U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
Sponsored Chemical
Chloroacetyl chloride
(CASRN 79-04-9)
Supporting Chemical
Chloroacetic acid
(CASRN 79-11-8)
The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary
initiative aimed at developing and making publicly available screening-level health and
environmental effects information on chemicals manufactured in or imported into the United
States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship
entailed the identification and initial assessment of the adequacy of existing toxicity
data/information, conducting new testing if adequate data did not exist, and making both new
and existing data and information available to the public. Each complete data submission
contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'2)
endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the
environment.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is
evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored
chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions.
They are not intended to be definitive statements regarding the possibility of unreasonable risk of
injury to health or the environment.
The evaluation is performed according to established EPA guidance2'3 and is based primarily on
hazard data provided by sponsors; however, in preparing the hazard characterization, EPA
considered its own comments and public comments on the original submission as well as the
sponsor's responses to comments and revisions made to the submission. In order to determine
whether any new hazard information was developed since the time of the HPV submission, a
search of the following databases was made from one year prior to the date of the HPV
Challenge submission to the present: (ChemID to locate available data sources including
Medline/PubMed, Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.),
STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS,
Merck, etc.) and Science Direct. OPPT's focus on these specific sources is based on their being
of high quality, highly relevant to hazard characterization, and publicly available.
OPPT does not develop HCs for those HPV chemicals which have already been assessed
internationally through the HPV program of the Organization for Economic Cooperation and
1	U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
2	U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
3	U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.

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Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment
Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are
presented in an international forum that involves review and endorsement by governmental
authorities around the world. OPPT is an active participant in these meetings and accepts these
documents as reliable screening-level hazard assessments.
These hazard characterizations are technical documents intended to inform subsequent decisions
and actions by OPPT. Accordingly, the documents are not written with the goal of informing the
general public. However, they do provide a vehicle for public access to a concise assessment of
the raw technical data on HPV chemicals and provide information previously not readily
available to the public.
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Chemical Abstract Service
Registry Number	79-04-9
	(CASRN)	
Chemical Abstract Index	Acetyl chloride, 2-chloro-
	Name	
Structural Formula	0
	cr 	
Summary
This chemical is a liquid at room temperature with high vapor pressure and its water solubility
cannot be measured due to its rapid hydrolysis in water. However, the major hydrolysis
products, chloroacetic acid (CASRN 79-11-8) and hydrogen chloride, exhibit high solubility in
water. This chemical and its aqueous hydrolysis products are expected to be highly mobile in
soil. Its rate of hydrolysis is considered rapid under environmental conditions (pH 5-9). The
rate of biodegradation for the organic hydrolysis product (CASRN 79-11-8) was rapid based on
the results of a ready biodegradation test. Volatilization is not an important fate property since
hydrolysis occurs rapidly and the organic hydrolysis product exists as an anion in the
environment. The hydrogen chloride hydrolysis product exists mainly as hydrochloric acid in
the aqueous phase. The rate of vapor-phase photooxidation in the ambient atmosphere is
negligible. CASRN 79-04-9 is expected to have low persistence potential (PI) and low
bioaccumulation potential (Bl).
The acute oral, inhalation and dermal toxicity of this chemical (CASRN 79-04-9) is moderate.
Acute oral and dermal toxicity of the hydrolysis product (CASRN 79-11-8) is also moderate.
CASRN 79-04-9 is corrosive to rabbit eyes and skin. Systemic toxicity in inhalation repeated-
dose studies with CASRN 79-04-9 in rats and mice showed mortality at low doses (LOAEL of
0.011 mg/L) and local effects (inflammation/cellular abnormalities in the nasal mucosa) at the
lowest tested dose (LOAEL of 0.002 mg/L). In oral repeated-dose studies with CASRN 79-11-8,
effects on the liver and heart (rats - LOAEL of 60 mg/kg-bw/day; NOAEL of 30 mg/kg-bw/day)
and mortality (mice - LOAEL of 200 mg/kg-bw/day; NOAEL of 150 mg/kg-bw/day) were
observed. Although there were no reproductive toxicity studies with either CASRN 79-04-9 or
CASRN 79-11-8, there were no effects in reproductive organs in oral repeated-dose studies with
CASRN 79-11-8 at doses up to 200 mg/kg-bw/day in rats and 150 mg/kg-bw/day in mice. A
developmental toxicity study with CASRN 79-11-8 in rats showed maternal toxicity (reduction
in both body weight and weight gain) and developmental toxicity (increased cardiovascular
malformations in fetuses) at the same dose (LOAEL of 140 mg/kg-bw/day; NOAEL of 70
mg/kg-bw/day]). CASRN 79-04-9 did not induce gene mutations in bacteria. In in vitro studies
with mammalian cell cultures, CASRN 79-11-8 did not induce chromosomal aberrations, but did
induce sister chromatid exchanges. Oral exposure to CASRN 79-11-8 for 104 weeks did not
result in increase in tumor incidence in rats or mice compared to controls.
