Consideration of neurologic effects in case of exceeding toxicological threshold value ?

Abstract : When exposure levels exceed recommended toxicological threshold value, calculated to protect human to adverse effects, without working circumstances and independently of carcinogenic aspects, the most sensitive effects are neurologic ones for various pollutants such as organic solvents or some metals. The consideration of these effects for exposed population in hazard assessment is difficult and especially for the most sensitive sub-populations as children. A methodology for hazard assessment is under development to give information to the risk managers in the case of exceeding of these recommended threshold value. This methodology is based on effects that occur after short time exposure (between few weeks and one year or more) and for not too high levels of exposure. Results of two case-studies on perchloroethylene (tetrachloroethylene) and mercury (metallic form) have shown that neurologic effects are really the most sensitive ones and there is a lack of data for exposure from one week to 3-4 years. An extrapolation by PBPK model from available data has to be proposed but there are difficulties in establishment of a relation between internal dose and these effects. Extrapolation for other critical effects like renal or hepatic is in progress for perchloroethylene. These effects usually occur at little higher exposure levels but are easier quantified by early biomarkers. First results will able to offer useful information and improve protection of population but they are probably not as sufficient to taking into account neurologic effects such as impact on learning abilities during childhood or those of early exposure in the development neurologic diseases in the adulthood.