Pesticides and Human Health: The Influence of Pesticides on Levels

Chapter 12

Downloaded by UNIV MASSACHUSETTS AMHERST on September 23, 2012 | http://pubs.acs.org Publication Date: July 16, 1999 | doi: 10.1021/bk-1999-0734.ch012

Pesticides and Human Health: The Influence of Pesticides on Levels of Naturally-Occurring Plant and Fungal Toxins Carl K. Winter Department of Food Science and Technology, University of California, Davis, CA 95616

While the potential health risks from pesticide residues generate significant public, legislative, and regulatory concern, it is possible that agricultural pesticide use may, on occasion, influence dietary risks. It has been proposed that pesticide use may reduce the risks associated with naturally-occurring toxins of plants and fungi by reducing the pest pressures which may stress plants into producing their own toxins or by controlling the fungi responsible for mycotoxin production. Very little direct research has been published investigating such pesticide/natural toxin relationships, however; the limited results have indicated that pesticide use may increase or decrease naturally -occurring toxin levels. Current regulatory programs to examine such relationships are burdened by statutory limitations and jurisdictional issues. Present U.S. pesticide regulations allow only very limited consideration of benefits such as decreased risks from naturally -occurring toxins, and separate federal agencies control the regulation of pesticides and the regulation of naturally-occurring food toxins.

Pesticide residues and their potential human health effects continue to receive considerable public, legislative, and regulatory attention while media accounts of this controversial topic remain frequent. The passage of the Food Quality Protection Act (FQPA) of 1996 (7) has presented tremendous challenges to pesticide regulators as they strive to more effectively perform risk assessments that consider factors such as cumulative and aggregate exposure and the special exposure and susceptibility issues of sub-populations (i.e. infants and children). Enforcement of FQPA may result in a significant number of regulatory actions limiting the uses of many pesticides, particularly those which belong to families of chemicals that share common toxicological mechanisms of action such as the organophosphate insecticides, the carbamate insecticides, and the triazine herbicides.

© 1999 American Chemical Society In Pesticides: Managing Risks and Optimizing Benefits; Ragsdale, N., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.

165

166


Naturally Occurring Toxins in Food It has been commonly argued that the level of public concern and regulatory scrutiny directed towards pesticide residues in foods is unwarranted given the low relative risks of pesticide residues in the diet and that such attention detracts from the far more serious food safety concerns of microbiological contamination and nutritional imbalance (2). In addition, the National Research Council (NRC) recently concluded that the naturally-occurring components of the diet may present greater theoretical cancer risks than synthetic chemicals such as pesticides (3). The finding of the N R C supports more than a decade of research by Ames and coworkers who, by comparing the risks of naturally-occurring and synthetic carcinogens quantitatively using their HERP (Human Exposure/Rodent Potency) index, reached a similar conclusion (4,5). Communicating Risks from Naturally Occurring Toxins. If one accepts the conclusion that naturally-occurring chemicals in food pose much greater potential human health risks than pesticide residues, it is tempting to use this as evidence that pesticides may be receiving excessive regulatory scrutiny and that public concern over pesticide residues is misguided. It is important to realize, however, that public and personal decisions also involve critical elements concerning public values and the acceptability of different types of risks. Risk acceptability, while influenced by the magnitude of the risk calculated in the risk assessment process, also includes a number of qualitative factors such as the voluntariness of exposure, controllability, familiarity, origin, memorability, fairness, effects on children, and the level of trust in institutions (6). The direct comparison of seemingly unrelated risks such as pesticide residues and naturally-occurring toxins ignores many of these qualitative factors. This type of risk comparison, according to Covello et al. (7), represents a poor risk communication strategy that is likely to be ineffective and, in fact, may not only fail but also may provoke outrage. Relationship Between Pesticides and Naturally Occurring Toxins. On closer examination, it appears that the risks of pesticide residues and naturally-occurring toxins may not be completely unrelated. The use of pesticides may, in some cases, actually affect levels of naturally-occurring toxins. This relationship enables the use of a higher ranking comparison, according to Covello et al. ( 7), involving the comparison of the risk of doing something (using pesticides) with the risk of not doing something (unaltered naturally-occurring toxin risk); such a comparison is far more likely to be successful as a risk communication tool than comparing seemingly unrelated risks. One link between pesticide use and levels of naturally-occurring toxins is based upon the premise that plants, when under stress, may produce their own natural toxins, known as phytoalexins (phyton = plant; alexin = defend) (8). By reducing plant stress from insect attack, weed competition, or plant pathogens, pesticides may affect changes in phytoalexin synthesis. Hundreds of different phytoalexins have been identified and their occurrence is comprehensively reviewed by Beier and Nigg (9). A variety of stimuli have been shown to induce phytoalexin synthesis

In Pesticides: Managing Risks and Optimizing Benefits; Ragsdale, N., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.

