuffalo, NY 14203-1102

Warren S Oliveri JrKing & Nordlinger, LLP3030 Clarendon Blvd. Suite 300Arlington, VA 22201

Dr. Richard L. Shames, MD 4340 Redwood Highway Building A, Suite 22San Rafael, CA 94903

Dr. William J. Rea, MD8345 Walnut Hill LaneSuite 220Dallas, Texas 75231

Dr. Nathan Becker, MD, FACE, FACP350 Parnassus Ave Suite 707 San Francisco, CA 94117

Heather Gingerich, MSc. 172 Albert StreetIngersoll, ON N5C 2Y4Canada

Dr. Ellie Phillips, DDS4301 W. William Cannon DrSuite B-150Austin, Texas 78749

Marcus L. Scott, Esq. Scott Collins Law, LLP30 Massachusetts Ave. #102 North Andover, MA 01845

Communication to American Thyroid Association re fluoridation science, 11 Feb 2016 "1

5.5-2

3. We believe that the examination by the National Toxicology Program (NTP) into the science indicating fluoridated waters are neurotoxic to fetuses and young children, although commendable, may be too limited. We know that exposure to fluoride lowers thyroid function, and that even subclinical hypothyroidism during pregnancy and childhood can and does result in lowered IQ, learning disabilities, and other psychomotor deficits, whether or not fluoride is characterized as “neurotoxic.” We suggest the ATA go on record with this medical fact sooner rather than later. Although the public comment period to the NTP on this topic closed January 8, 2016, we suspect the ATA will be able to provide a comment past that date.

4. We believe that the science published in 2014 and 2015 is sufficient on its own to recast artificial fluoridation as a public harm rather than as a public good. Consistent with science dating back a hundred years, recent science confirms that community water fluoridation is medically inadvisable for thyroid patients and most, if not all, of the population. We are attaching supporting resources to the end of this letter for your convenience.

We suggest that the cornerstone for an ATA public stand can be found in the 2015 report out of England that documents a significant increase in diagnosed cases of hypothyroidism in artificially fluoridated communities with a .7 ppm water concentration as compared to communities with .3 ppm naturally occurring fluoride (Peckham 2015) This finding is no surprise to us. Our medical community has known since the early 20th century that fluoride lowers thyroid function, and even prescribed fluoride tablets and baths as an effective treatment for hyperthyroidism. We also labeled a malaise seen in the 1950s during the early years of community fluoridation as “fluoride fatigue.” That term was subsequently replaced with the diagnosis of fibromyalgia or ME/CFS, conditions with no known etiology often accompanied by thyroid disorders as well as autoimmune and inflammatory diseases that are also linked to fluoride poisoning. (Galetti 1958; Laylander 1999a, 1999b; PFPC 1996; Waldbott 1978, 1998)

We find it very telling that, in stark contrast to our colleagues from the 1930s and 1940s, instead of regularly prescribing fluoride to lower thyroid function, modern endocrinologists regularly prescribe Synthroid to increase thyroid hormone levels. As you know, Synthroid is now one of the most common prescriptions in the United States. American fluoridation began in 1945.

The 2006 National Research Council (NRC) panelists who evaluated EPA fluoride contaminant levels (MCL/MCLG) in drinking water reviewed dozens of endocrine studies. They found the evidence of adverse thyroid impact to be among the most compelling (NRC, Chapter 8 and Appendix E). NRC panelist Dr. Kathleen Thiessen, who authored much of the endocrine disruption section of NRC report, filed a comment with the US EPA in 2011 and submitted an affidavit in 2014 for a pending lawsuit in Ontario, Canada that details the risk posed by artificial community water fluoridation to susceptible populations such as diabetics, cancer patients and those with low iodine levels.

Dr. Thiessen also has reminded the EPA and the Ontario courts that the 2006 NRC wrote, “Fluoride appears to have the potential to initiate or promote cancers, particularly of the bone.” (NRC, p 336) Additionally, the NRC reported that fluoride’s interference with calcium metabolism and in the presence of calcium deficiency has direct and indirect impacts on the functioning of the parathyroid, which in turn has an impact on the bones (NRC, 236-251). This should not be surprising, since Table 9 of a ten years later study of the first fluoridation trial revealed a number of notable differences on X-rays, such as children growing up in fluoridated Newburgh, NY had the twice cortical bone defects and twice the


“Thyroid dysfunction and Type II diabetes presently pose substantial health concerns in the U.S. (NRC 2006). Of particular concern is an inverse correlation between maternal subclinical hypothyroidism and the IQ of the offspring. In addition, maternal subclinical hypothyroidism has been proposed as a cause of or contributor to development of autism in the child (Román 2007; Sullivan 2009). Calcium deficiency induced or exacerbated by fluoride exposure may contribute to a variety of other health effects (NRC 2006).” - Dr. Kathleen Thiessen (2011 p 8)

