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ACETONE

(CAS #67-64-1)

GREENSCREEN® FOR SAFER CHEMICALS (GREENSCREEN®) ASSESSMENT

Prepared by:

ToxServices LLC

Assessment Date: April 10, 2017

Expiration Date: April 10, 2020

1367 Connecticut Ave., N.W., Suite 300

Washington, D.C. 20036





TABLE OF CONTENTS

GreenScreen® Executive Summary for Acetone (CAS #67-64-1) .............................................................. i

Chemical Name ........................................................................................................................................... 1

GreenScreen® Summary Rating for Acetone .............................................................................................. 2

Transformation Products and Ratings ......................................................................................................... 3

Introduction ................................................................................................................................................. 3

Hazard Statement and Occupational Control .............................................................................................. 4

Physicochemical Properties of Acetone ...................................................................................................... 4

Toxicokinetics ............................................................................................................................................. 5

Group I Human Health Effects (Group I Human) ...................................................................................... 8

Carcinogenicity (C) Score ....................................................................................................................... 8

Mutagenicity/Genotoxicity (M) Score .................................................................................................... 8

Reproductive Toxicity (R) Score ............................................................................................................. 9

Developmental Toxicity incl. Developmental Neurotoxicity (D) Score ............................................... 10

Endocrine Activity (E) Score ................................................................................................................ 11

Group II and II* Human Health Effects (Group II and II* Human) ......................................................... 12

Acute Mammalian Toxicity (AT) Group II Score ................................................................................. 12

Systemic Toxicity/Organ Effects incl. Immunotoxicity (ST) ............................................................... 13

Group II Score (single dose) .............................................................................................................. 13

Group II* Score (repeated dose) ........................................................................................................ 13

Neurotoxicity (N) .................................................................................................................................. 15

Group II Score (single dose) .............................................................................................................. 15

Group II* Score (repeated dose) ........................................................................................................ 16

Skin Sensitization (SnS) Group II* Score ............................................................................................. 17

Respiratory Sensitization (SnR) Group II* Score ................................................................................. 18

Skin Irritation/Corrosivity (IrS) Group II Score .................................................................................... 18

Eye Irritation/Corrosivity (IrE) Group II Score ..................................................................................... 19

Ecotoxicity (Ecotox) ................................................................................................................................. 19

Acute Aquatic Toxicity (AA) Score ...................................................................................................... 19

Chronic Aquatic Toxicity (CA) Score ................................................................................................... 20

Environmental Fate (Fate) ........................................................................................................................ 21

Persistence (P) Score ............................................................................................................................. 21

Bioaccumulation (B) Score ................................................................................................................... 22

Physical Hazards (Physical) ...................................................................................................................... 22

Reactivity (Rx) Score ............................................................................................................................ 22

Flammability (F) Score.......................................................................................................................... 22

References ................................................................................................................................................. 24

APPENDIX A: Hazard Benchmark Acronyms ........................................................................................ 27





APPENDIX B: Results of Automated GreenScreen® Score Calculation for Acetone (CAS #67-64-1) .. 28

APPENDIX C: Pharos Output for Acetone (CAS #67-64-1) ................................................................... 29

APPENDIX D: OECD Toolbox Respiratory Sensitization Results for Acetone (CAS #67-64-1) .......... 31

APPENDIX E: EPISuite Modeling Results for Acetone (CAS #67-64-1) ............................................... 32

Licensed GreenScreen® Profilers .............................................................................................................. 35

TABLE OF FIGURES

Figure 1: GreenScreen® Hazard Ratings for Acetone ................................................................................. 2

TABLE OF TABLES

Table 1: H Statements for Acetone (CAS #67-64-1) (ECHA 2017a) ......................................................... 4 Table 2: Occupational Exposure Limits and Recommended Personal Protective Equipment for Acetone

(CAS #67-64-1) .......................................................................................................................................... 4 Table 3: Physical and Chemical Properties of Acetone (CAS #67-64-1) ................................................... 4




resale, and distribution are expressly prohibited. Page i

GreenScreen® Executive Summary for Acetone (CAS #67-64-1)

Acetone is a chemical that functions as a chemical feedstock, solvent for commercial products, and

solvent for commercial processes.

Acetone was assigned a GreenScreen Benchmark™ Score of 2 (“Use but Search for Safer

Substitutes”). This score is based on the following hazard score combinations:

Benchmark 2e

o Moderate Group I Human Toxicity (reproductive toxicity-R, developmental toxicity-D and

endocrine activity-E)

Benchmark 2g

o High Flammability-F

No data gaps (DG) exist for this chemical.

GreenScreen® Benchmark Score for Relevant Route of Exposure:

As a standard approach for GreenScreen® evaluations, all exposure routes (oral, dermal, and inhalation)

were evaluated together, so the GreenScreen® Benchmark Score of 2 (“Use but Search for Safer

Substitutes”) is applicable for all routes of exposure.

GreenScreen® Hazard Ratings for Acetone

C M R D E AT SnS* SnR* IrS IrE AA CA P B Rx F

single repeated* single repeated*

L L M M M L M M M M L L M H L L vL vL L H

Fate Physical

ST N

Group I Human Group II and II* Human Ecotox

Note: Hazard levels (Very High (vH), High (H), Moderate (M), Low (L), Very Low (vL)) in italics reflect estimated

values, authoritative B lists, screening lists, weak analogues, and lower confidence. Hazard levels in BOLD font are

used with good quality data, authoritative A lists, or strong analogues. Group II Human Health endpoints differ from

Group II* Human Health endpoints in that they have four hazard scores (i.e., vH, H, M, and L) instead of three (i.e., H,

M, and L), and are based on single exposures instead of repeated exposures. Please see Appendix A for a glossary of

hazard acronyms.




resale, and distribution are expressly prohibited. Page 1 of 35

GreenScreen® Assessment for Acetone (CAS #67-64-1)

Method Version: GreenScreen® Version 1.31

Assessment Type2: Certified

Assessor Type: Licensed GreenScreen® Profiler

GreenScreen® Assessment Prepared By: Quality Control Performed By:

Name: Jennifer Rutkiewicz, Ph.D. Name: Bingxuan Wang, Ph.D.

Title: Toxicologist Title: Toxicologist

Organization: ToxServices LLC Organization: ToxServices LLC

Date: June 23, 2014 Date: July 24, 2014

GreenScreen® Assessment Updated By: Quality Control Performed By:

Name: Rachel Galante Name: Bingxuan Wang, Ph.D., D.A.B.T.

Title: Associate Toxicologist Title: Toxicologist

Organization: ToxServices LLC Organization: ToxServices LLC

Date: April 10, 2017 Date: April 10, 2017

Expiration Date3: April 10, 2020

Confirm application of the Disclosure and Assessment Rules and Best Practice4: Acetone is

produced industrially in high purity grade (>99.5% purity), with the main impurity being water (HSDB

2015). Acetone may also contain 0.002% acidity, as free acetic acid (CAS #64-19-7, LT-U) (UNEP

1999). Other impurities that have been identified include benzene (0-50 ppm, CAS #71-43-2, BM 1),

acetaldehyde (0-70 ppm, CAS #75-07-0, BM 1), methanol (0-500 ppm, CAS #67-56-1, LT-1), diacetone

alcohol (0-300 ppm, CAS #123-42-2, LT-U), mesityl oxide (0-10 ppm, CAS #141-79-7, LT-U),

formaldehyde (0-1 ppm, CAS #50-00-0, LT-1) and isopropanol (0-100 ppm, CAS #67-63-0, BM 2)

(UNEP 1999).

Notes related to production specific attributes5: Acid catalyzed hydrolytic cleavage of cumene hydroperoxide results in the formation of acetone and

phenol as co-products at a ratio of 0.6 to 1.00 (UNEP 1999). No additional information was identified,

and this screen is performed on the theoretical pure substance.

Chemical Name: Acetone

CAS Number: 67-64-1

1 Use GreenScreen® Hazard Assessment Guidance (Guidance) v1.3 2 GreenScreen® reports are either “UNACCREDITED” (by unaccredited person), “AUTHORIZED” (by Authorized GreenScreen®

Practitioner), “CERTIFIED” (by Licensed GreenScreen® Profiler or equivalent) or “CERTIFIED WITH VERIFICATION” (Certified

or Authorized assessment that has passed GreenScreen® Verification Program) 3 Assessments expire three years from the date of completion. 4 Every chemical in a material or formulation should be assessed if it is:

1. intentionally added and/or

2. present at greater than or equal to 100 ppm 5 Note any composition or hazard attributes of the chemical product relevant to how it is manufactured. For example, certain

synthetic pathways or processes result in typical contaminants, by-products or transformation products. Explain any differences

between the manufactured chemical product and the GreenScreen assessment of the generic chemical by CAS #.





Chemical Structure(s):

Also called: 2-Propanone; beta-Ketopropane; Dimethyl ketone; Dimethylformaldehyde; Dimethylketal;

EINECS 200-662-2; Ketone propane; Ketone, dimethyl; Methyl ketone; Propanone; Pyroacetic acid;

Pyroacetic ether (ChemIDplus 2017)

Suitable analogs or moieties of chemicals used in this assessment (CAS #’s):

No chemical surrogates were sought due to the complete dataset for acetone.

Identify Applications/Functional Uses: (UNEP 1999)

1. Chemical feedstock

2. Solvent for commercial products

3. Solvent for commercial processes

GreenScreen® Summary Rating for Acetone6,7 8,9: Acetone was assigned a GreenScreen

Benchmark™ Score of 2 (“Use but Search for Safer Substitutes”) (CPA 2017a). This score is based on

the following hazard score combinations:

Benchmark 2e

o Moderate Group I Human Toxicity (reproductive toxicity-R, developmental toxicity-D and

endocrine activity-E)

Benchmark 2g

o High Flammability-F

No data gaps (DG) exist for this chemical.

Figure 1: GreenScreen® Hazard Ratings for Acetone

C M R D E AT SnS* SnR* IrS IrE AA CA P B Rx F

single repeated* single repeated*

L L M M M L M M M M L L M H L L vL vL L H

Fate Physical

ST N

Group I Human Group II and II* Human Ecotox

Note: Hazard levels (Very High (vH), High (H), Moderate (M), Low (L), Very Low (vL)) in italics reflect estimated

(modeled) values, authoritative B lists, screening lists, weak analogues and lower confidence. Hazard levels in BOLD

font are used with good quality data, authoritative A lists, or strong analogues. Group II Human Health endpoints differ

6 For inorganic chemicals with low human and ecotoxicity across all hazard endpoints and low bioaccumulation potential, persistence

alone will not be deemed problematic. Inorganic chemicals that are only persistent will be evaluated under the criteria for

Benchmark 4. 7 See Appendix A for a glossary of hazard endpoint acronyms 8 For inorganic chemicals only, see GreenScreen® Guidance v1.3 Section 13 (Exceptions for Persistence). 9 For Systemic Toxicity and Neurotoxicity, repeated exposure data are preferred. Lack of single exposure data is not a Data Gap

when repeated exposure data are available. In that case, lack of single exposure data may be represented as NA instead of DG. See

GreenScreen Guidance v1.3 Section 8.2.1.





from Group II* Human Health endpoints in that they have four hazard scores (i.e. vH, H, M, and L) instead of three (i.e.

