ticularly with regard to potential effects on the developing or young animal. Implicit inherent limitations of toxicologic studies are that relatively homogeneous populations of laboratory animals are used and exposures are typically to single chemicals. On average, the lowest increase in effect that can usually be detected (LOAEL) is around 10% due to statistical power related to the number of animals that can be tested in any one study. In the instances of TCE and PCE, however, rodents are more susceptible to toxic effects.

A central issue in toxicology (and at Camp Lejeune) is whether doses were sufficient to produce specific adverse effects. The lowest doses at which adverse health effects have been seen in animal or clinical studies are many times higher than the worst-case (highest) assumed exposures at Camp Lejeune. However, that does not rule out the possibility that other, more subtle health effects that have not been well studied could occur, although it somewhat diminishes their likelihood.

Another important issue is whether any adverse effects that may have occurred were reversible or permanent and (still) detectable when an epidemiology study might be conducted. Observations in animal studies indicate that very high acute or chronic doses of TCE or PCE are necessary to injure renal proximal tubular cells. Results of occupational-exposure studies indicate that relatively high, chronic exposures result in modest, reversible changes in the most sensitive indexes of renal injury in workers. Thus, it is unlikely that renal toxicity would be a useful end point to examine in future epidemiology study of Camp Lejeune residents. A similar conclusion can be drawn with regard to the occurrence and detection of hepatic toxicity. Reproductive and developmental effects in rodents were quite modest and often secondary to general toxicity, decreased food intake, and reduced body-weight gain resulting from high maternal doses of TCE and PCE. The toxicologic data provide strong evidence that neither solvent is associated with congenital malformations in rats. Thus, on the basis of this review, reproductive effects and hepatorenal toxicity are probably not of great concern at Camp Lejeune.

There is reasonable interspecies concordance between rats and humans in the bioactivation of TCE and PCE and in their mode of induction of kidney cancer. A low incidence of kidney cancer has been seen in workers exposed for many years to TCE at concentrations high enough to cause dizziness, headache, and other reversible neurologic effects. The background incidence of kidney cancers in unexposed persons is minimal. Nevertheless, there is little likelihood of identifying any increased incidence of renal tumors in the relatively small population that may be available for study at Camp Lejuene.

Irreversible neurobehavioral effects associated with solvent exposure generally are chronic and result from high doses. Solvent abusers and workers chronically exposed to high vapor concentrations may exhibit various neurobehavioral effects and residual brain damage. Fetuses, infants, and young children exposed to such organic solvents as TCE and PCE at lower concentrations may experience subtle neurodevelopmental effects, but no relevant investigations were identified. There are few data from animal studies on this topic.

Immune suppression and autoimmunity related to TCE exposure have been demonstrated in some sensitive animal models. TCE-induced glomerulonephritis and scleroderma occur in low incidences in highly exposed worker populations. Much less is known about the potential immunologic effects of PCE (particularly as related to exposures during development), which may warrant further consideration for inclusion in studies of populations exposed to TCE or PCE.



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