Ethylene dibromide: toxicology and risk assessment

Since the 1920s ethylene dibromide's (EDB's) primary use has been as a scavenger of lead compounds in gasoline. Gasoline evaporation contributed to EDB emissions into the environment. In 1973, the United States Environmental Protection Agency (EPA) issued regulations to reduce the use of leaded gasoline and this has resulted in lower EDB usage and emissions. In addition, EDB has been used extensively as a fumigant since 1948. Its volatility and versatility, based on chemical and biocidal properties, led to its use as a soil sterilant, as a spot fumigant of grain milling machinery, and as a control agent in grain, fruit and vegetable infestations. In 1977 the EPA began a review of EDB's pesticidal uses which eventually led to its cancellation for most agricultural applications. Disposal of EDB and contamination of water supplies remain major environmental concerns. EDB can be absorbed via the dermal, oral and inhalation routes. It appears to be metabolized in vivo by an oxidative pathway (cytochrome P-450) and a conjugation pathway (glutathione S-transferase). The metabolites play an important role in exerting its toxicity. Few human poisonings have been reported from either acute or chronic exposure. However, EDB is irritating to the skin and eyes. Limited information indicates that EDB can damage the liver and kidneys following extensive or prolonged exposure. The genotoxicity of EDB has been clearly demonstrated. It binds to DNA in vivo and in vitro, and a DNA adduct has been identified. EDB has been shown to be mutagenic in numerous bacterial assays, in fungi, in plants, in insects, and in mammalian cell culture. Some evidence indicates that EDB can cause sister chromatid exchange and chromosomal aberrations. EDB is a reproductive toxin, but it does not appear to be teratogenic. It has been shown to affect spermatogenesis in rats, bulls and rams and to affect fertility in fowl. Human studies indicate that EDB exposure may harm sperm and decrease fertility. The toxic effect of greatest concern that may result from EDB exposure is cancer. In rats and mice, EDB produced tumors at the application site and at distant sites. When given orally, EDB has produced tumors in the forestomach, lung, and the circulatory system. When administered by inhalation, EDB produced tumors in the nasal cavity, lung, and the circulatory system. Dermal application of EDB produced skin and lung tumors. Analyses of risks from EDB exposure have focused on potential carcinogenic effects. Initial risk estimates, based on animal studies, indicated that citrus workers had essentially a 100% chance of contracting cancer.(ABSTRACT TRUNCATED AT 400 WORDS)