National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• 2-Chloroacetophenone (CN)
• CN
• 2-CHLORO-1-PHENYLETHANONE

Human Toxicity Excerpts

• SYMPTOMS INCL TEARING, BURNING OF THE EYES & DIFFICULTY IN BREATHING, BUT SELDOM ANY PERSISTENT OR PERMANENT DISABILITY. HIGH CONCN MAY LEAD TO ... ACUTE PULMONARY EDEMA AFTER LATENCIES OF 8 HR TO SEVERAL DAYS. FIRST & PERHAPS SECOND DEGREE BURNS OF SKIN MAY OCCUR, PARTICULARLY IF IN CONTACT WITH ABRADED AREAS. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-96]**PEER REVIEWED**
  
• A PECULIAR, SHORT LIVED (45 MIN) RAPIDLY DEVELOPING TOLERANCE OCCURS TO /2-CHLOROACETOPHENONE/ WHEN EXPOSURE CONCN ... HIGH TO CAUSE PROFUSE LACRIMATION & OTHER SIGNS OF IRRITATION; PERSISTENCE OF CYANIDE IN THE ATMOSPHERE LEADS TO CESSATION OF SYMPTOMS. CROSS TOLERANCE RAPIDLY DEVELOPS ALSO TO BROMBENZYL CYANIDE, CHLOROPICRIN, CHLOROCROTONALDEHYDE, ETHYL-CHLOROFORMATE AND TRICHLOROMETHYL FORMATE. ... TWO REPORTS SUGGEST THAT INDIVIDUALS CAN BE SENSITIZED TO ... /2-CHLOROACETOPHENONE/ WITH CROSS OVER REACTIONS WITH O-CHLOROBENZILIDINE MALONONITRILE. SENSITIZATION WAS MORE READILY PRODUCED & REACTIONS MORE SEVERE WITH ... /2-CHLOROACETOPHENONE/. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 264]**PEER REVIEWED**
  
• ... 12 PATIENTS ... SPRAYED IN THE EYES WITH CHEM MACE ... @ DISTANCE OF 6-12 INCHES ... HAD INJURIES OF EPITHELIUM OF CORNEA & CONJUNCTIVA DEMONSTRABLE BY STAINING WITH FLUORESCEIN ... 9/12 HEALED IN 72 HR. THE OTHER 3 HAD MORE EXTENSIVE EPITHELIAL INJURY WHICH TOOK 14-21 DAYS TO HEAL COMPLETELY ... IN 1 EYE A SUPERFICIAL STROMAL OPACITY ... /PERSISTED/ FOR 5 MO, BUT THIS WAS SUPERFICIAL AND LOCATED PERIPHERALLY IN THE CORNEA. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 885]**PEER REVIEWED**
  
• Skin reactions of sensitized guinea pigs to challenging doses of chloroacetophone included erythema, edema, induration, necrosis, and eschar formation. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 265]**PEER REVIEWED**
  
• ACCIDENTAL OVEREXPOSURE OF EYES ... CAN RESULT IN PERMANENT PARTIAL OPACITY. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 264]**PEER REVIEWED**
  
• Some prisoners sprayed with 2-chloroacetophenone during a disturbance at San Quentin Prison in April 1981 required hospitalization because of severe laryngotracheobronchitis, chemical skin burns, conjunctivitis, and apparent allergic reactions. [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.14 Technical Report Series No.379 (1990) NIH Pub No.90 2834]**PEER REVIEWED**
  
• Solid chloroacetophenone also caused significant damage to the cornea, iris, conjunctiva, and eyelids ... . [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 277]**PEER REVIEWED**
  
• The uses of tear gas, its toxicity, and treatment for exposure were reviewed. The two compounds most commonly used in recent years were identified as omega-chloroacetophenone (CN) and o-chlorobenzylidenemalononitrile (CS). Previous reports and reviews of tear gas usage and exposure effects were considered. The results of a survey of tear gas use in civil disturbances in Seoul, Korea were summarized. The agent used in these events was identified as CS; in exposed persons near exploding tear gas canisters, effects included penetration trauma, skin burns, and impaired lung function. The Korean medical community was not found to have access to information necessary for treating those who were exposed. A similar report of tear gas use in Gaza and the West Bank of Israel was cited. The development of CS as the predominant tear gas agent, and its use in riot control and in Vietnam was described, as was its toxicology. Inhalation studies showing an association between high level CS exposure and pneumonitis, pulmonary edema, heart failure, hepatic damage, and death were cited. The use of tear gas in enclosed spaces, or detonating gas grenades or canisters directly into crowded gatherings could result in exposures to much higher levels that use in the open. Studies of long term pulmonary and genotoxic effects were appraised as inconclusive, and the lack of reproductive epidemiologic studies was noted. CS was hypothesized to be genotoxic, due to its ability to alkylate sulfhydryl groups. The toxicity of CN was compared to CS. Treatment for CS and CN exposures was described, including skin washes, supportive pulmonary therapy, and observation. The authors conclude that there is a need for further investigations into the toxicological potential of tear gas chemicals. [Hu H et al; J of the American Medical Association 262 (5): 660-3 (1989)]**PEER REVIEWED**
  

