SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
Acetylene (CAS No. 74-86-2)
[9th CI Name: Ethyne]
SUPPORTING CHEMICAL
Propyne (CAS No. 74-99-7)
[9th CI Name: 1-Propyne]
June 2008
INTERIM
Prepared by
High Production Volume Chemicals Branch
Risk Assessment Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001
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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
The High Production Volume (HPV) Challenge Program1 is 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 sponsor chemicals; sponsorship entails the identification and
initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data do
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. OPPT is using a hazard-
based screening process to prioritize review of the submissions. The hazard-based screening process consists of two
tiers described below briefly and in more detail on the Hazard Characterization website3.
Tier 1 is a computerized sorting process whereby key elements of a submitted data set are compared to established
criteria to "bin" chemicals/categories for OPPT review. This is an automated process performed on the data as
submitted by the sponsor. It does not include evaluation of the quality or completeness of the data.
In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is
performed according to established EPA guidance2'4 and is based primarily on hazard data provided by sponsors.
EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have
become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent
data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar
chemical structures, properties and biological activities may be grouped together and their data shared across the
resulting category. This approach often significantly reduces the need for conducting tests for all endpoints for all
category members. As part of Tier 2, evaluation of chemical category rationale and composition and data
extrapolation(s) among category members is performed in accord with established EPA2 and OECD5 guidance.
The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing
chemicals review process. These hazard characterizations are technical documents intended to support 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. The public, including
sponsors, may offer comments on the hazard characterization documents.
The screening-level hazard characterizations, as the name indicates, do not evaluate the potential risks of a chemical
or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of
and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the
Inventory Update Reporting (IUR) rule. For the chemicals in the HPV Challenge Program, EPA will review the
IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the
screening-level hazard characterizations to develop screening-level risk characterizations4'6. The screening-level
risk characterizations will inform EPA on the need for further work on individual chemicals or categories. Efforts
are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk-
based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production
Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.
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. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html).
4 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
5 OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf.
6 U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm.
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SCREENING-LEVEL HAZARD CHARACTERIZATION
Acetylene (CAS No. 74-86-2)
Introduction
The sponsor, American Chemistry Council Acetylene Panel, submitted a Test Plan and Robust Summaries to EPA
for acetylene (CAS No. 74-86-2; 9th CI name: ethyne) on December 30, 2003. EPA posted the submission on the
ChemRTK HPV Challenge website on February 26, 2004 (http://www.epa.gov/chemrtk/pubs/summaries/acetvlen/
cl5005tc.htm). EPA comments on the original submission were posted to the website on May 16, 2005. Public
comments were also received and posted to the website. The sponsor submitted updated/revised documents on
November 16, 2005 and March 13, 2007, which were posted to the ChemRTK website on January 26, 2006 and July
20, 2007, respectively.
This screening level hazard characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsor(s) under the HPV Challenge Program. 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. A summary table of SIDS endpoint data with the
structure(s) of the sponsored chemical(s) is included in the Appendix. The screening-level hazard characterization
for environmental and human health effects is based largely on SIDS endpoints and is described according to
established EPA or OECD effect level definitions and hazard assessment practices.
Since acetylene is a gas that partitions to air and rapidly evaporates from the aqueous environment, EPA agreed with
the sponsor that ecotoxicity testing is not considered relevant. Therefore, the ECOSAR estimated values address the
endpoints for the purposes of the HPV Challenge Program.
Justification for Supporting Chemical
The sponsor submitted data for the supporting chemical, propyne (CAS No. 74-99-7), also known as
methylacetylene. Propyne is the most closely related chemical to acetylene in molecular structure, size and
functionality. EPA considers propyne to be a reasonable supporting chemical for acetylene.