H, M, and L), and are based on single exposures instead of repeated exposures. Please see Appendix A for a glossary of

hazard acronyms.

Transformation Products and Ratings10:

Identify feasible and relevant fate and transformation products (i.e., dissociation products,

transformation products, valence states) and/or moieties of concern11

No feasible or relevant transformation products were identified. Acetone is readily biodegradable and is

thus not expected to produce relevant transformation products.

Introduction

Acetone is a high production volume chemical worldwide. Worldwide production capacity was 3.8

million tons in 1995. It is produced through hydrolytic cleavage of cumene hydroperoxide or catalytic

dehydrogenation of isopropyl alcohol. Its major uses include as a chemical feedstock, solvent for

commercial products, and solvent for commercial processes (UNEP 1999).

ToxServices assessed acetone against GreenScreen® Version 1.3 (CPA 2017b) following procedures

outlined in ToxServices’ SOPs (GreenScreen® Hazard Assessment) (ToxServices 2016).

U.S. EPA Safer Choice Program’s Safer Chemical Ingredients List

The SCIL is a list of chemicals that meet the Safer Choice standard (U.S. EPA 2017). It can be accessed

at: http://www2.epa.gov/saferchoice/safer-ingredients. Chemicals on the SCIL have been assessed for

compliance with the Safer Choice Standard and Criteria for Safer Chemical Ingredients (U.S. EPA

2015).

Acetone is not present on the SCIL.

GreenScreen® List Translator Screening Results

The GreenScreen® List Translator identifies specific authoritative or screening lists that should be

searched to identify GreenScreen® benchmark 1 chemicals (CPA 2017b,c). Pharos (Pharos 2017) is an

online list-searching tool that is used to screen chemicals against the List Translator electronically. It

checks all of the lists in the List Translator with the exception of the U.S. Department of Transportation

(U.S. DOT) lists (U.S. DOT 2008a,b)12 and these should be checked separately in conjunction with

running the Pharos query. The output indicates benchmark or possible benchmark scores for each

human health and environmental endpoint. The output for acetone can be found in Appendix C.

Acetone is a Benchmark 2 chemical in Pharos, according to a version 1.2 GreenScreen® performed

by Rosenblum Environmental in 2012. Since a GreenScreen® expires after three years, a new full

GreenScreen® is performed.

Acetone is listed on the U.S. DOT list as a Class 3 Group II chemical

10 See GreenScreen® Guidance v1.3 Section 12. 11 A moiety is a discrete chemical entity that is a constituent part or component of a substance. A moiety of concern is often the

parent substance itself for organic compounds. For inorganic compounds, the moiety of concern is typically a dissociated component

of the substance or a transformation product. 12 DOT lists are not required lists for GreenScreen List Translator v1.3. They are reference lists only.

http://www2.epa.gov/saferchoice/safer-ingredients





Hazard Statement and Occupational Control

Harmonized H statements reported in the ECHA C&L Inventory are included in Table 1 below.

Occupational exposure limits and recommended personal protective equipment is presented in Table 2.

Table 1: H Statements for Acetone (CAS #67-64-1) (ECHA 2017a)

H Statement H Statement Details

H225 Highly flammable liquid and vapor

H319 Causes serious eye irritation

H336 May cause drowsiness or dizziness

Table 2: Occupational Exposure Limits and Recommended Personal Protective Equipment for

Acetone (CAS #67-64-1)

Personal Protective Equipment

(PPE) Reference

Occupational Exposure

Limits (OEL) Reference

Eye/face protection (faceshield and

safety goggles); gloves; impervious

clothing; respiratory protection (when

appropriate)

HSDB 2015

ACGIH TLV: 500 ppm as

TWA, 750 ppm as STEL

NIOSH 2008

MAK: 500 ppm (1,200

mg/m3)

OSHA PEL: TWA 1,000

ppm (2,400 mg/m3)

NIOSH REL: TWA 250 ppm

(590 mg/m3)

NIOSH IDLH 2,500 ppm

(10% LEL) ACGIH: American Conference of Governmental Industrial Hygienists; TLV: Threshold Limit Value; TWA: Time

Weighted Average; STEL: Short-Term Exposure Limit; MAK: Maximum Concentrations at the Workplace; OSHA:

Occupational Safety and Health Administration; PEL: Permissible Exposure Limit; NIOSH: National Institute for

Occupational Safety and Health; REL: Recommended Exposure Limit; IDLH: Immediately Dangerous to Life; LEL:

Lower Explosive Limit

Physicochemical Properties of Acetone

Acetone is a colorless liquid at room temperature. Its high vapor pressure of 232 mmHg indicates that it

is likely to vaporize at room temperature. It is highly soluble in water, and its log Kow of -0.24 indicates

low potential for bioaccumulation.

Table 3: Physical and Chemical Properties of Acetone (CAS #67-64-1)

Property Value Reference

Molecular formula C3H6O ChemIDplus 2017

SMILES Notation C(C)(C)=O ChemIDplus 2017

Molecular weight 58.0794 ChemIDplus 2017

Physical state Liquid ECHA 2017b

Appearance Colorless ECHA 2017b

Melting point -94.8°C ChemIDplus 2017

Vapor pressure 232 mmHg at 25°C ChemIDplus 2017

Water solubility 1 x 106 mg/L at 25°C ChemIDplus 2017

Dissociation constant pKa = 20 ChemIDplus 2017

Density/specific gravity 0.79 g/mL at 20°C ECHA 2017b





Table 3: Physical and Chemical Properties of Acetone (CAS #67-64-1)

Property Value Reference

Partition coefficient log Kow = -0.24 ChemIDplus 2017

Toxicokinetics

Available data indicate acetone is readily absorbed by rodents and humans via oral, dermal, and

inhalation routes of exposure, and will be broadly distributed throughout the body, particularly to organs

with high water content. Data additionally indicates the toxicokinetics of acetone are dose-related. At

low concentrations, the primary metabolic pathway appears to be through the formation of

methylglyoxal; however, as concentrations increase, the propanediol pathway becomes more

predominant. The latter pathway may be involved in gluconeogenesis, and may also facilitate excretion.

Excretion, however, also appears to be dose-related; low levels of acetone are excreted through

expiration, while urinary excretion generally occurs when concentration exceed 15 ppm in the air. The

proportion of acetone lost though expiration will also increase at higher concentrations (U.S. EPA

2003).

Absorption: Acetone is readily absorbed via oral, dermal, and inhalation routes of exposure.

o Oral: When 50 mg/kg acetone diluted in water was administered to male human subjects,

between 65 and 93% of the acetone was metabolized, while remaining material was excreted

from the body in a period of 2 hours, indicating rapid oral absorption. Rapid oral absorption

of acetone was also demonstrated in rats administered 0.22 mg of 14C-acetone in water.

Within 13.5 hours, 47% of the acetone was expelled as 14CO2. Rats orally administered

pulses of 14C-acetone daily over 7.5 days, expelled 67-76% of the administered acetone as 14CO2 over the ensuing 24 hours period.

o Inhalation: Upon inhalation exposure, relative uptake ranged from 39-52% for male human

volunteers exposed to 1,300 mg/m3 acetone at rest or 700 mg/m3 with exercise for two

hours. Acetone concentrations on the arterial blood were 15 and 75 mg/kg, respectively.

Mean relative acetone uptake average 53% in volunteers expose to 21-211 ppm acetone for

up to 4 hours at rest or 2 hours with intermittent exercise. Similar results have been reported

in dogs and rats.

o Dermal: Dermal absorption is also expected to be rapid. Cotton soaked in acetone and

applied to the skin of human volunteers for 2 hours/day for 4 days (dose not specified)

resulted in levels of acetone of 5-12 mg/L in blood, 5-12 ppm in alveolar air, and 8-14 mg/L

in urine. Absorption was immediate and peak levels occurred at the end of each application

period. When daily exposure was increased to 4 hours, the body burden more than doubled.

Distribution: Acetone distributes fairly evenly in body water and does not accumulate with repeated

exposure. In a mouse study, steady state concentrations were reached in the blood, lung, kidney,

brain, pancreas, spleen, thymus, heart, testis, vas deferens, muscle, and subcutaneous and

intraperitoneal white adipose tissue within 6 hours following exposure to 1,200 mg/m3 (500 ppm) of 14C-acetone via inhalation. There was little to no evidence of accumulation with prolonged or

repeated exposures. Conversely, the liver and brown adipose tissue concentrations continued to

increase at longer exposures. Of all the tissues studied, the liver contained the highest level of

radioactivity and the adipose tissues the lowest. By 24 hours after exposure, concentrations had

returned to endogenous levels in all tissues. In rats, mean concentrations of acetone following

exposure to 1,000 ppm (2,400 mg/m3) 3 hours/day for 10 days were 35.3, 13.2, 11.4, and 21.8 µg/g

for the plasma, liver, lung, and kidney, respectively. The higher concentration in the plasma

compared to the other three organs reflects acetones high water solubility.





Metabolism: Acetone plays a role in normal metabolism; it is naturally formed in humans and

rodents under normal metabolic conditions, and at higher concentrations under certain “diseased

state” conditions (i.e. fasting conditions, high-fat low-cab diets, uncontrolled diabetes). There are at

least two pathways involved in the metabolism of acetone to glucose, and these pathways are

dependent on both the site of metabolism (hepatic and extrahepatic) and the concentration of

acetone. Both pathways begin with the conversion of acetone to acetol mediated by acetone

monoxygenase. From acetol, the pathway diverges to (1) the formation of methylglyoxal via the

CYP2E1 enzyme system or (2) the formation of 1,2-propanediol. Methylglyoxyl is converted either

directly to glucose or to D-lactate, which is then converted to glucose; however, data support the

direct pathway to methylglyoxyl as opposed to the D-lactate route. In the 1,2-propanediol pathway,

acetol is converted to L-1,2-propanediol by an extrahepatic mechanism that has not been fully

characterized. 1,2-Propanediol may be converted to glucose through a series of intermediates

including lactate. The metabolites from each pathway are incorporated into glucose and other

substrates of intermediary metabolism that ultimately produce CO2. A study of the disposition of 14C-label in rats administered “trace” amounts or 1.6 mmol of 2-14C-acetone demonstrates the

methylglyoxyl pathway predominates at lower concentrations and the 1,2-propanediol pathway

predominates at higher concentrations. The location of the incorporated 14C-label in the resulting

glucose molecule can determine the starting metabolite. Infusion of “trace” amounts of 14C-acetone

into the rat resulted in 5-10% of the radiolabel in the 3 or 4 positions of the glucose molecule, while

23-40% of the 14C-label was in either the 3 or 4 positions on the resulting glucose in rats which

received the 1.6 mmol acetone solution infusion. Metabolism studies show at low plasma

concentrations acetone serves as a gluconeogenic substrate, at higher concentrations an alternate

pathway predominates and mediates the conversion of acetone to 1,2-propanediol. Although some

studies indicate that 1,2- propanediol serves as an intermediate in the production of glucose, it is

conceivable that the conversion from acetone to the diol diverts acetone from gluconeogenesis and

facilitates the loss of acetone via urine. A minor third pathway, which involves the production of

formic acid or acetic acid has been proposed but supporting data are sparse. The proposed

metabolism of acetone is shown below:





(from U.S. EPA 2003)

Excretion: The mode of acetone excretion appears to be dose-related, with it excreted primarily

though expiration at low concentrations, and through the urine at higher concentrations. Workers

with a mean occupational exposure to acetone of 141.8 ppm, had blood and urine concentrations at

the end of a shift of 23 mg/L and 22 mg/L, respectively; acetone concentrations remained slightly

elevated 16 hours after the end of the shift and the blood half-life was calculated to be 5.8 hours. A

positive linear correlation has been shown between acetone concentrations in the breathing zone of

workers and urinary, blood, and alveolar concentrations. However, urine concentrations were

shown to increase only when workers were exposed to acetone concentrations greater than 15 ppm.

The data indicate that the percent of acetone lost by elimination in the urine and expiration is

directly proportional and that lost via metabolism is inversely proportional to the blood acetone

content. At higher blood concentrations acetone is predominantly lost via elimination, whereas at





low concentrations it is metabolized; a critical point of approximately 100 mg acetone/L blood has

been predicted.

Hazard Classification Summary Section:

Group I Human Health Effects (Group I Human)

Carcinogenicity (C) Score (H, M, or L): L

Acetone was assigned a score of Low for carcinogenicity based on negative findings in chronic

carcinogenicity studies in mice. GreenScreen® criteria classify chemicals as a Low hazard for

carcinogenicity when adequate data are available and negative, there are no structural alerts, and it is not

GHS classified (CPA 2017c). Confidence in the score is reduced because histopathology was

performed on only a limited number of tissues in these studies.

Authoritative and Screening Lists

o Authoritative: Not present on any authoritative lists

o Screening: Not present on any screening lists

ECHA 2017b

o Acetone was tested in a dermal carcinogenicity study in female ICR mice. Animals

(29/does, 249/control) were dermally administered (shaved skin) 0.1 mL 100% acetone (79

mg/mouse) or 0.1 mL 90% acetone (71 mg/mouse) 3 times/week for 424 days (100%, 182

applications) or 365 days (90%, 156 applications). Gross pathology was performed on all

animals, and histopathology was performed on all abnormal tissues, as well as skin, liver,

and kidney of all animals dying during the test period and 20% of animals euthanized at the

conclusion of the study. No treatment related effects on survival or tumor incidence were

seen.

o Acetone has been used as a vehicle in several dermal carcinogenicity studies in several

strains of mice and was not associated with increased tumor incidence. No additional details

were provided.

HSDB 2015

o Acetone was used as a solvent control in a two-year carcinogenicity study in mice. Male

and female SHEL:CF1 SPF mice (50/sex) were administered 0.2 mL acetone to the shaved

dorsa once per week from six weeks of age to two years. Autopsy of dead and alive animals

at two years showed no increase in tumor incidence over historical control values (primarily

tumors of the lymphoreticular or hematopoietic system). A second two year study in mice

(100/sex) with identical treatment and autopsy regimes also resulted in negative results for

the skin and similar background rates for tumors of the lymphoreticular or hematopoietic

systems.

Mutagenicity/Genotoxicity (M) Score (H, M, or L): L

Acetone was assigned a score of Low for mutagenicity/genotoxicity based on negative in vitro

mammalian cell and bacterial mutagenicity, in vitro mammalian cell clastogenicity, and in vivo

chromosome aberration assays. GreenScreen® criteria classify chemicals as a Low hazard for

mutagenicity/genotoxicity when negative data for mutagenicity and clastogenicity are available, there

are not structural alerts, and it is not GHS classified (CPA 2017c). Confidence in the score is high as it

based on high-quality studies.








ECHA 2017b (Note: Numerous in vitro genotoxicity assays were located in the literature, but only

those reported with a Klimisch score of 1 or 2 for reliability were considered in the assessment.)

o In vitro: Acetone was negative in an in vitro mammalian cell gene mutation assay similar to

OECD Guideline 476 in mouse lymphoma L5178Y cells at concentrations up to 27.4

mg/mL (purity not specified) without metabolic activation. No tests were performed with

metabolic activation.

o In vitro: Acetone (> 99% purity) was negative in an Ames reverse mutation assay similar to

OECD Guideline 471 conducted by NTP. S. typhimurium strains TA1535, TA1537, TA97,

TA98, and TA100 was tested at concentrations of 0, 100, 333, 1000, 3333, 10,000 µg/plate

with and without metabolic activation and no increase in mutation frequency was seen.

o In vitro: Acetone was negative in an in vitro chromosome aberration assay similar to OECD

Guideline 473 conducted by NTP. No increase in structural aberrations was seen in Chinese

hamster ovary (CHO) cells treated with up to 5 mg/mL acetone (>99% purity) with and

without metabolic activation.

o In vivo: Acetone was negative for clastogenicity in an in vivo micronucleus assay in male

and female B6C3F1 mice conducted by NTP. Animals (10/sex/dose) were administered

acetone (purity not specified) in drinking water at concentrations of 5,000, 10,000, or 20,000

ppm (1,569, 3,023, or 5,481 mg/kg/day for males and 2,007, 4,156, and 5,945 mg/kg/day for

females) for 13 weeks, and no increased in micronuclei in normochromatic peripheral blood

erythrocytes was seen.

o In vivo: Acetone was negative in an in vivo micronucleus assay in male and female Chinese

hamsters that were administered a single dose of 865 mg/kg acetone (purity not specified)

via i.p. injection. No increase in micronucleated erythrocytes in bone marrow was seen 12,

24, 28, or 72 hours post administration.

Reproductive Toxicity (R) Score (H, M, or L): M

Acetone was assigned a score of Moderate for reproductive toxicity based on effects on the male

reproductive system in a 13-week oral toxicity study in rats. GreenScreen® criteria classify chemicals as

a Moderate hazard for reproductive toxicity when there is limited or marginal evidence of reproductive

toxicity in animal studies (CPA 2017c). Confidence in the score is reduced as effects occurred at

extremely high doses, reproductive function was not evaluated in this study, and no studies of female

reproductive performance were available.



o Screening: Japan GHS – Toxic to Reproduction – Category 2

ECHA 2017b

o Male Wistar rats (10/dose) were administered acetone in drinking water at concentrations of

1% (1,300 mg/kg/day) for 4 weeks. During the last week males were mated with untreated

females. No effects on male fertility were seen and authors identified a NOAEL of 1,300

mg/kg/day.

o In the 13-week study in male and female B6C3F1 mice described below for systemic

toxicity, animals were administered 1,250, 2,500, 5,000, 10,000, or 20,000 ppm (380, 611,

1,353, 2,258, or 4,858 mg/kg/day for males and 892, 2,007, 4,156, 5,945, or 11,298

mg/kg/day for females) acetone (>99% purity) in drinking water for 13-weeks. Several

reproductive parameters were examined, including weights of right testis, of cauda

epididymis, and of right epididymis, histopathology of epididymis, seminal vesicles,

prostate, and testes, sperm morphology, density and motility in males, and histopathology of





ovaries and uterus and stage and length of estrous cycle via vaginal cytology in females. No

effects on reproductive parameters were seen.

o In the 13-week study in male and female Fischer 344 rats described below for systemic

toxicity, animals were administered 1,250, 2,500, 5,000, 10,000, or 20,000 ppm (200, 400,

900, 1,700, 3,400 mg/kg/day for males and 300, 600, 1,200, 1,600, 3,100 mg/kg/day for

females) acetone (>99% purity) in drinking water for 13-weeks. Several reproductive

parameters were examined, including weights of right testis, of cauda epididymis, and of

right epididymis, histopathology of epididymis, seminal vesicles, prostate, and testes, sperm

morphology, density and motility in males, and histopathology of ovaries and uterus and

stage and length of estrous cycle via vaginal cytology in females. No overt clinical signs of

toxicity or mortality were observed in the study. At the highest dose, decreased testis

weights, sperm motility, cauda epididymal weights, and epididymal weights, and an

increased incidence of abnormal sperm were seen. Authors identified a NOAEL of 1,700

mg/kg/day and LOAEL of 3,400 mg/kg/day for effects on the male reproductive system.

o No adverse effects on testis weights, microscopic changes of testes and seminiferous tubular

diameters, or effects on fertility after mating with untreated females was seen in 10 male

Wistar rats administered 5,000 mg/L acetone in drinking water for 6 weeks during the last

weeks of treatment. Authors identified a NOAEL of 5,000 mg/L (735 mg/kg/day13).

NITE 2006, 2014

o Acetone was classified as GHS Category 2 based on embryotoxicity in rodents. These

effects will be assessed for developmental toxicity, below.

Based on the weight of evidence, a conservative score of Moderate was assigned. Effects on the

male reproductive system occurred at extremely high doses in a 13-week study in rats. The GHS

criteria (UN 2015) specify that adverse effects on reproduction only seen at very high doses would

not normally lead to classification, unless human exposure could occur at similar doses. However,

GHS defined “very high doses” as those that “cause prostration, severe inappetance, excessive

mortality”, which were not observed in the studies described above on acetone. In addition, while

GHS criteria agree with the concept of a limit dose above which adverse effects would not lead to

classification, the actual limit dose could not be established due to species differences in

toxicokinetics and lack of information on human exposure levels. Therefore, ToxServices

conservatively considered the observed reproductive effects in males for acetone reflective of

specific reproductive effects rather than secondary to systemic toxicity. Confidence in this

conclusion is reduced as reproductive function was not evaluated in this study, and no studies of

female reproductive performance were available.

Developmental Toxicity incl. Developmental Neurotoxicity (D) Score (H, M, or L): M

Acetone was assigned a score of Moderate for developmental toxicity based on effects on embryo

weight and implantation in inhalation studies in rats and mice in the presence of maternal toxicity, and

presence on authoritative and screening lists. GreenScreen® criteria classify chemicals as a Moderate

hazard for developmental toxicity when there are limited or marginal evidence of developmental

toxicity in animals, and the chemical is classified as German MAK - Pregnancy Risk Group B or GHS

Category 2 on a GHS country list (CPA 2017c). Confidence in the score is reduced as the effects may

be secondary to maternal toxicity.


o Authoritative: MAK Pregnancy Risk Group B – Damage to embryo or fetus cannot be

excluded when exposed at MAK and BAT levels. “The documentation indicates, when the

13 5,000 mg/L water * 0.147 mL water/kg rat = 735 mg/kg/day





Commission’s assessment of the data makes it possible, which concentration would

correspond to the classification in Pregnancy Risk Group C”.

o Screening: Japan GHS – Toxic to Reproduction – Category 2

ECHA 2017b

o In a developmental toxicity study similar to OECD Guideline 414 in Sprague-Dawley rats,

dams were exposed to 0, 1,060, 5,300, or 26,500 mg/m3 (0, 1.06, 5.3, or 26.5 mg/L) acetone

(100% purity) vapors via whole body inhalation on gestation days 6-20. Maternal weight

gain, body weight, gravid uterine weight and extra-gestational weight gain were statistically

significantly reduced at the high dose. The incidence of fetal malformations was not

increased. The percent of litters with at least one malformation was increased at the high

dose but was not considered by authors to be indicative of acetone-induced developmental

toxicity. Authors identified a LOAEC of 26.5 mg/L based on effects on fetal weights, and

concluded that the high dose did not lead to selective developmental toxicity.

o In a developmental toxicity study similar to OECD Guideline 414, CD-1 mice were

administered 1,060, 5,300, 15,900 mg/m3 (1.06, 5.3, or 15.9 mg/L) acetone (100% purity)

via whole body inhalation on gestation days 6-17. Maternal toxicity included increased

absolute and relative liver weights at 15.9 mg/L and narcosis at the dose almost twice as

high as the high dose which was then reduced to the high dose as a result. No effects on

malformations, number of implantations, the mean percent of live pups/litter, or the fetal sex

ratio were seen. Fetal weights were significantly decreased at the high dose, and the

incidence of late resorptions was increased. Authors identified a LOAEC of 15.9 mg/L

based on effects on fetal weight and resorptions.

