| Toxicity summary | IDENTIFICATION AND USE: Ethylene dibromide (1,2-Dibromoethane) is a colorless liquid. Historically, the primary use of 1,2-dibromoethane has been as a lead scavenger in antiknock mixtures added to gasolines. Another major past use of 1,2-dibromoethane was as a pesticide and an ingredient of soil and grain fumigants and for post-harvest application. 1,2-Dibromoethane has been used as a chemical intermediate in the manufacture of resins, gums, waxes, dyes, and pharmaceuticals and as a high-density, nonflammable solvent. HUMAN STUDIES: 1,2-Dibromoethane has produced oral ulcerations, followed by liver and renal toxicity. Cases of fatal poisoning have been reported. It was a DNA damaging agent when tested in human lymphocytes, but positive results were noted only after metabolic activation. ANIMAL STUDIES: Dogs exposed for 1 to 1.5 hr to vapor of 1,2-dibromoethane developed clouding of corneas several hours after removal from the exposure chamber. Rats tolerated exposure to 25 ppm 1,2-dibromoethane in air over 7 hr/day for 151 days, but 63 similar exposures to levels of 50 ppm were lethal to 20-50% of animals. Deaths from acute exposure were usually due to lung congestion and hemorrhage although liver and kidney damage, as well as corneal injury, were also observed. 1,2-Dibromoethane caused tumors in rats and mice at several different tissue sites and by several different routes of exposure. Inhalation exposure to 1,2-dibromoethane caused cancer of the nasal cavity and the blood vessels in rats of both sexes and in female micebenign or malignant lung tumors in mice of both sexes and in female ratsand benign or malignant mammary gland tumors in females of both species. It also caused testicular tumors in male rats and cancer of the subcutaneous tissue in female mice. Dermal exposure to 1,2-dibromoethane caused lung and skin tumors in female mice. In mice, administration of 1,2-dibromoethane in the drinking water caused forestomach tumors in both sexes and benign tumors of the esophagus in females. Some of the male reproductive effects of ethylene dibromide in the human have been modelled in the rabbit, although the rabbit appears not to be as sensitive, since semen parameters were affected only at doses close to the LD50 (55 mg/kg). When given ip at dose of 10 mg/kg on 5 successive days to rats it damaged spermatogenic cells. Two to three weeks after start of oral treatment of bulls with 4 mg/kg bw 1,2-dibromoethane on alternate days, abnormal spermatozoa were observed, indicating interference with spermatogenesis and with maturation of spermatozoa in epididymis. Fetal abnormalities were observed when pregnant rats and mice were exposed at 31.6 ppm 1,2-dibromoethane for 23 hr a day during the 6th-15th days of gestation. 1,2-Dibromoethane bound covalently to liver DNA of rats treated in vivo. It was selectively lethal to DNA-repair-deficient bacteria, and provoked DNA repair in cultured mammalian cells. It was mutagenic to bacteria, fungi, vascular plants, insects and cultured mammalian cells in the absence of an exogenous metabolic activation system. It induced chromosomal aberrations and sister chromatid exchanges in cultured mammalian cells. ECOTOXICITY STUDIES: 1,2-Dibromoethene showed low toxicity to most aquatic species tested. It was phytotoxic for green plants and germinating seed.The metabolite 2-bromoacetaldehyde produces liver damage by binding to cellular proteins. S-(2-bromoethyl)glutathione, another metabolite, exerts genotoxic and carcinogenic effects by binding to DNA. Antispermatogenic effects of 1,2-dibromoethanes metabolites may be caused by their covalent binding to thiol groups of nucleoproteins in nuclei of spermatozoa. Such adduct formation interferes with DNA, causing improper packing of the chromatin. (L120) |
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