Because CASRN 79-04-9 undergoes rapid hydrolysis to CASRN 79-11-8 in water, data on
aquatic organisms are available for the hydrolysis product. For CASRN 79-11-8, the measured
96-hour LC50 for fish is 369 mg/L, the measured 48-hour EC50 for aquatic invertebrates is 77
mg/L and the measured 72-hour EC50 for aquatic plants is 0.025 mg/L (biomass) and 0.033 mg/L
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(growth rate).
There were no data gaps identified under the HPV Challenge Program.
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The sponsor, Dow Chemical Company, submitted a Test Plan and Robust Summaries to EPA for
chloroacetyl chloride (CASRN 79-04-9; CA index name: acetyl chloride, 2-chloro-) on
December 18, 2001. EPA posted the submission on the ChemRTK HPV Challenge website on
January 23, 2002 (http://www.epa.gov/oppt/chemrtk/pubs/summaries/chloroa/cl3405tc.htm).
EPA comments on the original submission were posted to the website on August 22, 2002.
Public comments were also received and posted to the website. The sponsor submitted
updated/revised documents on November 10, 2006, which were posted to the ChemRTK website
on December 22, 2006.
The sponsor proposed reduced health effects testing, claiming that chloroacetyl chloride is a
closed-system intermediate (CSI) under the HPV Challenge Program. EPA's evaluation of the
original and revised/updated information indicates that the chemical does not meet the criteria to
fully support the CSI status for this chemical and that the chemical does not qualify for reduced
testing. Therefore data for repeated-dose and reproductive toxicity endpoints are needed for the
purposes of the HPV Challenge Program.
Justification for Supporting Chemical
Chloroacetyl chloride undergoes rapid hydrolysis (half life less than 30 minutes) to form
chloroacetic acid. Therefore, the sponsor has provided data for chloroacetic acid (CASRN 79-
11-8) as a hydrolysis product. EPA agrees that data for chloroacetic acid can be used to address
the SIDS endpoints for chloroacetyl chloride for environmental fate, ecological and human
health endpoints for the purposes of the HPV Challenge Program. Chloroacetic acid has been
reviewed in the OECD HPV program and the data can be found at the following website:
http ://cs3 -hq. oecd. org/ scripts/hpv/
1 Chemical Identity
1.1 Identification and Purity
The HPV Challenge submission reports that the organic liquid CASRN 79-04-9 has a purity of
99.4%.
The structures of the supporting chemical and the sponsored chemical are shown in Table 1.
Table 1. Structures of Sponsored and Supporting Chemicals

SPONSORED CHEMICAL
Chloroacetyl chloride
(CASRN 79-04-9)
SUPPORTING CHEMICAL
Chloroacetic acid
(CASRN 79-11-8)
Structure
O
cr
0
HO
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1.2 Physical-Chemical Properties
The physical-chemical properties of CASRN 79-04-9 and its major organic hydrolysis product,
CASRN 79-11-8, are summarized in Table 2. CASRN 79-04-9 is a liquid at room temperature.
It has high vapor pressure and reacts rapidly with water.
Table 2. Physical-Chemical Properties of Chloroacetyl Chloride and Chloroacetic Acid1
Property
Chloroacetyl Chloride
Chloroacetic Acid
CASRN
79-04-9
79-11-8
Molecular Weight
112.9
94.50
Physical State
Colorless to light yellow liquid
White solid
Melting Point
-22°C (measured)
63°C (measured)
Boiling Point
106°C (measured)
189°C (measured)
Vapor Pressure
25.0 mm Hg at 25°C
(measured)
0.065 mm Hg (measured)
Water Solubility
Decomposes
1.95x10 s (measured)
Dissociation Constant (pKa)
Not applicable
2.872
Henry's Law Constant
2.63xlO"5 atm-nrVmole
(estimated)
1.57 x 10"7 atm-nrVmole
(estimated)
Log Kow
-0.22 (estimated), decomposes in
water
0.22 (measured)
1	Eastman Chemical Company. 2003. Robust Summary for 3,4-Dichlorotrifluorotoluene.
http://www.epa.gov/chemrtk/pubs/summaries/eth3meth/cl4884tc.htm.
2	Estimated by Sparc, May 2008 release w4.21405-s4.21408 (http://ibmlc2.chem.uga.edu/sparc).
2 General Information on Exposure
2.1	Production Volume and Use Pattern
This HPV chemical had an aggregated production and/or import volume in the U.S. in the range
of 50 to 100 million pounds in 2005.
Non-confidential information in the IUR indicated that the industrial processing and uses of this
chemical includes processing as a reactant in pesticide and other agricultural chemical
manufacturing. Non-confidential information in the IUR indicated that commercial and
consumer products are listed as "other." Information from the HSDB and the HPV Challenge
Program submission indicates that this chemical is primarily used as an intermediate in the
manufacture of tear gas, pharmaceutical compounds, herbicides and surfactants.
2.2	Environmental Exposure and Fate
No quantitative information is available on releases of this chemical to the environment.