Sum man-Conclusion
\cel> lone is a gas that forms e\plosi\ e mi Mines in air I lie lower e\plosi\ e 11 mil is 2 5".. < 25.t>uu ppmi
I lie log k of acel> lene indicates ilial iIs poieniial lo hioaccuniulale is e\peeled lo he low l.iodcgiadaliou is noi a
rele\aiil eiidpomi lor acel> lene
I lie e\ aliialion of esiimaled lo\icil> dala lor fish, aquatic m\ eriehrales and aquatic plants indicate that the potential
acute lia/ard of acet> lene lo aquatic organisms is low
\cutc inhalation to\icil> ofacculcue in humans is low The niaioichuical signsohser\ed are mild iiitoMcaliou.
and increased aggressis euess . and capillars lis peremia in the li\ or. kidnev s and spleen Morialils was
also ohser\ ed in mice, guinea pigs and rahhils kals rcpcaledK exposed lo the supporting chemical, props lie.
showed ataxia. gross tremors of head and eMremiiiev rcco\ er\ occurring alter exposure terniination I)iscoloialiou
and increased piilniouaix irritation in the lungs were seen histopalhologicalK lu dogs. exposure to props lie resulted
mi marked salisaliou. excilahihis. muscular fasciciilaliou. ;il;i\i;i. mydriasis and tome cou\ ulsious. and signs of
iiitoMcaliou. I listopalhological examination showed no abnormalities \o dala were pro\ ided for the
rcpioduclis e de\ elopnienial loxicils eiidpoiuts \cel> lene did not induce gene mutation in /•./> /r/7./ or chromosomal
aberrations in mammalian cells in viini I lie supporting chemical, props no. induced gcuc mutation in haclcria in
vitro.
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The potential health hazard of acetylene is low.
Data gaps for the reproductive and developmental toxicity endpoinls were identified under the HPV Challenge
Program.
1. Physical-Chemical Properties and Environmental Fate
A summary of physical-chemical and environmental fate data submitted is provided in the Appendix. For the
purpose of the screening-level hazard characterization, the review and summary of these data were limited to the
octanol-water partition coefficient and biodegradation endpoints as indicators of bioaccumulation and persistence,
respectively.
Acetylene is a gas that forms explosive mixtures in air. The lower explosive limit is 2.5% (25,000 ppm).
Octanol-Water Partition Coefficient
Acetylene (CAS No. 74-86-2)
Log Kow: 0.37 (estimated)
Biodegradation
Acetylene (CAS No. 74-86-2)
Biodegradation is not a relevant endpoint for acetylene since this substance exists as a gas in the environment.
Conclusion: The log Kow of acetylene indicates that its potential to bioaccumulate is expected to be low.
Biodegradation is not a relevant endpoint for acetylene.
2. Environmental Effects - Aquatic Toxicity
Since acetylene is a gas that partitions to air and rapidly evaporates from the aqueous environment, EPA agrees with
the sponsor that ecotoxicity testing is not considered relevant. Therefore, the ECOSAR estimated values address the
endpoints for the purposes of the HPV Challenge Program.
Acute Toxicity to Fish
Acetylene (CAS No. 74-86-2)
96-h ECS0= 496.15 mg/L (ECOSAR)
Acute Toxicity to Aquatic Invertebrates
Acetylene (CAS No. 74-86-2)
48-h ECS0= 479.30 mg/L (ECOSAR)
Toxicity to Aquatic Plants
Acetylene (CAS No. 74-86-2)
96-h ECS0 (growth) = 274.86 mg/L (ECOSAR)
Conclusion: The evaluation of estimated toxicity data for fish, aquatic invertebrates and aquatic plants indicate that
the potential acute hazard of acetylene to aquatic organisms is low.
