TY - JOUR
T1 - Endpoints and surrogates for use in population studies in toxicology
AU - Greim, Helmut
PY - 2001/3/31
Y1 - 2001/3/31
N2 - Risk characterisation of human exposure to chemicals requires information on the intrinsic toxic (hazardous) properties of the chemical, dose response of effects for the critical endpoints and exposure of the population. Information on hazardous properties, including data on mechanism and toxicokinetics, is necessary to define the critical endpoints and the relevant parameters to assess internal exposure and its relation to external exposure. Consequently the design of population studies to evaluate toxic effects or to monitor exposed cohorts must consider the critical endpoints of toxic effects and exposure. External exposure is determined by chemical analysis of the chemicals in food, water or air. The more relevant internal exposure is assessed by analysis of the chemical or its metabolites in body fluids and, if appropriate, by protein- or DNA-adducts. Effects are monitored by determining the relevant organ-specific parameters. In the case of genotoxic agents, effect biomonitoring parameters, like cytogenetic effects in peripheral blood cells or DNA strand breaks, are applied. Genotyping to detect deficiencies in the expression of enzymes, e.g. those involved in metabolic activation or inactivation, may explain interindividual differences in susceptibility. Overall prospective population studies allow exposure monitoring and risk assessment of human exposure only when such parameters are included.
AB - Risk characterisation of human exposure to chemicals requires information on the intrinsic toxic (hazardous) properties of the chemical, dose response of effects for the critical endpoints and exposure of the population. Information on hazardous properties, including data on mechanism and toxicokinetics, is necessary to define the critical endpoints and the relevant parameters to assess internal exposure and its relation to external exposure. Consequently the design of population studies to evaluate toxic effects or to monitor exposed cohorts must consider the critical endpoints of toxic effects and exposure. External exposure is determined by chemical analysis of the chemicals in food, water or air. The more relevant internal exposure is assessed by analysis of the chemical or its metabolites in body fluids and, if appropriate, by protein- or DNA-adducts. Effects are monitored by determining the relevant organ-specific parameters. In the case of genotoxic agents, effect biomonitoring parameters, like cytogenetic effects in peripheral blood cells or DNA strand breaks, are applied. Genotyping to detect deficiencies in the expression of enzymes, e.g. those involved in metabolic activation or inactivation, may explain interindividual differences in susceptibility. Overall prospective population studies allow exposure monitoring and risk assessment of human exposure only when such parameters are included.
KW - Biomarkers of effect
KW - Biomarkers of exposure
KW - Genetic susceptibility
KW - Internal exposure
UR - http://www.scopus.com/inward/record.url?scp=0035977872&partnerID=8YFLogxK
U2 - 10.1016/S0378-4274(01)00271-5
DO - 10.1016/S0378-4274(01)00271-5
M3 - Article
C2 - 11323199
AN - SCOPUS:0035977872
SN - 0378-4274
VL - 120
SP - 395
EP - 403
JO - Toxicology Letters
JF - Toxicology Letters
IS - 1-3
ER -