Toxicological Sciences 66, 261-273 (2002)
Copyright © 2002 by the Society of Toxicology
REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY |
Disposition of Inhaled Mercury Vapor in Pregnant Rats: Maternal Toxicity and Effects on Developmental Outcome
* National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709;
ManTech Environmental Technology, Inc., Research Triangle Park, North Carolina 27709;
Research Triangle Institute, Research Triangle Park, North Carolina 27709;
National Cancer Institute at NIEHS, Research Triangle Park, North Carolina 27709;
¶ U.S. Environmental Protection Agency, ORD, NCEA, Washington, District of Columbia 20460; and
|| Neurotoxicology Division, NHEERL, U.S. Environmental Protection Agency, ORD, Research Triangle Park, North Carolina 27709
The disposition and toxicity of inhaled elemental mercury (Hg0) vapor for pregnant Long-Evans rats, and potential adverse effects on reproductive outcome were investigated. Rats were exposed to 0, 1, 2, 4, or 8 mg Hg0/m3 for 2 h/day from gestation day (GD) 6 through GD 15. Maternal toxicity occurred primarily in rats exposed to 4 and 8 mg/m3 and was manifested as a concentration-related decrease in body weight gain and mild nephrotoxicity. Control rats gained about 13% of their initial body weight during the 10-day exposure. Rats exposed to 4 mg/m3 Hg0 gained about 7% less than controls, and rats exposed to 8 mg/m3 Hg0 lost about 17% of their initial body weight during the 10-day exposure period. Maternal kidney weights were significantly increased in the 4 and 8 mg/m3 concentration groups, and urinalysis revealed increased levels of protein and alkaline phosphatase activity in urine of all Hg0-exposed rats. Dams exposed to 8 mg/m3 were euthanized in moribund condition on postnatal day (PND) 1. There was no histopathological evidence of toxicity in maternal lung, liver, or kidney of exposed rats at GD 6, GD 15, or PND 1. The incidence of resorptions was significantly increased, litter size and PND 1 neonatal body weights were significantly decreased only in the 8-mg/m3 group. Total Hg concentrations in maternal tissues increased with increasing number of exposure days and concentration. In general, approximately 70% of Hg was eliminated from maternal tissues during the week following the last exposure (GD 15 to PND 1). Elimination of Hg from maternal brain and kidney was slower than in other tissues, possibly due to higher levels of metallothionein. Total Hg concentrations in fetal tissues increased with increasing number of exposure days and concentration, demonstrating that a significant amount of Hg crossed the placenta. One week after the last exposure, significant amounts of Hg were still present in brain, liver, and kidney of PND 1 neonates. Metallothionein levels in neonatal tissues were not significantly increased by exposure to 4 mg/m3 Hg0. The total amount of Hg in neonatal brain (ng/brain) continued to increase after termination of inhalation exposure, suggesting a redistribution of Hg from the dam to neonatal brain. These data demonstrate that inhaled Hg0 vapor is distributed to all maternal and fetal tissues in a dose-dependent manner. Adverse effects of Hg on developmental outcome occurred only at a concentration that caused maternal toxicity.
Key Words: mercury vapor; elemental mercury; metallic mercury; inhalation; developmental toxicity; maternal toxicity; fetal toxicity; metallothionein; developmental neurotoxicity.
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