plasticisers: an update
DESCRIPTION
Plasticisers: An Update. David Cadogan Plasttekniske Dager Oslo, 8-9 November 2006. Outline. ECPI Plasticiser requirements Are phthalates a threat to human health Legislative actions Classification and labelling Risk assessments Toys, food contact materials, medical devices Reach - PowerPoint PPT PresentationTRANSCRIPT
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Outline
ECPI
Plasticiser requirements
Are phthalates a threat to human health
Legislative actions
– Classification and labelling
– Risk assessments
– Toys, food contact materials, medical devices
– Reach
Market trends
Summary
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ECPI
European Council for Plasticisers and Intermediates
A Sector Group of CEFIC – the European Chemical Industry Council
European producers of plasticisers, alcohols and acids
Sponsorship of scientific studies by independent experts
Provide users, legislators and other interested bodies with information on safety, health and the environment
Close liaison with trade organisations in USA and Japan
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Plasticiser requirements
Compatible with PVC
Efficient
Ease of processing
Low volatility
Low migration/extraction
Flexibility at low temperatures
High temperature performance
Electrical resistance
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93% of Plasticisers are Phthalates
Phthalates have :Optimum balance of polar / non-polar groupsBest all round performance / price ratio
C4 - C7 alcohol : Lower viscosity, faster processingC8 – C10 alcohols : General purpose C11-C13 alcohols : High temperature performance>80% linear : Better low / high temperature performance
DEHP
Performance can be fine tuned by using appropriate alcohol
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93% of Plasticisers are Phthalates
More polar groups – Increased compatibility with PVC and easier processing BBP – Fast processing and stain resistance
BBP
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Potential Health Impact - Carcinogenicity
1982 – Liver tumours in rodents caused IARC to classify DEHP as “possibly carcinogenic to humans”
18 years of research showed :
Phthalates, hypolipidaemic drugs and other chemicals cause tumours in rodents by peroxisome proliferation (PP)
No PP or liver damage in monkeys fed DEHP and DINP
No PP or liver damage in humans taking hypolipidaemic drugs
No DEHP induced liver tumours in mice lacking PP receptor
2000 - IARC Reclassified DEHP - Phthalate induced liver cancer in rats and mice is not relevant to humans
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Potential Health Impact - Reproductive Effects
High levels of some phthalates produce testicular atrophy in rodents
Little, if any, effects seen with DMP, DEP, DINP and DIDP
Levels can be defined at which no effects occur (NOAEL)
In general NOAELs are orders of magnitude higher than levels of exposure. Therefore no risk
Studies ongoing to identify the mechanism underlying the reproductive effects in rodents – are they relevant to humans?
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The facts are:No evidence of any phthalate having an adverse effect on human health
20 year follow-up study on 242 low birth weight individuals (high DEHP exposure in intensive care) showed no effects on male fertility
Adolescents exposed to DEHP via ECMO as neonates show no adverse effects on growth or sexual maturity
Adverse effects are only seen in rodent studies
Adverse effects not seen in non-human primates
However - There are now two studies claiming to see effects in humans
Adverse Effects on Human Health
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Swan et al. (August 2005) measured Anogenital Index (AGI) in 85 boys aged between 2 and 36 months. (AGI = AGD / Weight).
Smaller AGI in boys said to correlate with higher levels of metabolites of DEP, DBP, DIBP and BBP in mothers urine during pregnancy
AGI is smaller in females than in males hence these phthalates are said to have a feminising effect
Highly publicised – press conference more important than peer review.
Baby Boys Feminised by Prenatal Phthalate Exposure - Claims
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Inadequate measurement of maternal phthalate exposure
Only one urine sample taken during pregnancy
Studies by Hauser et al (2004) and Hoppin et al (2002) indicate that repeated urine measurements are necessary to determine exposure
Concerns re measurement of AGD in boys
Poor planning. AGD changes rapidly with age but they measured at ages ranging from 2 – 36 months. Hence needed extensive regression analysis
The only other study (Salazar-Martinez et al, 2004) was systematic - 45 boys measured at 6 hours old. No regression needed – apparently less variation in AGD / weight
Prenatal Phthalates Feminise Baby Boys – The Facts
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Authors attempt to make case stronger than it is
Independent statisticians find the conclusions are unsound
US National Toxicology Programme panel of 11 toxicologists have concluded that the findings are not reliable
No correlation between AGI and primary metabolite of DEHP in mother’s urine but weak correlation with the level of secondary metabolites - not logical
Strong correlation with MEP in urine – contrary to many other studies on DEP
Prenatal Phthalates Feminise Baby Boys – The Facts
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Main et al. (February 2006) measured levels of phthalate monoesters in breast milk of 130 mothers of baby boys at 1-3 months postnatally.
