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EFFECTS ON ANIMALS

LT50s for rats were determined for VDC by Andersen et al. (1979):

Concentration, ppm

Time, h

100

8.0

200

4.1

500

3.0

1,000

2.4

2,000

1.4

Inhalation of VDC by the rat can result in irritation of the eyes and nose, excessive salivation, respiratory distress, tremors, convulsions, incoordination, prostration, narcosis, and death due to vascular collapse and shock (Carpenter et al., 1949; Jaeger et al., 1973). Exposure to VDC at 200 ppm in air for 4 h produced severe liver damage in rats (Carpenter et al., 1949). Mild liver damage resulted from a 23-h exposure at 60 ppm (Short et al., 1977). Mice exposed at 50 ppm showed progressive renal necrosis in the first 24 h (Reitz et al., 1979); severe tubular necrosis has been reported in mice exposed at 15 ppm for 23 h (Short et al., 1977).

Dogs, rats, guinea pigs, rabbits, and monkeys exposed to VDC by inhalation at 99 ppm, 8 h/d, 5 d/wk for 6 wk showed no mortality or evidence of toxicity. However, in continuous exposure at 15 ppm, deaths occurred in 7 of 15 guinea pigs (between days 4 and 9) and 3 of 9 monkeys (days 26, 60, and 64) (Prendergast et al., 1967).

Liver damage and kidney damage were seen in most of the animals exposed continuously at 189 mg/m3. Nonspecific lung damage was also seen in most animals (Prendergast et al., 1967).

VDC caused epinephrine-induced arrhythmias in rats. Epinephrine in doses as low as 0.5 μg/kg produced a series of premature ventricular contractions in rats exposed to VDC at about 25,000 ppm for 47 min. The cardiac effects were completely reversible on discontinuation of VDC inhalation. Pretreatment of the animals with phenobarbital increased the cardiac effects; that suggests they were due to a metabolite of VDC, in that phenobarbital induces microsomal enzymes (Siletchnik and Carlson, 1974).

Rampy et al. (1977) published an interim report of a 2-yr study on VDC toxicity. Sprague Dawley rats that inhaled VDC at 25 or 75 ppm, 6 h/d, 5 d/wk, for 18 mo failed to develop VDC-related tumors, as judged by gross examination 24 mo after the beginning of exposure.

Maltoni et al. (1977) exposed Sprague Dawley rats to VDC at 10, 25, 50, 100, and 150 ppm, 4 h/d, 4–5 d/wk, for 12 mo and, under a similar protocol, Swiss mice at 10 and 25 ppm. Early results, 30 wk after the last exposure (animal ages, 91–98 wk), showed an increase in the incidence of mammary tumors in treated groups, but the increase was not dose-related; one Zymbal’s-gland carcinoma was seen in a rat exposed at 100 ppm. VDC did produce renal adenocarcinomas without metastases in



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