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Shuval and Gruener (1972; 1977) reported about the epidemiological and toxicological aspects of nitrates and nitrites in the environment. The authors concluded that the nitrite levels increased in fetal blood with a lag of about 20 min behind the mother; this increase was followed by a rise in MetHb levels. The kinetic picture was similar between the dam and the fetuses. The threshold of the transplacental transfer effect was observed at 2.5 mg NaNO2/kg b.w. Higher doses caused a rapid increase in the NaNO2 level of maternal and fetal blood. The results of this study demonstrated that nitrites were apparently not transferred in appreciable amounts to suckling rats (Shuval and Gruener, 1972).

In rats which received drinking water with the highest concentrations of NaNO2 (1000, 2000 or 3000 mg/l), the levels of MetHb were increased after 1 month of treatment and throughout the rest of the study. The group treated with NaNO2 at 1000 mg/l (100 mg/kg b.w.) showed what might be considered subclinical levels, while groups exposed to 2000 and 3000 mg/l (200 or 300 mg/kg b.w.), exhibited levels which would be considered clinically significant in humans. After a single i.p. administration of NaNO2, maximal concentrations of MetHb were found at 20 - 90 min later and then declined in a long recovery phase with complete recovery followed a first order reaction with a t1/2 of about 90 minutes. When levels of the methemoglobin reductase were compared among groups at each time of the determination, there was a definite decrease in enzyme activity in groups exposed to nitrite after a lag period of 1 month of exposure and in recovery to control levels toward the end of the experiment (Shuval and Gruener, 1977).

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