Subjects selected so that approximately half of the boys had undescended testes.
No correlation found between undescended testes and monoesters in breast milk – main aim of the study but gets little mention in the report
Measured levels of reproductive hormones in boys at three months and investigated link with levels of phthalate monoesters in breast milk.
A link is proposed between levels of some phthalate metabolites in breast milk and some hormone levels in male offspring
Phthalates in Breast Milk Effect Baby Boys - Claims
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Statistical treatment of data and interpretation of results questioned
Independent statisticians agree that there is no real correlation.
The authors discount results which do not fit their hypothesis as being “random findings”
The lack of a link between MEHP and hormone levels is said to be due to the “limited number of samples in the study”
Study rejected by EU Member States Experts in DEHP Risk Assessment
US Expert Panel on Human Reproduction believes that some hormone measurements are not relevant and breast milk samples are most likely contaminated
Phthalates in Breast Milk Effect Baby Boys – The Facts
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Legislative Actions
Classification and labelling of dangerous substances
Existing substances legislation – Risk assessment and management
Toys and childcare articles
Food contact materials
Medical devices
REACH
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Hazard - Classification and Labelling
Category 1 Substances known to cause effects in humans. Based on epidemiological data. Category 2 Substances to be regarded as if they cause effects in humans. Based on clear evidence in animal studies. Category 3 Substances causing concern for humans. Based on less convincing evidence in animal studies.
Classification and labelling does not apply to articles
Aim – To ensure safe handling and use in the workplace
Backbone Fertility
Developmental
DMP 1 None None
DEP 2 None None
DPrP 3 None None
DIBP SCL = 25% 3 Cat 3 Cat 2
DBP 4 Cat 3 Cat 2
DPP 4 - 5 Cat 2 Cat 2BBP 4 - 7 Cat 3 Cat 2DIHP 5 - 6 None Cat 2
DEHP 6 Cat 2 Cat 2
711P (Branched) 5 - 9 Cat 3 Cat 2
DINP 7 - 8 None None
DIDP 8 - 9 None None
79P (Linear) 7 - 9 None None
911P (Linear) 9 - 11 None None
Classification and Labelling
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Existing Substances Legislation
To properly assess the risks imparted by all chemicals
To both humans and the environment
Margin of Safety (MOS) = NOAEL / Exposure
MOS > 100 = No Risk
To identify risk management requirements if necessary and implement a Risk Reduction Strategy
Council Regulation EEC / 793 / 93 on the evaluation and control of the risks of existing substances
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Risk Assessments and Risk Reduction Strategies published in Official Journal on 13 April 2006
Human health risks:DBP – No consumer risks including cosmetics. Risk to workers assuming worst case exposure – OEL to be implemented DIDP – Theoretical risks for children via toys – Toy legislation
DINP – No risks in any current use – Toy legislation due to difference of opinion between RAR and CSTEE
Environmental risks:DBP – Possible risk to vegetation near some processing plants - Extra monitoring data on exhaust air
DINP and DIDP – No risks
DBP, DINP, DIDP Risk Assessments / Reduction
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Two versatile high volume phthalates
Finally perceived as being “Risk Free” following revision of legislation for use in toys
For both health and environmental effects
Can be used in all applications except toys and childcare articles “which can be put in the mouth”
Not hazardous - not classified CMR or Dangerous to the Environment
Large shift in consumption to DINP and DIDP
DINP & DIDP Risk Assessments / Risk Reduction
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Risk assessments to be completed via “written procedure” during Q4 2006. Publication in 2006 / 2007
Human health risks:BBP – few, if any, risks anticipated – Consumption falling rapidlyDEHP
Workers – OEL to be defined and implementedChildren via toys – New legislation Haemodialysis and long term transfusion in children / neonates - Requested opinion of expert medical committee Possibly children living near some processing plants – Agree Marketing and Use Directive to control DEHP emissions
BBP & DEHP Risk Assessments / Risk Reduction
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Environmental risks:
BBP – Possible risk to water and sediment near processing plants - Fish study and processing plant emission data
DEHP –Risks only seen for default emission levels from hypothetical plants. No risks when using real emission data which are 1000 times lower.
General population via the environment - Kemi wanted to ban DEHP in all outdoor applications. Commission not convinced – no risk identified.
