An analysis of the need for an additional uncertainty factor for infants and children.
Uncertainty factors have been used for over 40 years to establish safe intakes of threshold toxicants. Tenfold factors are used to allow for species differences and for human variability, with extra factors for database inadequacies. The proposal to introduce an additional 10-fold factor for pesticides when exposure of infants and children is anticipated implies either age-related differences between species or differences within humans which exceed those present in adults. Alternatively, the extra factor could be related to deficiencies of current testing methods or concerns over irreversibility in developing organ systems. Available data do not provide a scientific rationale for the extra factor due to inadequacy of inter- and intraspecies uncertainty factors. Justification for the factor therefore must relate to the adequacy and sensitivity of current methods or concern about irreversible effects in the developing organism.
Renwick
A G
AG
Clinical Pharmacology Group, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton, SO16 7PX, United Kingdom.
Dorne
J L
JL
Walton
K
K
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002648:Child; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D016208:Databases, Factual; D015386:Hazardous Substances / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008452:Maximum Allowable Concentration; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment; D017751:Safety Management; D013045:Species Specificity
D015386:Hazardous Substances