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

MERCURY 192
2. HEALTH EFFECTS
excretion in the rats, with males excreting slightly faster than females. Interestingly, a sex-difference
elimination rate was not observed in rats dosed at 24 days or younger (Thomas et al. 1982).
The rate of mercury excretion was also slower in younger animals (7 or 15 days) than in older animals
(24 and 56 days) (Thomas et al. 1982). This age-dependent difference in the rate of mercury excretion may
reflect differences in the sites of mercury deposition (i.e., hair, red blood cells, skin). In neonatal rats, the
excretion of methylmercury is longer than in adult rats because of the inability of the neonatal liver to
secrete the toxicant into the bile. Therefore, the immaturity of the transport system in neonatal rats affects
the elimination of mercury.
Methylmercury is also excreted in the breast milk of rats, humans, and guinea pigs (Sundberg and
Oskarsson 1992; Yoshida et al. 1992). In pups exposed only through milk, approximately 80% of the total
mercury in blood was present as methylmercury. Because suckling animals have a limited ability to
demethylate methylmercury, the inorganic mercury present in the blood of the offspring probably originated
from inorganic mercury in the milk. Since the dams were exposed only to methylmercury in their diet,
some demethylation occurred in the dams, followed by the transport of the inorganic mercury to the
sucklings via milk.
Sundberg et al. (1998) studied the elimination of radiolabeled methylmercury in lactating and nonlactating
mice exposed to methylmercuric chloride via a single intravenous injection at 0.5 mg Hg/kg body weight.
A comparison of the results for methylmercury with results for inorganic mercury is discussed in the section
above on elimination of “Inorganic Mercury.” A three compartment pharmacokinetic model was used to fit
the data. 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. Mercury concentrations in milk were constant throughout the
9-day follow-up period postexposure. The results indicate that physiological changes during lactation alter
the pharmacokinetics for methylmercury in mice.