Human Health Effects of Low-Level Methylmercury Exposure
Human Health Effects of Low-Level Methylmercury Exposure
In 2000, the NRC summarized the available literature on immunotoxicity of mercury (NRC 2000). Study results showed that occupational exposure to inorganic forms of mercury was associated with alterations in B lymphocytes, T-helper cells, T-suppressor cells, and T-cell proliferative responses (Moszczynski et al. 1995; Queiroz and Dantas 1997a, 1997b). The NRC report also cited several animal studies involving exposure to MeHg and indicators of immunotoxicity (e.g., Ilbäck et al. 1991). The NRC (2000) concluded that the immune system appears to be sensitive to mercury and noted that toxicologic studies have observed effects on immune-cell ratios, cellular response, and the developing immune system. However, at the time of the NRC report, there were no published epidemiologic studies of MeHg and immune function.
For immunologic outcomes, we focused on studies published since the comprehensive NRC report (i.e., post-1999), most of which have hair or blood mercury levels well in excess of the low-level range of our review or focus on elemental mercury exposure. For example, evidence of mercury-associated immunotoxicity, including increased frequency of antinuclear autoantibodies, changes in serum cytokine levels, and risk of malaria infection, has been observed in studies of heavily exposed Amazonian fish eaters and gold-mining populations (Alves et al. 2006; Crompton et al. 2002; Gardner et al. 2010; Nyland et al. 2011b). However, urinary mercury levels reflective of elemental mercury exposure from amalgam dental restorations in children has not been associated with immunotoxicity (Shenker et al. 2008).
Table 1 and Supplemental Material, Table S4 (http://dx.doi.org/10.1289/ehp.1104494) summarize the studies with low-level MeHg exposures that we reviewed. Nyland et al. (2011a) reported significant correlations of both maternal and cord blood mercury (respective geometric means of 6.9 µg/L and 9.6 µg/L) with increases in cord blood total IgG among 61 mother–infant pairs in the Brazilian Amazon. In that study, which did not adjust for fish consumption, blood mercury was not associated with either maternal or fetal levels of antinuclear autoantibodies or serum cytokines. In a recent population-based survey of Korean adults (n = 1,990), higher blood mercury (geometric mean, 4.3 µg/L) was associated with increased risk of self-reported atopic dermatitis in multivariable analyses adjusted for fish consumption (Park and Kim 2011). As part of the Osaka Maternal and Child Health Study, Miyake et al. (2011) evaluated 582 mother–child pairs in Japan for mercury exposure, using both maternal hair (median, 1.5 µg/g) and hair collected from their offspring 29–39 months of age (median, 1.4 µg/g). After adjustment for multiple potential confounders, including maternal fish consumption during pregnancy and child fish consumption, the authors detected no association between either maternal or child hair mercury and risk of childhood wheeze or eczema.
Belles-Isles et al. (2002) compared Canadian infants (n = 48) born to a population of subsistence fishers with a reference population (n = 60 infants) from coastal towns (geometric mean cord blood mercury of 1.8 and 0.9 µg/L, respectively). Cord blood mercury was inversely correlated with the proportion of naive helper T cells and plasma IgM levels in cord blood but unrelated to multiple other measures of T-, B-, and natural killer cell proportions and function. Of note, these analyses were not adjusted for potential confounding, including the substantial organochlorine exposures and greater prevalence of smoking during pregnancy among subsistence fishers compared with referent mothers. Bilrha et al. (2003) studied children born to subsistence fishers (n = 47) and town residents (n = 65) from the same Canadian region to expand on assessments in Belles-Isles et al. (2002). In correlational analyses (unadjusted for potential confounders), the authors observed no relationship between cord blood mercury and cord blood lymphocyte activation markers or cytokine secretion.
Immunologic Outcomes
In 2000, the NRC summarized the available literature on immunotoxicity of mercury (NRC 2000). Study results showed that occupational exposure to inorganic forms of mercury was associated with alterations in B lymphocytes, T-helper cells, T-suppressor cells, and T-cell proliferative responses (Moszczynski et al. 1995; Queiroz and Dantas 1997a, 1997b). The NRC report also cited several animal studies involving exposure to MeHg and indicators of immunotoxicity (e.g., Ilbäck et al. 1991). The NRC (2000) concluded that the immune system appears to be sensitive to mercury and noted that toxicologic studies have observed effects on immune-cell ratios, cellular response, and the developing immune system. However, at the time of the NRC report, there were no published epidemiologic studies of MeHg and immune function.
For immunologic outcomes, we focused on studies published since the comprehensive NRC report (i.e., post-1999), most of which have hair or blood mercury levels well in excess of the low-level range of our review or focus on elemental mercury exposure. For example, evidence of mercury-associated immunotoxicity, including increased frequency of antinuclear autoantibodies, changes in serum cytokine levels, and risk of malaria infection, has been observed in studies of heavily exposed Amazonian fish eaters and gold-mining populations (Alves et al. 2006; Crompton et al. 2002; Gardner et al. 2010; Nyland et al. 2011b). However, urinary mercury levels reflective of elemental mercury exposure from amalgam dental restorations in children has not been associated with immunotoxicity (Shenker et al. 2008).
Table 1 and Supplemental Material, Table S4 (http://dx.doi.org/10.1289/ehp.1104494) summarize the studies with low-level MeHg exposures that we reviewed. Nyland et al. (2011a) reported significant correlations of both maternal and cord blood mercury (respective geometric means of 6.9 µg/L and 9.6 µg/L) with increases in cord blood total IgG among 61 mother–infant pairs in the Brazilian Amazon. In that study, which did not adjust for fish consumption, blood mercury was not associated with either maternal or fetal levels of antinuclear autoantibodies or serum cytokines. In a recent population-based survey of Korean adults (n = 1,990), higher blood mercury (geometric mean, 4.3 µg/L) was associated with increased risk of self-reported atopic dermatitis in multivariable analyses adjusted for fish consumption (Park and Kim 2011). As part of the Osaka Maternal and Child Health Study, Miyake et al. (2011) evaluated 582 mother–child pairs in Japan for mercury exposure, using both maternal hair (median, 1.5 µg/g) and hair collected from their offspring 29–39 months of age (median, 1.4 µg/g). After adjustment for multiple potential confounders, including maternal fish consumption during pregnancy and child fish consumption, the authors detected no association between either maternal or child hair mercury and risk of childhood wheeze or eczema.
Belles-Isles et al. (2002) compared Canadian infants (n = 48) born to a population of subsistence fishers with a reference population (n = 60 infants) from coastal towns (geometric mean cord blood mercury of 1.8 and 0.9 µg/L, respectively). Cord blood mercury was inversely correlated with the proportion of naive helper T cells and plasma IgM levels in cord blood but unrelated to multiple other measures of T-, B-, and natural killer cell proportions and function. Of note, these analyses were not adjusted for potential confounding, including the substantial organochlorine exposures and greater prevalence of smoking during pregnancy among subsistence fishers compared with referent mothers. Bilrha et al. (2003) studied children born to subsistence fishers (n = 47) and town residents (n = 65) from the same Canadian region to expand on assessments in Belles-Isles et al. (2002). In correlational analyses (unadjusted for potential confounders), the authors observed no relationship between cord blood mercury and cord blood lymphocyte activation markers or cytokine secretion.