The environmental fate properties of both the sponsored and supporting chemicals are shown in
Table 3. CASRN 79-04-9 and its hydrolysis product are expected to be highly mobile in soil. Its
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rate of hydrolysis is considered rapid under environmental conditions (pH 5-9). The rate of
biodegradation for its organic hydrolysis product (CASRN 79-11-8) was rapid based on the
results of a ready biodegradation test. Volatilization is not an important fate property since
hydrolysis occurs rapidly; the organic hydrolysis product, CASRN 79-11-8, exists as an anion in
the environment and the hydrogen chloride exits as hydrochloric acid in the aqueous phase. The
rate of vapor-phase photooxidation in the ambient atmosphere is negligible. CASRN 79-04-9 is
expected to have low persistence potential (PI) and low bioaccumulation potential (Bl).
Table 3. Environmental Fate Characteristics of Chloroacetyl Chloride and Chloroacetic
Acid1
Property
Chloroacetyl Chloride
Chloroacetic Acid
Photodegradation Half-life
450 days (estimated; assumes
12-hour day and 1.5xlO6
hydroxyl radicals/cm3)2
13.65 days (estimated;
assumes 12-hour day and
1.5xlO6 hydroxyl
radical s/cm3)2
Hydrolysis Half-life
<30 minutes at 25°C
(measured)
Dissociates in water
Biodegradation
100%) after 28 days (readily
biodegradable)
100%) after 28 days (readily
biodegradable)
Bioconcentration
BCF = 3.162 (estimated)2
BCF = 3.162 (estimated)2
Log Koc
0.6 (estimated)
0.08 (estimated)
Fugacity
(Level III Model)
Air = 16%
Water = 84%
Soil = 0%
Sediment = 0%
Air = 0.2%
Water = 38.3%
Soil = 61.4%
Sediment = 0.1%
Persistence
PI (low)3
PI (low)3
Bioaccumulation
Bl (low)3
Bl (low)3
1 Dow AgroSciences LLC. 2006. Revised Robust Summary for the Chloroacetyl Chloride.
http://www.epa.gov/chemrtk/pubs/summaries/chloroa/cl3405tc.htm.
2U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. U.S. Environmental
Protection Agency, Washington, DC, USA. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
3Federal. Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal
Register 64, Number 213 (November 4, 1999) pp. 60194-60204.
3. Human Health Hazard
Acute Oral Toxicity
Chloroacetyl chloride (CASRN79-04-9)
(1) Rats (2/sex; strain not provided) were administered chloroacetyl chloride as a 10% solution in
corn oil at 1260 (male) or 2500 (female) mg/kg-bw and observed for 14 days. Mortality (100%)
occurred in males at 1260 mg/kg-bw, and there were no mortalities in females at 2500 mg/kg-
bw.
LD50 (males) < 1260 mg/kg-bw
LD50 (females) > 2500 mg/kg-bw
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(2) Sprague-Dawley rats (2/sex/dose) were administered chloroacetyl chloride as a 50% solution
in corn oil at 126, 158, 200 or 251 mg/kg-bw and observed for 9 days. Survival time was several
hours to 2 days with most deaths occurring within 1 day. Toxic signs included increasing
weakness, collapse and death. Survivors at higher (unspecified) doses showed only a slight
weight gain. Necropsy of animals not surviving the observation period revealed hemorrhagic
lungs and inflammation of liver and gastrointestinal tract. Necropsy findings of those surviving
until terminal sacrifice revealed lung congestion, slight liver discoloration and gastrointestinal
inflammation.
LD50 = 207 mg/kg-bw
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
(1)	Female rats (strain and number per dose not provided) were dosed with unspecified
concentrations of chloroacetic acid. No details on the number of deaths or clinical signs of
toxicity were provided.
LD50 = 90.4 mg/kg-bw
(2)	Mice (strain, number and gender not provided) were dosed with unspecified concentrations of
chloroacetic acid in two studies. No details on deaths or clinical signs of toxicity were provided.
LD50 = 165 - 260 mg/kg-bw
Acute Inhalation Toxicity
Chloroacetyl chloride (CASRN79-04-9)
(1) Fischer 344 rats (6/sex/concentration) were exposed to chloroacetyl chloride vapors at
measured concentrations of 32, 208, 522 or 747 ppm (~ 0.15, 0.96, 2.41 or 3.45 mg/L,
respectively) for 1 hour and observed for 14 days. The 1-hour exposures were universally
marked by signs of ocular irritation, including squinting and tearing, and by signs of respiratory
distress from exposures to 208 ppm and above, including gasping and labored breathing. During
the 2-week post-exposure observation, treated animals showed persisting eye squint (208 ppm
and above), tearing (522 ppm and above), labored breathing (522 ppm and above) and
progressive irritative or stress-related clinical signs, including urine stained perineums (32 ppm
and above), lethargy (208 ppm and above), reddish periocular stains (208 ppm and above), and
salivation with reddish muzzle stains (522 ppm and above). Generally, weight loss during week
1 post-exposure was regained during week 2. Mortality consisted of 5/6 males and 1/6 females
and was consistent with a 1-hour LC50 of 660 ppm for males and greater than 747 ppm for
female rats. Necropsy of study lethalities revealed lung and nasal tissue congestion or general
circulatory collapse (shock). One male lethality and 5/6 female survivors also had bilaterally
enlarged adrenals which, with facial and perineal soiling, the study authors attributed to stress.
