Methylmercury fetus

Pregnant or nursing women exposed to methylmercury through their diet or otherwise also expose their developing fetus or breast-fed infant to the chemical, since methylmercury passes through placental membranes and enters the fetal bloodstream, and also enters breast milk. This is particularly problematic since fetuses and infants (and toddlers) are more susceptible and sensitive to the neurotoxic properties of mercury than are adults. 

Genetic and Neonatal Toxicity. The ability of heavy metals readily to cross the placenta and disrupt nucleic acids coupled with the high sensitivity of the fetus and neonate increases the potential dangers of congenital and neonatal toxicity. In mammalian leukocyte cultures, chromosomal aberrations have been reported with lead (112), arsenic (113), mercury (114), and methylmercury (115). Charbonneau, et al. (116) reported a lack of mutagenic effect for methylmercury. 

It can assess in utero exposure. Any substance in the maternal circulation can be transferred across the placenta to the developing fetus unless it is first metabolized and eliminated (Ginsberg et al. 2004). Risk assessment of the fetal period typically relies on maternal dose. However, biomonitoring of cord blood relative to maternal blood may be important to document whether there are substantial maternal-fetal differences in exposure. Evidence on methylmercury suggests that it concentrates in the fetus (Stern and Smith 2003), whereas an evaluation of 29 pesticides suggests similar concentrations across the maternal-fetal unit (Whyatt et al. 2003). 

In the case of methylmercury, toxicodynamic data were used to reduce the intraspecies UF to 3 (EPA 1995b). The RfD was based on a benchmark dose computed as the lower 95% confidence limit on the 10% increase over the background for human childhood neurologic abnormalities (this level has been used to represent the NOAEL) in the susceptible subpopulation (the developing fetus). Therefore, the default intraspecies UF of 10 was reduced to 3. Since the susceptible subpopulation had been identified, the toxicodynamic part of the UF had been addressed. However, variability due to toxicokinetics was maintained with the use of the 3-fold UF. 

Methylmercury causes subtle to severe neurologic effects depending on dose and individual susceptibility. EPA considers methylmercury to have sufficient human and animal data to be classified as a developmental toxicant. Methylmercury accumulates in body tissue consequently, maternal exposure occurring prior to pregnancy can contribute to the overall maternal body burden and result in exposure to the developing fetus. In addition, infants may be exposed to methylmercury through breast milk. 

The joint expert committee for food additives and contaminants revised the Provisional Tolerable Weekly Intake for methylmercury, recommending that it be reduced to l.fipgkg body weight per week in order to sufficiently protect the developing fetus. 

In critical periods of development before they are born, and in the early months after birth, children and fetuses are particularly sensitive to the harmful effects of metallic mercury and methylmercury on the nervous system. Harmful developmental effects may occur when a pregnant woman is exposed to metallic mercury and some of the mercury is transferred into her developing child. Thus, women who are normally exposed to mercury vapors in the workplace (such as those working in thermometer/barometer or fluorescent light manufacturing or the chlor-alkali industry) should take measures to avoid mercury vapor exposures during pregnancy. Exposures to mercury vapors are relatively rare outside of the workplace, unless metallic mercury is present in the home. 

Effects were not observed at 2 mg Hg/kg/day. Similarly, female mice administered 20 mg Hg/kg/day as methylmercuric chloride by gavage on Gd 10 had increased resorptions, decreased live fetuses per litter, and decreased numbers of fetuses per litter (Fuyuta et al. 1978). After guinea pigs were exposed to 11.5 mg Hg/kg as methylmercuric chloride by gavage on Gd 21, 28, 35, 42, or 49, half of the litters were aborted 4-6 days after treatment (Inouye and Kajiwara 1988). An increased rate of reproductive failure due to decreased conceptions and increased early abortions and stillbirths occurred in female monkeys exposed to 0.06 or 0.08 mg Hg/kg/day as methylmercury for 4 months (Burbacher et al. 1988). The menstrual cycle length was not affected at these dose levels. Reproductive effects were not observed in monkeys exposed to 0.04 mg/kg/day for the same duration. 

Organic Mercury. Distribution of organic mercury compounds in humans and animals is similar to that of metallic mercury. Methylmercury distributes readily to all tissues, including the brain and fetus, after absorption from the gastrointestinal tract. The uniform tissue distribution is due to methylmercury s ability to cross diffusion barriers and penetrate all membranes without difficulty (Aberg et al. 1969 Miettinen 1973). Thus, tissue concentrations tend to remain constant relative to blood levels. About 90% of the methylmercury in blood is found in the red blood cells (Kershaw et al. 1980). The mean mercury concentrations in red blood cells were 27.5 ng/g and 20.4 ng/g in males and females, respectively, exposed to mercury, primarily from mercury-contaminated fish (Sakamoto et al. 1991). Because of this uniform distribution in tissues, blood levels are a good indicator of tissue concentrations independent of dose (Nordberg 1976). 

The Gray (1995) PBPK model simulates the kinetics of methylmercury in the pregnant rat and fetus. The Gray model was developed to provide fetal and maternal organ methylmercury concentration-time profiles for any maternal dosing regimen. 

Infants and developing fetuses may be exposed to methylmercury if their mothers consume certain methylmercury-contaminated fish, shellfish, or wildlife species from contaminated waters prior to their pregnancy, during their pregnancy, or while nursing. Older children also may be exposed to methylmercury by eating contaminated fish and wildlife species. Certain states, Native American tribes, and U.S. Territories have issued fish and wildlife advisories for mercury in fresh water, estuarine, and saltwater fish and in freshwater turtles (see Section 5.7). 

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