Incorporation of a micronucleus study into a developmental toxicology and pharmacokinetic study of L‐selenomethionine in nonhuman primates

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Abstract
Concomitant to a developmental toxicology study of selenium in long-tailed macaques (Macaca fascicularis), a transplacental bone marrow micronucleus assay was conducted in the fetuses of treated animals. Selenium was administered as L-selenomethionine by nasogastric intubation at 0, 150 or 300 μg/kg-day to pregnant macaques daily throughout organogenesis (gestation days 20–50). Pregnancy was terminated on gestation day 100 ± 2 and fetuses were obtained by hysterotomy. Selenium concentrations in maternal blood were monitored throughout pregnancy and selenium concentrations in fetal blood were measured at hysterotomy. Maternal circulating selenium did not exceed 4 ppm in plasma or 3.7 ppm in erythrocytes. Selenium in cord blood was ≤ 0.1 ppm in plasma and ≤ 1.1 ppm in erythrocytes at 300 μg/kg-day. Fetal bone marrow smears were prepared from the humerus and micronucleated polychromatic erythrocytes were scored. No increase of micronucleus frequency was detected in any dose group, although signs of maternal selenosis were obvious. This finding is compared to the previous observation that micronuclei were induced in the bone marrow of adult nonpregnant macaques treated at 600 μg/kg-day, a lethal dose yielding blood selenium levels to 7.3 ppm in plasma and 5.7 ppm in erythrocytes after 15 days of daily treatment, when death occurred. These data demonstrate that measurement of circulating xenobiotics can be useful for the interpretation of genetic toxicology results.

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