5.5-3

exostoses compared to those found in the control population of un-fluoridated Kingston. Since we know that dental fluorosis is a poisoning of ameloblast mitochondria that results in a structural change to the composition of the tooth, it is not unreasonable to suspect a similar fluoride mediated etiology is at play in bones. We also know that the increased fluoride levels in tooth and bone may increase hardness and density, but reduce elasticity resulting in more brittleness. Some studies, as well as clinical reports, demonstrate that the 41% of children with dental fluorosis have more non-traumatic bone fractures than children without dental fluorosis correlated with the severity of their visible dental fluorosis. (Schlesinger 1956, Thiessen 2011, Beltran 2010, Alarcón-Herrera 2001)

Most disconcerting, the 2006 study by Bassin et al. published in Cancer Causes & Control identified an age-specific increased risk of osteosarcoma in boys drinking artificially fluoridated water in the US. This also should not be surprising, given our increasing awareness of the impact of environmental toxins on the genesis of cancers. In addition to being an endocrine disruptor, fluoride is a poison, an adjuvant and an inflammatory drug with an affinity for bone. What is surprising is that none of our professional organizations have clamored for follow-up on these alarming anomalies that suggest fluoride contributes to pediatric cancer, or called for a fluoridation moratorium as evidence of harm continues to mount.

The one other attempt to seriously investigate the connection between cancer and fluoride resulted in allegations of data tampering, harassment, and intimidation. In that instance, the accidental whistle blower, Senior Science Advisor Wm. Marcus of the EPA, was vindicated, reinstated and awarded back pay and legal fees. However, the falsified report that downgraded multiple cancerous tumors in thyroid, liver, kidney and bone to benign was allowed to stand. The matter of fluoridated water and cancer was dropped. Incredibly, the ADA partnering with the Centers for Disease Control (CDC) and American Academy of Pediatrics (AAP) returned to their mantra of “safe and effective” in their promotion of artificial water fluoridation that casts fluoride as an optimization of community water supplies with a naturally occurring mineral necessary to dental health. Municipal water fluoridation products are the contaminated waste products of industry, harvested from toxic slurry. (Marcus 1990, Dearen 2015, Mullenix 2014)

The ATA would not be the first medical association to break ranks with the ADA’s, AAP’s and AMA’s unequivocal support of fluoridation as a safe practice implemented for the public good. The National Kidney Foundation (NKF) removed their name from the list of fluoridation endorsors in 2008. As you know, inadequate kidney function results in a higher percentage of ingested fluoride being sequestered in the body where it can build up in soft tissues as well as bone, even causing calcification (Martín 2014, Waldbott 1978). The NKF took a neutral stand on the topic of fluoridation rather than opposing fluoridation, while officially recommending that those with Stage 4 kidney disease be advised to avoid fluoridated water and foods. It hasn’t been made clear whose responsibility it is to do the advising.

The NKF also advised that it would be “prudent” for children, those with renal impairment, and those with prolonged health conditions to “monitor” their fluoride intake, while acknowledging that they knew no way to do so since once fluoride is in the water it becomes ubiquitous in our diets and individual dosage is dependent on a myriad of factors. The NKF also implied that those who drink a lot of water should be concerned about their fluoride intake and its impact on their health. We can only assume that this weak stand was made in an effort to avoid angering the dental lobby who loudly insisted, then as now, that fluoridation prevents cavities and is perfectly safe for the general population. We suggest that the science since 2008 makes it easier for the ATA to take a stronger stand with firm footing in 2016.


Expert in Chemical Research: "Fluoride is an enzyme poison, in the same class as cyanide, oxalate, or azide ... it is capable of a very wide variety of harmful effects, even at low doses. It is a scientific disgrace that a well organized lobby of the American Dental Association ever managed to stampede American legislators into ignoring the highly technical but very cogent objection to fluoridation." - James B. Patrick, Ph.D., National

Institute of Health statement to Congress (1982)

5.5-4

In 2015, a US study found that even after adjusting for confounding factors such as socioeconomic status, fluoridated regions have between 67,000 and 131,000 more diagnosed cases of hyperactivity among school children than non fluoridated regions (Malin et al.) This is consistent with twenty years of science that include animal studies, ecologic studies, and studies that evaluated individuals that found exposure to fluoridated water as a fetus or during youth results in cognitive and emotional deficits correlated with severity of dental fluorosis in those individuals. Put more simply, in fluoridated communities, there are more tired moms and hyperactive special needs children, both explainable by fluoride’s impact on thyroid hormones. (See Resources)

Consistent with these findings is the presentation at 27th Conference of the International Society for Environmental Epidemiology (Aug 30- Sept 3, 2015) entitled “Evaluation of thyroid hormones (TSH and T4) in pregnant women exposed to fluoride (F-) in drinking water” by Rocha Amador D, et al. Using ATA guidelines, the team demonstrated F- toxicity on CNS during human pregnancy.

