Although a number of studies have identified dose-dependent increases in fetal brain Hg concentrations, dose–response data related to fetal neurotoxicity are non-existent with the exception of a single study (Morgan, et al., 2002) that reported a no-effect-level of 108.5 ng Hg/fetus (whole body) in rats. As a result, the potential for fetal exposure and effects must beconsidered in REL development, but at present must be addressed as a limitation of the database available for the determination of a REL for Hg°.
The uptake and distribution of Hg in the fetus following maternal exposure has been extensively reviewed (ATSDR, 1999; WHO, 2003). Animal studies suggest that the CNS issensitive to prenatal Hg° exposure. However, clear dose–response data in relation to maternalinhalation exposure to Hg° is lacking. In addition, available data relate to Hg° air concentrationstwo to three orders of magnitude greater than that generally encountered in the non-occupationalenvironment. High quality epidemiological data (e.g., with good exposure data and control ofconfounding factors) is lacking concerning the potential for CNS effects in children exposedin utero. Therefore, while there is evidence to demonstrate that fetal exposure does occur, andto suggest potential concern for fetal neurobehavioural effects following maternal inhalationexposure to Hg°, data are lacking to quantify potential risks.
As Hg° can readily cross the placenta (WHO, 2003), fetal exposure represents a concernin association with the inhalation of Hg0 by pregnant women (WHO, 1991; Drasch, et al.,1994; Yang, et al., 1997; Vimy, et al., 1990; Yoshida, et al., 1986, 1990). No hepatic or renaleffects have been noted as a result of in utero exposure despite the fact that the liver and kidney accumulate the highest levels of Hg in the fetus (Drasch, et al., 1994; Morgan, et al., 2002;Yoshida, 2002; Yoshida, et al., 2002). A number of recent studies have examined the effects dueto in utero exposure to Hg and have pointed to potentially irreversible neurological effects as the key concern (Ramirez. et al., 2003). This highlights the sensitivity of the developing CNS to Hg,with one author attributing this sensitivity to Hg’s slow elimination from these tissues (Yoshidaet al.,1999).
There have been a few studies published since the previously cited reviews werecompleted. Yoshida, et al. (2005) repeatedly exposed pregnant mice of metallothionein (MT)-nulland wildtype strains to Hg0 at concentrations of 0.5 mg/m3 and 0.56 mg/m3, respectively, for 6h/day from gestational day (GD) 1 through 18.
Hg concentrations in the brain and kidney in the offspring were found to be significantlyhigher in the exposed groups (MT-null and wildtype) than in the controls. In the brain, Hgconcentrations in the exposed males were not significantly different between the two strains, butthe exposed MT-null females had significantly higher levels of Hg than the wildtype females. Ahistological examination did not reveal any abnormalities in the nerve tissues of the exposed miceregardless of strain or sex of the offspring.
Hg-exposed MT-null mice exhibited a significant decrease in total locomotor activity inmales, and a learning disability in the passive avoidance response and a retarded acquisition inthe Morris water maze in females, as compared with the controls. The authors concluded that MTmay play a protective role for neurological effects associated with in utero Hg exposure, with itsinfluence being more pronounced in females.
Another recent study examined the disposition and toxicity of inhaled Hg° in rats and thepotential adverse effects on reproductive outcomes (Morgan, et al., 2002). Rats were exposed to0, 1, 2, 4 or 8 mg Hg/m3 for 2 h/day from GD 6 through 15. Maternal toxicity was noted in the4 and 8 mg Hg/m3 groups, which was characterized as a concentration-related decrease in bodyweight gain and mild nephrotoxicity. The accumulation of Hg in fetuses was found to be dosedependent,however, no statistically significant effects on fetal brain weights or on fetal bodyweights were noted even with fetal Hg concentrations being noted to reach a mean of 108.8 ngHg/fetus (whole body) on GD 10 (the only day on which whole body burden was examined)and 1.93 ng/brain by GD 15. The authors also noted a dose-related increase in levels of Hgin the fetal brain. While no effects were noted in the offspring following in utero exposure, asignificant increase in the number of resorptions was noted in the highest dose group, wherematernal toxicity was observed. In the same dose group, post-natal litter size and body weightsof neonates were significantly less than controls. The direct maternal toxicity reported at thisexposure level confounds the interpretation of effects on reproductive outcomes.
A recent study in humans examined the presence and levels of total Hg in chord bloodand meconium as an indicator of prenatal exposure and the potential for neurodevelopmentaleffects (examined using cognitive adaptive tests and clinical linguistic auditory milestonescale—CATS/CLAMS) (Ramirez, et al., 2003). The authors did not provide details concerningthe source of the exposures to Hg (both elemental and methyl Hg) in the study, but noted that there was likely some exposure to methyl Hg via the diet due to the consumption of fish. The study reported that Hg levels in hair and cord blood were negatively correlated with CATS/CLAMS results in both the control and exposed groups at two years of age. However, those exposed also had documented indicators of Hg presence at birth (presence of Hg in the meconium) and,therefore, the authors suggested that prenatal exposure, and not necessarily current exposure toHg in children (e.g., birth to two years of age), was the cause of the observed neurodevelopmental effects. While this study suggests that in utero exposure may result in neurological effects, theseresults should be interpreted with caution, as the authors did not control for confounding variables,such as concomitant exposure to other neurotoxicants and nutritional deficiencies.