1.2- Dibromoethane studies

No studies were located regarding death in humans after inhalation exposure to 1,2-dibromoethane. However, inhalation exposure as well as dermal exposure may have played a role in the deaths of two pesticide workers exposed to 1,2-dibromoethane. For a discussion of this report by Letz et al. (1984), see Section 2.2.3.1. 

Older studies have established lethal concentrations of inhalation exposure to 1,2-dibromoethane for experimental animals. Groups of rats were exposed to 1,2-dibromoethane at concentrations of 100-10,000 ppm and durations of 0.02-16 hours (Rowe et al. 1952). For each exposure concentration tested, several exposure durations were selected that were expected to encompass 0%-100% mortality. A total of 40 combinations of exposure concentration and duration were tested, using a total of 711 rats. Plots were constructed of concentration versus exposure duration expected to produce 99.99%, 50%, and 0.01 % mortality. Selected points from the 50% plot are illustrated in Figure 2-1 and recorded in Table 2-1. 

Deaths in rats resulting from single-exposure concentration/duration combinations expected to produce 50%-90% mortality usually occurred within 24 hours. These deaths were attributed to cardiac or respiratory failure and were probably a direct effect of 1,2-dibromoethane toxicity. Deaths resulting from exposure concentration/duration combinations expected to produce 0.01%-50% mortality occurred as long as 12 days after exposure and were due to pneumonia. The authors attributed pneumonia to 1,2-dibromoethane-induced lung injury, but this lesion could also have been due to intercurrent bacterial or mycoplasmal pulmonary infection. Rats free of enzootic respiratory infections were not available in 1952. More contemporary inhalation studies of 1,2-dibromoethane using commercially produced rats (Nitschke et al. 1981 NTP 1982) did not report pneumonic lesions or pneumonia-related mortality. 

Deaths occurred in pregnant female Crl CD rats and CD mice exposed to 1,2-dibromoethane for 23 hours per day over a 10-day period. Female rats and mice had increased mortality when exposed to 80 ppm of 1,2-dibromoethane while female mice also had significant mortality when exposed to concentrations of 38 ppm 1,2-dibromoethane (Short et al. 1978). Twenty percent mortality occurred in female Crl CD rats exposed to 80 ppm 1,2-dibromoethane over a 3-week period mortality did not occur at lower concentrations of 20 or 39 ppm. Male rats exposed to 89 ppm 1,2-dibromoethane over a 10-week period had 21% mortality but mortality did not occur at lower concentrations of 19 or 39 ppm (Short et al. 1979). There was no gross necropsy or histopathologic examination to establish the cause of death as related to chemical toxicity in either of these studies, which were focused primarily on development and reproduction. 

Rats and mice exposed chronically to 1,2-dibromoethane by inhalation had high mortality (NTP 1982 Wong et al. 1982). The majority of deaths were related to cancer rather than direct toxic effects of 1,2-dibromoethane. Both studies are discussed further in Section 2.2.1.8. 

No studies were located regarding cardiovascular, gastrointestinal, or musculoskeletal effects in humans or animals after inhalation exposure to 1,2-dibromoethane. 

A possible case of chronic intoxication by 1,2-dibromoethane occurred in a worker involved in 1,2-dibromoethane production (Kochmann 1928). Symptoms were nonspecific. Upper respiratory symptoms consisted of pharyngitis and bronchitis other symptoms were lymphadenopathy, conjunctivitis, anorexia, headache, and depression. The worker s condition improved upon cessation of exposure. No other studies were located regarding respiratory effects in humans after inhalation exposure to 1,2-dibromoethane. 

There have been several subchronic studies of 1,2-dibromoethane. In one, rats and guinea pigs... 

To determine doses to be used in chronic inhalation studies, F344 rats and B6C3Fi mice of both sexes were exposed to 0, 3, 15, or 75 ppm 1,2-dibromoethane for 13 weeks (NTP 1982 Reznik et al. 1980). Lesions occurred in respiratory turbinates in the dorsal portion of the nasal cavity of rats and mice exposed to 75 ppm. Respiratory epithelium was affected with cytomegaly of basal cells, focal hyperplasia, loss of cilia, and squamous metaplasia. Rats exposed to 15 ppm... 

A study was conducted to examine proliferative nasal epithelial lesions in F344 rats following subchronic inhalation of 1,2-dibromoethane at concentrations of 0, 3, 10, or 40 ppm (Nitschke et al. 1981). The study incorporated serial sacrifices and sacrifices after an 88-89-day postexposure period. Rats in the mid - and high-dose groups had hyperplasia of nasal turbinate epithelium rats at the highest dose also exhibited nonkeratinizing squamous metaplasia of respiratory epithelium of the nasal turbinates. 