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3. Human Health Effects
Acute Inhalation Toxicity
Acetylene (CAS No. 74-86-2)
(1) Humans (number and gender were not listed) were administered acetylene 10 - 50% (~ 106.5 to 532.5 mg/L)
from a Douglas bag in the sitting position. No re-breathing was allowed. Inhalation of 10% acetylene for 1 hour
caused feelings of mild intoxication with parethesia (numbness) and had a slight effect on reaction time. Fifteen
percent acetylene caused distinct intoxication with talkativeness, sleepiness and inability to walk a straight line, but
did not include symptoms of marked intoxication (even after a 1 hour inhalation period). After inhalation of 20%
acetylene for 4 minutes marked intoxication was evident. Slight incoordination of head movements was noticed after
20% had been inhaled for 18 minutes. Twenty-five percent acetylene caused similar, but more marked, symptoms.
General incoordination and aggressive behavior were noted after inhalation of 30% acetylene for 13 minutes.
Inhalation of 33 or 35% caused unconsciousness within 7 or 5 minutes, respectively. Inhalation of 50% acetylene
produced feelings of intense intoxication within 35 seconds and an unbearable feeling of suffocation within 70
seconds (after which the experiment was stopped).
(2) In rats a concentration of 780,000 ppm produced anesthesia in 15 minutes and at 900,000 ppm, respiratory
failure was seen in approximately 2 hours. (No additional information is available.)
Repeated-Dose Toxicity
Acetylene (CAS No. 74-86-2)
Rats, mice, guinea pigs, rabbits and dogs (number/sex unspecified) were exposed to acetylene in oxygen at
concentrations of 250,000, 500,000 or 800,000 ppm (equivalent to 25, 50 or 80% or approximately 266.3, 532.5 or
852 mg/L) daily. Numbers of animals, exposures, durations of exposure and deaths were as follows:
Animal
Concentration
(percent)
Daily exposure
time (h)
Number of days
exposed
Total exposure
time (h)
Deaths/total
animals
Rat
25
1
7-93
7-93
6/16
Rat
50
2
1-8
2-16
9/10
Guinea pig
50
2
1-9
2-18
7/7
Mouse
50
2
1-6
2-12
5/5
Rat
80
!/2
2-36
1 - 18
36/47
Rat
80
1
14
14
0/8
Guinea pig
80
1
10
10
0/6
Rabbit
80
1
6-10
6-10
3/4
Dog
80
1
12
12
1/2
Animals were exposed to the acetylene/oxygen mix in air-tight glass cages. Mortality was observed in most
treatment groups, including the lowest exposure for the shortest duration. (The study suggests that the deaths were
mostly caused by pneumonia, which was also found in the control animals.) At the lower concentrations
(concentrations were not stated) the animals appeared slightly sleepy. At higher concentrations (70-80%), the
majority of animals fell asleep after 15-20 minutes. The rats, rabbits, guinea pigs and dogs generally recovered from
narcosis in a short time. The mice did not survive treatment. Treated animals that survived to termination, showed
no evidence of cellular injury to the parenchymatous cells of the heart, lungs, liver, kidneys, or spleen. Capillary
hyperemia was observed in the liver, kidneys and spleen of rats exposed to 250,000 ppm (the number was not
stated). This effect was observed until at least the second day after the last exposure to the gas and was not observed
in animals sacrificed 5 or 14 days after the last exposure.
LOAEL (rat) = 266.3 mg/L (250,000 ppm) (based on increased mortality and capillary hyperemia in liver, kidney
and spleen)
NOAEL = Not established
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Propyne (CASNo. 74-99-7, supporting chemical)
(1) Albino rats (20 males, species not stated) were exposed to propyne at an average concentration of 28,700 ppm
(approximately 30.6 mg/L) for 6 hours/day, 5 days/week for 6 months. Eight deaths occurred from exposure day 21
- 103. Signs of toxicity included ataxia, gross tremors of head and extremities; recovery occurring after exposure
termination. Body-weight gain was reduced. Treatment-related effects on the lungs included discoloration, purulent
empyema, cysts and pulmonary irritation. Remaining organs appeared to be normal.
LOAEL = 30.6 mg/L (28,700 ppm) (based on mortality and pulmonary irritation of the lungs)
NOAEL = Not established
(2) Dogs (one/sex) were exposed to propyne at an average concentration of 28,700 ppm (approximately 30.6 mg/L)
for 6 hours/day, 5 days/week for 6 months. No deaths occurred during the study. Signs of toxicity during exposure
included marked salivation, excitability and muscular fasciculations within 7 minutes of exposure. After 13
minutes, the dogs exhibited ataxia and mydriasis, within 15 minutes of exposure, dogs appeared to be intoxicated
(similar to alcohol) and after 30 minutes, one dog showed effects of anesthesia. Throughout the remaining
exposures, similar signs of toxicity were observed. Excitability and occasionally staggering and falling on the floor
were also seen. Tonic convulsions occurred in at least one of the dogs on days 22, 110, 123 and 137. Body weights
were reduced up to the first 6 weeks of the study and increased overall by study completion. No treatment-related
effects were observed on any hematological, urinalysis or biochemical indices of toxicity or during the gross
pathological examinations of the lungs, liver, kidney, heart, spleen and gastrointestinal tract.
LOAEL = 30.6 mg/L (28,700 ppm) (based on clinical signs)
NOAEL = No established
Reproductive Toxicity
Data gap
Developmental Toxicity
Data gap
Genetic Toxicity - Gene Mutation
In vitro
Acetylene (CAS No. 74-86-2)
Salmonella typhimurium strains TA97, TA98 and TA100 were exposed to acetylene in acetone at concentrations of
0.3, 1, 3, 10 or 31 |ig/plate in the presence and absence of metabolic activation. Positive controls produced an
appropriate response. Cytotoxicity was not determined.
Acetylene was not mutagenic in this assay.
Propyne (CASNo. 74-99-7, supporting chemical)
Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli WP2uvrA were exposed
to propyne at concentrations of 0, 5, 10, 21 or 50% in the presence and absence of metabolic activation.
Cytotoxicity was not determined. Propyne did not induce genetic mutation in any of the S. typhimurium strains
tested at any concentration in the presence or absence of metabolic activation, but did cause a dose-dependent
increase in the number of mutations in E. coli WP2uvrA in the presence and absence of metabolic activation
(positive at concentrations > 21% without S9 mix and > 5% with S9 mix).
Propyne was mutagenic in this assay.
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Genetic Toxicity - Chromosomal Aberrations
In vitro
Acetylene (CAS No. 74-86-2)
Chinese Hamster lung (CHL) cells were exposed to acetylene at concentrations up to 1.25% for 6 or 24 hours.
Positive controls produced an appropriate response. Acetylene did not induce any dose-related increases in the
frequency of cells with structural or numerical chromosome aberrations either in the presence or absence of
metabolic activation.
Acetylene did not induce chromosomal aberrations in this assay.
Conclusion: Acute inhalation toxicity of acetylene in humans is low. The major clinical signs were from mild
intoxication to incoordination, effect on reaction time, memory, writing, inability to walk straight and
aggressiveness. In rats and dogs, at high concentrations, respiratory failure was noted. Repeated inhalation
exposure to rats resulted in mortality, intoxication or anesthesia related toxicity, and capillary hyperemia in the liver,
kidneys and spleen. Mortality was also observed in mice, guinea pigs and rabbits. Rats repeatedly exposed to the
supporting chemical, propyne, showed ataxia, rats lying down on the abdomen or on the side with gross tremors of
head and extremities; recovery occurring after exposure termination. Body-weight gain was reduced. Discoloration
and increased pulmonary irritation in the lungs were seen histopathologically. In dogs, exposure to propyne resulted
in marked salivation, excitability, muscular fasciculations, ataxia, mydriasis, and tonic convulsions, signs of
intoxication. Histopathological examination showed no abnormalities. No data were provided for the
reproductive/developmental toxicity endpoints. Acetylene did not induce gene mutation in bacteria or chromosomal
aberrations in mammalian cells in vitro. The supporting chemical, propyne, induced gene mutation in bacteria in
vitro.