(Note: Some of the above study details were not in the submitted robust summary but were
obtained from a literature search.)
LC50 = ~ 3.05 mg/L
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(2) Mice (10/concentration, sex and strain not provided) were exposed to chloroacetyl chloride at
a range of concentrations between 0.5 and 30 mg/L for 2 hours or to concentrations ranging from
10 to 65 mg/L for 5 minutes. The animals were observed for 5 days. Clinical signs, necropsy
results and mortalities were not provided.
LC50 = ~ 11.09 mg/L
Acute Dermal Toxicity
Chloroacetyl chloride (CASRN79-04-9)
New Zealand White rabbits (2/sex/dose) were administered chloroacetyl chloride at 126, 200,
316, 501, 794, 1260, 2000, 5010 or 10,000 mg/kg to clipped, intact skin under occluded
conditions for 24 hours and observed for 14 days. Chloroacetyl chloride was corrosive,
extending into the dermis. Mortalities occurred within 3 hours to 2 days. Clinical signs included
reduced appetite for 2 - 5 days in survivors, increasing weakness, dyspnea and collapse.
Enlarged gall bladders and hemorrhagic lungs and livers were seen in animals dying prior to the
end of the observation period.
LD50 = 316 - 501 mg/kg
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
(1)	Female rats (strain and number not provided) were exposed to chloroacetic acid at
unspecified concentrations. No details on the method, number of deaths or signs of toxicity were
provided.
LD50 = 305 mg/kg-bw
(2)	Rabbits (gender, strain and number per concentration not provided) were exposed to
chloroacetic acid at unspecified concentrations. No details on the method, number of deaths or
signs of toxicity were provided.
LD50 = 250 mg/kg-bw
Repeated-Dose Toxicity
Chloroacetyl chloride (CASRN79-04-9)
Fischer 344 rats, CD-I mice and Golden Syrian hamsters (10/sex/concentration) were exposed to
chloroacetyl chloride vapors at 0, 0.5, 1, 2.5 or 5 ppm (0, 0.002, 0.005, 0.011 or 0.023 mg/L,
respectively) for 6 hours/day 5 days/week for 4 weeks. Mortality in rats was 17/20 and 19/20 at
0.011 and 0.023 mg/L respectively during the first two weeks of exposure. Mortality in mice at
0.011 and 0.023 mg/L was 20 and 30% respectively. All rats and mice in the other exposure
groups and all the hamsters survived. Other signs of toxicity observed in rats (0.011 and 0.023
mg/L) and mice (0.023mg/L) included rough and discolored fur, irritability, sneezing, lethargy,
nasal exudates, rales and eye irritation. The signs of clinical toxicity in hamsters included dose
related sneezing and eye closure. Dose related decreases in body weight occurred in mice and
rats exposed at 0.005 mg/L and above. Body weight decrease was observed in female hamsters
at 0.011 and 0.023 mg/L and at 0.023 mg/L in male hamsters. Gross and microscopic changes
were observed in the respiratory tract in rats and mice at 0.011 and 0.023 mg/L. Changes were
most severe in the lungs (darkened, hemorrhagic, failure to collapse on puncture) and nasal
regions (rhinitis). Histological examination revealed inflammation, hypertrophy and hyperplasia
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with occasional squamous metaplasia in the mucosa of the rat respiratory epithelium and
intracytoplasmic eosinophilic inclusions in mice. These changes were slight to moderate at 0.002
mg/L in rats and mice. Numbers of macrophages surrounding the large bronchi, with red
indistinct cytoplasmic masses increased in mice. Additional cellular changes observed in the
mice include accentuated hepatic lobules, depletion of mesenteric adipose tissue, and ovarian,
uterine and cervical epithelial atrophy at 0.011 and 0.023 mg/L, and microvesicular changes in
periportal hepatocytes of male mice at 0.002 and 0.005 mg/L. Hamsters showed no gross
pathological respiratory effects and were not assessed histopathologically. (Note: Some of the
above study details were not in the submitted robust summary but were obtained from a literature
search.)