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. 

Rats in a subchronic inhalation study exposed to 50 ppm 1,2-dibromoethane had intercurrent infectious disease that severely complicated experimental results (see the discussion in this section on Respiratory Effects). No liver lesions were reported in surviving rats (Rowe et al. 1952). Guinea pigs exposed to 50 ppm 1,2-dibromoethane did not develop respiratory disease. Their liver lesions consisted of minimal centrilobular hepatocellular fatty change (Rowe et al. 1952). Liver lesions were not induced in F344 rats or B6C3i mice following subchronic exposure to any concentrations of... 

In the subchronic inhalation study of 1,2-dibromoethane in rodents conducted by NTP (1982), eye irritation was noted at study conclusion (weeks 12 and 13) in mice receiving the highest concentration (75 ppm). 

There are no studies in animals focusing specifically on the nervous system. In the lethality studies of Rowe et al. (1952) discussed in Section 2.2.1.1, rats and guinea pigs exposed by inhalation to higher concentrations of 1,2-dibromoethane had central nervous system depression (exact clinical signs not specified). Brain tissue apparently was not examined histologically. 

Dibromoethane can induce developmental effects in rodents (Short et al. 1978, 1979 Smith and Goldman 1983). The results of these studies indicate that 1,2-dibromoethane is more toxic to pregnant mice than pregnant rats (Short et al. 1978). It produces maternal toxicity as evidenced by decreases in food consumption, body weight gain, and survival (Short et al. 1978, 1979). Developmental effects observed include anatomical and skeletal defects and reduced survival of fetuses. However, these adverse developmental effects have been observed in animals at doses that induce maternal toxicity. 

Antispermatogenic effects of 1,2-dibromoethane have been observed in humans occupationally exposed to 1,2-dibromoethane (Ratcliffe et al. 1987 Takahashi et al. 1981 Ter Haar 1980). These effects include changes in sperm velocity and count. Whether or not these effects are associated with reduced fertility in humans cannot be totally addressed, since the epidemiologic study (Wong et al. 1979) was not capable of detecting such a sensitive effect. Although this study had several limitations, it indicates a potential for adverse effects of 1,2-dibromoethane on fertility. 

The direct effect of inhalation exposure to 1,2-dibromoethane on spermatogenesis in animals has not been studied. Nonetheless, the available data from animal studies indicate that the male reproductive system in rats is affected by exposure to 1,2-dibromoethane at high doses. In all studies discussed below, however, rats had high mortality associated with chemical toxicity and/or chemically-induced neoplasia. It is therefore difficult to attribute effects on the reproductive organs to... 

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). 

Cancer mortality and mortality due to respiratory disease were studied in 161 male employees exposed to 1,2-dibromoethane in two 1,2-dibromoethane manufacturing plants located in Texas and Michigan (Ott et al. 1980). Because the Texas and Michigan plants ceased operations in 1969 and 1976, respectively, environmental assessments were based on existing records and discussions with workers formerly associated with the plants. No statistically significant increase in deaths was observed when data were examined in terms of duration of exposure or interval since first exposure. Although there was an increase in cancer mortality among employees with more than 6 years of... 

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. 

Single-dose oral LD o values in rats, guinea pigs, rabbits, and mice were determined by Rowe et al. (1952) in a gavage study using 1,2-dibromoethane in olive oil. All reliable LDso values (lethal dose, 50% kill) for each species for the acute-duration category are recorded in Table 2-2 and plotted in Figure 2-2. 

Nonneoplastic proliferative lesions of the forestomach were observed in high-dose Osborne-Mendel rats in the chronic gavage study of 1,2-dibromoethane conducted by the National Cancer Institute (NCI 1978). These consisted of acanthosis and hyperkeratosis of forestomach squamous epithelium. Similar lesions occurred in high-dose B6C3Fi mice. These dose levels are not plotted and recorded in Figure 2-2 and Table 2-2, respectively, since these doses also caused forestomach squamous cell tumors. 

Liver was not examined histologically in the subchronic study used to set concentrations for the NCI chronic gavage bioassay of 1,2-dibromoethane (NC11978). In the NCI (1978) gavage bioassay (discussed in detail in Section 2.2.2.8), a nonneoplastic hepatic lesion, peliosis hepatis, occurred in a small number of treated male and female Osborne-Mendel rats and had an equivocal relationship to... 

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