Mechanisms of toxicity and risk assessment.
Incorporating mechanistic information into the risk assessment process is necessary because proliferation of in vitro and in vivo tests of uncertain significance has led to the realisation that the quantity of toxicological information may undermine its own value. Default options in risk assessment to be used in the absence of mechanistic data are mainly derived from extrapolations. Examples from mechanistic studies on organophosphate-induced delayed polyneuropathy (OPIDP) will illustrate 3 main areas of extrapolation where mechanistic data might allow meaningful conclusions for risk assessment: (i) from animal to humans; (ii) from high to low levels of exposure; (iii) from disaggregated systems to complex systems. The continuing effort to understand the mechanisms of toxicity will reduce uncertainty in these and other areas of the extrapolation processes. It could also lead to better appreciation of the significance of biomarkers (such as lymphocyte neuropathy target esterase (NTE) for OPIDP) to be used in biomonitoring programs.
Lotti
M
M
Università degli Studi di Padova, Istituto di Medicina del Lavoro, Italy.
D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D002265:Carboxylic Ester Hydrolases; D006801:Humans; D009468:Neuromuscular Diseases / Q000139:chemically induced / Q000175:diagnosis; D009943:Organophosphorus Compounds / Q000009:adverse effects* / Q000633:toxicity*; D018570:Risk Assessment; D014116:Toxicology / Q000379:methods*
D015415:Biomarkers; D009943:Organophosphorus Compounds; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase