2Chloroacetophenone [factsheet]

2-CHLOROACETOPHENONE

Please Note: The main source of information for this fact sheet is EPA's Integrated Risk Information System (IRIS), which contains information on inhalation chronic toxicity of 2-chloroacetophenone and the RfC. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

* The use of tear gas and Chemical Mace to control riots and disable attackers causes direct exposure to 2-chloroacetophenone through skin contact and inhalation. (1)

* Occupational exposure may occur during its manufacture and use by inhalation and dermal contact. (1)

Assessing Personal Exposure

* No information was located regarding the measurement of personal exposure to 2-chloroacetophenone.

Health Hazard Information

Acute Effects:

* 2-Chloroacetophenone is a potent eye, throat, and skin irritant. Acute (short-term) inhalation exposure of humans causes burning of the eyes with lacrimation; some degree of blurred vision; possible corneal damage; irritation and burning of the nose, throat, and skin; burning in the chest with dyspnea; and laryngotracheobronchitis. (1-4)

* Acute dermal exposure is irritating and can result in first, second, and third degree chemical burns in humans; these effects are exacerbated when the skin is wet. (4)

* Acute animal tests, such as the LD₅₀ test in rats, mice, rabbits, and guinea pigs, have demonstrated 2-chloroacetophenone to have high acute toxicity from oral exposure. (5)

Chronic Effects (Noncancer):

* No information is available on the chronic (long-term) effects of 2-chloroacetophenone in humans.

* Squamous hyperplasia of the nasal respiratory epithelium was reported in rats chronically exposed via inhalation. (3,4)

* The RfC for 2-chloroacetophenone is 0.00003 mg/m³ based on squamous hyperplasia of the nasal respiratory epithelium in rats. (4)

* EPA has medium confidence in the study on which the RfC was based because, even though the study used an adequate experimental design (number of animals, exposure concentrations, controls), and the incidence and severity of the nasal lesions were exposure-related and seen in both genders of rats, there were other materials present in the exposure atmosphere, the nasal lesions may have been exacerbated by concurrent viral infection in the exposed rats, and reflex apnea may have occurred to a greater degree in mice, thereby skewing the concentration-response relationship. EPA has low to medium confidence in the database because there are no data on the toxicokinetics, reproductive, or developmental toxicity for 2-chloroacetophenone; and, consequently, low to medium confidence in the RfC. (4)

* EPA has not established an RfD for 2-chloroacetophenone. (4)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has evaluated 2-chloroacetophenone for chronic toxicity and has given it a composite score of 32 (scores range from 1 to 100, with 100 being the most toxic). These scores are nonlinear and are the product of two ratings: a rating based on the minimal-effect-dose and a rating based on the type of effect. (6)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, considers 2-chloroacetophenone to be a "high concern" pollutant based on severe chronic toxicity. (6)

Reproductive/Developmental Effects:

* No information is available on the reproductive or developmental effects of 2-chloroacetophenone in humans or animals.

Cancer Risk:

* No information is available on the carcinogenic effects of 2-chloroacetophenone in humans.

* In a National Toxicology Program study, rats and mice were chronically exposed to 2-chloroacetophenone by inhalation. A marginal increase in fibroadenomas of the mammary gland was observed in female rats. No exposure-related increase in the incidence of tumors was observed in mice. (1,3)

* EPA has not classified 2-chloroacetophenone with respect to potential carcinogenicity. (4)

Physical Properties

* The chemical formula for 2-chloroacetophenone is C₈H₇ClO, and its molecular weight is 154.59 g/mol. (2)

* 2-Chloroacetophenone occurs as colorless to gray crystals that are practically insoluble in water. (1-3)

* In low concentrations, 2-chloroacetophenone has an odor resembling apple blossoms, with an odor threshold of 0.035 ppm. (1,7)

* The vapor pressure for 2-chloroacetophenone is 0.0054 mm Hg at 20 EC, and its log octanol/water partition coefficient (log K_ow) is 2.09. (1,3)

Uses

* 2-Chloroacetophenone is primarily used as a riot-control agent (tear gas) and in Chemical Mace. (1-3,8)

* It is also used as a pharmaceutical intermediate and formerly as an alcohol denaturant. (1)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
10.0
_ _ _ _ 1.0	* LOAEL^c (rats) (1 mg/m³)		4
_ _ _ _ 0.1		* ACGIH TLV, NIOSH REL, MSHA standard, and OSHA PEL (0.3 mg/m³)	5
_ _ _ _ 0.01
_ _ _ _ 0.001
_ _ _ _ 0.0001
_ _ _ _ 0.00001	* RfC = 0.00003 mg/m³		7

ACGIH TLVCAmerican Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effects.

LOAELCLowest-observed-adverse-effect level.

MSHACMine Safety and Health Administration.

NIOSH RELCNational Institute of Occupational Safety and Health recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PELCOccupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

RfCCReference concentration.

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.

^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.

^c The LOAEL is from the critical study used as the basis for the EPA RfC.

References

1. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

2. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

3. National Toxicology Program. Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone (CAS No. 532-27-4) in F344/N Rats and B6C3F₁ Mice (Inhalation Studies). TR No. 379. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, MD. 1990.

4. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on 2-Chloroacetophenone. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air ActCSection 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPAB450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.

7. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

8. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes Publications, Park Ridge, NJ. 1985.