Pesticide uncertainty factor

Considerations for the acceptability of the are similar to those for the uncertainty factor used to calculate the RfD, RfC or other reference values from the NOAEL or BMD. The has been calculated from reproductive toxicity data for several chemicals. Examples include dinoseb (US EPA, 1986), lithium (Moore, 1995) and boric acid and borax (Moore, 1997). In the case of dinoseb, the MOEs were very low, in some cases less than one, indicating toxicity in the animal studies at levels to which people are exposed. This information on dinoseb led to an emergency suspension of use of this pesticide in the USA in 1986 and ultimately led to its removal from the market (Kimmel Kimmel, 1994,1996). 

For most pesticides evaluated, an uncertainty factor of 10 to 15 seems to suffice to extrapolate a median acute HC5 to a median chronic HC5, at least when based on toxicity data of sensitive taxonomic groups. In addition, it appears from model ecosystem experiments with pesticides that threshold concentrations for chronic exposures are approximately a factor of 10 lower than those for acute exposure. For a wider generalization, however, more data are required on compounds that differ in toxic mode of action (Section 6.2.4). 

The next step is to calculate a reference dose (RfD) by dividing the NOAEL by the safety or uncertainty factors appropriate for the pesticide under review. Additional safety factors can be used for severity of the toxicological effect, if sensitive sub-populations such as children are likely to be exposed to the pesticide and if there are scientific uncertainties in the data. This approach is used for establishing the risk from exposure to threshold chemicals. 

The following example using aldicarb illustrates how to derive an ADI. Aldicarb is a pesticide that has been detected in ground water in Florida and elsewhere. The EPA is currently in the process of establishing a drinking water criterion for aldicarb. Weil and Carpenter (19) studied the effects of aldicarb sulfoxide on rats and determined a NOEL of 0.125 mg/kg/day. This is supported by another rat study by Mirrow et al. (20), which resulted in a NOEL equal to 0.12 mg/kg/day. An ADI is estimated for aldicarb, using the NOEL from the Weil and Carpenter study and an uncertainty factor of 100 ... 

National Research Council. Pesticides in the Diets of Infants and Children. Washington, D.C. National Academy Press, 1993. (Note See the Executive Summary on pgs 1-12 for a concise discussion on the adequacy of the existing uncertainty factors). 

The comparative cholinesterase studies, as described, provide infonnation on adverse outcomes (cholinesterase inhibition) following cither acute or repeated exposures in populations at various life stages. In a review of cumulative risk assessment procedures for the OP pesticides (EPA, 2(K)2b), acute and/or repeated dose comparative cholinestera.se data in rats were available for a limited number of OP pesticides. These data raised uncertainties regarding the adequacy of adult risk potency factors to be protective of potential age-dependent. sensitivity to cholinestera.se inhibition and of potential adverse neurodevelopmental outcomes that arc a result of the inhibition t)f cholinesterase. As a re,sull, a thrcc-fold database uncertainty factor was applied in the cumulative risk calculation for those chemicals that did not have comparative cholinesterase data twailable for evaluation. This... 

Federal agencies such as the FDA and EPA require a battery of toxicity tests in laboratory animals to determine an additive s or a pesticide s potential for causing adverse health effects, such as cancer, birth defects, and adverse effects on the nervous system or other organs. Tests are conducted for both short-term (acute) and long-term (chronic) toxicity. For chronic effects other than cancer, laboratory animals are exposed to different doses to determine the level at which no adverse effects occur. This level is divided by an uncertainty or safety factor (usually 100) to account for the uncertainty of extrapolating from laboratory animals to humans and for individual human differences in... 

In addition to considering the FQPA-relevant areas of uncertainty, assessments of pesticide risk to children also consider applying part or all of the FQPA factors in certain situations to account for... 

The question of an extra assessment factor in the hazard and risk assessment for chemicals of concern for children is specifically addressed in Section 5.2.1.13. The U.S. Food Quality Protection Act (FQPA) (US-EPA 1996) directed the US-EPA to apply an extra safety factor of 10 in assessing the risks of pesticides to infants and children. The US-EPA (2002) noted the overlap of areas covered by the FQPA factor and those addressed by the traditional UFs, and it was concluded that an additional UF (children-specific) is not needed in the setting of reference values because the currently available UFs (interspecies, intraspecies, LQAEL-to-NOAEL, subchronic-to-chronic, and database-deficiency) were considered sufficient to account for uncertainties in the database from which the reference values are derived. Renwick et al. (2000) concluded that the available data did not provide a scientific rationale for an additional 10-fold UF for infants and children and pointed out that when adequate reproduction, multigeneration, or developmental studies are conducted, there will be no need for an additional 10-fold factor. 

FIGURE 8.1 The risk curve lines shown represent thresholds between different types of decisions (based on ECOFRAM 1999a and 1999b). These thresholds would be determined by decision makers and may move location subject to other factors that affect the decision (e.g., pesticide benefits). The bottom graph shows an example risk curve with uncertainty bounds. The curve clearly fits within the acceptable risk category however the upper uncertainty bound does not, indicating a need for risk mitigation or further refinement of the risk assessment. 

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