Organophosphate exposure: "response to Krieger et al. and Charnley.

Our recent study of children's dietary exposure to organophosphorus (OP) pesticides (Curl et al. 2003) has elicited two very different responses from readers. In that paper we demonstrated a 6-fold difference in median dialkylphosphate (DAP) concentrations in the urine of children who consumed primarily organically grown or conventionally grown produce. We concluded that consumption of organic rather than conventional produce would result in a reduction of OP pesticide exposure for these children. Krieger et al. respond to our study by suggesting that, since some fraction of the DAP compounds measured in urine samples could be the result of exposure to DAPs present in foods, our conclusions are "not justified by available data." However, Krieger et al. provide little evidence in their letter to support their argument that DAP concentrations measured in urine are the result of DAPs in food.

Krieger et al. mistakenly state that "it seems to have escaped notice" that breakdown products of OP pesticides occur in the environment, including food. In fact, this issue has been discussed at numerous scientific meetings in recent years, and has been well documented during the investigations of methyl parathion misapplications conducted by the Centers for Disease Control and Prevention (Hryhorczuk et al. 2002; Imtiaz and Haugh 2002; Rubin et al. 2002). In regard to the DAP compounds specifically, we raised this issue several years ago in our discussion of biologically based dose estimates of OP pesticide exposure (Fenske et al. 2000). The reason that the issue has not received more prominence is that data to support this viewpoint are not available. At present the argument is largely hypothetical, and Krieger et al. provide only a modicum of new information to inform this discussion.

It is certainly true that pesticide breakdown products can be present in the environment and in food. However, the article cited by Krieger et al. to support this point (Casida 1961) makes clear that OP pesticides can be metabolized by plants to a number of compounds, including the mono-alkyl phosphates and phosphoric acid, none of which would impact DAP measurements in urine. Thus, the extent to which urinary DAPs are by-products of plant metabolism remains unclear. Krieger et al. also cite preliminary data from their own laboratory as evidence of DAPs in food. If correct, these findings would be helpful documentation of the extent to which DAP formation can occur in dietary samples, and we look forward to the publication of these data.

It is also possible, as Krieger et al. argue, that some fraction of DAPs present on food could be absorbed throUgh the gastrointestinal tract, but to our knowledge no studies have been conducted to estimate the extent of such absorption. Finally, their argument rests on the assumption that DAPs, once absorbed, will pass through the body unchanged and appear in the urine. Krieger et al. do not even acknowledge this assumption, and no data are provided to support it. We know of only one study that has attempted to examine the fate of the DAPs in biological systems (Imaizumi et al. 1993). In this study, rats were administered high doses of several DAP compounds. Only small fractions of the administered doses were recovered in urine, suggesting that these compounds were metabolized rather than excreted unchanged. Furthermore, at least one of the DAPs (diethylthiophosphate) inhibited cholinesterase in the rat brain, raising a question as to whether the DAP compounds themselves carry some' risk, in contrast to the assertion by Krieger et al. that these compounds are "nontoxic."

In summary, Krieger et al. have put forth a criticism based largely on conjecture. We cannot conclude from their evidence that the 6-fold difference we report in urinary DAP concentrations between the two groups of children in our study can be explained by DAPs in food. After all, it is well recognized that conventionally grown foods contain more pesticides than do organic foods (Baker et al. 2002). We believe that differential exposure to OP pesticides is a far more likely explanation of this observed difference. We welcome further research in this area, as it will assist all of us in our efforts to develop more accurate estimates of human exposures to hazardous chemicals.

In a second response to our study, Charnley calls attention to the presence of natural toxins in food, echoing a view set forth recently by Mattsson (2000). Charnley is critical of our statement that consumption of organic produce shifts children's OP pesticide exposures from a range of uncertain risk to a range of negligible risk because we have not accounted for risks associated with natural toxins. This criticism raises an important question regarding the proper framework for risk evaluation. More than two decades of study have shown that the context in which risk is evaluated is fundamental to how one goes about the calculation of risk (Presidential/Congressional Commission on Risk Assessment and Risk Management 1997; Slovic 1987).

We stated very clearly that the framework for our risk evaluation is based on "current U.S. Environmental Protection Agency guidelines" (Curl et al. 2003). Charnley (in her letter) and Mattsson (2000) would broaden the risk framework for pesticides to include natural plant toxins, and their argument is beguiling: Plants produce toxins as a stress response to predators; pesticides reduce predator populations and therefore stress; ergo, pesticide-treated plants have less stress and can produce more nutritious chemicals. What is wrong with this proposition, which seems to take us through the looking glass to a world where pesticides are a kind of chemical therapy for plants?

First, this argument rests on a reductionist view of sustainable agriculture in which organic farming is simply conventional farming without pesticides. In fact, sustainable agriculture promotes a host of cultivation practices that differ markedly from the practices of what is often referred to as industrial agriculture (Horrigan et al. 2002). None of the studies cited by Charnley report results from organic farming practices. It seems plausible that many of the practices that differentiate organic and industrial agriculture could be at play in the elaboration of natural plant toxins, and not simply pesticide use.