LOAEL (systemic toxicity) = 0.011 mg/L (based on mortality in rats and mice)
NOAEL (systemic toxicity) = 0.005 mg/L
LOAEL (local effects) = 0.002 mg/L (based on inflammation, hypertrophy, hyperplasia and
occasionally squamous metaplasia in the respiratory epithelium of the nasal mucosa in rats and
mice)
NOAEL (local effects) = Not established
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
1) In an NTP study, F344/N rats (20/sex/dose) were administered monochloroacetic acid via
gavage at 0, 30, 60, 90, 120 or 150 mg/kg-bw/day 5 days/week for 13 weeks. All animals
administered 120 and 150 mg/kg-bw/day and 9/10 of the males and all females administered 90
mg/kg-bw/day doses died. For the remaining doses (30 and 60 mg/kg-bw/day), surviving
animals exhibited dose-dependant increases in blood urea nitrogen (BUN), alanine
aminotransferase (ALT), and aspartate aminotransferase (AST) levels, and decreases in
cholinesterase. Elevated relative kidney and liver weights (without any histopathology), and
increases in absolute and relative heart weights with associated histological effects (myocardial
degeneration with an associated inflammatory response) were observed at 60 mg/kg-bw/day.
According to the NTP study report and evaluation, increased serum levels of AST is consistent
with this finding of heart effects; however, the study report further states that a tissue source for
this enzyme other than the heart cannot be ruled out. Elevated ALT and decreased cholinesterase
levels, in conjunction with the increased liver weight, may suggest, according to the NTP report,
that the liver is also affected. The report finally concluded the elevation in BUN was a
secondary effect, not related to kidney toxicity. No other effects were reported. No treatment
related effects were seen in the reproductive organs (right testis, ovaries, prostate gland and
uterus) evaluated. (Note: The full NTP report can be obtained at
http://ntp.Mehs.Mfa. gov/?obiectid=03F26i	)
LOAEL = 60 mg/kg-bw/day (based on signs of liver toxicity and heart lesions with
corresponding changes in blood chemistry parameters)
NOAEL = 30 mg/kg-bw/day
(2) In a NTP study, B6C3F1 mice (20/sex/dose) were administered monochloroacetic acid via
gavage at 0, 25, 50, 100, 150 or 200 mg/kg-bw/day 5 days/week for 13 weeks. All males and
2/10 females at 200 mg/kg-bw/day died and exhibited cytoplasmic vacuolation of the liver. Of
the surviving females in the 200 mg/kg-bw/day dose group, significantly reduced body weight
gains were observed. This effect was not observed at any other dose level, and did not show
dose-trend. Absolute and relative liver weights were significantly increased in female mice at
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the 200 mg/kg-bw/day dose group, along with decreases in cholinesterase levels in females at the
150 and 200 mg/kg-bw/day dose levels. The study authors concluded that decreases in
cholinesterase levels could be an indicator of liver toxicity in females. No other treatment-
related serum chemistry or histopathological changes were reported. No treatment related
effects were seen in the reproductive organs (right testis, ovaries, prostate gland and uterus)
evaluated. (Note: The full NTP report can be obtained at
http://ntp.niehs.nih.gov/7obiecticN03F26Q44-E. 1S1 -SEP 1-4D2D72F43E351DB4)
LOAEL = 200 mg/kg-bw/day (based on mortality in males and females)
NOAEL = 150 mg/kg-bw/day
(3) There were three other repeated-dose toxicity studies performed with chloroacetic acid.
These studies used a lower number of animals/dose than required by the guidelines, only one sex
(males) of animals and only one dose in 2 of the 3 studies. These studies lend limited
information to the overall weight of evidence and therefore, are not used in this hazard
characterization.
Reproductive Toxicity
There were no studies specifically designed to assess the reproductive toxicity of either
chloroacetyl chloride or chloroacetic acid. Available data from a 28-day study with chloroacetyl
chloride in mice showed effects on the uterus following inhalation exposure (but no such effects
were observed in rats and hamsters under similar exposure conditions). There were no effects
on reproductive organs in either mice or rats exposed via gavage to chloroacetic acid in the 13-
week NTP studies described above. In the chloroacetic acid NTP cancer studies described below
under carcinogenicity, there were no effects on reproductive organs in rats or male mice, but
female mice had uterine stromal polyps (2/60, 7/57, and 10/60 for the control, low and high dose
groups, respectively). The only tumor, however, was in the control group. The NTP dismissed
the polyp findings as all being within historical controls (range of 10-38%) and the concurrent
control group having a lower incidence (3%) than normal (mean of 21%). (Note: The full NTP
report can be obtained at http://ntp-
apps.niehs.nih.gov/ritp tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=79-l 1-8)
Developmental Toxicity
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
Pregnant Long-Evans rats (number unspecified) were administered chloroacetic acid in distilled
water via oral gavage at 0, 17, 35, 70 or 140 mg/kg-bw/day during gestation days 6-15. Maternal
animals were observed for clinical signs, body weights, gross evaluation of organ weights and
uterine contents at necropsy. Live fetuses were examined for external, skeletal and soft tissue
malformations. At 140 mg/kg-bw/day, a significant decrease in maternal body weight gain was
observed (p-level not stated) and a significantly elevated number of fetal cardiovascular
malformations were observed (p-level not stated). The malformations consisted primarily of
levocardia (abnormal positioning of abdominal and thoracic organs other than the heart). No
fetal skeletal malformations or toxicity were observed at any dose. No differences were seen in
mean percent resorptions per litter or live fetal weights when comparing treated groups with
controls. The study (Smith et al. 1990) was available as an abstract and limited information was
provided. Developmental studies (Smith et al., 1989, 1992) with dichloroacetic acid and
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trichloroacetic acid showed similar signs of toxicity that included reduced fetal crown rump
length, decreased fetal body weight and increased cardiovascular soft tissue anomalies.
