Sensitizing potential of chlorothalonil in the guinea pig and the mouse.

The fungicide chlorothalonil is used extensively under several tradenames for the protection of various horticultural and fruit crops and bananas against fungal infections. It is also used as fungicide in wood preservation and as a preservative in paints. Clinical experience has shown chlorothalonil to be a contact allergen and several cases of allergic contact dermatitis attributed to chlorothalonil have been described. 2 previous guinea pig maximization test studies have shown the sensitizing potential of chlorothalonil to be high. The sensitizing property of chlorothalonil was studied by us with the predictive test methods the local lymph node assay and the cumulative contact enhancement test. In the local lymph node assay, chlorothalonil induced a dose-dependent increase in proliferation with a maximal stimulation index of 19.2 and 27.2. In the cumulative contact enhancement test, a statistically significant dose-dependent high sensitization rate was seen with a maximal sensitization rate of 100%. In conclusion, it is evident that chlorothalonil is an extremely potent contact allergen, inducing sensitization using only topical exposure on intact skin.

Metabolism of mercury in hamster pups administered a single dose of 203Hg-labeled methyl mercury.

Golden Syrian hamster pups were administered a single subcutaneous dose of 203Hg-labeled methyl mercury (MeHg), 0.4 nmol/g body weight, seven days after birth, and were sacrificed 2, 7, 14, 21 or 28 days later. The excretion of 203Hg followed a biphasic elimination pattern with an average half-time of 8.7 days for the rapid component. The slow component had a much longer half-time and probably reflects binding of 203Hg to growing hair. The concentration of 203Hg in the liver, kidneys and brain two days after administration was 0.44, 0.38 and 0.19 nmol/g, respectively. The retention of 203Hg was higher in the kidney than in the liver and the brain. The content of inorganic 203Hg in the liver and kidneys increased the first weeks after administration, demonstrating that hamsters are able to demethylate MeHg before two weeks of age.

Demethylation and placental transfer of methyl mercury in the pregnant hamster.

The demethylation and placental transfer of methylmercury (MeHg) was studied in Syrian Golden hamsters administered a single oral dose of 203Hg-labeled MeHgCl, 1.6 mumol/kg body weight, on day 2 or 9 of gestation and sacrificed 1 day before expected parturition. In order to evaluate the role of demethylation for transplacental transport of MeHg, four hamsters were administered 203Hg-labeled HgCl2 intravenously on day 9 of gestation. The mean biological halftime of 203Hg in animals administered radiolabeled MeHg was 7.7 days and the fecal route was the main excretory pathway. The fetal content of 203Hg in hamsters administered radiolabeled MeHg on gestational day 2 or 9 corresponded to 1.3% and 4.6% of the administered dose, respectively. The distribution of 203Hg in the fetus was more even than in the dam and the concentration of 203Hg in the fetal brain, liver and kidney was similar to that of the placenta. Inorganic Hg was found in maternal liver (18% of total Hg), kidney (31%) and placenta (21%) and fetal liver (3%). The amount of inorganic 203Hg in fetal liver corresponded to about 0.015% of the dose administered to the dam as MeHg. When hamsters were administered 203HgCl2 by intravenous injection on day 9 of gestation, the concentration of 203Hg in fetal liver corresponded to 0.03% of the administered dose. The inorganic 203Hg detected in fetal liver after maternal exposure to MeHg was probably due to demethylation of MeHg in the dam and transplacental transfer of inorganic Hg.