Chloroanilines carcinogenicity

The 2003 ACGIH threshold limit valuetime-weighted average (TLV-TWA) for 4,4 -methylene bis(2-chloroaniline) is 0.01 ppm (O.llmg/m ) with an A2-suspected human carcinogen designation and a notation for skin absorption. 

Aromatic amines as a compound class account for many of the known carcinogenic organic chemicals. Perhaps the most widely publicized compounds are benzidine and 3,31-dichlorobenzidine (DCB)(4>5)which until recently were widely used in the manufacture of dyestuffs. Another widely publicized suspected car-cinogenic aromatic amine is 4-methoxy-m-phenylenediamine (MMPDA)(6)which is used as an ingredient in many permanent hair dye formulations. 4,4,-methylenebis(2-chloroaniline) or MBOCA(Z)and 4,4-methylenedianiline (MDA) are widely used as curing agents in polyurethane resins and are said to be carcinogenic. ... 

Figure 6.55 Log-log plot of relative carcinogenic potencies for a group of chemicals against mutagenic potency as determined by the Ames test. The potency is the amount of chemical giving tumors in 50% of the animals or 100 mutant colonies (revertants) of Salmonella bacteria. Aflatoxin B, is the most potent and benzidine the least potent. Abbreviations Moca, 4,4,-methylene-b/s-(2-chloroaniline) mms, methylmethane sulfonate. Source From Ref. 16.

Analysis of Carcinogens. HPLC methods for the determination of polynuclear aromatic hydrocarbons benzidine and 3,3 -dichlorobenzidine and 4,4 -methylenebis(2-chloroaniline) (MOCA) are discussed. 

Many compounds of this class hydrolyze to produce chloroanilines, which can cause anemia and methemoglobinemia. Such hydrolysis may occur both under acidic and alkaline conditions, and the degree of hydrolysis depends on the water solubility. Although these substances may form nitrosamines under certain conditions, there is no report of carcinogenicity. Chemical structures, physical properties, and toxicity data for a few selected herbicides of this class are presented in the following sections. 

Butler MA, Guengerich FP, Kadlubar FF. 1989. Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4,4 -methylene-bis(2-chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases. Cancer Res 49(1) 25-31. 

Kuslikis Bl. 1989. Metabolic activation in the rat, dog, guinea pig and human of the suspect carcinogen 4,4 -methylenebis(2-chloroaniline). Diss Abstr Int 50(3) 825-B. 

McQueen CA, Williams GM. 1990. Review of the genotoxicity and carcinogenicity of 4,4 -methylene-dianiline and 4,4 -methylene-bis-2-chloroaniline. Mutat Res 239(2) 133-142. 

NIOSH. 1977. 104-Week carcinogenicity study in male rats 4,4 -methylene-bis(2-chloroaniline) (MOCA). Cincinnati, OH National Institute for Occupational Safety and Health. Document No. PB83-239475. 

Purnell CJ, Warwick CJ. 1981. Method 3 - analysis of 3,3 -dichloro-4,4 -diaminodiphenyl methane (MOCA) and 2-chloroaniline in air. In Egan H, ed. Environmental carcinogens Selected methods of analysis. Vol. 4 Some aromatic amines and azo dyes in the general and industrial environment. Lyon, France World Health Organization, International Agency for Research on Cancer. lARC scientific publication No. 40, 133-140. 

Russfield AB, Homburger F, Boger E, et al. 1975. The carcinogenic effect of 4,4 -methylene-bis-(2-chloroaniline) in mice and rats. Toxicol AppI Pharmacol 31(1) 47-54. 

MOCA n. DuPont s trade name for methy-lene-bis-o-chloroaniline, much used until about 1980 as a curing agent for urethane rubbers and epoxy resins, prior to its being declared to be a carcinogen by OSHA. 

Methylenedianiline and 4,4 -methylene-bis-chloroaniline are two widely used aromatic amines employed in the manufacture of polyurethane foams, epoxy resins and as a curing agent in rubber manufacture. These two chemicals have been shown to be carcinogenic and mutagenic in a number of animal species, and they are structurally similar to the known human bladder carcinogen benzidine (McQueen et al. 1981 Lamb et al. 1986). Both chemicals have been detected in the urine of factory workers (Cocker et al. 1988), and Hotchkiss et al. (1993) reported substantial absorption through human skin in vitro. 

Hecht SS (2003) Carcinogen derived biomarkers applications in studies of human exposure to secondhand tobacco smoke. Tob Control 13 48-56. doi 10.1136/tc.2002.002816 Hinteregger C, Loidl M, Streichsbier F (1992) Characterization of isofunctional ring cleaving enzymes in aniline and 3-chloroaniline degradation by Pseudomonas acidovorans CA28. FEMS Microbiol Lett 97 261-266. http //www.doi.oig/10.1016/0378-1097(92)90346-P Hodne O, Boufatit M, Khouider A (2004) Use of montmorillonite clays as adsorbents of hazardous pollutants. Desalination 167 141—145... 

---