LOAEL (maternal/developmental toxicity) = 140 mg/kg-bw/day (based on reduced body
weight and weight gain in dams and increased cardiovascular malformations in fetuses)
NOAEL (maternal/developmental toxicity) = 70 mg/kg-bw/day
Genetic Toxicity — Gene Mutations
In vitro
Chloroacetyl chloride (CASRN79-04-9)
(1) Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed
to chloroacetyl chloride at 0.5 - 500 |ig/plate, in the presence and absence of metabolic
activation. Information on positive and negative controls or cytotoxicity was not provided.
Chloroacetyl chloride was not mutagenic in this assay.
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
(1)	Salmonella typhimurium strains TA97, TA98, TA100, TA1535 and TA1537 were exposed to
chloroacetic acid at 0.8 - 3333 |ig/plate and TA1530 was exposed to 10,206 |ig/plate, in the
presence and absence of metabolic activation. Cytotoxicity was seen within the range of
concentrations tested. Two to four replicates per concentration were tested. Information on
positive and negative controls was not provided.
Chloroacetic acid was not mutagenic in this assay.
(2)	Mouse lymphoma cells (L5178Y TK +/-) were exposed to chloroacetic acid at concentrations
of 139.4 - 1048.2 |ig/mL in one assay in the presence of metabolic activation and 50 - 800
|ig/mL in another assay in the absence of metabolic activation. Positive results were obtained in
both assays at cytotoxic concentrations (above 400 |ig/mL). The test substance was negative at
noncytotoxic concentrations. Information on positive and negative controls was not provided.
Chloroacetic acid was not mutagenic in these assays.
(3)	In an HGPRT assay, V79 cells were exposed to < 198.45 jag/mL of chloroacetic acid in the
absence of metabolic activation. No information on positive and negative controls, number of
replicates, cytotoxicity or methodology was provided.
Chloroacetic acid was not mutagenic in this assay.
Genetic Toxicity — Chromosomal Aberrations
In vitro
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
(1) Chinese hamster ovary cells (CHO-W-B1) were exposed to chloroacetic acid at
concentrations ranging from 50 to 500 |ag/m L in the absence of metabolic activation. No
information on positive and negative controls, number of replicates, cytotoxicity or methodology
was provided. Sister chromatid exchanges were observed at concentrations above 160 |ig/mL.
Chloroacetic acid induced sister chromatid exchanges in this assay.
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(2)	Chinese hamster ovary cells (CHO-W-B1) were exposed to chloroacetic acid at
concentrations ranging from 50 to 1600 |ag/m L in the presence of metabolic activation. No
information on positive and negative controls, number of replicates, cytotoxicity or methodology
was provided.
Chloroacetic acid did not induce chromosomal aberrations in this assay.
(3)	Chinese hamster lung fibroblasts (CHL) were exposed to chloroacetic acid at 0.06 - 0.25
mg/mL in the absence of metabolic activation. No information on positive and negative controls,
number of replicates, cytotoxicity or methodology was provided.
Chloroacetic acid did not induce chromosomal aberrations in this assay.
Genetic Toxicity — Other
In vitro
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
Rat bone marrow cells were exposed to chloroacetic acid at 1.5 - 151.2 jag/mL and examined for
inhibition of DNA synthesis. No information on positive and negative controls, number of
replicates, cytotoxicity or methodology was provided.
Chloroacetic acid was negative for inhibiting DNA synthesis in rat bone marrow in this
assay.
Additional Information
Skin Irritation
Chloroacetyl chloride (CASRN 79-04-9)
(1)	Chloroacetyl chloride was applied dermally to intact sites on the shaved abdomens of rabbits
(1 male/dose) under semi-occlusive conditions for 0.5, 1 or 3 minutes. Redness, swelling and
necrosis were observed at the application sites with time-related increasing severity. Exposure
for 3 minutes caused slight redness and moderate necrosis, which, upon healing, left a scar.
Chloroacetyl chloride was corrosive to rabbit skin in this study.
(2)	Undiluted chloroacetyl chloride was applied dermally to the clipped backs of 3 male and 3
female rabbits under occlusive conditions for 24 hours. The rabbits were observed for several
days following application. The maximum Draize score was 8 out of 8 within 2 hours and there
was no change within 168 hours except that the edema and erythema gradually disappeared.
Chloroacetyl chloride was corrosive to rabbit skin in this study.
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
Rabbits were exposed to chloroacetic acid dermally under occlusive patches for 24 hours. No
information concerning site preparation was provided.
Chloroacetic acid was corrosive to rabbit skin in this study.