Back to Top

Non-Human Toxicity Excerpts

• AT HIGH CONCN ... PERMANENT OPACIFICATION, ULCERATION WITH VASCULARIZATION AND PERFORATIONS CAN BE PRODUCED IN THE EYES OF LAB ANIMALS. POSSIBLE SYSTEMIC MANIFESTATIONS INCL AGITATION, MIOSIS, COMA, AREFLEXIA AND FATTY INFILTRATION OF LIVER. [Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-68]**PEER REVIEWED**
  
• ... LIQ RESIDUE @ ATMOSPHERIC PRESSURE OBTAINED FROM SPRAY CANS OF CHEM MACE ... DROPPED DIRECTLY ON THE EYES OF UNANESTHETIZED ANIMALS CAUSED LOSS OF CORNEAL EPITHELIUM & CLOUDING OF THE STROMA, BUT THESE HEALED IN 3-10 DAYS. IF RABBITS WERE ANESTHETIZED BEFORE /APPLICATION/ THE REACTION WAS MUCH MORE SEVERE, CONSISTING OF GREATER STROMAL EDEMA, DEVELOPMENT OF CORNEAL OPACITY, IRIDOCYCLITIS, & HYPOPYON, WITH SERIOUS DEGENERATIVE CHANGES IN THE CORNEAS IN SOME ANIMALS. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 884]**PEER REVIEWED**
  
• THE TOXICITY OF ALPHA-CHLOROACETOPHENONE IN TEST ANIMALS IS DESCRIBED AND DATA ARE EXTRAPOLATED TO HUMANS. NO CARCINOGENICITY COULD BE FOUND, ALTHOUGH CMPD WAS EMBRYOTOXIC AND DID CAUSE ALLERGIC SENSITIZATION. [ELSKAMP DM W; TOXIC PROPERTIES OF CN AND CS; REPORT (MBL-1976-14) (1976)]**PEER REVIEWED**
  
• 1-CHLOROACETOPHENONE CAUSED CONTACT SENSITIZATION OR DELAYED HYPERSENSITIVITY IN GUINEA PIGS BY TOPICAL OR INTRADERMAL ADMIN. IT IS MORE IRRITATING TO SKIN & MORE ALLERGENIC WHEN ADMIN AS MACE THAN IN ACETONE. INTRADERMAL ADMIN CAUSED ERYTHEMA, EDEMA, INDURATION, NECROSIS; DERMAL APPLICATION CAUSED THE SAME EFFECTS PLUS ESCHAR. [CHUNG CW, GILES AL JR; J IMMUNOL 109 (2): 284 (1972)]**PEER REVIEWED**
  
• RABBIT EYES DOSED WITH 1-CHLOROACETOPHENONE 1-10% IN POLYETHYLENE GLYCOL 300 SOLN SHOWED INFLAMMATION, CORNEAL DAMAGE (5-10% SOLN), KERATITIS, INCR IN CORNEAL THICKNESS & INTRAOCULAR TENSION. SOLID FORM: SIMILAR BUT MORE SEVERE EFFECTS. USING AEROSOL: CONJUNCTIVAL & LID IRRITATION. [BALLANTYNE B ET AL; ARCH TOXICOL 34 (3): 183 (1975)]**PEER REVIEWED**
  
• Chloroacetophenone was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using the standard protocol approved by the National Toxicology Program. The chemical was tested at doses of 0, 0.3, 1, 3, 10, 33, 100, and 333 ug/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor induced rat or hamster liver S9. Chloroacetophenone was negative in these tests and the highest ineffective dose level tested (not causing a complete clearing of the background lawn) in any Salmonella tester strain was 100 ug/plate. [Zeiger E et al; Environ Mutagen 9: 1-110 (1987)]**PEER REVIEWED**
  
