Blood lead levels animal studies

An adverse effect of lead on pregnancy rate has been noted in some animal studies (Kennedy et al. 1975). Acute-duration gavage administration of 390 mg lead/kg/day as lead acetate to rats resulted in a sharp decrease in pregnancy rates. This effect was not noted at 39 mg lead/kg/day. The study limitations include a lack of measurement of blood lead levels and lack of statistical analysis of pregnancy incidence. A decrease in the number of implantations was noted in untreated female mice that were mated to males that had been treated with 141 mg/kg/day lead chloride in the drinking water for 3 months... 

In contrast to the animal studies for prenatal exposure, animal studies for postnatal exposure report effects at blood lead levels similar to those associated with effects in humans. 

Ferguson and Bowman 1990 Gilbert and Rice 1987 Hopper et al. 1986 Krasovskii et al. 1979 Levin et al. 1988 Massaro and Massaro 1987 Overmann 1977 Rice 1985a). It appears that animals are affected at roughly the same blood lead levels as humans. Measured neurotoxic effects in animals include significantly delayed motor function and reflexes, decreased performance on learning tasks, and impaired spatial discrimination. Additional animal studies are needed to investigate the neurotoxic effects of subchronic inhalation exposures to establish external dose-effect relationships. 

A desirable feature of succimer is that it does not significantly mobilize essential metals such as zinc, copper, or iron. Animal studies suggest that succimer is effective as a chelator of arsenic, cadmium, mercury, and other metals. Succimer has been approved in the U.S. for treatment of children with blood lead levels >45 pg/dL. 

Early studies showed that lead was present in the brain of lead-dosed animals in appreciable quantities (e.g. Sauerhoff and Michaelson, 1973). The accumulation of lead in the brain is related to blood lead levels (Goldstein et al., 1974), although the levels of lead within different brain areas show considerable variability. 

In animal studies, decreased zinc status also contributes to lead and cadmium toxicity. In studies with rats, Cerklewski and Forbes (1976) demonstrated that an increase of zinc in the diet decreased the tissue lead levels and reduced other indicators of lead toxicity. Cerklewski (1979) also demonstrated that high levels of zinc fed to pregnant rats resulted in significantly lower levels of lead in the blood and liver of the rat pups. Using Japanese quail, Jacobs et al. (1977) reported that supplemental zinc markedly decreased concentrations of cadmium in the liver, kidney and small intestine, while Fox et al. (1979) showed that marginally adequate levels of dietary zinc markedly increased retention of cadmium in the duodenum, jejunum, ileum and liver as compared with zinc-supplemented birds. The association between increased lead burdens and lower serum zinc levels in children was reported by Markowitz and Rosen (1981). However, the mean levels of serum zinc in the children with elevated blood lead levels were not considered to be outside the lower limits of normal for plasma cited by Hambidge (1977). 

Although studies in animals have shown that administration of vitamin D to vitamin D-deficient rats increased lead absorption, no similar association has been found in children to date. In fact, 1,25-dihydroxy vitamin (1.25-(OH) ) levels in children with high blood lead levels were significantly reduced compared to controls as reported by Rosen et al. (1980). Plasma levels of 1.25-(OH)2 Ds rose to normal values in these children following EDTA chelation therapy, which reduced the children s blood lead levels. Reduced levels of 1.25-dihydroxy vitamin D have been observed in lead-fed rats (Smith et al., 1981). 

The literature on the neurobehavioral effects of oral exposure to lead in animals is extensive. Only those studies considered key to clarifying human health issues will be presented here. High levels of exposure to lead produce encephalopathy in several species, but blood lead data for this effect are generally not available. 

Nephropathy has been associated with chronic lead poisoning. " A study of two large cohorts of heavily exposed lead workers followed through 1980 demonstrated a nearly threefold excess of deaths attributed to chronic nephritis or other hypertensive disease, primarily kidney disease. Most of the excess deaths occurred before 1970, among men who began work before 1946, suggesting that current lower levels of exposure may reduce the risk. Experimental animal studies suggest there may be a threshold for lead nephrotoxicity, and in workers, nephropathy occurred only in those with blood levels over 62p,g/dl for up to 12 years."... 

Epidemiologic, experimental, and in vitro mechanistic data indicate that lead exposure elevates blood pressure in susceptible individuals. In populations with environmental or occupational lead exposure, blood lead concentration is linked with increases in systolic and diastolic blood pressure. Studies of middle-aged and elderly men and women have identified relatively low levels of lead exposure sustained by the general population to be an independent risk factor for hypertension. In addition, epidemiologic studies suggest that low to moderate levels of lead exposure are risk factors for increased cardiovascular mortality. Lead can also elevate blood pressure in experimental animals. The pressor effect of lead may be mediated by an interaction with calcium mediated contraction of vascular smooth muscle, as well as generation of oxidative stress and an associated interference in nitric oxide signaling pathways. 

---