Several other 2015 studies, although not as specific to thyroid function, should also be of interest to the ATA. One found that even the low concentration of fluoride in “optimally” fluoridated drinking water causes inflammation of the immune system. Another found that the central nervous system has lymphatic/immune structures vulnerable to inflammation. A third identified a gene that predicts who will have a lower tolerance to fluoride and therefore exhibit both dental fluorosis and measurable neuro-developmental deficits if exposed to fluoridated water in utero or during early childhood. (Resources)

Also in 2015, the Cochrane Review panel agreed with the 2000 York Review panel that the dental proclamations regarding fluoridation were overstated. Both international reviews of fluoridation literature found the low quality studies to be of high risk of bias with limited evidence of reduction in childhood cavities amounting to a lifetime benefit of perhaps one or two fewer cavities. The expert panels could not confirm that fluoridation reduced socioeconomic inequities among children or provided any benefit to adults in their reviews of the evidence. Moreover, both reviews confirmed that 12% of the general population living in artificially fluoridated communities would consider their fluoridation caused dental fluorosis ‘aesthetically displeasing.’ Finally, both reviews found there was neither any serious attempt to prove whole health safety nor evidence of safety. (Iheozor-Ejiofor et al. 2015, McDonagh et al. 2000)

For your convenience, we have included references to the York and Cochrane dental reviews together with a selection of relevant studies and reports in the Resources section of this communication. We suggest the ATA also carefully consider the three recent aggregate documents we’ve attached which include significant scientific citations:

i. The 2014 analysis by Prof. Rita Barnett-Rose JD on the legal and ethical implications of the current municipal water fluoridation practice

ii. The 2014 legal memo with attached scientific affidavit of NAS/NRC panelist Dr. Kathleen Thiessen prepared by Nader R. Hasan, Esq. in the Peel, Ontario lawsuit based on disproportionate harm

iii. The 2015 letter to the Institute of Medicine (IOM) signed by safe water consumer advocate Erin Brockovich, Dr. Wm. Ingram as president of the American Academy of Environmental Medicine on its behalf, “super lawyer” David P. Matthews of Matthews & Associates, and others regarding the failure of the IOM to update age specific fluoride dietary intake references published by the IOM in 1997 in light of 21st century science.


UNESCO on Bioethics and Human Rights

”Any preventive, diagnostic and therapeutic medical intervention is only to be carried out with the prior, free and informed consent of the person concerned.” (2005)

”In no case should a collective community agreement or the consent of a community leader or other authority substitute for an individual’s informed consent.” (2010)

5.5-5

Moreover, corrosive fluoridation chemicals increase blood lead levels. (Coplan 2007, Maas 2007, Masters 2000)

The weight of the evidence is undeniable. We know fluoridation is unsafe. We’ve hundreds of studies and reports attesting to that fact. We know that thyroid and parathyroid diseases cause misery. We see that in our clinical practices. We know that fluoridation is mass medication without medical consent, and consequently an immoral act. We owe it to our patients, to the general public, and to ATA membership to exemplify medical integrity and scientific courage. The American Thyroid Association should be the spokesmen on thyroid health, not dentists or marketeers funded by the fluoride industry.

We are petitioning the American Thyroid Association to:

1. Publish a position statement opposing the practice of community water fluoridation (CWF) based on its impact on thyroid hormones, interference with glucose and calcium metabolism in susceptible populations, and general capacity for endocrine disruption.

2. Send a copy of that position statement to the National Toxicology Program in North Carolina with a cover letter that reminds them that the impact of hypothyroidism on the developing brain might not be scientifically categorized as neurotoxic but that medical fact is a distinction without a difference.

In closing, given the fluoridation lawsuit pending in Peel, Ontario based on the principle of disproportionate harm, i.e. an action that may have small benefit to some is not justified when that action poses a risk of great harm to others, and other anticipated American lawsuits yet to be filed, we suggest that the ATA leadership and directors should be prepared to demonstrate their scientific integrity and professional ethics. We suggest the ATA speak for themselves, as physicians and endocrinologists with specialities that range from nutrition to cancer, as to the interpretation of relevant scientific studies and testify on behalf of their patients as to the impact of fluoridation and endocrine disruption on thyroid health.

