Cumulative Neurotoxicity of Mercury Vapors in Animal Model Experiments at Various Time Patterns of Exposure

Emil Frantík1, Miroslava Hornychová1, Jana Nerudová1, Zdena Cábelková2, and Miroslav Cikrt1

1 Center of Industrial Hygiene and Occupational Diseases, National Institute of Public Health
2 Charles University, 3rd School of Medicine, Prague

Corresponding author: MUDr. Miroslava Hornychová
    National Institute of Public Health,
    Center of Industrial Hygiene and Occupational Diseases
    Šrobárova 48, 100 42 Prague 10
    Telephone: +420-2-6708-2901
    Fax number: +420-2-6731-1236
    E-mail: mhornych@szu.cz

CEJOEM 2000, Vol.6. No.1.:38-49

Key words:
Mercury, subchronic inhalation exposure, neurotoxicity, brain concentrations, and dose-response

Abstract:
The importance of the kinetic conditions of the saturation phase for the resulting neurotoxic damage produced by inhalation of mercury vapors is systematically analyzed in model experiments on rats. In the present experimental series, preceded by several pilot studies, the neurobehavioral effects and tissue mercury concentrations in three groups of rats differing in the time pattern of exposure were compared: two groups had the same weekly intake of mercury (0.12 mg per animal) and equal cumulative external dose (3.2 mg per animal at 27 weeks), but the inhaled mercury concentrations differed by one order of magnitude: 0.8 mg/m3, 6 h/d, 5 d/w, and 8 mg/m3, 36 min/d, 5 d/w, in groups 1 and 2, respectively. Rats of group 3 were exposed to an airborne concentration of 8 mg/m3 for 3 hours per day, 5 d/w: the weekly intake was 5-fold (0.6 mg per animal) and the cumulative dose by 31% higher than that in groups 1 and 2 (4.2 mg at 7 weeks).
    Summing up the results of the present study with preliminary experiments: 1) Two-month exposures to mercury vapors in concentrations lower than 0.1 mg/m3, i.e., at a daily intake lower than 0.01 mg/kg and cumulative external dose lower than 0.5 mg/kg (0.15 mg per rat), the Hg concentration in brain remained below 0.5 mg/kg (1 microgram per brain) and no neurotoxicity was detected. 2) Typical behavioral changes were found in rats exposed to concentrations 0.8-2 mg/m3 (daily intake 0.08-0.2 mg/kg) when the cumulative dose reached 5-7 mg/kg (2-2.5 mg per rat); corresponding concentration of mercury in the brain was 1.5-4 mg/kg. Increased emotional reactivity, hyperactivity and aggressivity prevailed in the profile of neurotoxicity beyond excitomotoric phenomena and ataxia. 3) Severe neurobehavioral toxicity corresponded to cumulative doses exceeding 10 mg/kg (4-5 mg per rat) and brain mercury of 6-10 mg/kg; exaggerated behavioral changes, tremor, ataxia and extremity weakness persisted for months after exposure. And 4) inhalation of higher airborne concentrations of Hg0 led to higher brain-to-kidney ratio of mercury concentration. Higher daily intake at similar cumulative doses tended to evoke more serious injury, including tremor, ataxia and weakness of extremities, and higher brain concentrations. On the other hand, the duration of the daily exposure had only slight influence both on tissue concentrations and on effect, provided that the daily intake was constant. This discrepancy between the impact of saturation steepness in the range of minutes and hours, and in the range of days and weeks would require further kinetic analysis.

Received:   13 July 2000
Accepted:  28 August 2000
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