revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 189
2. HEALTH EFFECTS
for inorganic mercury varied between 0.1 and 3.6, with a mean of 0.64 at plasma levels below 300 ng Hg/g
(in the linear region of the relationship) and a mean of 0.17 at higher plasma mercury levels. In contrast,
the values for the methylmercury kinetic parameters were significantly higher in lactating than nonlactating
mice: plasma clearance (93.5 and 47.1 mL/hour/kg, respectively) and volume of distribution (18,500 and
9,400 mL/kg, respectively). The terminal half-life of methylmercury in plasma was 170 hours for lactating
and 158 hours for nonlactating mice. The milk-to- plasma concentration ratios for total mercury after
methylmercury administration were lower than those seen with inorganic mercury, and varied between
0.1 and 0.7 with a mean of 0.20. The nearly five-fold higher peak value for plasma to blood mercury levels
observed for inorganic mercury reflects the more efficient migration of inorganic mercury from blood to
milk compared with that for methylmercury. Mercury concentrations in milk also decreased more quickly
for inorganic (terminal half-life of 107 hours) than for methylmercury (constant levels throughout the 9-day
follow-up period postexposure). The authors hypothesize that the nonlinear relationship between mercury
in milk and plasma following inorganic mercury administration suggests that inorganic mercury enters the
mammary gland via a carrier-mediated transport system that is saturated at high plasma levels of inorganic
mercury. The results suggest that the physiological changes during lactation alter the pharmacokinetics for
methylmercury in mice, but not for inorganic mercury.
Organic Mercury. The fecal (biliary) pathway is the predominant excretory route for methylmercury, with
less than one-third of the total mercury excretion occurring through the urine, following oral and inhalation
exposure (Norseth and Clarkson 1970). In humans, nearly all of the total mercury in the feces after organic
mercury administration is in the inorganic form. The conversion of methylmercury to inorganic mercury is
a major step that is dependent on the duration of exposure and/or the duration after cessation of exposure.
In rats and nonhuman primates, methylmercury is secreted in the bile and can be reabsorbed in the intestine
(Berlin et al. 1975; Norseth and Clarkson 1971; Urano et al. 1990). It is believed that methylmercury is
complexed to nonprotein sulfhydryl compounds in the bile and reabsorbed in this form by a transport
system (Ballatori and Clarkson 1982; Urano et al. 1990). In guinea pigs, hamsters, and monkeys, methylmercury,
but not inorganic mercury, is extensively reabsorbed from the gall bladder, providing evidence for
the biliary-hepatic recycling of this metal (Dutczak et al. 1991). The biliary-hepatic cycle probably
contributes to the long biological half-life and toxicity of methylmercury. However, methylmercury can be
converted into its inorganic form in the gastrointestinal lumen by intestinal flora (Nakamura et al. 1977;