Page 492 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Mercury Chapter | 31 459

VetBooks.ir studies indicate that organic mercury is a potent neurotoxi- concentrations of mercury, damage to CNS becomes irre-
Both human epidemiology and experimental animal
versible. Rabbits appear to be less sensitive to mercury
following inhalation exposure.
cant (Ni et al., 2017). Studies suggest that cats and mon-
keys are more sensitive than rodents to the neurotoxic
effects of mercury (especially methylmercury). In several
Renal System
animal species, the major effects that are seen across the
studies include motor disturbances, such as ataxia and tre- Mercury, in all forms, has been shown to cause renal toxic-
mors, as well as signs of sensory dysfunction, such as ity (structural and functional damage) in humans and ani-
impaired vision. The predominant pathological feature is mal species that are tested. Renal toxicity has been
degenerative changes in the cerebellum, which is likely to observed in rats (Fisher 344) and mice (B6C3F 1 ) following
be the mechanism involved in many of the motor dysfunc- acute, intermediate and chronic exposures to mercuric
tions. In a chronic study, cats fed tuna contaminated with chloride (Dieter et al., 1992; NTP, 1993). In a 14-day
methylmercury showed degenerative changes in the cere- study, male and female rats were exposed by gavage to
bellum and the cortex (Chang et al., 1974). Neonatal mon- 0.93 14.8 mg Hg/kg/day as mercuric chloride for 5 days a
keys exposed to methylmercuric chloride at 0.5 mg Hg/kg/ week. There was a significant increase in the absolute and
day for 28 29 days exhibited stumbling, falling, blind- relative kidney weights of males beginning at the 1.9 mg
ness, crying, temper tantrums and coma. Histopathological Hg/kg/day dose level. An increased incidence of tubular
analysis revealed diffuse degeneration in the cerebral cor- necrosis was observed in rats exposed to at least 3.7 mg
tex, cerebellum basal ganglia, thalamus, amygdala and lat- Hg/kg/day. Severity was dose dependent. In chronic stud-
eral geniculate nuclei (Willes et al., 1978). ies, mercuric chloride produced a variety of pathological
Rats acutely intoxicated with methylmercury (19.9 mg changes in kidneys (Carmignani et al., 1992; Hultman and
Hg/kg, oral gavage) showed signs of lethargy and ataxia, Enestrom, 1992; NTP, 1993). Degenerative effects have
which was not accompanied by histopathological changes. been found in the kidneys of animals exposed to moderate
Symptoms disappeared within 2 3 h. Administration of a to high levels of metallic mercury vapors following acute
single dose of methylmercuric chloride (0.8 mg Hg/kg) or subacute exposures (Ashe, 1953). Effects ranging from
produced BBB dysfunction in rats (Chang and Hartman, marked cellular degeneration to tissue destruction and
1972) similar to that described for inorganic mercury. widespread necrosis were observed in rabbits exposed to
Neurotoxic signs observed in rats exposed to methylmer- mercury vapor at a concentration of 28.8 mg/m 3 for
cury (4 mg Hg/kg/day for 8 days) include muscle spasms, 2 3 h. In rats, slight degenerative changes (i.e., dense
gait disturbances, flailing and hind limb crossing (Inouye deposits in tubule cells and lysosomal inclusions) in the
and Murakami, 1975; Fuyuta et al., 1978; Magos et al., renal tubular epithelium were evident following exposure
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1980, 1985). Histopathological examination of the ner- to 3 mg/m mercury vapor for 3 h/day/5 days a week, for
vous system of affected rats has shown degeneration of 12 42 weeks (Kishi et al., 1978). Low-level, long-term
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cerebellar granular cells and dorsal root ganglia (Magos exposure to mercury (0.1 mg/m ) has not been found toxic
et al., 1980, 1985) and degenerative changes in peripheral to the kidneys of rats, rabbits, and dogs (Ashe, 1953).
nerves (Fehling et al., 1975; Miyakawa et al., 1976).
Mice exposed to 1.9 or 9.5 mg Hg/kg/day as methyl- Cardiovascular System
mercury in the drinking water for 28 weeks exhibited
degeneration of Purkinje cells and loss of granular cells Mercury has been shown to produce adverse effects on the
in the cerebellum (MacDonald and Harbison, 1977). At cardiovascular system. A decrease in heart rate was observed
higher doses, hind limb paralysis was observed. Neuronal in male rats given two gavage doses of 2 mg Hg/kg as
degeneration and microgliosis were observed in the corpus methylmercuric chloride (Arito and Takahashi, 1991). An
striatum, cerebral cortex, thalamus and hypothalamus, increase in systolic blood pressure was observed in male rats
accompanied by hind leg weakness, in mice given 1 or after daily oral gavage doses of 0.4 mg Hg/kg/day as methyl-
4 mg Hg/kg/day as methylmercuric chloride by gavage for mercuric chloride for 3 4weeks (Wakita, 1987). This effect
60 days (Berthoud et al., 1976). In rabbits given 5.5 mg began approximately 60 days after initiation of exposure and
Hg/kg as methylmercuric acetate for 1 4 days, persisted for at least 9 months.
widespread neuronal degenerative changes in cervical gan-
glia cells, cerebellum and cerebral cortex have been
GI Tract
observed without accompanying behavioral changes
(Jacobs et al., 1977). Ingestion of mercuric chloride is highly irritating to the
Following inhalation exposure to metallic mercury tissues of the GI tract. Inflammation and necrosis of the
vapors, the CNS has been found to be the most sensitive glandular stomach were observed in mice that were given
organ in guinea pigs, rats and mice. With increasing oral doses of 59 mg/kg as mercuric chloride 5 days a week