NITE 2006, 2014

o The GHS Category 2 classification by Japan was based on “slight developmental toxicity” of

decreased embryo weight in rats at a high concentration of 11,000 ppm (20 mg/L), and

decreased embryo weight and late embryo absorption rate in mice at a high concentration of

6,600 ppm (15.6 mg/L).

Based on the weight of evidence, a score of Moderate was assigned. Classification as Pregnancy

Risk Group B on the authoritative German MAK - List of Substances corresponds to a score of

Moderate-High, while classification as GHS Category 2 in Japan corresponds to a score of

Moderate. Effects on fetal weights and resorptions at high inhalation doses in rats and mice

provides some evidence of adverse effects on development in the presence of maternal toxicity,

which indicates that GHS Category 2 (suspected human reproductive toxicant) is appropriate.

Therefore a score of Moderate was assigned.

Endocrine Activity (E) Score (H, M, or L): M

Acetone was assigned a score of Moderate for endocrine activity based on its presence on the TEDX –

Potential Endocrine Disruptor screening list. GreenScreen® criteria classify chemicals as a Moderate

hazard for endocrine activity when they are present on the TEDX screening list but there is no clear

related adverse human health effect (CPA 2017c). Confidence in the score is reduced as it is based on a

screening list.



o Screening: TEDX – Potential Endocrine Disruptor

Not listed as a potential endocrine disruptor on the EU Priority List of Suspected Endocrine

Disruptors.

Not listed as a potential endocrine disruptor on the OSPAR List of Chemicals of Possible Concern.





TEDX 2017

o Acetone was placed on the TEDX list of potential endocrine disruptors in 2015. This listing

appears to be based on neurotoxicity associated with occupational exposure to acetone. The

study abstract was reviewed and is summarized below:

Mitran et al. (1997) reported on the neurotoxic effects of acetone on Romanian

workers in regards to change in the central and peripheral nervous systems. Results

showed those workers exposed to acetone were most affected in terms of human

performance and evidence of neurotoxicity compared to other solvents methyl ethyl

ketone and cyclohexanone.

Based on the weight of evidence a score of Moderate was assigned. Acetone is present on the

TEDX - Potential Endocrine Disruptors screening list, which corresponds to a score of Moderate to

High. The reason provided for classification appears to be based on neurotoxic effects observed in

Romanian workers. Neurotoxicity may occur as a result of indirect effects such as interference with

the endocrine systems (Giordano and Costa 2012). However, it was not clear from the Mitran et al.

study that acetone-related neurotoxicity was causally related to endocrine disruption. According to

GreenScreen® guidance, a chemical should be assigned a Moderate hazard if there is an indication of

endocrine activity in the scientific literature, and a High score is only assigned when there is a

plausible related adverse effect. In terms of neurotoxicity, acetone was assigned a score of

Moderate due to evidence of neurological effects in at vapor concentrations of 2.38 mg/L and higher

in animal studies (see repeated dose neurotoxicity section below). However, it is not clear if the

neurotoxic mechanism of action of acetone is mediated by endocrine activity, therefore, the

preliminary Moderate score was not modified to High.

Group II and II* Human Health Effects (Group II and II* Human)

Note: Group II and Group II* endpoints are distinguished in the v 1.2 Benchmark system. For

Systemic Toxicity and Neurotoxicity, Group II and II* are considered sub-endpoints and test data for

single or repeated exposures may be used. If data exist for single OR repeated exposures, then the

endpoint is not considered a data gap. If data are available for both single and repeated exposures,

then the more conservative value is used.

Acute Mammalian Toxicity (AT) Group II Score (vH, H, M, or L): L

Acetone was assigned a score of Low for acute toxicity based on oral LD50 values in rats, mice, and

rabbits, dermal LD50 values in rabbits and guinea pigs, and inhalation LC50 values in rats. GreenScreen®

criteria classify chemicals as a Low hazard for acute toxicity when oral and dermal LD50 values are >

2,000 mg/kg and inhalation LC50 values are > 20 mg/L for a vapor (CPA 2017c).



o Screening: New Zealand GHS – 6.1E (oral): Acutely toxic (Category 5)

ECHA 2017b (Note: Numerous acute toxicity studies were located in the literature, but only those

reported with a Klimisch score of 1 or 2 for reliability were considered in the assessment.)

o Oral: LD50 (rat, female Sprague-Dawley) = 5,800 mg/kg

o Dermal: LD50 (rabbit, male and female, strain not specified) > 7,426 mg/kg

o Dermal: LD50 (guinea pig, male Hartley) > 7,426 mg/kg

o Dermal: LD50 (rabbit, male New Zealand White) > 15,800 mg/kg

o Inhalation: LC50 (rat, male Sprague-Dawley) = 132 mg/L (3-h) vapor

o Inhalation: LC50 (rat, female Carworth Farms-Nelson) = 76 mg/L (4-h); 50.1 mg/L (8-h)

vapor





UNEP 1999

o Oral: LD50 (rat, sex and strain not specified) = 8,400 mg/kg

o Oral: LD50 (mouse, sex and strain not specified) = 5,250 mg/kg

o Oral: LD50 (rabbit, sex and strain not specified) = 5,300 mg/kg

o Inhalation: LC50 (rat, sex and strain not specified) = 50 mg/L

Systemic Toxicity/Organ Effects incl. Immunotoxicity (ST)

Group II Score (single dose) (vH, H, M, or L): M

Acetone was assigned a score of Moderate for systemic toxicity (single dose) based on transient

respiratory tract irritation in humans and mice, and classification as GHS Category 3 in Japan.

GreenScreen® criteria classify chemicals as a Moderate hazard for systemic toxicity (single dose) when

available data indicate that GHS Category 3 classification is warranted and the chemical is classified as

Category 3 on a GHS country list (CPA 2017c). Confidence in the score is high as it is based on human

and animal data with support from a screening list.



o Screening: Japan GHS – Specific Target Organ/Systemic Toxicity Following Single

Exposure – Category 3 (may cause respiratory tract irritation)

NITE 2006, 2014

o Acetone was classified as GHS Category 3 for transient respiratory effects based on reports

of irritation of the throat, nasal cavity, and trachea in humans exposed to acetone vapors

UNEP 1999

o Respiratory distress has been seen in humans with accidental exposure to acetone vapors

when concentrations exceed 1,000 mg/L in the blood.

o Acetone was weakly irritating to the respiratory tract of mice. RD50 values of 184 mg/L and

557 mg/L were measured in two studies.

ATSDR 2011

o In one case report, a 49-year-old male developed bronchial tree edema after accidental

exposure to acetone during roadwork spray application.

o There was increased prevalence of upper respiratory tract irritation in 71 acetone-exposed

workers compared with 86 matched controls.

Group II* Score (repeated dose) (H, M, or L): M

Acetone was assigned a score of Moderate for systemic toxicity (repeated dose) based on ToxServices

classifying it to GHS Category 2. GreenScreen® criteria classify chemicals as a Moderate hazard for

systemic toxicity (repeated dose) when the chemical is classified as a GHS Category 2 (CPA 2017c).

Confidence in the score is reduced due to the limited human data available.



o Screening: Japan GHS – Specific Target Organ/Systemic Toxicity Following Repeated

Exposure – Category 1 (respiratory system, gastrointestinal tract)

ECHA 2017b

o Oral: Acetone was tested in a subchronic oral toxicity study in male and female B6C3F1

mice. Animals (10/sex/dose) were administered 1,250, 2,500, 5,000, 10,000, or 20,000 ppm

(380, 611, 1,353, 2,258, or 4,858 mg/kg/day for males and 892, 2,007, 4,156, 5,945, or

11,298 mg/kg/day for females) acetone (>99% purity) in drinking water for 13-weeks.

Clinical signs, body weight and food consumption, hematology, ophthalmoscopic exam,





organ weights, gross pathology, and histopathology were evaluated. No treatment related

effects were seen in males at up to the highest dose. In females, absolute and relative spleen

weights were decreased, absolute and relative liver weights were increased, and centrilobular

hypertrophy of the liver was observed at the highest dose. Authors identified a NOAEL of

10,000 ppm (5,945 mg/kg/day) based on effects on the liver of females.

o Oral: Acetone was tested in a subchronic oral toxicity study in male and female Fischer 344

rats. Animals (10/sex/dose) were administered 1,250, 2,500, 5,000, 10,000, or 20,000 ppm

(200, 400, 900, 1,700, 3,400 mg/kg/day for males and 300, 600, 1,200, 1,600, 3,100

mg/kg/day for females) acetone (>99% purity) in drinking water for 13-weeks. Clinical

signs, body weight and food consumption, hematology, ophthalmoscopic exam, organ

weights, gross pathology, and histopathology were evaluated. No adverse effects were seen

in females at up to the highest dose. In males, histopathological changes in the kidney and

spleen and mild macrocytic normochromic anemia were seen at a dose of 20,000 ppm. At

the highest dose, decreased testis weights, sperm motility, cauda epididymis weights, and

epididymal weights, and an increased incidence of abnormal sperm were seen. Authors

identified a NOAEL of 10,000 ppm (900 mg/kg/day) based on effects on males at higher

doses.

o Inhalation: In a subchronic inhalation toxicity study in male Sprague-Dawley rats, animals

(9/group) were administered 19,000 ppm (45,000 mg/m3 or 45 mg/L) acetone vapor via

whole body inhalation for 3 hours/day, 5 days/week for 2, 4, or 8 weeks. No adverse

treatment related effects on body weight, organ weights, clinical chemistry, or

histopathology of liver, kidney, brain, lung, and heart were seen. Authors identified a

NOAEC of 19,000 ppm (45 mg/L) based on the lack of adverse effects.