167


such as ultraviolet light and heavy-metal salts {10), attack by nematodes (77), and viral infections (72). Natural Toxin Examples. Notable phytoalexins include the glycoalkaloids produced from potatoes and the linear furanocoumarins produced by umbelliferous plants such as celery. The major glycoalkaloid from potatoes is cc-solanine, while others produced include oc-chaconine and leptine I (Figure 1); all of these compounds are inhibitors of cholinesterase enzymes that are presumably synthesized to provide insect resistance. Glycoalkaloid levels have been shown to increase as a result of exposure to light or when potatoes are wounded. Breeding programs to confer insect resistance have led to the development of varieties with high α-solanine content of acute toxicity concern to humans (9). Linear furanocoumarins are notorious for their ability to cause contact dermatitis in field workers handling celery plants and have been shown to intercalate into D N A and R N A . These compounds, which include psoralen, bergapten, isopimpinellin, and xanthotoxin (Figure 2), are photosentizing agents used medicinally to treat skin depigmentation and psoriasis. Animal and human epidemiological studies indicate potential carcinogenic risks from psoralen exposure. Under conditions of stress such as fungal attack (13), metal ions (10), and acidic fog (14), celery plants have produced elevated levels of furanocoumarins. Celery plants bred for pest resistance showed linear furanocoumarin levels elevated from 10- to 15-fold and caused photophytodermatitis in grocery store workers (9). Another mechanism by which pesticide use may influence naturally-occurring toxins is through interactions with mycotoxin-producing fungi that colonize food crops. It seems reasonable that pesticides such as fungicides may interfere with mycotoxin synthesis and could therefore reduce the potential health risks associated with consumption of mycotoxins in food. The best known and studied mycotoxins are the aflatoxins; these mycotoxins are frequently found in a variety of food products including corn and peanuts (75). They are produced by Aspergillus flavus and Aspergillus parasiticus and have been shown to be potent mutagens, carcinogens, and teratogens. Epidemiological studies indicate that aflatoxins may play a role in the development of human primary hepatocellular carcinoma, either independently or in combination with hepatitis Β virus (9). Considerable contemporary toxicological concern also surrounds the fumonisins which are mycotoxins produced by the corn pathogens Fusarium moniliforme and Fusarium proliferatum. Fumonisin B i (Figure 3) was discovered in 1988 by a South African research group investigating the cause of human esophageal cancer in parts of southern Africa (16) and fumonisin contamination of corn and cornbased food has since been associated by epidemiological data to high occurrences of esophageal cancer risk in Transkei, South Africa (77). Fumonisin B i has been shown to be hepatocarcinogenic and hepatotoxic in rats, causes



168

Figure 1. Potato glycoalkaloids



169

ÔCH

Xanthotoxin

3

Isopimpinellin

Figure 2. Linear furanocoumarins found in food plants

Figure 3. Fumonisin B

t


170 leukoencephalomalacia in horses, and causes pulmonary edema in pigs. A number of congeners of A A L toxins, which are structurally-related to the fumonisins, have been identified and are produced by the fungus Alternaria altemata f.sp. lycopersici (18, 19) while other toxins such as alternariol, alternariol monomethyl ether, and tenuazonic acid have also been produced by Alternaria species (20).


