Toxicokinetics - trdoer40197

Hematologic effects appear to be among the most sensitive indicators of lead

absorption. Lead interference with heme synthesis has been noted in humans and

other mammalian species at blood levels below 10-15 ug/dL. Lead can also lead

to the accumulation of porphyrin in erythrocytes with elevated levels of

erythrocyte protoporphyrin (EP) associated with blood lead levels of 25-

30 ug/dL in adults and 15 ug/dL in children. Anemia is characteristic of more

severe cases of lead poisoning, resulting from erythrocyte destruction and

reduced hemoglobin synthesis (ATSDR 1992).

Renal toxicity has also been observed in victims of lead intoxication.

Reversible proximal tubule damage has been observed primarily in cases of

short-term exposure with reduced glomerular function associated with more

chronic exposures (ATSDR 1992). In adults, chronic exposures to lead can result

in hypertension. Acute exposures can result in peripheral neuropathy and/or

nephropathy. Due to the relationship between maternal body lead stores and fetal

circulation, fetal development can be adversely affected by elevated maternal

body-lead burdens.

USEPA classifies inorganic lead as a category B2, probable human

carcinogen. There is inadequate evidence of carcinogenicity based on human

studies, but several animal bioassays have shown statistically significant

increases in renal tumors following dietary and drinking water exposure to lead

acetate or lead subacetate, two soluble lead salts (IRIS 1999). USEPA has not

calculated a cancer slope factor for inorganic lead because of the large

uncertainties involved, including the effect of age, health, nutritional status, and

body burden (IRIS 1999).

The USEPA has not established a risk reference dose (RfD) for lead because

it appears that some of the observed effects occur at such low doses as to be

essentially without a threshold (IRIS 1999). Because a USEPA derived reference

dose is not available, an alternative approach called the integrated uptake/

biokinetic model is used to evaluate the potential for adverse health effects due

to lead. This is a validated model that calculates blood-lead levels based on

estimated exposure doses of lead to children in to various media such as food,

soil, dust, and water. Once blood lead levels are estimated, adverse effects can be

predicted. To determine an estimation of the health risk due to exposure to lead

at the site of interest, a threshold based on blood lead has been defined, at

10 ug/dl (CDC 1991).

Toxicokinetics

Absorption through the gastrointestinal tract is a function of many factors

including the fasting state and nutritional status of the individual, solubility of

the lead, and particle size. For dietary lead, absorption in children is

approximately 50 percent compared with 5 to 15 percent gastrointestinal lead

absorption in adults (World Health Organization (WHO) 1995). Lead is not well

absorbed dermally, from 0.006 percent to less than 0.3 percent (WHO 1995).

Lead is well absorbed by the lungs, and absorption depends on a number of

factors. These include whether the lead is in particulate or vapor form and the

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Appendix D Toxicological Profiles