Respectfully,

CC: Dr. Sanjay Gupta at CNN, Dr. Stephen Peckham, Moms Against Fluoridation, Fluoride Action Network

Prepared by: KSpencer

"

Richard L. Shames, MDThyroid Physician, Health Author

Eleanor V. Phillips, DDSformer ADA & AAPD, Health Author

"

Nathan Becker, MD, FACE, FACPEndocrinologist, member AACE

"

Heather Dawn Gingerich, MSc. Medical Geologist, AAAS, UNESCO

"

William J. Rea, MDSurgeon, Founder EHC-D, Author

"

Marcus L. Scott, Esq.Attorney at Law


“It is reckless to assume that when fluoride is damaging the baby’s growing tooth cells, it is not damaging other delicate tissues like the bone, brain and endocrine system.” ~ Dr. Paul Connett, Professor Emeritus of

Chemistry (2015)

"Long-continued ingestion of minute quantities of fluorine causes disease of the thyroid gland." - Douglas D. Styne, MD

“There’s no doubt that the intake of fluoridated water is going to interrupt basic functions of nerve cells in the brain, and this is certainly not going to be [for] the benefit of anybody.” Dr. Robert Isaacson, 2006 NRC

5.5-6

RESOURCES2014-2015 Aggregations:

1. Rita Barnett-Rose. Compulsory Water Fluoridation: Justifiable Public Health Benefit or Human Experimental Research Without Informed Consent?, 39 Wm. & Mary Envtl. L. & Pol'y Rev. 201 (2014). http://works.bepress.com/rita_barnett/3/ • Excerpt: The cessation of all compulsory water fluoridation schemes should be the goal of all public

health agencies, ethical lawmakers, and informed citizens.2. Nader R. Hasan. Memorandum: Legal Arguments Against Artificial Water Fluoridation with Affidavit of Dr.

Kathleen Thiessen. Ruby, Shiller, Chan, & Hasan Barristers. Ontario, Canada. 23 June 2014. http://momsagainstfluoridation.org/sites/default/files/Fluoridation-Legal-Opinion-June-24-14.pdf • Excerpt: Marginal benefit in exchange for significant risk is the sine qua non of gross disproportionality…

the stronger the scientific evidence of risk of harm, the greater the gross disproportionality.3. Letter to Institute of Medicine from Erin Brockovich, American Academy of Environmental Medicine, Matthews

& Associates, et al. 27 April 2015. https://www.aaemonline.org/pdf/LetterIOM_2015.04.27.pdf • 19 Dec 2015 petition: http://petitions.moveon.org/sign/dietary-fluoride-and.fb48

Summary: • Fluoride is an enzyme poison and an endocrine disruptor• Fluoride is a potent adjuvant... causing or worsening allergies• Fluoride is a proliferative agent... causing or worsening inflammation • Fluoride accumulates in bones and tissue... causing or worsening arthritis and other ailments• Fluoride impacts thyroid hormones... resulting in both hypo and hyper disorders • Fluoride interferes with glucose metabolism... a concern for diabetics • Fluoride causes dental fluorosis... disproportionately by race and social economic status• Fluoride is neurotoxic to fetuses, infants and young children... resulting in permanent deficits• Fluoride is a burden to kidneys... resulting in increased fluoride retention and possible renal damage

in those with kidney disease.

Selected 2014-2015 Studies and Reports:

1. Navneet Singh, Kanika Gupta Verma, Pradhuman Verma, Gagandeep Kaur Sidhu and Suresh Sachdeva. A comparative study of fluoride ingestion levels, serum thyroid hormone & TSH level derangements, dental fluorosis status. Springerplus. 2014; 3: 7. 2014 Jan 3. doi: 10.1186/2193-1801-3-7. PMCID: PMC3890436. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890436/pdf/40064_2013_Article_766.pdf

2. S Peckham, D Lowery, S Spencer. Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data and fluoride levels in drinking water. J Epidemiol Community Health. 24 February 2015. doi:10.1136/jech-2014-204971. http://jech.bmj.com/content/early/2015/02/09/jech-2014-204971

3. I. Gutowskaa, I. Baranowska-Bosiackab, M. Goschorskab, A. Kolasac, A.Lukomskaa, K. Jakubczyka, K. Deca, D. Chlubekb. Fluoride as a factor initiating and potentiating inflammation in THP1 differentiated monocytes/macrophages. Toxicology in Vitro. Volume 29, Issue 7, October 2015, Pages 1661–1668. http://www.sciencedirect.com/science/article/pii/S0887233315001605

4. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jul 16;523(7560):337-41. doi:10.1038/nature14432. Epub 2015 Jun 1. http://www.ncbi.nlm.nih.gov/pubmed/26030524

5. Sarkar C, Pal S. Effects of sub-acute fluoride exposure on discrete regions of rat brain associated with thyroid dysfunction: a comparative study. International Journal of Biomedical Research. 2015. 6(09): 647-660.