Reductions in Naturally Occurring Toxin Levels from Pesticide Use While it seems plausible that the use of pesticides may reduce levels of phytoalexins and mycotoxins in foodstuffs by reducing plant stress and/or controlling toxin-producing fungi, the available research base investigating such pesticide/natural-toxin relationships is quite sparse, particularly in the case of pesticide/phytoalexin relationships. Effects of Fungicides. A handful of research papers have been published that investigate the direct relationship between fungicide use and mycotoxin production. Results from fungal culture studies indicate that aflatoxin B i levels from Aspergillus flavus were reduced by chlorothalonil, dichloran, and mancozeb with chlorothalonil being significantly more effective than the other two fungicides (21). Carboxin/captan, tolclofos-methyl/thiram, and procymidone fungicide applications to liquid cultures of Aspergillus flavus and to corn grains and sunflower seeds all showed at least some decrease in aflatoxin production at the levels tested (22). Iprodione inhibited aflatoxin production from a strain of Aspergillus parasiticus grown in culture (23), while the use of propionic acid (as ammonium propionate) sprayed on moist unshelled peanuts effectively reduced aflatoxin levels (24). The fungicide cuprosan (a mixture of manganese and zinc ethylenebisdithiocarbamates and copper oxychloride), when applied to two strains of Alternaria altemata isolated from decayed fruits, inhibited synthesis of alternariol and its monomethyl ether (25). Effects of Insecticides/Nematicides. A small number of studies have investigated the relationship between insecticide/nematicide use and mycotoxin production. While the insecticides may not affect toxigenic fungi directly, they may control damage to food crops that provides opportunities for fungal colonization (26,27). Application of the nematicides fenamiphos, carbofuran, and aldicarb reduced the occurrence of Fusarium species naturally contaminating roots and fruits of tomato plants and inhibited or reduced production of the mycotoxin zearalenone (28). Addition of dichlorvos to culture media of two strains of Alternaria altemata and application of dichlorvos to sunflower seeds showed marked decreases in alternariol, alternariol monomethyl ether, and tenuazonic acid levels (20). In a different study, sumi oil also reduced levels of alternariol and alternariol monomethyl ether when added to cultures of two strains of Alternaria altemata isolated from decayed fruits (25).


171


Increases in Naturally Occurring Toxin Levels from Pesticide Use Interestingly, some published reports indicate increases in naturally-occurring toxin levels following pesticide application. Applications of a mixture of the fungicides tebuconazole and triadimenol decreased the incidence of Fusarium headblight from Fusarium culmorum in winter wheat but produced much higher levels of the mycotoxin nivalenol (29), indicating that the fungus may itself respond to stress by producing greater levels of toxins. While Trumble et al. (30) reported relatively little effect of the herbicide prometryn and the insecticides Bacillus thuringiensis, naled, and methomyl on the induction of linear furanocoumarin production in celery, Nigg, et al. (31) demonstrated that treatment of a commercial Florida celery cultivar with the fungicides chlorothalonil, manganese ethylenebisdithiocarbamate, and copper hydroxide did not increase psoralen levels but did increase bergapten levels in leaves and stalk by factors of 2 to 4, xanthotoxin levels in stalk by factors of 2 to 3, and isopimpinellin levels in leaves by factors of 2 to 3. Application of the diphenyl ether herbicide acifluorfen to a variety of plants greatly increased the synthesis of several phytoalexins in broad beans (glyceollins, glyceofuran, medicarpin, and wyerone), beans and pinto beans (phaseollin), peas (pisatin), celery (xanthotoxin), and cotton (hemigossypol) (32). Such enhancements of natural toxin levels may have been caused by induction of phenylalanine ammonia-lyase, a key enzyme in the synthesis of several phytoalexins (32). Regulatory Implications Statutory Issues. The potential influence of pesticide applications on levels of naturally-occurring toxins has not received much regulatory attention. The Food Quality Protection Act of 1996 does include provisions that would allow the use of a pesticide that does not meet "reasonable certainty of no harm" criteria in cases where the "use of the pesticide chemical that produces the residue protects consumers from adverse effects on health that would pose a greater risk than the dietary risk from the residue" (1). The consideration of such benefits, however, are limited only to non-threshold (cancer) endpoints that present an annual risk of no more than ten times the yearly allowable (1 χ 10" ) risk and no more than two times the lifetime risk (7). As such, benefits would not be allowed in cases where the pesticide residue risks exceeded these levels even though the pesticides might reduce the cancer risks from naturally-occurring toxins to a far greater amount. Practical Issues. Aside from the quantitative statutory restrictions on benefits consideration, practical barriers also exist. The FQPA contains provisions requiring the EPA to publish information concerning the risks and benefits of pesticides to be provided for distribution to consumers at the retail grocery level (7). In cases where benefits considerations are used to allow registrations of specific pesticides on particular commodities, it is required that these pesticide/commodity combinations be listed. From a practical standpoint, significant public concern and avoidance of "identified" commodities might be anticipated that would discourage pesticide manufacturers and growers to pursue pesticide registrations on the basis of benefits. 6