UNEP 1999

o Oral: In a subchronic oral toxicity study in male and female Sprague-Dawley rats, animals

(30/sex/dose) were administered 100, 500, or 2,500 mg/kg/day acetone via gavage for 93-95

days. No effects on body weight or food intake were seen. Hemoglobin, hematocrit, and

mean cell volume were significantly increased in males at the highest dose at the interim

(46-47 day) sacrifice, and hemoglobin, hematocrit, mean cell hemoglobin, and mean cell

volume were significantly increased in both sexes at the highest dose. At the interim

sacrifice, platelets were significantly decreased in males at the high dose, mean cell volume

was decreased in females at the mid-dose, and alanine amino-transferase was increased in

females at the high dose. At the final sacrifice, alanine amino-transferase was increased and

glucose and potassium levels were decreased in males at the high dose. Kidney weights

were increased in females at the mid and high doses, relative kidney weights were increased

in both sexes at the high dose, and relative liver weighs were increased in males and females

at the high dose. Relative brain weights were decreased in males and the heart/brain weight

ratio was increased in females at the high dose. Renal proximal tubule degeneration and

hyaline droplets were seen in males and females in both the control and treated groups, but

severity was increased with treatment. ToxServices identified a NOAEL of 500 mg/kg/day

and LOAEL of 2,500 mg/kg/day based on effects on hematology and organ weights of both

sexes at the high dose.

NITE 2006

o Acetone is categorized as GHS Category 2 in Japan based on effects on white corpuscles,

eosinophils, and neutrophils in humans exposed to 500 ppm for 6 hours/day for 6 days.

Original study details were not available. The classification report notes that hematological

effects in humans are similar to those seen at high doses in rodents.

NITE 2014





o Acetone is categorized as a GHS Category 1 in Japan based on effects to the central nervous

system, respiratory system and gastrointestinal system. However no details on the

classification were reported.

ATSDR 2011

o There is apparent sensory adaptation to acetone by inhalation, based on reduced sensitivity

(adaptation) to odor and irritancy of acetone in occupationally exposed workers compared to

naïve controls after a 20-minute exposure to 200 ppm acetone.

o Increased prevalence of gastrointestinal effects (loss of appetite, hyperacidity, bad taste, and

abdominal pain) and rheumatic symptoms (pain in bones, joints, and muscles) were

observed in 71 acetone-exposed workers compared to 86 matched controls in a coin-printing

factory.

o In a case report, a 55-year-old woman occupationally exposed to a cleansing solution mainly

consisted of acetone developed minimal glomerulopathy and moderate tubulointerstitial

nephritis.

Based on the weight of evidence, a score of Moderate was assigned. Although no adverse effects

were seen below the guidance values in subchronic toxicity studies in rats and mice, acetone is

classified as GHS Category 1 and 2 in Japan. The Category 2 classification was made in 2006,

which was based on hematological effects in humans; the Category 1 classification was made in

2014 and overrode the 2006 classification. It was based on effects to the central nervous system,

respiratory system and gastrointestinal system, however, no data to support the classification was

presented and the original study descriptions were not available. The GHS criteria specify that

Category 1 classification can be based on reliable human cases or epidemiological studies, or on

LOAEL/C values in animal studies. In exceptional cases, human evidence may also be used as basis

for Category 2 classification, based on expert judgment. ToxServices did not consider available

human data sufficient for Category 1 classification, as human data were limited by concurrent

exposure to other chemicals or preexisting disease conditions. However, a Category 2 classification

may be warranted. Therefore, ToxServices conservatively assigned a score of Moderate based on

GHS classification to GHS Category 2..

Neurotoxicity (N)

Group II Score (single dose) (vH, H, M, or L): M

Acetone was assigned a score of Moderate for neurotoxicity (single dose) based on transient narcotic

effects seen in acute oral and inhalation toxicity studies in rats. GreenScreen® criteria classify chemicals

as a Moderate hazard for neurotoxicity (single dose) when available data indicate that GHS Category 3

classification is warranted (CPA 2017c). Confidence in the score is high as it is based on well

conducted studies and authoritative listings.


o Authoritative: EU R Phrases – R67: Vapors may cause drowsiness and dizziness

o Authoritative: EU GHS H-Statements – H336: May cause drowsiness or dizziness

o Screening: Grandjean & Landrigan – Neurotoxic Chemicals: Neurotoxic

o Screening: Boyes – Neurotoxicants: Neurotoxic Classified as a developmental neurotoxicant (Grandjean and Landrigan 2006, 2014).

ECHA 2017b

o In the acute oral toxicity study in female Sprague-Dawley rats that identified an LD50 of

5,800 mg/kg, animals were administered doses of 5,370-6,980 mg/kg. Initial signs of

toxicity include decreased activity and ataxia which resolved by 24 hours. Animals that died

displayed tremors, tonus, and convulsions.





o In the acute inhalation toxicity study in male Sprague-Dawley rats that identified an LC50 of

132 mg/L, animals were exposed to 30, 45, 60, or 120 mg/L. At doses up to 60 mg/L, ataxia,

difficulty in locomotion, immobility, and hypnosis were seen. All effects were reversible

within 21 hours. Rats at the highest dose displayed hypnosis and died with a 2-hour

exposure.

ATSDR 1994

o Volunteers exposed at 237 ppm for 4 hours had increased anger and hostility, increased

response time and rate of false negative in auditory tone discrimination tests.

Based on the weight of evidence, a score of Moderate was assigned. Acetone is associated with R-

phrase R67 and H-Statement H336, which correspond to a score of Low-Moderate. Acetone caused

reversible narcotic effects in acute oral and inhalation toxicity studies, which corresponds to GHS

Category 3 for transient narcotic effects. Therefore, the score of Moderate is appropriate.

Group II* Score (repeated dose) (H, M, or L): M

Acetone was assigned a score of Moderate for neurotoxicity (repeated dose) based on its presence on

screening lists. GreenScreen® criteria classify chemicals as a Moderate hazard for neurotoxicity

(repeated dose) when he chemical is listed on Grandjean & Landrigan list of chemicals known to be

neurotoxic in man (CPA 2017c). Confidence in the score is reduced as it is based on limited human data

and screening lists.



o Screening: Grandjean & Landrigan – Neurotoxic Chemicals: Neurotoxic

o Screening: Boyes – Neurotoxicants: Neurotoxic

Classified as a developmental neurotoxicant (Grandjean and Landrigan 2006, 2014).

ECHA 2017b

o Oral: Male Wistar rats (10/dose) were administered 0 or 1% acetone in drinking water for 4

weeks, or 0 and 0.5% acetone in drinking water for 9 weeks, and observed for clinical signs,

body weight, food and water consumption, clinical chemistry, and behavior. A functional

observation battery (FOB) was conducted to observe sensory, motor, and physiological

endpoints. A reduction in hindlimb and forelimb grip strength was noted after the 4-week

exposure to 1% acetone. There were no adverse effects after the 9-week exposure to 0.5%

acetone. The authors reported neurobehavioral toxicity NOAEL and LOAEL values of 650

and 1,300 mg/kg/day, respectively.

UNEP 1999

o Inhalation: When female rats (number and strain not specified) were administered 7,120,

14,240, 28,480, and 37,975 mg/m3 (7.12, 14.24, 28.48, or 37.98 mg/L) acetone vapors for 4

hours/day for 2 weeks, inhibition of avoidance behavior was seen at a concentration of 14.24

mg/L. No signs of motor imbalance were seen. The two highest doses produced ataxia after

the first dose but not after subsequent doses. ToxServices identified a NOAEL of 7.12 mg/L

and LOAEL of 14.24 mg/L based on effects on avoidance behavior.

o Inhalation: No permanent neurological effects were seen in rats administered 2,375, 4,750,

and 9,495 mg/m3 (2.38, 4.75, or 9.50 mg/L) acetone vapors for 13 weeks. ToxServices

identified a NOAEL of 9.5 mg/L.

o Acetone is considered to have low potential for neurological risk to humans. Based on

clinical case studies, human volunteer studies, animal research, and occupational field

evaluations, the NOAEL for neurological effects is approximately 2,375 mg/m3 (2.38 mg/L).

ATSDR 2011





o There was increased prevalence of neurotoxicity, including mood disorders, irritability,

memory difficulty, sleep disturbances, and headache among 71 acetone-exposed workers

compared to 86 matched controls, with the 8h TWA acetone exposure of 0.988 – 2.144 mg/L

for a mean duration of 14 years.

o No correlation was found between acetone urine concentrations and neurological symptoms

of annoyance, tension, tiredness and discomfort in eight workers occupationally exposed to

1,138 ppm acetone in the first half of work shift and 717 ppm in the second haft, compared to

eight unexposed controls.

o There were increased symptoms of heavy, vague, or faint feelings in the head and impaired

neurobehavioral responses in 110 male workers at an acetate fiber manufacturing plant in

which acetone was used with the exposure level of 5 – 1,211 ppm in the breathing zone.

o In a study of olfactory sensitivity, female mice were exposed to approximately 8,000 ppm

acetone for 5 hours/day, 5 days/week for 4 weeks. Olfactory sensitivity (avoidance of

acetone in the maze) increased after during weeks 2 and 4 as well as during weeks 6 and 8

(post-exposure). There was a significant decrease in the number of cells in olfactory

neuroepithelium in week 2, which increased in week 4, remained at the same level in week 6,

and recovered by week 8. There were no changes in olfactory marker protein and

proliferating cell nuclear antigen (PCNA), indicating no damage to the olfactory

neuroreceptors. There was, however, a decrease in the number of PCNA-positive cells in the

basal layer during week 2 that sustained in weeks 4 and 6. This indicated an increase in

mitotic activity.

ATSDR 1994

o Inhalation: ATSDR established a subchronic and chronic duration inhalation minimum risk

level (MRL) of 13 ppm for acetone based on a LOAEL of 1,250 ppm for neurological effects

in a 6-week study in volunteers. The critical effects were statistically significant increases in

the amplitude of the visual evoked response. In addition, lack of energy, general weakness,

delayed visual reaction time and headache were reported in another study at 250 ppm

exposure level for 5.25 hours and for 6 hours per day for 6 days in humans.

Based on the weight of evidence, a score of Moderate was assigned. Acetone is present on

Grandjean & Landrigan list of chemicals known to be neurotoxic in man, which corresponds to a

score of Moderate-High, and is classified as neurotoxic by Pattys Toxicology - Boyes

Neurotoxicants, which corresponds to a score of Low-High. It should be noted that these two lists

include both single exposure and repeat exposure effects. Available data indicate that neurological

effects are observed only at high doses in animals that exceed the guidance value of 1 mg/L for an

inhalation (vapor) study and 100 mg/kg/day for an oral study. However GHS classification can also

be based on adverse human effects. The available human data suggest that acetone causes reversible

neurological effects but no lasting neurological damages were found. Therefore, ToxServices

conservatively classified acetone to GHS Category 2.

Skin Sensitization (SnS) Group II* Score (H, M, or L): L

Acetone was assigned a score of Low for skin sensitization based on negative results in a guinea pig

maximization test and mouse ear swelling test. GreenScreen® criteria classify chemicals as a Low

hazard for skin sensitization when adequate data are available and negative, there are no structural

alerts, and it is not GHS classified (CPA 2017c). Confidence in the score is high as it is based on well-

conducted studies.








