1.2- Dibromoethane, carcinogenicity

Levels of exposure associated with the carcinogenic effects of 1,2-dibromoethane are indicated in Figures 2-1 and 2-2. Because cancer effects could occur at lower exposure levels, the figures also show a range for the upper bound of estimated excess risks, ranging from a risk of one in 10,000 to one in 10,000,000 (10 to 10 as developed by EPA. 

In a chronic inhalation study conducted by NTP (1982), carcinogenic end points were nasal tumors in rats and mice and pulmonary tumors in mice (see Section 2.2.1.8). A nonneoplastic lesion of epithelial hyperplasia occurring throughout the respiratory tract was a prominent histologic feature in the 1,2-dibromoethane-exposed mice. 

There have been two epidemiological studies regarding carcinogenic effects in workers exposed occupationally to 1,2-dibromoethane, primarily by the respiratory route (Ott et al. 1980 Turner and Barry 1979). 

Chronic inhalation exposure of rodents to 1,2-dibromoethane has been associated with neoplasms in the respiratory tract, as well as in other organ systems. Two studies have examined the carcinogenic potential of 1,2-dibromoethane in rodents after inhalation exposure (NTP 1982 Wong et al. 1982). There was also an A strain mouse assay (Adkins et al. 1986). 

In summary, two epidemiological studies have not identified an increased risk of cancer in people occupationally exposed by inhalation to 1,2-dibromoethane. In experimental animals exposed by the inhalation route, 1,2-dibromoethane is a potent carcinogen, producing cancer at the point-of-contact-the upper respiratory tract - as well as in numerous organs and tissues throughout the body. 

The rat liver foci assay is a short-term in vivo test to predict carcinogenic potential of a chemical. In this assay, 1,2-dibromoethane has both initiating and promoting activity, which correlates well with its carcinogenic effects in animals. 

The carcinogenicity of 1,2-dibromoethane by the oral route has been examined in a chronic bioassay conducted by NCI (1978). The chemical was administered by gavage in corn oil to rats and mice. Because of dose adjustments during the study, doses were expressed as time-weighted average (TWA) as follows high doses for rats were 41 mg/kg/day (males) and 39 mg/kg/day (females) low doses for rats were 38 mg/kg/day (males) and 37 mg/kg/day (females) the high dose for male and female mice was 107 mg/kg/day and the low dose for male and female mice was 62 mg/kg/day. 

Evidence from animal bioassays supports the hypothesis that it is the cytosolic system and not the microsomal oxidative system that is responsible for the carcinogenicity of 1,2-dibromoethane. 

Dibromoethane is a potent carcinogen in rats and mice, causing malignant and benign neoplasms of epithelial and mesenchymal origin in multiple organ systems when administered by inhalation, oral, or dermal routes. Cancer was also induced at initial point of contact with... 

Disulfiram is the generic name for Antabuse, a drug used in the treatment of chronic alcoholism. Disulfiram potentiates the toxic and carcinogenic effects of 1,2-dibromoethane in experimental animals. Presumably, this occurs by blocking conversion of the aldehyde metabolite as with acetaldehyde from ethanol. There is no evidence that similar effects occur in humans. Based on animal data, however, Ayerst Laboratories, producers of Antabuse (disulfiram), recommended the following in the package insert "Patients taking Antabuse tablets should not be exposed to ethylene dibromide or its vapors" (PDR 1991). 

The carcinogenic and mutagenic effects of 1,2-dibromoethane is due to its ability to bind to DNA and RNA with metabolic activation. The mechanism of action for the antispermatogenic effects is probably related to the removal of sulphur from cysteine in the nucleus of the spermatozoa. Clinical intervention to interfere with these mechanisms has yet to be developed. 

Limited epidemiological studies have been conducted involving occupational exposure in workers, primarily by the respiratory route (Ratcliffe et al. 1987 Takahashi et al. 1981 Ter Haar 1980 Wong et al. 1979). These studies neither confirm nor refute the possibility of 1,2-dibromoethane as a human carcinogen. Carcinogenicity bioassays have been conducted in animals via the inhalation. 

Wong et al. 1982). These studies have found cancer in multiple organ systems in two species of rodents. Thus, the carcinogenic effects of 1,2-dibromoethane appear to be well characterized, and additional studies are not necessary. Because the use of 1,2-dibromoethane has diminished considerably since its registration was canceled in 1984, the potential for additional long-term exposure is lower. 

In view of the limited and somewhat conflicting evidence for the carcinogenicity of 1,2-dibromoethane in exposed human populations, data on the clastogenic and genotoxic effects in humans could offer insight into potential human health risks from 1,2-dibromoethane. 

Heilman B, Brandt I. 1986. Effects of carcinogenic halogenated aliphatic hydrocarbons on [ H] thymidine incorporation into various organs of the mouse A comparison between 1,2-dibromoethane and 1,2-dichloroethane. Mutat Res 163 193-199. 

NCI. 1978. Bioassay of 1,2-dibromoethane for possible carcinogenicity. Bethesda, MD National Cancer Institute. NTIS no. PB 288428... 

Ozawa N, Guengerich FP. 1983. Evidence for formation of an S-[2(N -guanyl]ethyl) glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA. Proc Natl Acad Sci USA 80 5266-5270. 

Van Duuren BL, Seidman I, Melchionne S, et al. 1985. Carcinogenicity bioassays of bromoacetaldehyde and bromoethanol-potential metabolites of dibromoethane. Teratogenesis Carcinog Mutagen 5 393-403. 

Wong LC, Winston JM, Hong CB, et al. 1982. Carcinogenicity and toxicity of 1,2-dibromoethane in the rat. Toxicol AppI Pharmacol 63 155-165. 

Caution. 1,2-Dibromoethane is a suspected carcinogen. It should be used only in an efficient hood. Gloves should be worn. 

Hendricks, J.D., Shelton, D.W., Loveland, P.M., Pereira, C.B. Bailey, GS. (1995) Carcinogenicity of dietary dimethylnitrosomorpholine, A-methyl-V -nitro-V-nitrosoguanidine, and dibromoethane in rainbow trout. Toxicol. Pathol., 23, 447-457... 

United States National Cancer Institute (1978) Bioassay of 1,2-Dibromoethane for Possible Carcinogenicity (CASNo. 106-93—1) (Tech. Rep. Ser. No. 86 DHEWPubl. No. (NIH) 78-1336), Bethesda, MD, United States Department of Health, Education, and Welfare... 

VanDnnren, B.L., Seidman, I., Melchionne, S. Kline, S.A. (1985) Carcinogenicity bioassays of bromoacetaldehyde and bromoethanol—potential metabolites of dibromoethane. Teratog. Carcinog. Mutag., 5,. 39.3-40.3... 

Many halogenated compounds are carcinogenic. Among these is 1,2-dibromoethane, which has been... 

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