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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
1974; Turnlund and Keyes, 2000). Thus, reproductive effects in rats were selected as the most definitive toxicological indices.
Data Selection. In the absence of adequate human studies, animal studies were evaluated. Rats, mice, and rabbits appear to be more sensitive than guinea pigs to the adverse effects of dietary molybdenum. The effects of molybdenum on reproduction and fetal development in rats and mice were found to be the most sensitive and therefore were used to set the UL.
Identification of a No-Observed-Adverse-Effect Level (NOAEL) and Lowest-Observed-Adverse-Effect Level (LOAEL). The study of Fungwe and coworkers (1990) provides a dose-response relationship for adverse reproductive effects in female rats. The NOAEL from this study was 0.9 mg/kg/day and the LOAEL was 1.6 mg/kg/day of molybdenum. This study is supported by observations of reproductive effects in mice in a three-generation study at a single dose of 1.5 mg/kg/day (Schroeder and Mitchener, 1971). Since only one level was used in this study, it is difficult to use this study independently to determine a LOAEL. In addition, Jeter and Davis (1954) noted decreased fertility in male rats after 13 weeks of exposure to 8 mg/ kg/day of molybdenum. The NOAEL from that study was 2 mg/ kg/day. Taken together, these observations suggest that numerous adverse reproductive effects were encountered in rats and mice at dietary molybdenum levels exceeding the NOAEL of 0.9 mg/kg/ day established from the study of Fungwe and coworkers (1990).
Uncertainty Assessment. There do not appear to be sufficient data to justify lowering the degree of uncertainty from the usual uncertainty factor (UF) for extrapolating from experimental animals to humans. Thus, the usual value of 10 was selected. A UF of 3 for intraspecies variation was based on the expected similarity in pharmokinetics of molybdenum among humans. Although Vyskocil and Viau (1999) have argued for a larger UF for intraspecies differences, they have based their concerns on possible interactions with copper and concerns about copper-deficient humans. Recent information suggests that molybdenum does not have any effect on copper metabolism in humans (Turnlund and Keyes, 2000). Thus, these two UFs are multiplied to yield a UF of 30.