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Eye Irritation
Chloroacetyl chloride (CASRN 79-04-9)
(1)	Two drops of the undiluted chloroacetyl chloride were instilled into the right eye of a male
New Zealand white rabbit. The eye was washed within 30 seconds for 2 minutes with a stream
of tepid water. Two drops of the material were instilled into the left eye, which was left
unwashed. The eyes were examined at 2 - 3 minutes, 1, 24 and 48 hours and 6-8 days post-
treatment. Both washed and unwashed eyes had similar reactions: slight pain and very severe
conjunctival and corneal irritation, which had not healed within one week.
Chloroacetyl chloride was corrosive to rabbit eyes in this assay.
(2)	Chloroacetyl chloride (0.1 mL) was instilled into the right eyes of 1 male and 1 female rabbit.
In one rabbit, the eye was washed within 30 seconds with warm isotonic saline. In the other
rabbit, the eye was washed with warm isotonic saline within 5 seconds. The eyes were examined
immediately following instillation and for several days after. The Draize score in each eye was
110 out of 110. Immediately after instillation, the rabbits exhibited signs of severe discomfort.
Within 10 minutes, the eyes had moderate erythema, edema and discharge. Corneal opacity and
severe irisitis were seen.
Chloroacetyl chloride was corrosive to rabbit eyes in this assay.
Chronic Toxicity/Carcinogenicity
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
(1)	In an NTP study, F344/N rats (70/sex/dose) were administered chloroacetic acid via gavage
at 0, 15 or 30 mg /kg-bw/day for 5 days/week for 104 weeks. Complete necropsy and
histological examinations were performed on all animals. Ten animals/sex/dose and control
group were selected for an interim sacrifice after 6 months and seven animal s/sex/dose were
selected for a second interim sacrifice after 15 months. Mortality was elevated in high-dose
males and treated females compared to controls. After 30 weeks of exposure, the mean body
weights of high-dose males were 8 - 10% less than controls. No increase in tumor incidence was
noted compared to controls.
No increase in tumor incidence was noted in this study.
(2)	In an NTP study, B6C3F1 mice (60/sex/dose) were administered chloroacetic acid via gavage
at 0, 50 or 100 mg/kg-bw/day 5 days/week for 104 weeks. Mortality was increased in high-dose
males compared to controls. Mean body weights of male mice were similar to those of controls.
Mean body weights in females of both treatment groups were decreased by 6 - 10% compared to
controls after 52 weeks. An increase in the incidence of nasal mucous membrane inflammations,
epithelial metaplasia of the olfactory epithelium and squamous cell hyperplasia in the
forestomach was noted in treated mice. No increase in the incidence of tumors was noted.
No increase in tumor incidence was noted in this study.
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Neurotoxicity
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
Swiss-Webster mice (males, number not stated) were administered monochloroacetic acid via
gavage at 260 or 380 mg/kg-bw. No information was provided on method, duration, controls or
GLP. Surviving animals exhibited limb rigidity, occasionally bent back and had severe
convulsions followed by death. Animals surviving up to 6 months showed no improvement in
symptoms. Histological examination revealed damage to the Purkinje cells primarily in the
cerebellum, but also in the hippocampus and cortex. Because the doses used were near the oral
LD50, the study was not considered suitable for this hazard characterization.
Conclusion: The acute oral, inhalation and dermal toxicity of this chemical (CASRN 79-04-9) is
moderate. Acute oral and dermal toxicity of its hydrolysis product (CASRN 79-11-8) is also
moderate. CASRN 79-04-9 is corrosive to rabbit eyes and skin. Systemic toxicity in inhalation
repeated-dose studies of CASRN 79-04-9 in rats and mice showed mortality at low doses
(LOAEL of 0.011 mg/L) and local effects (inflammation/cellular abnormalities in the nasal
mucosa) at the lowest tested dose (LOAEL of 0.002 mg/L). In oral repeated-dose studies of
CASRN 79-11-8 , effects on the liver and heart (rats - LOAEL of 60 mg/kg-bw/day; NOAEL of
30 mg/kg-bw/day) and mortality (mice - LOAEL of 200 mg/kg-bw/day; NOAEL of 150 mg/kg-
bw/day) were observed. Although there were no reproductive toxicity studies with either
CASRN 79-04-9 or CASRN 79-11-8, there were no effects in reproductive organs in oral
repeated-dose studies in rats or mice exposed to CASRN 79-11-8 at doses up to 200 mg/kg-
bw/day in mice. A developmental toxicity study with CASRN 79-11-8 in rats showed maternal
toxicity (reduction in both body weight and weight gain) and developmental toxicity (increased
cardiovascular malformations in fetuses) at the same dose (LOAEL of 140 mg/kg-bw/day;
NOAEL of 70 mg/kg-bw/day). CASRN 79-04-9 did not induce gene mutations in bacteria. In in
vitro studies with mammalian cell cultures, CASRN 79-11-8 did not induce chromosomal
aberrations, but did induce sister chromatid exchanges. Oral exposure to CASRN 79-11-8 for
104 weeks did not result in increase in tumor incidence in rats or mice compared to controls.
