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LEAD TOXICITY Case study for short course on Risk Analysis in Occupational and Environmental Health School of Public Health Harvard University September 4-6, 1991 Lead has been chosen for a case study, because it brings out a lot of different issues related to risk analysis. Moreover it is a problem of active interest at the present time. Lead acetate has been shown to be carcinogenic in animals, but lead acetate is not usually the form in which humans are exposed. An exception is the men's hair dye GRECIAN FORMULA which consists of lead acetate, but risk analyses both by the manufacturer and by FDA have shown that normal application to the scalp produces risks of less than one in a million per lifetime. It will not therefore be of concern to us here. EXPOSURE There are several exposure routes: (1) Dermal application of lead acetate as a hair dye (2) ][ngestion of lead from (i) water from lead pipes (ii) water from pipes soldered with lead solder (iii) eating from lead glazed dishes (iv) eating vegetables grown in soil containing lead ;(v) leachi,ng of lead from crystal and plastic food bags (3) Childhood ingestion of (i) peeling lead paint (ii) house dust from lead paint (iii) lead from soil (4) Inhalation of lead oxide (i) from combusted leaded gasoline (ii) from suspended soil dust (5) Inhaled/ingested lead from home renovation/paint stripping and welding/soldering. The calculation of exposure in environmental cases is often complex and fraught with approximations and possibly errors. Whenever the dose can be measured directly, it is clearly superior to using a complex calculation of exposure and,deriving the dose. Lead has appeared in the blood, and blood lead measurements can be and have been made. The averaging time for blood lead measurements'is not completely known but it is longer than a day, and shorter than a lifetime. Dentine (tooth) lead and bone lead levels have often been taken and are regarded to be superior when available. Blood lead levels can either be taken by themselves, or as calibrations for the complex exposure calculations.

-2- 'Today's major concerns are the neurobehavioral effects on children and blood pressure effects on adults. At the turn of the century, levels of lead in the blood averaged 30 Vg/dl in major cities, and often exceeded 100 Pg/dl. There were m,any cases of overt toxicity. Now the concentrations are down in the range 5 to 20 Vg/dl, the question arises: are there non-overt cases of intoxication? Is thare a threshold for such effects? and what are the effects on public health as a !whol e? It is these questions that we ask you to think about. Questions for consideration during the course The carcinogenicity of organic compounds is considered for each compound separately.' For example, chlorine by itself is not considered to be a carcinogen, but many chlorinated organic compounds are. Does the same rationale apply to inorganic compounds? Should we regard all lead compounds as carcinogenic because lead acetate is? What are the requirements for a direct dose measurement? Why is not presenc:e in,urine usually considered a good indicator of dose? Is it a good indicator of exposure? What would be the best marker for cumulative lead exposure? Should we be more or less careful in our (a) calculations (b) regulatory criteria because we have a more direct dose measurement than for most pollutants? Is it likely that there is a linear dose response relationship for effects of lead on: (i) IQ? (ii) neurobehavioral development? (iii) blood pressure? Several people have found that blood lead does not increase proportionally with soil lead above 2000 ppm in soil. What are the implications for a dose response relationship? Tlhere is a statistical reverse correlation of IQ with blood lead. What is the dirrction of causality? Does eating lead paint cause low IQ? Or do people with low IQ live in houses where the children eat lead paint? How can one tell? What are the public health implications of a 4 point reduction of IQ with N levels of lead at 40 Vg/dl? Of two 3 point increase in blood pressure 0 of 40 jac,I/dl ? ~y : CTI The average blood lead seems to have fallen from 30 Vg/dl in 1990 to below CA 10 today: What is/are the reason/s for the reduction? ~ (;ii) Is it low enough? ~ (iii) How can one tell? ~ (iv) If there are bad effects at 10 Vg/dl why were they not overt at 30?

-3- ATTACHMENTS (1} Toxicity profile for lead. (2) Paper: Lippmann, Morton. "Lead and Human Health: Background and Recent Findings". Environmental Research, 51, pp. 1-24 (1990). (3) Paper: Silbergeld, E.K. "Lead in Bone: Implications for Toxicology (4) Paper: during Pregnancy and Lactation". Environmental Health Perspectives, Vol. 91, pp. 63-70 (1991). Needleman, H.L. et al °'The Long-Term Effects of Low Doses of Lead in Childhood". The New England Journal of Medicine, Vol. 322, No. 2,pp. 83-88 (1990).

-4- CALCULATION FOR SOIL INGESTION Factors to be measured express results as: Concentrati'on of Pb in soil Mean (Geometric) Deviation Amount eaten by children Mean (Geometric) Deviation Absorption by gut Mean (Geometric) Deviation (includes solubility) Relationship of blood lead to gut absorption The resultant blood level is the product of all 4 factors. 'To the extent that the factors are independent, and the relationships are linear, the deviation of distribution of the blood lead is obtained by taking the root mean square of the deviations of the individual distributions.