6. Liu Q, Liu H, Yu X, Wang Y, Yang C, Xu H. Analysis of the role of insulin signaling in bone turnover induced by fluoride. Biological Trace Element Research. 2015 Oct 31. ePub ahead of print. http://www.ncbi.nlm.nih.gov/pubmed/26521058

7. Lei S, Zhang Y, Zhang K, Li J, Liu L. Effects of Fluoride on the Expression of Beclin1 and mTOR in Ameloblasts. Cells Tissues Organs. 2015 Dec;200(6):405-12. doi: 10.1159/000441052. Epub 2015 Nov 13. http://www.ncbi.nlm.nih.gov/pubmed/26562167


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8. Rocha Amador D, et al. Evaluation of thyroid hormones (TSH and T4) in pregnant women exposed to fluoride (F-) in drinking water. Presented at Conference of the International Society for Environmental Epidemiology. Aug 31 - Sept 3 2015

9. A Malin and C Till. Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence. Environmental Health 2015, 14:17 doi:10.1186/s12940-015-0003-1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389999/

10. Zhang S, Zhang X, Liu H, Qu W, Guan Z, Zeng Q, Jiang C, Gao H, Zhang C, Lei R, Xia T, Wang Z, Yang L, Chen Y, Wu X, Cui Y, Yu L, Wang A. Modifying Effect of COMT Gene Polymorphism and a Predictive Role for Proteomics Analysis in Children's Intelligence in Endemic Fluorosis Area in Tianjin, China. Toxicol Sci. 2015 Apr;144(2):238-45. doi: 10.1093/toxsci/kfu311. Epub 2015 Jan 1. PMID: 25556215. http://www.ncbi.nlm.nih.gov/pubmed/25556215

11. Anna L. Choi, Ying Zhang, Guifan Sun, David C. Bellinger, d, Kanglin Wang, Xiao Jing Yang, Jin Shu Li, Quanmei Zheng, Yuanli Fug, Philippe Grandjean, Association of lifetime exposure to fluoride and cognitive functions in Chinese children: A pilot study. Neurotoxicology and Teratology. Volume 47, January–February 2015, Pages 96–101. http://www.sciencedirect.com/science/article/pii/S0892036214001809

12. Khan SA, Singh RK, Navit S, Chadha D, Johri N, Navit P, Sharma A, Bahuguna R. Relationship Between Dental Fluorosis and Intelligence Quotient of School Going Children In and Around Lucknow District: A Cross-Sectional Study. J Clin Diagn Res. 2015 Nov;9(11):ZC10-5. doi: 10.7860/JCDR/2015/15518.6726. Epub 2015 Nov 1. http://www.ncbi.nlm.nih.gov/pubmed/26673535

13. Grandjean P, Landigran P. Neurobehavioural effects of developmental toxicity. The Lancet Neurology , Volume 13 , Issue 3 , 330 - 338. March 2014. http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(13)70278-3/abstract

14. F. Liu et al.. Fluoride exposure during development affects both cognition and emotion in mice. Physiol Behav. 2014 Jan 30;124:1-7. doi: 10.1016/j.physbeh.2013.10.027. http://www.ncbi.nlm.nih.gov/pubmed/24184405

15. Martín-Pardillos A, Sosa C, Millán Á, Sorribas V. Effect of water fluoridation on the development of medial vascular calcification in uremic rats. Toxicology. 2014 Apr 6;318:40-50. doi: 10.1016/j.tox.2014.01.012. Epub 2014 Feb 18. PMID: 24561004. http://www.ncbi.nlm.nih.gov/pubmed/24561004

16. Iheozor-Ejiofor Z, Worthington HV, Walsh T, O'Malley L, Clarkson JE, Macey R, Alam R, Tugwell P, Welch V, Glenny A. Water fluoridation for the prevention of dental caries. Cochrane Database of Systematic Reviews 2015, Issue 6. Art. No.: CD010856. DOI: 10.1002/14651858.CD010856.pub2. http://www.cochrane.org/CD010856/ORAL_water-fluoridation-prevent-tooth-decay

17. Main, Douglas. Fluoridation May Not Prevent Cavities, Scientific Review Shows. Newsweek (Tech and Science). 29 June 2015. http://www.newsweek.com/fluoridation-may-not-prevent-cavities-huge-study-shows-348251

18. Fluoridation Advocacy: Pew’s Contributions and Lessons that Emerge. Children’s Dental Health Project. July 2015. https://s3-us-west-2.amazonaws.com/cdhp-fluoridation/CDHP_FlouridationAdvocacyReport_FINAL.pdf.