• Incubation of chick embryos in the primitive streak stage with 0.5-3 mM 2-chloroacetophenone for 15-120 minutes increased the frequency of abnormalities in the nervous system, including improper differentiation and incomplete closure of the brain. Well differentiated closed neural tubes were observed in embryos incubated with 2-chloroacetophenone and subsequently exposed to sulfhydryl agents. Embryos incubated at the head process stage with 2-chloroacetophenone showed normal development. Thus, the inhibitory effect of 2-chloroacetophenone on morphogenesis of the nervous system in chick embryos was reversible. [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.15 Technical Report Series No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• 2-Chloroacetophenone ... increased incidence of epidermal papillomas in skin of mice previously given dermal applications of 0.3 ml of 0.15% 9,10-dimethyl-1,2-benzanthracene dissolved in acetone. Twenty-one days after exposure to 9,10-dimethyl-1,2-benzanthracene, mice received applications of 0.3 ml of 0.4%-0.8% 2-chloroacetophenone in acetone twice per week for 12 weeks and then once per week for 15 weeks. Twenty epidermal neoplasms were observed in 9/12 mice that received the 9,10-dimethyl-1,2-benzanthracene plus 2-chloroacetophenone applications, compared with 1 neoplasm in 12 control mice that received 9,10-dimethyl-1,2-benzanthracene followed by dermal applications of acetone on the same dosing schedule. Epidermal hyperplasia was also observed at the site of application of 2-chloroacetophenone. [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.15 Technical ReportSeries No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• 2-Chloroacetophenone toxicity may be due to the alkylation and consequent inhibition of sulfhydryl-containing enzymes because inhibition of lactate dehydrogenase activity by 2-chloroacetophenone in vitro was not reversed by glutathione and because intravenous administration of sodium thiosulfate did not protect rats from lethal doses of 2-chloroacetophenone given by intraperitoneal injection. [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.14 Technical Report Series No.379 (1990) NIH Pub No.90 2834]**PEER REVIEWED**
  
• 2-Chloroacetophenone was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation. In cytogenetic tests with CHO (Chinese hamster ovary) cells, 2-chloroacetophenone did not induce sister chromatid exchanges with or without activation, but a weak positive increase in chromosomal aberrations was observed in the absence of metabolic activation. [DHHS/NTP; Toxicology and Carcinoigenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.4 Technical ReportSeries No. 379 (1990) NIH Pub No. 90-2834]**PEER REVIEWED**
  
• The biochemical changes in blood samples of rats at different intervals after O-Chloracetophenone (CN) and Dibenz (b,f)-1,4 oxazepine (CR) were studied. After a single subacute (1/10 LC50) exposure, both the compounds induced hyperglycaemia which was abolished within 24 h. The level of plasma urea was unaltered. CR exposed animals did not show any significant changes in plasma GOT, acid and alkaline phosphase activities at different intervals. However, in CN exposed animals, a significant elevation of the activities of GOT, GPT, acid and alkaline phosphatase was observed at different intervals. All the parameters became normal within seven days after the exposure. Inhalation of CN aerosols can thus lead to tissue damaging effects in rats. [Husain K et al; Indian J Med Res Sect B 94 (FEB): 76-9 (1991)]**PEER REVIEWED**
  

Back to Top

Human Toxicity Values

• A 10 MINUTE EXPOSURE TO 0.85 MG/L IS ESTIMATED TO BE LETHAL IN MAN. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-96]**PEER REVIEWED**
  

Back to Top

Non-Human Toxicity Values

• LD50 Rat oral 127 mg/kg [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.13 Technical ReportSeries No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• LD50 Rabbit oral 118 mg/kg [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.13 Technical ReportSeries No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• LD50 Guinea pig oral 158 mg/kg [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.13 Technical ReportSeries No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• LD50 Mouse iv 81 mg/kg [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.13 Technical ReportSeries No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• LD50 Rat ip 36 mg/kg [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.13 Technical ReportSeries No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• LD50 Guinea pig iv 17 mg/kg [DHHS/NTP; Toxicology and Carcinogenesis Studies of 2-Chloroacetophenone in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.13 Technical Report Series No.379 (1990) NIH Pub No.90-2834]**PEER REVIEWED**
  
• LD50 Rat oral 1820 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 723]**PEER REVIEWED**
  

Back to Top

Absorption, Distribution and Excretion

• None found

Back to Top

Metabolism/Metabolites

• None found

Back to Top

TSCA Test Submissions

• None found

Back to Top

Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.