Sex and strain differences of susceptibility to methylmercury toxicity in mice

Excretion and organ distribution of mercury and susceptibility to methylmercury (MeHg) toxicity were compared between strains and sexes after successive oral administration of MeHg chloride (5 mg/kg per day) using BALB/cA (C) and C57BL/6N (B6) mice. Every mouse died several days after initiation of toxic symptoms, and significant strain and sex differences were found with regard to length of survival. C mice of both sexes died earlier than B6 mice. B6 males survived much longer (greater than 6 weeks) than B6 females (3 weeks), whereas C males died earlier than C females. B6 male mice showed remarkably higher urinary Hg excretion and lower Hg levels in the brain, liver, kidney and blood than the other 3 groups. With daily MeHg administration, the Hg levels in all tissues except the kidney showed linear increase until the manifestation of toxic symptoms. Mercury accumulation in the kidney, the tissue with the greatest uptake of Hg in the mice examined herein, was biphasic: accumulation was rapid for 7-10 days after which the rate of increase was greatly reduced until death. It is suggested that conditions resulting in saturation of the rate of kidney Hg uptake might cause inhibition of urinary Hg excretion via some disturbance of renal function. Subsequently, Hg accumulation would be accelerated in various tissues, including the brain, leading to manifestation of toxic symptoms.