Acetophenone [factsheet]

ACETOPHENONE

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on oral chronic toxicity of acetophenone and the RfD, and EPA's Health and Environmental Effects Document for Acetophenone. 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literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.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

* Occupational exposure to acetophenone may occur during its manufacture and use. (1)

* Acetophenone has been detected in ambient air and drinking water; exposure of the general public may occur through the inhalation of contaminated air or the consumption of contaminated water. (2)

Assessing Personal Exposure

* Hippuric acid may be monitored in the urine to determine whether or not exposure to acetophenone has occurred. (1)

Health Hazard Information

Acute Effects:

* Acute (short-term) exposure of humans to acetophenone vapor may produce skin irritation and transient corneal injury. One study noted a decrease in light sensitivity in exposed humans. (2,3)

* Acute oral exposure has been observed to cause hypnotic or sedative effects, hematological effects, and a weakened pulse in humans. (1,3)

* Congestion of the lungs, kidneys, and liver were reported in rats acutely exposed to high levels of acetophenone via inhalation. (3)

* Tests involving acute exposure of animals, such as the LD₅₀ test in rats, mice, and rabbits, have demonstrated acetophenone to have moderate acute toxicity from oral or dermal exposure. (4)

Chronic Effects (Noncancer):

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

* Degeneration of olfactory bulb cells was reported in rats chronically exposed via inhalation. In another study, chronic inhalation exposure of rats produced hematological effects and, at high doses, congestion of cardiac vessels and pronounced dystrophy of the liver. (2,3)

* In two studies, no effects were observed in rats chronically exposed to acetophenone in their diet. (2,3,5)

* The RfC for acetophenone is under review by EPA. (5)

* The RfD for acetophenone is 0.1 mg/kg/d based on general toxicity in rats. (5)

* EPA has low confidence in the study on which the RfD was based because, although the animals were tested by a relevant route of administration at three levels in a subchronic study and several endpoints were monitored, the sample size was inadequate and the range of doses tested did not define a lowest-observed-adverse-effect level (LOAEL); low confidence in the database because, although no-observed-adverse-effect levels (NOAELs) were defined, supporting studies could not be located in the available literature; and, consequently, low confidence in the RfD.

* 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 acetophenone for chronic toxicity and has given it a composite score of 37 (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 acetophenone 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 acetophenone in humans.

* In one study of pregnant rats exposed dermally, no effects on reproduction or development were noted. (2,3)

Cancer Risk:

* No information is available on the carcinogenic effects of acetophenone in humans or animals.

* EPA has classified acetophenone as a Group D, not classifiable as to human carcinogenicity. (5)

Physical Properties

* The chemical formula for acetophenone is C₈H₈O, and its molecular weight is 120.15 g/mol. (2,7)

* Acetophenone occurs as a colorless liquid that is slightly soluble in water. (2,3,7)

* Acetophenone has a sweet pungent odor of orange blossom or jasmine, with an odor threshold of about 0.83 mg/m³. (2,3,7)

* The vapor pressure for acetophenone is 0.372 mm Hg at 25 EC, and its log octanol/water partition coefficient (log K_ow) is 1.58. (2)

Uses

* Acetophenone is used in perfumery as a fragrance ingredient in soaps, detergents, creams, lotions, and perfumes; as a flavoring agent in foods, nonalcoholic beverages, and tobacco; as a specialty solvent for plastics and resins; as a catalyst for the polymerization of olefins; and in organic syntheses as a photosensitizer. (2,3,7)

Health Data from Oral Exposure

Concentration (mg/kg/d)	Health numbers^a	Regulatory, advisory numbers^b	Reference
1,000.0
_ _ _ _ 100.0	* LD₅₀ (rats) (815 mg/kg) * LD₅₀ (mice) (740 mg/kg) * NOAEL^c (rats) (423 mg/kg/d)		4 4 5
_ _ _ _ 10.0
_ _ _ _ 1.0
_ _ _ _ 0.1	* RfD = 0.1 mg/kg/d		5

LD₅₀ (Lethal Dose₅₀)CA calculated dose of a chemical in water to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population.

NOAELCNo-observed-adverse-effect level.

RfDCReference dose.

^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 This NOAEL is from the critical study used as the basis for the EPA RfD.

References

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

2. U.S. Environmental Protection Agency. Health and Environmental Effects Document for Acetophenone. ECAO-CIN-G001. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1987.

3. 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.

4. 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.

5. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Acetophenone. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 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. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, NJ. 1989.