Second, analysis of the risks of natural toxins is most certainly more complex than Charnley indicates. To take but one example, she notes that glycoalkaloids in potatoes have demonstrated toxic effects in laboratory studies. However, these chemicals also appear to have beneficial health effects, such as conferring protection from viral and bacterial infections (Friedman et al. 2003), a fact that neither Charnley nor Mattsson (2000) choose to mention. Similarly, a recent study of conventional and organic crops indicated that plants grown organically produced higher levels of antioxidants, a presumed benefit to human health (Asami et al. 2003). Charnley also overlooks the fact that many plant toxins would greatly degrade the taste and palatability of fruits and vegetables at doses sufficient to produce acute toxicity in humans (Drewnowski and Gomez-Carneros 2000).

Beyond these arguments, it should be noted that natural toxins generally fall outside of current regulatory boundaries. As Charnley herself points out, natural toxins are "seldom characterized or limited by law." Her argument thus seeks to expand the scope of risk assessment beyond that considered in our analysis. However, a full accounting of the risks associated with pesticide use would need to include several other types of risk, including those faced by agricultural workers. Workers who handle pesticides or who enter pesticide-treated fields can suffer serious illnesses from overexposures to these compounds. For instance, the California Environmental Protection Agency (2002) reported five confirmed "group poisonings" due to OP pesticides in 2000, affecting a total of 151 workers. Farming with pesticides makes such events possible and raises an important environmental justice issue: Should agricultural workers be placed at greater risk so that consumers can purchase foods with reduced natural toxin content? The risk evaluation framework could be further expanded to include community pesticide exposures (e.g., spray drift, groundwater contamination) and ecologic risks.

As our society not so long ago examined pesticide risks from each source in isolation (e.g., residues on food, residential use) and evaluated chemicals with a common mechanism of action separate from one another (e.g., OP pesticides), today we compartmentalize occupational, ecologic, and consumer risks. However, a fully comprehensive risk analysis will need to integrate all of these risks to produce a fair evaluation of the use of pesticides in agriculture.

Both Krieger et al. and Charnley raise important issues. However, we believe that the difference in children's exposure levels found in our study cannot be dismissed based on the evidence they provide. We look forward to future research on pesticide biomarkers and to the development of a broader evaluative framework for the analysis of the risks and benefits of pesticide use in agriculture.

The authors declare they have no conflict of interest.

REFERENCES

Asami DK, Hong YJ, Barrett DM, Mitchell AE. 2003. Comparison of the total phenolic and ascorbic acid content of freeze-dried and air-dried marionberry, strawberry, and corn grown using conventional, organic, and sustainable agricultural practices. J Agric Food Chem 51:1237-1241.

Baker BP, Benbrook CM, Groth E III, Lutz Benbrook K. 2002. Pesticide residues in conventional, integrated pest management (IPM)-grown and organic foods: insights from three US data sets. Food Addit Contam 19:427-446.

California Environmental Protection Agency. 2002. Summary of Results from the California Pesticide Illness Surveillance Program, 2000. Report No. HS-1831. Sacramento, CA:Department of Pesticide Regulation.

Casida J. 1961. Metabolism of organophosphate insecticides by plants: a review. In: Radioisotopes and Radiation in Entomology. Vienna:International Atomic Energy Agency, 49-64.

Curl CL, Fenske RA, Elgethun, K. 2003. Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Environ Health Perspect 111: 377-382.

Drewnowski A, Gomez-Carneros C. 2000. Bitter taste, phytonutrients, and the consumer: a review. Am J Clin Nutr 72:1424-1435.

Fenske RA, Kissel JC, Lu C, Kalman DA, Simcox N J, Allen EH, et al. 2000. Biologically based pesticide dose estimates for children in an agricultural community. Environ Health Perspect 108:515-520.

Friedman M, Henika PR, Mackey BE. 2003. Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice. Food Chem Toxico141:61-71.

Horrigan L, Lawrence RS, Walker P. 2002. How sustainable agriculture can address the environmental and human health harms of industrial agriculture. Environ Health Perspect 110:445-456.

Hryhorczuk DO, Moomey M, Burton A, Runkle K, Chen E, Saxer T, et al. Urinary p-nitrophenol as a biomarker of household exposure to methyl parathion. Environ Health Perspect 110(suppl 6):1041-1046.

Imaizumi H, Nagamatsu K, Hasegawa A, 0hno Y, Takanaka A. 1993. Metabolism and toxicity of acid phosphate esters, metabolites of organophosphorus insecticides in rats. Jpn J Toxicol Environ Health 39:566-571.

Imtiaz R, Haugh G. 2002. Analysis of environmental and biologic methyl parathion data to improve future data collection. Environ Health Perspect 110(suppl 6):1071-1074.

Mattsson JL. 2000. Do pesticides reduce our total exposure to food borne toxicants? Neurotoxico121:195-202.

Presidential/Congressional Commission on Risk Assessment and Risk Management. 1997. Risk Assessment and Risk Management in Regulatory Decision-Making. Final Report, Vol 2. Washington, DC:Presidential/Congressional Commission on Risk Assessment and Risk Management. Available: http://www.riskworld.com/Nreports/1997/ risk-rpt/volume2/pdf/v2epa.PDF [accessed 11 August 2003].

Rubin C, Esteban E, Hill RH, Pearce K. 2002. Introduction--the methyl parathion story: a chronicle of misuse and preventable human exposure. Environ Health Perspect 110(suppl 6):1037-1040.

Slovic P. 1987. Perception of risk. Science 236(4799):280-285.

Cynthia L. Curl Richard A. Fenske Kai Elgethun

Department of Environmental and Occupational Health Sciences School of Public Health and Community Medicine University of Washington Seattle, Washington E-mail: [e-mail]