ECHA 2017b

o Acetone was negative in a guinea pig maximization test in ten female Hartley guinea pigs

that were induced intradermally and topically with 100% acetone and challenged with 100%

acetone after 21 days. No indication of sensitization was seen in any animal.

o Acetone was tested in an ear swelling test in male and female Balb/c mice. Animals were

topically induced with acetone on the ear on days 0 and 2 and, with a scapular subcutaneous

injection on of Freund’s adjuvant on day 5. Ear thickness was measured before and after

topical application of acetone on day 10. No increase in ear thickness was seen, indicating a

lack of sensitization.

Respiratory Sensitization (SnR) Group II* Score (H, M, or L): L

Acetone was assigned a score of Low for respiratory sensitization based on lack of dermal sensitization

potential, according to ECHA’s guidelines (ECHA 2016). GreenScreen® criteria classify chemicals as a

Low hazard for respiratory sensitization when adequate data are available and negative, there are no

structural alerts, and it is not GHS classified (CPA 2017c). Confidence in the score is reduced as no

specific respiratory sensitization data are available.




OECD 2016

o Acetone does not contain any structural alerts for respiratory sensitization (Appendix D).

No data were identified. Therefore, ToxServices evaluate the respiratory sensitization potential of

acetone according to ECHA’s guideline (ECHA 2016), which indicates that a chemical that is not a

dermal sensitizer is not likely to be a respiratory sensitizer because the two share similar

mechanisms of action. However, this evaluation strategy does not cover effects caused by non-

immunological mechanisms. Chemicals with these mechanisms are usually identified based on

human evidence. Acetone was not a dermal sensitizer to guinea pigs in a guinea pig maximization

test, nor to mice in a mouse ear swelling test, and there is no other evidence indicating acetone is a

dermal or respiratory sensitizer. Therefore, acetone is unlikely to be a respiratory sensitizer.

Skin Irritation/Corrosivity (IrS) Group II Score (vH, H, M, or L): M

Acetone was assigned a score of Moderate for skin irritation/corrosivity based on GHS classification in

New Zealand. GreenScreen® criteria classify chemicals as a Moderate hazard for skin

irritation/corrosivity when the chemical is classified as a GHS Category 3 on a GHS country list (CPA

2017c). Confidence in the score is reduced because it is based on a screening list and limited human

data.



o Screening: New Zealand GHS – 6.3B: Mildly irritating to the skin

ECHA 2017b

o A single open application of 10 µL acetone to the shaved skin of 5 albino rabbits did not

cause dermal irritation. A score of 1/10 was assigned. This study is reported with a

Klimisch score of 3 (not reliable) for reliability due to methodological deficiencies (low test

volume, open application of volatile compound).

o Repeated open application of 10 µL acetone to the shaved skin of 10 Dunkin-Hartley guinea

pigs 3 times/day for 3 days was not irritating based on macroscopic scores for erythema and

edema, and measurements of epidermal thickness and cellular inflammatory responses.





ATSDR 2011

o A 49-year-old male accidentally exposed to acetone during roadwork spray application had

superficial burns to the skin.

Based on the weight of evidence, a score of Moderate was assigned. No dermal irritation was seen

in studies in rabbits and guinea pigs, but these studies involved application of only 10 µL acetone.

Acetone is classified as Category 6.3B (GHS Category 3) in New Zealand based on mild irritation in

rabbits (no additional details were provided) (CCID 2017). In the absence of a standard dermal

irritation study for acetone, the conservative score of Moderate was assigned based on the GHS

classification in New Zealand and limited human data.

Eye Irritation/Corrosivity (IrE) Group II Score (vH, H, M, or L): H

Acetone was assigned a score of High for eye irritation/corrosivity based on presence on an authoritative

list. GreenScreen® criteria classify chemicals as a High hazard for eye irritation/corrosivity when the

chemical is associated with the H statement H319: causes serious eye irritation (CPA 2017c).

Confidence in the score is high as it is based on an authoritative list.


o Authoritative: EU R Phrases – R36: Irritating to eyes

o Authoritative: EU GHS – H319: Causes serious eye irritation

o Screening: Japan GHS –Category 2B: Causes eye irritation

o Screening: New Zealand GHS – 6.4A: Irritating to the eye

UNEP 1999

o Acetone caused severe eye irritation three days after 0.1 mL undiluted acetone was

administered to the eyes of rabbits. No additional details were provided.

o A 3.1M solution of acetone caused a 50% increase in ocular edema after a 1 hour exposure.

Treatment for several minutes destroyed the corneal epithelium but not stroma. Injuries

reversed within 4-6 days. Acetone was not corrosive. No additional details were provided.

o Rabbit studies demonstrated that undiluted acetone can be a severe eye irritant when left in

contact with the cornea.

o Exposure to high concentrations of acetone vapor is irritating to the eyes.

Ecotoxicity (Ecotox)

Acute Aquatic Toxicity (AA) Score (vH, H, M, or L): L

Acetone was assigned a score of Low for acute aquatic toxicity based on L/EC50 values in fish,

invertebrates, and algae. GreenScreen® criteria classify chemicals as a Low hazard for acute aquatic

toxicity when acute L/EC50 values are > 100 mg/L (CPA 2017c). Confidence in the score is high as it is

based on multiple well conducted studies.




ECHA 2017b

o 96-hour LC50 (Pimephales promelas, fathead minnow) = 6,210 – 8,120 mg/L

o 48-hour LC50 (P. promelas, fathead minnow) = 14,300 mg/L

o 48-hour LC50 (P. promelas, fathead minnow) = 12,000 mg/L

o 96-hour LC50 (Oncorhynchus mykiss, rainbow trout) = 5,540 mg/L

o 24-hour LC50 (O. mykiss, rainbow trout) = 6,100 mg/L

o 48-hour LC50 (O. mykiss, rainbow trout) = 7,400 mg/L





o 96-hour LC50 (Alburnus alburnus, common bleak) = 11,000 mg/L

o 96-hour LC50 (A. alburnus, common bleak) = 11,000 mg/L

o 48-hour EC50 (Daphnia pulex, aquatic invertebrate) = 8,800 mg/L

o 24-hour EC50 (Artemia salina, aquatic invertebrate) = 2,100 mg/L

o 48-hour EC50 (Hydra oligactis, aquatic invertebrate) = 11,500 mg/L

o 24-hour EC50 (Daphnia magna, aquatic invertebrate) > 10,000 mg/L

o 48-hour EC50 (D. magna, aquatic invertebrate) = 30,806 mg/L

o 48-hour EC50 (D. magna, aquatic invertebrate) = 12,600 – 12,700 mg/L

o 48-hour EC50 (D. magna, aquatic invertebrate) = 12,600 – 12,700 mg/L

o 96-hour EC50 (Nitocra spinipes, aquatic invertebrate) = 15,000 mg/L

o 48-hour EC50 (Lymnaea stagnalis, great pond snail) = 7,000 mg/L

o 8-day NOEC (Microcystis aeruginosa, green algae) = 530 mg/L (therefore EC50 > 530

mg/L)

UNEP 1999

o 48-hour LC50 (Fathead minnow) = 15,000 mg/L

o 96-hour LC50 (Fathead minnow) = 9,100 mg/L

o 48-hour LC50 (Japanese medaka) = 14,300 mg/L

o 96-hour LC50 (Mosquito fish) = 13,000 mg/L

o 24-hour LC50 (Goldfish) > 5,000 mg/L

o 48-hour LC50 (Golden orfe) = 9,880 mg/L

o 96-hour LC50 (Bluegill sunfish) = 8,300 mg/L

o 96-hour LC50 (Brook trout) = 6,070 mg/L

o 48-hour LC50 (Guppy) = 9,600 mg/L

o 96-hour LC50 (Nitocra spinipes, aquatic invertebrate) = 16,700 mg/L

o 48-hour LC50 (D. magna, aquatic invertebrate) = 15,800 mg/L

o 48-hour LC50 (Daphnia cucullata, aquatic invertebrate) = 7,635 mg/L

o 168-hour NOEC (Scenedesmus quadricauda, green algae) = 7,500 mg/L (therefore EC50 >

7,500 mg/L)

o 96-hour NOEC (Selenastrum capricornutum, green algae) = 7,000 mg/L (therefore EC50 >

7,000 mg/L)

o 48-hour NOEC (Chlorella pyrenoidosa, green algae) = 3,400 mg/L (therefore EC50 > 3,400

mg/L)

o 48-hour NOEC (Scenedesmus pannonicus, green algae) = 4,740 mg/L (therefore EC50 >

4,740 mg/L)

o 7-day NOEC (Lemna gibba, duckweed) = 5,400 mg/L (therefore EC50 > 5,400 mg/L)

o 7-day NOEC (Lemna mino, duckweed) = 5,400 mg/L (therefore EC50 > 5,400 mg/L)

Chronic Aquatic Toxicity (CA) Score (vH, H, M, or L): L

Acetone was assigned a score of Low for chronic aquatic toxicity based on NOEC values in

invertebrates and algae. While no data were identified for fish, acute toxicity studies did not suggest

that fish is more sensitive to acetone than other trophic levels. GreenScreen® criteria classify chemicals

as a Low hazard for chronic aquatic toxicity when chronic aquatic toxicity values are > 10 mg/L (CPA

2017c). Confidence in the score is high as it is based on multiple well-conducted studies.




ECHA 2017b

o 28-day NOEC (D. magna, aquatic invertebrate) = 2,212 mg/L (reproduction); > 1,106 mg/L





and < 2,212 mg/L (mortality)

o 21-day NOEC (D. magna, aquatic invertebrate) > 79 mg/L (reproduction)

o 8-day NOEC (M. aeruginosa, green algae) = 530 mg/L

UNEP 1999

o 168-hour NOEC (Scenedesmus quadricauda, green algae) = 7,500 mg/L

o 96-hour NOEC (Selenastrum capricornutum, green algae) = 7,000 mg/L

o 48-hour NOEC (Chlorella pyrenoidosa, green algae) = 3,400 mg/L

o 48-hour NOEC (Scenedesmus pannonicus, green algae) = 4,740 mg/L

o 7-day NOEC (Lemna gibba, duckweed) = 5,400 mg/L

o 7-day NOEC (Lemna mino, duckweed) = 5,400 mg/L

o 10-day NOEC (Ceriodaphnia dubia, aquatic invertebrate) = 1,866 mg/L

o 28-day NOEC (D. magna, aquatic invertebrate) = 1,660 mg/L

Environmental Fate (Fate)

Persistence (P) Score (vH, H, M, L, or vL): vL

Acetone was assigned a score of Very Low for persistence based on results of ready biodegradation

assays. GreenScreen® criteria classify chemicals as a Very Low hazard for persistence when the

chemical meets the 10-day biodegradation window for “ready biodegradation” and its dominant

compartments is soil or water (CPA 2017c). Confidence in the score is high as it is based on high

quality data.



o Screening: Environment Canada – CEPA Domestic Substances List – Persistent

ECHA 2017b

o Acetone achieved 60% biodegradation in 5 days, > 80% biodegradation in 10 days and

90.9% biodegradation in 28 days in a biodegradation test similar to OECD Guideline 301 B

(Ready Biodegradability: CO2 Evolution Test) using a starting concentration of 7.8-15.7

µg/L and secondary effluent from an activated sludge plant as inoculum. Authors concluded

that acetone is readily biodegradable.

o Acetone achieved 84% biodegradation based on ThOD in 5 days in a biodegradation test

according to APHA Standard methods No. 219. Authors concluded that acetone is readily

biodegradable.

o Acetone (500 mg/L) degraded completely (100%) within 4 days after a lag phase of 5 days

under anaerobic (methanogenous) conditions in Hungate serum bottles with activated sludge

inoculum.

