The repeated dose toxicity of a zinc oxide/hexachloroethane smoke

Abstract

Mice, rats and guinea pigs were exposed to the smoke produced by ignition of a zinc oxide/hexachloroethane pyrotechnic composition, 1 h/day, 5 days/week, at three different dose levels, together with controls. The animals received 100 exposures except for the high dose guinea pigs, which underwent 15 exposures, because of high death rate during the first few days of exposure. The test material had very little effect on weight gain, but there was a high rate of early deaths in the top dose of mice. A variety of incidental findings was seen in both decedents and survivors, but organ specific toxicity was, with one exception, confined to the respiratory tract. The most important of these findings was a statistically significant increase in the frequency of alveologenic carcinoma in the high dose group mice (p less than 0.01) and a statistically significant trend in the prevalence of the same tumour over all dose groups and the controls. A variety of inflammatory changes was seen in the lungs of all species and some appeared to be treatment-related. Fatty change in the mouse liver was more common in the middle and high dose groups than the controls. The aetiology of the tumour incidence is discussed and it is pointed out that hexachloroethane and zinc, as well as carbon tetrachloride, which may be present in the smoke, may be animal carcinogens in appropriate circumstances. Carbon tetrachloride is a known human carcinogen.

A fatal case following exposure to zinc chloride and hexachloroethane from a smoke bomb in a fire simulation at a school

“…Likewise, in experimental animals histological changes derived from ZnCl exposure are also consistent with those described in humans (17).…”

Toxicological Profile for Zinc

“…However, Schenker et al (1981) did not provide information on how this value was determined. Following exposure to zinc chloride smoke for 3-20 weeks, mortality was 50% in mice exposed to 121.7 mg zinc/m 3 (compared to 20% in controls) and 22% in guinea pigs exposed to 119.3 mg zinc/m 3 (compared to 8% in controls) (Marrs et al 1988). The smoke was similar to that described by Evans (1945) and also contained zinc oxide, hexachloroethane, and other compounds.…”

“…Routine gross and microscopic examination of the hearts of rats and mice revealed no adverse effects 13 months after exposure to 121.7 mg zinc/m 3 as zinc chloride smoke (also containing other compounds) for 1 hour/day, 5 days/week, for 20 weeks (Marrs et al 1988). Similarly, no changes were observed in the hearts of guinea pigs exposed to 119.3 mg zinc/m 3 as zinc chloride smoke for 1 hour/day, 5 days/week, for 20 weeks, and then observed for an additional 17 months (Marrs et al 1988). …”

“…Focal alveolitis, consolidation, emphysema, infiltration with macrophages, and fibrosis were observed in guinea pigs that died following exposure to 119 mg zinc/m 3 as zinc chloride smoke for 1 hour/day, 5 days/week, for 3-20 weeks (Marrs et al 1988); no changes were seen in guinea pigs that survived 13 months after the 20-week exposure. Thirteen months after a 20-week exposure, rats similarly exposed to 12.8 mg zinc/m 3 showed an increase in peribronchial inflammatory cell (lymphocytes and macrophage)…”

“…Mice exposed to 121.7 mg zinc/m 3 as zinc chloride smoke, but not to lower doses, for 1 hour/day, 5 days/week, showed increased macrophages and lymphocytes in the lungs (Marrs et al 1988). The smoke also contained zinc oxide, hexachloroethane, and other compounds.…”