Subclinical Lead Exposure

There is a growing body of evidence that suggests that the performance of young children in neuropsychological tests may be impaired by exposure to lead levels below those that produce obvious cliniced s3miptoms. The literature indicates that there is a relationship between such as3miptomatic or subclinical elevation of blood lead levels emd a number of CNS effects, including 

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Needleman, H.L., Davidson, I., Sewell, E.M., Shapiro, I.M., 1974. Subclinical lead exposure in Philadelphia school children identification by dentine lead analysis. N. Engl. J. Med. 290, 245 -258. 

Needleman H. L. (1977). Studies in subclinical lead exposure. Envir. Hlth. Res. Ser. June 1977, PB-271649. Health Effects Research Laboratories USEPA Research Triangle Park North Carolina. 

Both of the above philosophies have been employed in experiments to assess the effects of subclinical lead exposure on CNS morphology, with essentially similar results. Prompted by the observation that Purkinje cell dendritic morphology is markedly abnormal in experimentally lead-poisoned rat pups, McConnell ... 

Winneke G, Beginn U, Ewert T, et al. 1984. [Understanding of subclinical lead effects on the nervous system of children with known prenatal exposure in Nordenhami], Schriftenr Ver Wasser Boden Lufthyg 59 215-230. (German)... 

Pedraza MA, Anzinger F Lead encephalopathy report of a case associated with industrial exposure. Ohio State Medical Journal 70 319-321, 1974 Perino J, Ernhart CB The relation of subclinical lead level to cognitive and sensorimotor impairment in black preschoolers. J Learn Disabil 7 616-620,1974 Perlstein MA, Attala R Neurologic sequelae of plumbism in children. Clin Pediatr 5 292-298, 1966... 

Despite the substantial research, no single mechanism or simple set of mechanisms has emerged to explain the wide spectrum of effects of lead exposure on the brain. Indeed, all of the molecular mechanisms proposed to date can still be fairly characterized as tentative hypotheses about the many ways that lead might alter brain function. On the other hand, the extensive data and hypotheses gained from this research may serve as the best model available for investigating other neurotoxicants with effects that can range from subclinical CNS impairment to overt encephalopathy. There are many such... 

As stated above, the NTP (2012) report suggested that the evidence regarding an association of low-level lead exposure with other cardiovascular outcomes, including subclinical measures, was limited. The corrunittee identified 10 studies that examined subclinical measures—such as ventricular function, heart rate variability, and pulse pressure—and homocysteine, a biomatker of cardiovascular and neurodegenerative diseases. 

Sachs, 1974) indicated that the incidence of high lead exposure appeared to be falling. This was due to such factors as the changes in the population of the children being screened, increased awareness about lead neurotoxicity, and slum clearance programmes. Death from lead poisoning is now almost zero and encephalopathy is rare. This in turn has focussed attention on the subclinical effects of lead toxicity. 

At lower exposures, the effects of lead are more difficult to examine. It appears that data from recent studies on developing rats with low blood levels (up to 100/(g Pb/lOOml) appear to show effects of lead on maturing and differentiated nerve cell populations. The relevance of these changes to human subclinical lead intoxication is not clear. However, the overall correspondence in lead-poisoned man and rat would make further investigation in this area appear necessary. 

Seppalainen, A. M., Tola, S., Hernberg, S. and Kock, B. (1975). Subclin-ical neuropathy at safe levels of lead exposure. Arch. Environ. Hlth. 30, 180-183. 

Emhart, C.B., Landa, B. and Schell, N.B. (1981). Subclinical levels of lead and developmental deficit - a multivariate follow-up reassessment. Pediatrics, 67, 911-919 Emhart, C.B., Landa, B. and Wolf, A.W. (1985). Subclinical lead level and developmental deficit reanalyses of data. ]. Learn. Disabil, 18, 475-479 Emhart, C.B., Wolf, A.W., Kennard, M.]., Erhard, P., Filipovich, H.F. and Sokol, R.J. (1986). Intrauterine exposure to low levels of lead the status of the neonate. Arch. Environ. Health, 41, 287-291... 

So far only acute adverse effects which could be readily associated with excessive lead exposure have been considered. However, studies on lead workers have elicited symptoms of lassitude, anorexia, abdominal discomfort, constipation, insomnia, irritability, pallor and anaemia - complaints which are common in the general population. The recent development of environmental and biological monitoring procedures, and of epidemiological methodology, now enables us to investigate non-specific and subclinical effects in relation to lead exposure with greater precision. 

Chronic low-level lead exposure (neural development of children (Needleman et al, 1979 Yule el al, 1981 Winneke et al, 1982, 1983) however, as yet the significance of the confounding variables in these studies remains to be resolved (Rutter, 1980 Yule, 1986). Consequently it is necessary to identify a molecular basis by which relevant, subclinical blood lead levels may impair the structuring of the central nervous system and lead to neurobehavioural deficits. 

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