UNEP 1999

o Acetone meets OECD ready biodegradability criteria. Biodegradation is expected to be the

dominant removal process for acetone in the environment. Due to its biodegradability,

acetone is not persistent in the environment.

U.S. EPA 2012

o Fugacity modeling predicts 45.5% will partition to soil with a half-life of 30 days, 42.1%

will partition to water with a half-life of 15 days, and 12.3% will partition to air with a half-

life of 48.75 days. See Appendix E for output. CCR 2017

o Acetone is listed as persistent on Environment Canada’s DSL based on its predicted

biodegradation in air.





Based on the weight of evidence, a score of Very Low was assigned. Although acetone is classified

as persistent on Environment Canada’s DSL, this chemical met ready biodegradability criteria in

several aerobic and anaerobic biodegradation tests. Fugacity modeling predicts that acetone will

partition primarily to soil and water. When the major compartment is soil or water, GreenScreen®

criteria specify a score of Very Low if the chemical meets the 10-day window in a ready

biodegradation test.

Bioaccumulation (B) Score (vH, H, M, L, or vL): vL

Acetone was assigned a score of Very Low for bioaccumulation based on its log Kow of -0.24 and a

measured BCF of 0.69 in haddock. GreenScreen® criteria classify chemicals as a Very Low hazard for

bioaccumulation when the log Kow is < 4 and the BCF is < 100 (CPA 2017c). Confidence in the score is

high as it is based on experimentally determined values.




UNEP 1999

o A BCF of 0.69 was measured in adult haddock tested under static conditions. No additional

details were provided.

ChemIDplus 2014

o Log Kow = -0.24 (measured)

Physical Hazards (Physical)

Reactivity (Rx) Score (vH, H, M, or L): L

Acetone was assigned a score of Low for reactivity based on it not being explosive or oxidizing.

GreenScreen® criteria classify chemicals as a Low hazard for reactivity when the chemical is not

explosive or oxidizing, and there is no evidence indicating they are otherwise reactive (CPA 2017c).

Confidence in the score is reduced due to the lack of experimental details.




UNEP 1999

o Acetone is not explosive.

ECHA 2017b

o Acetone is not an oxidizing agent.

Flammability (F) Score (vH, H, M, or L): H

Acetone was assigned a score of High for flammability based on measure data and presence on

authoritative lists. GreenScreen® criteria classify chemicals as a High hazard for flammability when the

chemical is classified as U.S. DOT Hazard Class 3, Packing group II, EU H-Statement H225, EU R-

phrase R11, and WHMIS Class B2, and the measured flash point and boiling point indicate that GHS

Category 2 classification is warranted (CPA 2017c). Confidence in the score is high as it is based on

experimentally determined values and authoritative listings.


o Authoritative: EU GHS H-Statements - H225: Highly flammable liquid and vapor

o Authoritative: Quebec CSST – WHMIS 1922 – Class B2: Flammable liquids

o Authoritative: EU R Phrases – R11: Highly Flammable (liquid)





o Authoritative: U.S. DOT Hazard Class 3, Packing group II


ECHA 2017b

o Acetone has a flash point of – 17°C.

o Acetone has a boiling point of 56°C.

Based on the weight of evidence, a score of High was assigned. Acetone is present on several

authoritative lists and is classified as U.S. DOT Hazard Class 3, Packing group II, EU H-Statement

H225 Highly flammable liquid and vapor, which correspond to a high, EU R-phrase R11 Highly

flammable liquid, which corresponds to a high-very high, and WHMIS Class B2 - Flammable

liquids, which corresponds to a moderate-very high. Acetone has a flash point of – 17°C and boiling

point of 56°C, which corresponds to GHS Category 2 for flammable liquids (flash point < 23°C and

boiling point > 35°C). Therefore, the score of High is appropriate.





References

Agency for Toxic Substances and Disease Registry (ATSDR). 1994. Toxicological profile for acetone.

Available at: www.toxplanet.com.

Agency for Toxic Substances and Disease Registry (ATSDR). 2011. Addendum to the toxicological

profile for acetone. Available at: www.toxplanet.com.

Canadian Categorization Results (CCR). 2017. Categorization Results from the Canadian Domestic

Substance List for 2-Propanone (CAS #67-64-1). Available at:

http://webnet.oecd.org/ccrweb/ChemicalDetails.aspx?ChemicalID=E008A932-8BD0-4439-ACB4-

D602FFEA49F7.

Chemical Classification and Information Database (CCID). 2017. Search Results for 2-Propanone

(CAS# 67-64-1). New Zealand Environmental Protection Authority. Available at:

http://www.epa.govt.nz/search-databases/Pages/ccid-details.aspx?SubstanceID=1489.

ChemIDplus. 2017. Entry for Acetone (CAS #67-64-1). United States National Library of Medicine.

Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Clean Production Action (CPA). 2017a. The GreenScreen® for Safer Chemicals Version 1.3 (2e)

GreenScreen Benchmarks™. Dated February 2017. Available at:

http://www.greenscreenchemicals.org/.

Clean Production Action (CPA). 2017b. The GreenScreen® for Safer Chemicals Chemical Hazard

Assessment Guidance. Version 1.3 (2e) Guidance. Dated February, 2017. Available at:

http://www.greenscreenchemicals.org/.

Clean Production Action (CPA). 2017c. GreenScreen Version 1.3 (2e) Hazard Criteria. Dated:

February 2017. Available at: http://www.greenscreenchemicals.org/.

European Chemicals Agency (ECHA). 2016. Guidance on information requirements and Chemical

Safety Assessment. Chapter R.7a: Endpoint specific guidance. Version 5.0. Dated: December 2016.

Available at: https://echa.europa.eu/documents/10162/13632/information_requirements_r7a_en.pdf.

European Chemicals Agency (ECHA). 2017a. C&L Inventroy. Available at:

https://echa.europa.eu/de/information-on-chemicals/cl-inventory-database.

European Chemicals Agency (ECHA). 2017b. REACH Dossier for Acetone (CAS #67-64-1).

Available at: https://echa.europa.eu/de/registration-dossier/-/registered-dossier/15460/1.

Giordano, G., and Costa, L.G. 2012. Developmental neurotoxicity: some old and new issues. ISRN

Toxicology. Volume 2012, Article ID 814795. Available at:

https://www.hindawi.com/journals/isrn/2012/814795/.

Grandjean, P., and P.J. Landrigan. 2006. Developmental neurotoxicity of industrial chemicals. Lancet

368: 2167-2178.

http://www.toxplanet.com/


http://webnet.oecd.org/ccrweb/ChemicalDetails.aspx?ChemicalID=E008A932-8BD0-4439-ACB4-D602FFEA49F7

http://webnet.oecd.org/ccrweb/ChemicalDetails.aspx?ChemicalID=E008A932-8BD0-4439-ACB4-D602FFEA49F7

http://www.epa.govt.nz/search-databases/Pages/ccid-details.aspx?SubstanceID=1489

http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp

http://www.greenscreenchemicals.org/



https://echa.europa.eu/documents/10162/13632/information_requirements_r7a_en.pdf

https://echa.europa.eu/de/information-on-chemicals/cl-inventory-database

https://echa.europa.eu/de/registration-dossier/-/registered-dossier/15460/1

https://www.hindawi.com/journals/isrn/2012/814795/





Grandjean, P., and P.J. Landrigan. 2014. Neurobehavioral effects of developmental toxicity. The

Lancet 13: 330-338.

Hazardous Substances Data Bank (HSDB). 2015. Entry for Acetone (CAS #67-64-1). United States

National Library of Medicine. Available at: https://toxnet.nlm.nih.gov/cgi-

bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+67-64-1.

Mitran, E., T. Callender, B. Orha, P. Dragnea, and G. Botezatu. 2009. Neurotoxicity associated with

occupational exposure to acetone, methyl ethyl ketone, and cyclohexanone. Environmental Research.

73(1-2): 181-188. Abstract Only.

National Institute for Occupational Safety and Health (NIOSH). 2008. International Chemical Safety

Card for Acetone (CAS #67-64-1). Last updated January 2008. Available at:

https://www.cdc.gov/niosh/ipcs/.

National Institute of Technology and Evaluation (NITE). 2006. GHS Japan Classification Results.

Dated March 23, 2006. Available at: http://www.safe.nite.go.jp/english/ghs/06-imcg-0627e.html

National Institute of Technology and Evaluation (NITE). 2014. GHS Japan Classification Results

(revision of past classification result). Dated 2014. Available at:

http://www.safe.nite.go.jp/english/ghs/14-mhlw-2006e.html.

Organisation for Economic Co-operation and Development (OECD). 2016. OECD QSAR Toolbox for

Grouping Chemicals into Categories Version 3.4.0.17. Available at: http://toolbox.oasis-

lmc.org/?section=download&version=latest.

Pharos. 2017. Pharos Chemical and Material Library Entry for Acetone (CAS #67-64-1). Available at:

http://www.pharosproject.net/material/.

ToxServices. 2016. SOP 1.37: GreenScreen® Hazard Assessments. Dated: August 30, 2016.

United Nations Environment Programme (UNEP). 1999. Acetone (CAS# 67-64-1) SIDS Initial

Assessment Report (SIAR) for the 9th SIAM. Dated July 1, 1999. Available at:

http://www.inchem.org/documents/sids/sids/67641.pdf

United States Department of Transportation (U.S. DOT). 2008a. Chemicals Listed with Classification.

49 CFR § 172.101. Available at: http://www.gpo.gov/fdsys/pkg/CFR-2008-title49-vol2/pdf/CFR-2008-

title49-vol2-sec172-101.pdf.

United States Department of Transportation (U.S. DOT). 2008b. Classification Criteria. 49 CFR § 173.

Available at: http://www.ecfr.gov/cgi-bin/text-

idx?c=ecfr&tpl=/ecfrbrowse/Title49/49cfr173_main_02.tpl.

United States Environmental Protection Agency (U.S. EPA). 2003. Toxicological Review of Acetone

(CAS #67-64-1). In support of summary information on the Integrated Risk Information System (IRIS).