19. Beware of newly formed, “The American Fluoridation Society.” Crescent City Times. 24 December 2015. http://www.crescentcitytimes.com/?p=13885

20. Holsted, David. Anti-fluoride group charges deception; Nonexistent report, conflict of interest. Harrison Daily News. Dec 4. 2015. http://harrisondaily.com/news/anti-fluoride-group-charges-deception-nonexistent-report-conflict-of-interest/article_5aaeabaa-9a97-11e5-a949-1fb6a372958a.html

21. Mullenix PJ. A new perspective on metals and other contaminants in fluoridation chemicals. International Journal of Occupational and Environmental Health. 2014 Apr-Jun;20(2):157-66. doi: 10.1179/2049396714Y.0000000062. Epub 2014 Mar 20. http://www.ncbi.nlm.nih.gov/pubmed/24999851

22. Dearen J., Biesecker M. Feds reach nearly $2B legal settlement with fertilizer maker. Associated Press. 1 Oct. 2015. http://bigstory.ap.org/article/73badc4f9aa74d06b654acbfc59f3ce9/feds-reach-nearly-2b-legal-settlement-fertilizer-maker

23. Fluoridation Chemical Company Fined $2 Billion. 7 Oct 2015. http://www.prnewswire.com/news-releases/fluoridation-chemical-company-fined-2-billion-300155874.html?$G1Ref

24. 2015 database of relevant studies. Fluoride Action Network. http://fluoridealert.org/studytracker/?effect=&type=&start_year=2015&end_year=2015&show=100&fulltext=&fantranslation=

25. 2014 database of relevant studies. Fluoride Action Network. http://fluoridealert.org/studytracker/?effect=&type=&start_year=2014&end_year=2014&show=100&fulltext=&fantranslation=


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Earlier References & Resources:

1. 2008 National Kidney Foundation Position Statement. http://www.kidney.org/sites/default/files/docs/fluoride_intake_in_ckd.pdf

2. 2006 American Academy of Environmental Medicine Resolution Opposing Fluoridation. https://www.aaemonline.org/pdf/FluorideResolution.pdf

3. Fluoride in Drinking Water: A Scientific Review of EPA's Standards. Washington, DC: The National Academies Press. 2006. http://www.nap.edu/openbook.php?record_id=11571

4. Anna L. Choi, Guifan Sun, Ying Zhang, and Philippe Grandjean. Developmental Fluoride Neurotoxicity: A Systematic Review and Meta-Analysis. Environ Health Perspect 120:1362–1368. October 2012. http://dx.doi.org/10.1289/ehp.1104912. http://ehp.niehs.nih.gov/1104912/

5. Wang H, Yang Z, Zhou B, Gao H, Yan X, Wang Fluoride-induced thyroid dysfunction in rats: roles of dietary protein and calcium level. J. Toxicol Ind Health. 2009 Feb;25(1):49-57. doi: 10.1177/0748233709102720. http://www.ncbi.nlm.nih.gov/pubmed/19318504

6. Mullenix PJ, Denbesten PK, Schunior A, Kernan WJ.. Neurotoxicity of sodium fluoride in rats. Neurotoxicology & Teratology. 1995 Mar-Apr;17(2):169-77. http://momsagainstfluoridation.org/sites/default/files/Mullenix%202014-2-2.pdf

7. Bassin EB, Wypij D, Davis RB, Mittleman MA. Age-specific fluoride exposure in drinking water and osteosarcoma (United States). Cancer Causes Control. 2006 May;17(4):421-8. http://www.ncbi.nlm.nih.gov/pubmed/16596294

8. Sauerheber R. Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride. Journal of Environmental and Public Health. 2013;2013:439490. doi:10.1155/2013/439490. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690253/

9. Thiessen, Kathleen. Comments to the EPA. 2011. http://www.fluoridealert.org/wp-content/uploads/thiessen.4-19-11.pdf

10.Coplan MJ, Patch SC, Masters RD, Bachman MS. Confirmation of and explanations for elevated blood lead and other disorders in children exposed to water disinfection and fluoridation chemicals. Neurotoxicology. 2007 Sep;28(5):1032-42. Epub 2007 Mar 1. http://www.ncbi.nlm.nih.gov/pubmed/17420053

11. Masters RD, Coplan MJ, Hone BT, Dykes JE. Association of silicofluoride treated water with elevated blood lead. Neurotoxicology. 2000 Dec;21(6):1091-100, http://www.ncbi.nlm.nih.gov/pubmed/11233755