The potential health hazard of acetylene is low.
4. Hazard Characterization
Acetylene is a gas that forms explosive mixtures in air. The lower explosive limit is 2.5% (25,000 ppm).
The log Kow of acetylene indicates that its potential to bioaccumulate is expected to be low. Biodegradation is not a
relevant endpoint for acetylene.
The evaluation of estimated toxicity data for fish, aquatic invertebrates and aquatic plants indicate that the potential
acute hazard of acetylene to aquatic organisms is low.
Acute inhalation toxicity of acetylene in humans is low. The major clinical signs observed are mild intoxication,
and increased aggressiveness (at high dose levels). Repeated inhalation exposure to rats resulted in mortality,
intoxication or anesthesia related toxicity, and capillary hyperemia in the liver, kidneys and spleen. Mortality was
also observed in mice, guinea pigs and rabbits. Rats repeatedly exposed to the supporting chemical, propyne,
showed ataxia, gross tremors of head and extremities; recovery occurring after exposure termination. Discoloration
and increased pulmonary irritation in the lungs were seen histopathologically. In dogs, exposure to propyne resulted
in marked salivation, excitability, muscular fasciculation, ataxia, mydriasis and tonic convulsions, and signs of
intoxication. Histopathological examination showed no abnormalities. No data were provided for the
reproductive/developmental toxicity endpoints. Acetylene did not induce gene mutation in bacteria or chromosomal
aberrations in mammalian cells in vitro. The supporting chemical, propyne, induced gene mutation in bacteria in
vitro.
The potential health hazard of acetylene is low.
5. Data Gaps
Data gaps for the reproductive and developmental toxicity endpoints were identified under the HPV Challenge
Program.
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APPENDIX
Summary Tabic of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Acetylene
(74-86-2)
SUPPORTING CHEMICAL
Propvnc
(74-99-7)
Structure
HC=CH
CH3C=CH
Summary of Physical-Chemical Properties and Environmental Fate Data
Melting Point (°C)
-80.8
-101.5
Boiling Point (°C)
-84 (sublimes)
-23.2
Vapor Pressure
(hPa at 25°C)
6969.2 (extrapolated)
5155 (20 °C)
Log K„w
0.37 (20 °C) (estimated)
0.94 (estimated)
Water Solubility
(mg/L at 25°C)
1230 (20 °C)
3,640
Indirect (OH) Photodegradation
Half-life (t1/2)
13.1 d (estimated)
Stability in Water (Hydrolysis)
(ti/2)
No hydrolysable functional groups
Fugacity
(Level III Model)
Air (%)
Water (%)
Soil (%)
Sediment (%)
99.9
0.104
0.0101
1.77 x 10"4
-
Biodegradation at 28 days (%)
Biodegradation is not a relevant endpoint for acetylene.
Summary of Environmental Effects-Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
496.15 (estimated)
-
Aquatic Invertebrates
48-h ECS0 (mg/L)
479.30 (estimated)
-
Aquatic Plants
72-h ECS0 (mg/L)
(growth)
(biomass)
274.86 (96-h, estimated)
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Summary Tabic of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Acetylene
(74-86-2)
SUPPORTING CHEMICAL
Propyne
(74-99-7)
Summary of Human Health Data
Acute Inhalation Toxicity
LCS0 (mg/L)
> 106.50 (1-h)
-
Repeated-Dose Toxicity
NOAEL/LOAEL
Inhalation (mg/L/day)
266.3
~ 30.6 (6-mo)
Reproductive Toxicity
NOAEL/LOAEL
Inhalation (mg/L/day)
Data gap
Developmental Toxicity
NOAEL/LOAEL
Inhalation (mg/L/day)
Data gap
Genetic Toxicity - Gene Mutation
In vitro
Negative
Positive
Genetic Toxicity - Chromosomal
Aberrations
In vitro
Negative
- Indicates that endpoint was not addressed for this chemical.
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