May 2003. Available at: www.toxplanet.com.

https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+67-64-1

https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+67-64-1

https://www.cdc.gov/niosh/ipcs/

http://www.safe.nite.go.jp/english/ghs/14-mhlw-2006e.html

http://toolbox.oasis-lmc.org/?section=download&version=latest

http://toolbox.oasis-lmc.org/?section=download&version=latest

http://www.pharosproject.net/material/

http://www.gpo.gov/fdsys/pkg/CFR-2008-title49-vol2/pdf/CFR-2008-title49-vol2-sec172-101.pdf

http://www.gpo.gov/fdsys/pkg/CFR-2008-title49-vol2/pdf/CFR-2008-title49-vol2-sec172-101.pdf

http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&tpl=/ecfrbrowse/Title49/49cfr173_main_02.tpl

http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&tpl=/ecfrbrowse/Title49/49cfr173_main_02.tpl






United States Environmental Protection Agency (U.S. EPA). 2012. Estimation Programs Interface

(EPI) SuiteTM Web, v4.11, Washington, DC, USA. Available at:

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.

United States Environmental Protection Agency (U.S. EPA). 2015. Safer Choice Standard. Available

at: http://www2.epa.gov/saferchoice/safer-choice-standard.

United States Environmental Protection Agency (U.S. EPA). 2017. Safer Chemical Ingredients List

(SCIL). Available at: http://www2.epa.gov/saferchoice/safer-ingredients.

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm

http://www2.epa.gov/saferchoice/safer-choice-standard

http://www2.epa.gov/saferchoice/safer-ingredients





APPENDIX A: Hazard Benchmark Acronyms

(in alphabetical order)

(AA) Acute Aquatic Toxicity

(AT) Acute Mammalian Toxicity

(B) Bioaccumulation

(C) Carcinogenicity

(CA) Chronic Aquatic Toxicity

(D) Developmental Toxicity

(E) Endocrine Activity

(F) Flammability

(IrE) Eye Irritation/Corrosivity

(IrS) Skin Irritation/Corrosivity

(M) Mutagenicity and Genotoxicity

(N) Neurotoxicity

(P) Persistence

(R) Reproductive Toxicity

(Rx) Reactivity

(SnS) Sensitization- Skin

(SnR) Sensitization- Respiratory

(ST) Systemic/Organ Toxicity


Limited license provided to University of Massachusetts Lowell for public distribution through the University of Massachusetts Lowell website, publications, presentations and for

no other purpose whatsoever. Further copying, resale, and distribution are expressly prohibited. Page 28 of 35

APPENDIX B: Results of Automated GreenScreen® Score Calculation for Acetone (CAS #67-64-1)

Ca

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Inorganic

Chemical?

Chemical

NameCAS# C M R D E AT STs STr Ns Nr SNS* SNR* IrS IrE AA CA P B Rx F

Yes Acetone 67-64-1 L L M M M L M M M M L L M H L L vL vL L H

a b c d e f g

No No No No No

No No No No Yes No Yes

STOP

STOP

a b c d e f g h i j bm4End

Result

Yes Yes Yes Yes Yes 22

3

4

22

Note: Chemical has not undergone a data gap

assessment. Not a Final GreenScreenTM

Score

After Data gap Assessment

Note: No Data gap Assessment Done if Preliminary

GS Benchmark Score is 1.4

Table 5: Data Gap Assessment Table

Datagap Criteria

3

Acetone

1

Table 6

Benchmark Chemical Name

Preliminary

GreenScreen®

Benchmark Score

Chemical Name

Table 4

Final

GreenScreen®

Benchmark Score

1Acetone 2

GreenScreen® Score Inspector

Table 1: Hazard Table

Group I Human Group II and II* Human Ecotox Fate Physical

Sy

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Table 2: Chemical Details

Table 3: Hazard Summary Table


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presentations and for no other purpose whatsoever. Further copying, resale, and distribution are expressly prohibited. Page 29 of 35

APPENDIX C: Pharos Output for Acetone (CAS #67-64-1)


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presentations and for no other purpose whatsoever. Further copying, resale, and distribution are expressly prohibited. Page 30 of 35



Massachusetts Lowell website, publications, presentation and for no other purpose whatsoever. Further copying,


APPENDIX D: OECD Toolbox Respiratory Sensitization Results for Acetone

(CAS #67-64-1)





APPENDIX E: EPISuite Modeling Results for Acetone (CAS #67-64-1)

CAS Number: 67641

SMILES: O=C(C)C

CHEM: 2-Propanone

MOL FOR: C3 H6 O1

MOL WT: 58.08

------------------------------ EPI SUMMARY (v4.11) --------------------------

Physical Property Inputs:

Log Kow (octanol-water): -0.24

Boiling Point (deg C): ------

Melting Point (deg C): -94.80

Vapor Pressure (mm Hg): 232

Water Solubility (mg/L): 1E+006

Henry LC (atm-m3/mole): ------

Log Octanol-Water Partition Coef (SRC):

Log Kow (KowWIN v1.68 estimate) = -0.24

Log Kow (Exper. database match) = -0.24

Exper. Ref: HANSCH, C. ET AL. (1995)

Boiling Pt, Melting Pt, Vapor Pressure Estimations (MPBPVP v1.43):

Boiling Pt (deg C): 44.80 (Adapted Stein & Brown method)

Melting Pt (deg C): -93.58 (Mean or Weighted MP)

VP (mm Hg, 25 deg C): 249 (Mean VP of Antoine & Grain methods)

VP (Pa, 25 deg C): 3.32E+004 (Mean VP of Antoine & Grain methods)

MP (exp database): -98.3 deg C

BP (exp database): 55.5 deg C

VP (exp database): 2.32E+02 mm Hg (3.09E+004 Pa) at 25 deg C

Water Solubility Estimate from Log Kow (WSKow v1.42):

Water Solubility at 25 deg C (mg/L): 3.199e+005

log Kow used: -0.24 (user entered)

melt pt used: -94.80 deg C

Water Sol (Exper. database match) = 1e+006 mg/L (25 deg C)

Exper. Ref: RIDDICK, J.A. ET AL. (1986)

Water Sol Estimate from Fragments:

Wat Sol (v1.01 est) = 2.6753e+005 mg/L

ECOSAR Class Program (ECOSAR v1.11):

Class(es) found:

Neutral Organics

Henrys Law Constant (25 deg C) [HENRYWIN v3.20]:

Bond Method: 4.96E-005 atm-m3/mole (5.02E+000 Pa-m3/mole)

Group Method: 3.97E-005 atm-m3/mole (4.02E+000 Pa-m3/mole)

Exper Database: 3.50E-05 atm-m3/mole (3.55E+000 Pa-m3/mole)





For Henry LC Comparison Purposes:

User-Entered Henry LC: not entered

Henrys LC [via VP/WSol estimate using User-Entered or Estimated values]:

HLC: 1.773E-005 atm-m3/mole (1.796E+000 Pa-m3/mole)

VP: 232 mm Hg (source: User-Entered)

WS: 1E+006 mg/L (source: User-Entered)

Log Octanol-Air Partition Coefficient (25 deg C) [KoaWIN v1.10]:

Log Kow used: -0.24 (user entered)

Log Kaw used: -2.844 (exp database)

Log Koa (KoaWIN v1.10 estimate): 2.604

Log Koa (experimental database): 2.310

Probability of Rapid Biodegradation (BIOWIN v4.10):

Biowin1 (Linear Model): 0.7267

Biowin2 (Non-Linear Model): 0.8495

Expert Survey Biodegradation Results:

Biowin3 (Ultimate Survey Model): 3.0483 (weeks)

Biowin4 (Primary Survey Model): 3.7417 (days-weeks)

MITI Biodegradation Probability:

Biowin5 (MITI Linear Model): 0.6579

Biowin6 (MITI Non-Linear Model): 0.8483

Anaerobic Biodegradation Probability:

Biowin7 (Anaerobic Linear Model): 0.2850

Ready Biodegradability Prediction: YES

Hydrocarbon Biodegradation (BioHCwin v1.01):

Structure incompatible with current estimation method!

Sorption to aerosols (25 Dec C)[AEROWIN v1.00]:

Vapor pressure (liquid/subcooled): 3.09E+004 Pa (232 mm Hg)

Log Koa (Exp database): 2.310

Kp (particle/gas partition coef. (m3/ug)):

Mackay model: 9.7E-011

Octanol/air (Koa) model: 5.01E-011

Fraction sorbed to airborne particulates (phi):

Junge-Pankow model: 3.5E-009

Mackay model: 7.76E-009

Octanol/air (Koa) model: 4.01E-009

Atmospheric Oxidation (25 deg C) [AopWin v1.92]:

Hydroxyl Radicals Reaction:

OVERALL OH Rate Constant = 0.2040 E-12 cm3/molecule-sec

Half-Life = 52.431 Days (12-hr day; 1.5E6 OH/cm3)

Ozone Reaction:

No Ozone Reaction Estimation

Fraction sorbed to airborne particulates (phi):

5.63E-009 (Junge-Pankow, Mackay avg)





4.01E-009 (Koa method)

Note: the sorbed fraction may be resistant to atmospheric oxidation

Soil Adsorption Coefficient (KocWIN v2.00):

Koc: 2.364 L/kg (MCI method)

Log Koc: 0.374 (MCI method)

Koc: 9.726 L/kg (Kow method)

Log Koc: 0.988 (Kow method)

Aqueous Base/Acid-Catalyzed Hydrolysis (25 deg C) [HYDROWIN v2.00]:

Rate constants can NOT be estimated for this structure!

Bioaccumulation Estimates (BCFBAF v3.01):

Log BCF from regression-based method = 0.500 (BCF = 3.162 L/kg wet-wt)

Log Biotransformation Half-life (HL) = -1.4496 days (HL = 0.03551 days)

Log BCF Arnot-Gobas method (upper trophic) = -0.032 (BCF = 0.929)

Log BAF Arnot-Gobas method (upper trophic) = -0.032 (BAF = 0.929)

log Kow used: -0.24 (user entered)

Volatilization from Water:

Henry LC: 3.5E-005 atm-m3/mole (Henry experimental database)

Half-Life from Model River: 13.53 hours

Half-Life from Model Lake: 211.5 hours (8.811 days)

Removal in Wastewater Treatment:

Total removal: 3.69 percent

Total biodegradation: 0.09 percent

Total sludge adsorption: 1.73 percent

Total to Air: 1.87 percent

(using 10,000 hr. Bio P,A,S)

Removal in Wastewater Treatment:

Total removal: 92.10 percent

Total biodegradation: 91.46 percent

Total sludge adsorption: 0.33 percent

Total to Air: 0.31 percent

(using Biowin/EPA draft method)

Level III Fugacity Model:

Mass Amount Half-Life Emissions

(percent) (hr.) (kg/hr.)

Air 12.3 1.17e+003 1000

Water 42.1 360 1000

Soil 45.5 720 1000

Sediment 0.0813 3.24e+003 0

Persistence Time: 336 hr.





Licensed GreenScreen® Profilers

Acetone GreenScreen® Evaluation Prepared by:

Jennifer Rutkiewicz, Ph.D.

Toxicologist

ToxServices LLC

Acetone GreenScreen® Evaluation QC’d by:

Bingxuan Wang, Ph.D.

Toxicologist

ToxServices LLC

Acetone GreenScreen® Update Prepared by:

Rachel Galante, M.P.H.

Associate Toxicologist

ToxServices LLC

Acetone GreenScreen® Update QC’d by:

Bingxuan Wang, Ph.D., D.A.B.T.

Senior Toxicologist

ToxServices LLC

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