Subtle consequences of methylmercury exposure: behavioral deviations in offspring of treated mothers.

Overt neurological impairment is the endpoint currently used to document a case of methylmercury poisoning. No consideration is given to possible subtle consequences. Offspring from mice exposed to methylmercury on day 7 or 9 of pregnancy were apparently unaffected during postnatal development. However, subtle behavioral differences between treated and control offspring were found when the overtly normal animals were tested in an open field and evaluated in a swimming apparatus at 1 month of age. Brain weight, protein, choline acetyltransferase, and cholinesterase were not significantly altered.

Assessing the impact of low level chemicals on development: behavioral and latent effects.

There is growing evidence that nervous tissue, especially the brain, is more sensitive to many foreign chemical substances than has previously been suspected, and that toxic effects may be manifested as subtle disturbances of behavior long before any classical symptoms of poisoning become apparent. Early detection of an insidious toxic process (behavioral toxicology) may enable the prevention or attenuation of harm to humans and other organisms. Adding to both the sensitivity and complexity of behavioral toxicologic testing is the increasing evidence that individuals are more vulnerable to adverse factors during the period of development (conception yields puberty) than at any other time in life. Subtle functional disturbances in organisms exposed while immature (behavioral teratology) may be one of the most sensitive indicators of chemical toxicity. Furthermore, defects in a developmental process may have only delayed effects. A morphological or biochemical lesion can be dormant and not manifest itself until later in life as a behavioral disorder, mental deficiency, or overt functional impairment. Longitudinal evaluation is required to detect long-term or delayed effects of a particular developmental influence on biological and behavioral functions. Examples from research on the subtle and latent consequences of prenatal and early postnatal exposure to methylmercury that illustrate the above principles are presented. It is concluded that behavioral and long-term evaluation of organisms exposed during development are essential for a thorough assessment of the impact of certain low level chemicals on human health.

Neurobehavioral effects of prenatal exposure to the organophosphate Diazinon in mice.

Pregnant mice were given to daily dose of 0, 0.18, or 9.0 mg Diazinon per kilogram body weight throughout gestation. Mothers of all dose groups gave birth to viable, overtly normal offspring. However, pups born to mothers receiving the higher dose of the organophosphate grew significantly slower than controls and remained significantly smaller at 1 month of age. Offspring of mothers receiving the lower dose apparently were unaffected, but systematic behavioral testing revealed subtle deviations from normal developmental ontogeny as shown by significant delays in the appearance of the contact placing reflex and of sexual maturity (descent of testes or vaginal opening). Mature offspring of mothers exposed to either dose of the pesticle displayed impaired endurance and coordination on rod cling and inclined plane tests of neuromuscular function. Offspring from the 9.0 mg/kg group, in addition, had slower running speeds in a Lashley III maze and less endurance in a swimming test. Brains obtained after sacrifice at 101 days of age revealed neuropathology in the forebrains of offspring born of mothers exposed to the higher dose. Despite functional impairments in offspring from the lower dose group, no corresponding brain pathology was observed by examination under the light microscope.

Postnatal endocrine dysfunction induced by prenatal methylmercury or cadmium exposure in mice.

The subtle and delayed effects of two heavy metals, cadmium and mercury, on the pituitary-adrenal axis of mice were examined. Exeprimental animals were exposed to the toxins both in utero and neonatally via treated mothers' milk. Plasma levels of corticosterone, adrenal production of corticosterone in vitro, and the capacity of the liver to metabolize corticosterone in vitro were studied in these animals as adults. Exposure to methylmercury resulted in diminished hepatic metabolism of corticosterone in vitro due to a loss of liver mass. Adrenal function and plasma levels of corticosterone were unaffected by treatment. Cadmium-exposed animals examined at 277 days of age showed no significant differences when compared to untreated controls. However, when studied at 460-480 days of age, a sex difference in the response to cadmium exposure was noted. In males, the major effect was enhancement of hepatic reductive capacity, while in females, adrenal secretory capacity was enhanced. Possible mechanisms of action and consequences of these effects are discussed.