Toxicokinetics of mercuric chloride and methylmercuric chloride in mice

Abstract

Future human exposure to inorganic mercury will probably lead to a few individuals occupationally exposed to high levels and much larger populations exposed to low or very low levels from dental fillings or from food items containing inorganic mercury; human exposure to methylmercury will be relatively low and depending on intake of marine food. Ideally, risk assessment is based on detailed knowledge of relations between external and internal dose, organ levels, and their relation to toxic symptoms. However, human data on these toxicokinetic parameters originate mainly from individuals or smaller populations accidentally exposed for shorter periods to relatively high mercury levels, but with unknown total body burden. Thus, assessment of risk associated with exposure to low levels of mercury will largely depend on data from animal experiments. Previous investigations of the toxicokinetics of mercuric compounds almost exclusively employed parenteral administration of relatively high doses of soluble mercuric salts. However, human exposure is primarily pulmonary or oral and at low doses. The present study validates an experimental model for investigating the toxicokinetics of orally administered mercuric chloride and methylmercuric chloride in mice. Major findings using this model are discussed in relation to previous knowledge. The toxicokinetics of inorganic mercury in mice depend on dose size, administration route, and sex, whereas the mouse strain used is less important. The "true absorption" of a single oral dose of HgCl2 was calculated to be about 20% at two different dose levels. Earlier studies that did not take into account the possible excretion of absorbed mercury and intestinal reabsorption during the experimental period report 7-10% intestinal uptake. The higher excretion rates observed after oral than after intraperitoneal administration of HgCl2 are most likely due to differences in disposition of systemically delivered and retained mercury. After methylmercury administration, mercury excretion followed first-order kinetics for 2 wk, independently of administration route, strain, or sex. However, during longer experimental periods, the increasing relative carcass retention (slower rate of excretion) caused the elimination to deviate from first-order kinetics. Extensive differences in the toxicokinetics of methylmercury with respect to excretion rates, organ deposition, and blood levels were observed between males and females.(ABSTRACT TRUNCATED AT 400 WORDS)

Neurotoxic effects of postnatal thimerosal are mouse strain dependent

“…Variation in toxicokinetics across strains may alter distribution, retention, or rates of metabolism from organic to inorganic mercury species. 40,41,43 Toxicokinetic explanations, however, predict lower thresholds for the induction of autoimmune disturbance following mercury administration to females of H-2-susceptible strains. 40 Here, we found no sexrelated effects on behavior at prepubertal time points in susceptible SJL mice, and only few postpubertally; in these instances, males were more significantly affected than females.…”

“…Genes outside the H-2 region influence both the autoimmune sequelae associated with mercury 40 and its toxicokinetics. [40][41][42] We compared three mouse strains with differing H-2 and non-H-2 backgrounds; such modulatory genetic factors might have been obscured. Variation in toxicokinetics across strains may alter distribution, retention, or rates of metabolism from organic to inorganic mercury species.…”

Exposure to Mercury Alters Early Activation Events in Fish Leukocytes

“…Even in unpolluted areas, natural fish populations may have substantial body burdens of mercury (50-400 pg Hg/kg), of which 20-40% is inorganic (23). In areas tainted with mercury, fish bioaccumulate and biomagnify this metal largely through lower trophic feeding.…”

Methylmercuric chloride induces activation of neuronal stress circuitry and alters exploratory behavior in the mouse

“…Upon arrival mice were acclimated for at least one week prior to experimentation. Six week old mice were chosen on the basis of previous research that found this age to show sufficient sexual and neurological maturity for studying the effects of methylmercury exposure in mice (Doi and Kobayashi, 1982;Yasutake et al, 1990;Nielsen, 1992;Adachi et al, 1994). All procedures were approved by the Rutgers Institutional Animal Care and Use Committee.…”

“…Recently, Cheng et al (2006) have shown that IP injection of MeHg results in MeHg accumulation in the brain and significant induction of c-Fos protein levels that may potentially predict MeHg-induced neurotoxicity in the rat. Further it has been demonstrated that route of exposure (whether IP or oral) to MeHg does not alter the toxicokinetic whole-body retention or distribution of MeHg in mice (Nielsen, 1992). In light of this, the question of whether functionally active doses of MeHg can temporarily or even permanently alter neuronal function in the adult brain, such that responses to subsequent exposure to heterotypic neurogenic stimuli other than MeHg are altered, has not been widely explored.…”