The significance of the subchronic toxicity in the dietary risk assessment of pesticides.
Based on 289 public pesticide evaluations, geometric means of subchronic/chronic No Observed Adverse Effect Level (NOAEL) ratios of 2.6, 2.5 and 1.6 in mice, rats and dogs were calculated. The 75th percentiles are 5.5, 5.1 and 3.2. Higher ratios correlate with increased dose spacing in chronic studies and may be mainly explained therewith. In rats fed at constant pesticide concentrations in feed, the mean chronic dose decreases by 1.7- and 2.7-fold compared to the subchronic and subacute phase. These dose decreases match the subchronic/chronic NOAEL ratios. The ratio of predicted rat chronic NOAEL (dose decrement adjusted subchronic NOAEL) to experimental chronic NOAEL is 1.5 and the 75th percentile is 3.0. In dietary risk assessment, the Acute Reference Dose and the Acceptable Daily Intake (derived from acute and chronic NOAEL) are compared to acute (IESTI) or mean (TMDI) exposure estimates. Because IESTI and TMDI base on acute or mean food consumption they differ by orders of magnitude for certain commodities. As subchronic and chronic NOAEL are similar, it remains to be shown whether pesticide intake estimates based on mean food consumption are adequate measures to compare against the ADI if repeated daily exposures considerably higher than mean exposures may occur.
Zarn
Jürg A
JA
Federal Office of Public Health FOPH, Food Safety Division, Stauffacherstrasse 101, 8004 Zürich, Switzerland. juerg.zarn@bag.admin.ch
Hänggi
Emanuel
E
Kuchen
Arnold
A
Schlatter
Josef R
JR
D000818:Animals; D004032:Diet; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis*; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D004787:Environmental Pollution / Q000706:statistics & numerical data; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D010575:Pesticides / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D018570:Risk Assessment
D004785:Environmental Pollutants; D010575:Pesticides