26. Maas RP, Patch SC, Christian AM, Coplan MJ. Effects of fluoridation and disinfection agent combinations on lead leaching from leaded-brass parts. Neurotoxicology. 2007 Sep;28(5):1023-31. Epub 2007 Jun 30. http://www.ncbi.nlm.nih.gov/pubmed/17697714

27. Masters R.D., Coplan M.J. Water Treatment with Silicofluorides and Lead Toxicity. Intern. J. Environ. Studies 56: 435-449 1999. http://www.slweb.org/IJES-silicofluorides.html

28. Editors: Olle Selinus, Robert B. Finkelman, Jose A. Centeno. Medical Geology: A Regional Synthesis. International Year of Planet Earth. Springer Dorsdrecht Heidelberg London New York. 2010. ISBN: 978-90-481-3429-8 (Print) 978-90-481-3430-4 (Online). http://link.springer.com/book/10.1007%2F978-90-481-3430-4

29. Peter Loskill, Christian Zeitz, Samuel Grandthyll, Nicolas Thewes, Frank Müller, Markus Bischoff, Mathias Herrmann, Karin Jacobs. Reduced Adhesion of Oral Bacteria on Hydroxyapatite by Fluoride Treatment. Langmuir, 2013; 130423132120002 DOI: 10.1021/la4008558. http://www.sciencedaily.com/releases/2013/05/130501112855.htm

12.Yoder KM, Maupome G, Ofner S, Swigonski NL. Knowledge and use of fluoride among Indiana dental professionals. J Public Health Dent. 2007 Summer;67(3):140-7. http://www.ncbi.nlm.nih.gov/pubmed/17899898

13.Hellwig E, Lennon AM. Systemic versus topical fluoride. Caries Res. 2004 May-Jun;38(3):258-62. http://www.ncbi.nlm.nih.gov/pubmed/15153698?dopt=Abstract

14.Warren, John J et al.. Current and future role of fluoride in nutrition. Dental Clinics, Volume 47, Issue 2, April 2003. pp 225 - 243 (IFS): http://www.dental.theclinics.com/article/S0011-8532(02)00098-8/abstract

15.McDonagh Marian S, Whiting Penny F, Wilson Paul M, Sutton Alex J, Chestnutt Ivor, Cooper Jan et al. Systematic review of water fluoridation BMJ 2000; 321:855. (2000 York Review) http://www.bmj.com/content/321/7265/855 and http://www.york.ac.uk/inst/crd/CRD_Reports/crdreport18.pdf

16.Cheng KK, Chalmers I, Sheldon TA. Adding fluoride to water supplies. BMJ : British Medical Journal. 2007;335(7622):699-702. doi:10.1136/bmj.39318.562951.BE. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001050/


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30. E. R. Schlesinger, D. E. Overton, H. C. Chase, and B. A. Cantwell, “Newburgh-Kingston Caries-Fluorine Study. XIII. Pediatric Findings After Ten Years,” Journal of the American Dental Association 52, no. 3 (1956): 296–306.

17.Hileman, Bette. “Fluoridation of Water: Questions about health risks and benefits remain after more than 40 years.” Special Report: Chemical & Engineering News. August 1, 1988. http://www.nofluoride.com/Chemical_&_Engr_News.cfm

18. Sutton, Philip R.N. “Fluoridation: Errors & Omissions in Experimental Trials”. 2nd ed. 1960. http://www.scribd.com/doc/212649060/Fluoridation-Errors-and-Omissions-in-Experimental-Trials-2-Ed-Phillip-Sutton-1960

19.Hsien-Wen Kuo, Chuan-Juan Lin, Li-Li Chen. Factors Affecting Urinary Fluoride Concentrations Among Patients With Renal Dysfunction. Institute of Environmental Health, and Department of Nursing, China Medical College; Department of Nursing, Hung-Kuang Technology College, Taichung, Taiwan, R.O.C. 2001. http://ir.cmu.edu.tw/ir/bitstream/310903500/1332/1/2001067481.pdf

20.Herta Spencer, MD; Lois Kramer; Carol Gatza, RN; Clemontain Norris, RN; Emilie Wiatrowski; Vasant C. Gandhi, MD. Fluoride Metabolism in Patients With Chronic Renal Failure. Arch Intern Med. 1980;140(10):1331-1335. doi:10.1001/archinte.1980.00330210079027. http://archinte.jamanetwork.com/article.aspx?articleid=600342

21.Hu CY, et. al. Effect of fluoride on insulin level of rats and insulin receptor expression in the MC3T3-E1 cells. Biol Trace Elem Res. 2012 Dec;150(1-3):297-305. doi: 10.1007/s12011-012-9482-x. Epub 2012 Aug 8.. http://www.ncbi.nlm.nih.gov/pubmed/22872571

22.Massler M, Schour I. Relation of endemic dental fluorosis to malnutrition. (1952). JADA. 44: 156-165. http://www.slweb.org/massler-schour.html

23.Beltran-Aguilar et al. CDC. Prevalence and Severity of Dental Fluorosis in the United States, 1999-2004. NCHS Data Brief No. 53, November 2010. http://www.cdc.gov/nchs/data/databriefs/db53.htm

24.Sauerheber R. Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride. Journal of Environmental and Public Health. 2013;2013:439490. doi:10.1155/2013/439490. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690253/

25.Shalu Chandna and Manish Bathla. Oral manifestations of thyroid disorders and its management. Indian J Endocrinol Metab. 2011 Jul; 15(Suppl2): S113–S116. PMCID: PMC3169868 doi: 10.4103/2230-8210.83343. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169868/

26.Spira L. Fluorosis and the parathyroid glands. The Journal of Hygiene. 1942;42(5):500-504. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199852/

27.Camille Jung, Jean-Pierre Hugot, and Frédérick Barreau, “Peyer's Patches: The Immune Sensors of the Intestine,” International Journal of Inflammation, vol. 2010, Article ID 823710, 12 pages, 2010. doi:10.4061/2010/823710. http://www.hindawi.com/journals/iji/2010/823710/

28.Waldbott George L, MD. The Preskeletal Phase of Chronic Fluoride Intoxication. 1998, Fluoride, 31:1, 13-20: http://www.fluoridation.com/waldbot.htm

29.Waldbott GL, Burgstahler AW, McKinney HL. Fluoridation: The Great Dilemma. Coronado Press. 1978. 30.Moolenburgh Hans. Affidavit filed in Wisconsin. 1993. https://fluorideinformationaustralia.wordpress.com/legal/

affidavits/ 31.Laylander, Julia A. A Nutrient/Toxin Interaction Theory of the etiology and Pathogenesis of Chronic Pain-

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32.Laylander, Julia A. A Nutrient/Toxin Interaction Theory of the etiology and Pathogenesis of Chronic Pain-Fatigue Syndromes, Part II. Journal of Chronic Fatigue Syndrome. vol 5(1) 1999. http://www.earthclinic.com/laylander-1999b.pdf

33.Galetti PM, Joyet, G. Effect of Fluorine On Thyroidal Iodine Metabolism in Hyperthyroidism. J Clin Endocrinol 18:1102-1110 (1958). See Fact 7 in: http://www.spiritofhealthkc.com/wp/wp-content/uploads/2014/03/FLUORIDE1-My-Fluoride-Facts-by-David-C.-Kennedy-DDS.pdf

34.Alarcón-Herrera MT, Martín-Domínguez IR, Trejo-Vázquez R, Rodriguez-Dozal S. Well water fluoride, dental fluorosis and bone fractures in the Guadiana Valley of Mexico. Fluoride 2001;34:139-149. https://www.researchgate.net/publication/236153410_Well_water_fluoride_dental_fluorosis_and_bone_fractures_in_the_Guadiana_Valley_of_Mexico

35.Editor: Parents of Fluoride Poisoned Children. Thyroid History: History of Fluoride/Iodine Antagonism. PFPC. 1996. http://poisonfluoride.com/pfpc/html/thyroid_history.html


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36.Kidney Disease statistics for the United States. NIDDK: National Institute of Health. http://kidney.niddk.nih.gov/KUDiseases/pubs/kustats/#3

37.Xiong X, Liu J, He W, Xia T, He P, Chen X, Yang K, Wang A. Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environ Res. 2007 Jan;103(1):112-6. Epub 2006 Jul 10. PMID: 16834990. http://www.ncbi.nlm.nih.gov/pubmed/16834990

38.Diesendorf, Mark. Suppression by medical journals of a warning about overdosing formula-fed infants with fluoride. Accountability in Research. 02/1997; 5(1-3):225-37. DOI: 10.1080/08989629708573911. http://www.researchgate.net/publication/11696965_Suppression_by_medical_journals_of_a_warning_about_overdosing_formula-fed_infants_with_fluoride

39.Diesendorf M, Sutton P. Fluoride: New Grounds for Concern. The Ecologist. Vol. 16, No. 6,1986. http://www.slweb.org/ecologist-1986.html

40.NRC panelist, Dr. Kathleen Thiessen. Comments to EPA. 2011. http://www.fluoridealert.org/wp-content/uploads/thiessen.4-19-11.pdf

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REFERRAL TO ______________________________

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