4 Hazards to the Environment
Acute Toxicity to Fish
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
(1)	Golden orfes (Leuciscus idus melantonus) were exposed to chloroacetic acid at nominal
concentrations of 1 - 500 mg/L under static conditions for 96 hours. No mortalities, changes in
behavior or gross physical changes were seen at the 1 - 100 mg/L concentrations (pH 8.3 - 8.7).
At 500 mg/L (pH 3.8) 100 % of the fish died 78 - 173 min after addition of the preparation,
likely due to the low pH.
96-h LC50 > 100 mg/L
(2)	Guppies (Poecilia reticulata) were exposed to chloroacetic acid at unspecified concentrations
under static conditions for 96 hours (pH 8.0 - 8.3 at 24 - 26°C). No further details were
provided.
96-h LC50 = 369 mg/L
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Acute Toxicity to Aquatic Invertebrates
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
Water fleas (D. magna) were exposed to chloroacetic acid at unspecified concentrations for 48
hours in two separate assays. Information was not provided for the conditions of assay,
analytical monitoring methods or water chemistry, except that the pH was > 7 (at 20 °C).
48-h ECso = 77-88 mg/L
Toxicity to Aquatic Plants
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
(1)	Green algae (Scenedesmus subspicatus) were exposed to chloroacetic acid at unspecified
nominal concentrations for 72 hours. Information was not provided for the conditions of assay,
photoperiod or water chemistry, except that the pH was 7.7-8.1.
72-h EC50 (biomass) = 0.025 mg/L
(2)	Green algae (S. subspicatus) were exposed to chloroacetic acid at unspecified nominal
concentrations for 72 hours. Information was not provided for the conditions of assay,
photoperiod or water chemistry, except that the pH was 7.7-8.1.
72-h EC50 (growth rate) = 0.033 mg/L
Chronic Toxicity to Daphnia
Chloroacetic acid (CASRN 79-11-8, Supporting Chemical)
Water fleas (D. magna) were exposed to chloroacetic acid at unspecified nominal concentrations
for 21 days. Test conditions, method of analytical monitoring and water chemistry were not
provided, except that the pH was not < 7 and the deviation between the concentration measured
and the nominal concentration was < 20%. The evaluated endpoints were reproduction rate,
mortality and first appearance of offspring.
21-d NOEC = 32 mg/L
Conclusion: Because CASRN 79-04-9 undergoes rapid hydrolysis to CASRN 79-11-8 in water,
data on aquatic organisms are available for the hydrolysis product. For CASRN 79-11-8, the
measured 96-hour LC50 for fish is 369 mg/L, the measured 48-hour EC50 for aquatic
invertebrates is 77 mg/L, and the measured 72-hour EC50 for aquatic plants is 0.025 mg/L
(biomass) and 0.033 mg/L (growth rate).
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Table 4: Summary Table of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Chloroacetyl chloride
(CASRN 79-04-9)
SUPPORTING CHEMICAL
Chloroacetic acid
(CASRN 79-.11-8)
Summary of Human Health Data
Acute Oral Toxicity
LD50 (mg/kg)
207
90.4
Acute Inhalation Toxicity
LC5o (mg/L)
-3.05

Acute Dermal Toxicity
LD50 (mg/kg)
316
250
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)

NOAEL = 30
LOAEL = 60
Repeated-Dose Toxicity
NOAEL/LOAEL
Inhalation (mg/L/day)
NOAEL = Not established
(4-wk)
LOAEL -0.002 (4-wk)

Reproductive Toxicity
NOAEL/LOAEL

No effects were seen following
evaluation of reproductive
organs in rats and mice in 13-
week and two-year oral gavage
repeated-dose studies.
Developmental Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)


Maternal
Developmental

NOAEL = 70
LOAEL = 140
NOAEL = 70
LOAEL = 140
Genetic Toxicity - Gene
Mutations
In vitro
Negative
Negative
Genetic Toxicity -
Chromosomal Aberrations
In vitro

Positive
Genetic Toxicity - Other
In vitro
Unscheduled DNA Synthesis

Negative
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Table 4: Summary Table of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Chloroacetyl chloride
(CASRN 79-04-9)
SUPPORTING CHEMICAL
Chloroacetic acid
(CASRN 79-11-8)
Additional Information
Skin Irritation
Eye Irritation
Chronic
Toxicity/Carcinogenicity
Corrosive
Corrosive
Corrosive
Negative
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCso (mg/L)

> 100
Aquatic Invertebrates
48-h ECso (mg/L)

77-88
Aquatic Plants
72-h ECso (mg/L)
(growth rate)
(biomass)

0.033
0.025
Chronic Aquatic Toxicity
(mg/L)

21-d NOEC = 32
- indicates that endpoint was not addressed for this chemical; * Chloroacetyl chloride rapidly hydrolyzes to
chloroacetic acid.
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