Biomonitoring more than 3.000 people - shows no risks to man at regional level (MOS range from 280 to 1700)
Risk Assessments / Risk Reduction
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Permanent measures published in the Official Journal on 27 December 2005
• DBP, BBP and DEHP banned in all toys and childcare articles
• DINP, DIDP and DNOP banned in toys and childcare articles which can be put in the mouth
• National legislation to be enacted from 16 January 2007
• Entirely political decision ignoring science based risk assessments
A range of alternative plasticisers available – citrates, etc.
Toys and Childcare Articles
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New legislation is expected to come into force in the EU during Q4 2006
EFSA Scientific Panel has re-examined the phthalate toxicity data and published TDI values.
Concluded that phthalates may be used in a variety of repeat and single use food contact applications
DEHA and polymeric plasticisers will continue to be used in a wide range of food contact applications, especially clingfilm
Food Contact Materials
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DEHP Risk Assessment identifies risks to patients (MOS < 100) via :• Long term haemodialysis (adults)• Transfusions (neonates)• Long term blood transfusion (children) (Lowest MOS via IV = 800)
It is possible that these three applications will move from DEHP to alternatives such as ATBC, DINCH, trimellitates, acetylated glycerol esters or polymeric plasticisers.
However this sector is conservative and reluctant to change away from plasticisers which have given no adverse effects in patients
Threats from activists (HCWH) and from other polymers continue but it is difficult to match the cost / performance characteristics of PVC
Medical Applications
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SCMPMD Opinion of September 2002 concluded that no specific recommendation could be made to limit the use of DEHP
We must await the Opinion of the new Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) – February 2006
However the attacks continue:
EU Parliament Environment Committee (w/c 2nd October) agreed an amendment to the Medical Devices Directive prohibiting the use of CMR substances in medical devices. This still has to be voted on in plenary
Many drugs are CMR but are used on a risk/benefit basis
This amendment is based on hazard – there may be little exposure and hence no risk
Medical Applications
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Phthalate Alternatives Confer Special Properties
Adipates – Low temperature flexibility - food and medical
Polyesters – Low migration into oil, etc - food and medical
Trimellitates – High temperature cable sheathing
Citrates – PVdC film, some medical – Some adverse human reactions
Benzoates – Easy processing like BBP
Phosphates – Fire resistance
Alkyl sulphonates – Easy processing, weather resistance
DINCH – Possible use in medical and food contact – EFSA approval
Acetylated glycerol esters – Food contact
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The commonly used plasticisers are data-rich and have been subjected to various risk assessments so no problems regarding registration.
CMR substances will be subject to authorisation to allow them to be used in each application.
We have the risk assessment data but will it be accepted or will substitution be demanded ?
Some Member States may propose that even those phthalates which are not classified as CMR should be subject to authorisation because they give rise to an “equivalent level of concern”
Environment Committee (10th October) voted to increase pressure for substitution and reduce level of scientific evidence needed to prove that a substance is of “equivalent concern”
Impact of REACH on Plasticisers
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Western Europe Plasticiser Consumption
0
200
400
600
800
1000
1200
19
79
19
80
19
81
19
82
19
83
19
84
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
(‘000s of tons)
Source: ECPI, 2006
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European Plasticiser Consumption - Trends
DEHP21%
Other Phthalates
12%
Other Plasticisers
7%
DINP/DIDP60%
DEHP42%Other
Phthalates15%
Other Plasticisers
8%
DINP/DIDP35%
1999
2005
Source: ECPI, 2006
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The family of phthalates satisfy the performance, health and safety requirements of the vast majority of applications.
Classification, labelling and risk assessment has resulted in a move to DINP and DIDP and a decrease in DEHP, DBP and BBP consumption
Alternatives to phthalates already exist or are being developed for certain applications
Food contact materials, medical devices, toys and childcare articles
• Low migrating plasticisers – polymerics and trimellitates
• Lower animal toxicity – adipates, citrates, terephthalates, DINCH, acetylated glycerol esters
Plasticisers – The Way Forward
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Phthalates and speciality esters meet the needs of all PVC applicationsIncrease in DINP and DIDP use due to positive risk assessmentsDecrease in DEHP, DBP and BBP due to Hazard ClassificationHealth effects not seen in primates - only in rodent studiesNo human cancer concern. Investigating relevance to humans of rodent reproductive effectsHigh profile human toxicological studies are not based on sound scienceBiomonitoring data very helpful in risk assessment and risk reduction There will be moves to new plasticisers due to new legislation and concerns regarding toys, food contact and medical devicesThere is still a very strong future for flexible PVC
Summary