Jurisdictional Issues. The regulatory system currently does not include considerations of cases where the use of pesticides may increase the production of


172 naturally-occurring toxins although the U.S. Food and Drug Administration (FDA) and E P A do consider increases in naturally-occurring toxins from the use of recombinant D N A technologies. This presents an interesting jurisdictional debate as E P A regulates pesticides while F D A has regulatory authority for naturallyoccurring toxins.


Conclusions In summary, it is concluded that knowledge about the potential effects of pesticide use on the production of naturally-occurring toxins is extremely limited. In some cases, pesticide use may decrease levels of natural toxins; in others, natural toxin levels may increase. The human health significance of pesticide/naturallyoccurring toxin relationships is also poorly understood; while the N R C concluded that the risks from naturally-occurring toxins may present greater potential human cancer risks than synthetic chemicals such as pesticides in the diet, it was also concluded that most naturally-occurring and synthetic chemicals in the diet appear to be present at levels so low that they are unlikely to pose an appreciable cancer risk or other significant adverse biological effects (3). Finally, in the event where the health significance of increasing or decreasing naturally-occurring toxins through pesticide use is deemed important, our present regulatory system is burdened by regulatory statutes and jurisdictional issues that may render regulatory efforts ineffective in terms of protecting public health.

Literature Cited 1.

Food Quality Protection Act of 1996. Public Law 104-170, 104th Congress,Washington, D.C. 1996. 2. Winter, C.K. Weed Technol. 1996, 10, 969-973. 3. Carcinogens and Anticarcinogens in the Human Diet. NRC. National Academy Press, Washington, D.C., 1996. 4. Ames, B.N., Magaw, R., Gold, L.S. Science 1987, 236, 271-280. 5. Gold, L.S., Slone, T.H., Stern, B.R., Manley, N.B., Ames, B.N. Science 1992, 258, 261-265. 6. Winter, C.K., Francis, F.J. FoodTechnol.1997, 51, 85-92. 7. Covello, V.T., Sandman, P.M., Slovic, P. Risk Communication, Risk Statistics, and Risk Comparisons: A Manual for Plant Managers.; Chemical Manufacturers Association, Washington, D.C., 1988. 8. Grisebach, H., Ebel, J. Angew. Chem. Int. Ed. Engl. 1978,17,635-647. 9. Beier, R.C., Nigg, H.N. In Foodborne Disease Handbook: Diseases Caused by Hazardous Substances. Hui, Y.H., Gorham, J.R., Murrell, K.D., Cliver, D.O., eds., Marcel Dekker, New York, N.Y., 1994; Vol. 3; pp. 1-186. 10. Beier, R.C., Oertli, E.H. Phytochemistry 1983, 22, 2595-2597. 11. Veech, J.A. J. Nematol. 1979,11,240-246. 12. Lord, K.M., Epton, H.A.S., Frost, R.R. Plant Pathol. 1988, 37, 385-389. 13. Wu, C.M., Koehler, P.E., Ayres, J.C. Appl. Microbiol. 1972, 23, 852-856. 14. Dercks, W., Trumble, J., Winter, C. J. Chem.Ecol.1990, 16, 443-454.


173 15.

16.


17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.

Hsieh, D.P.H., Gruenwedel, S.H.O. In: Chemicals in the Human Food Chain, Winter, C.K., Seiber, J.N., Nuckton, Eds.; Van Nostrand Reinhold, New York, N.Y., 1990 pp. 239-267. Bezuidenhout, S.C., Gelderblom, W.C.A., Gorst-Allman, C.P., Horak, R.M., Marasas, W.F.O., Spiteller, G., Vleggaar, R. J. Chem. Soc. Chem. Commun. 1988, 743-745. Rheeder, J.P., Marasas, W.F.O., Thiel, P.G., Sydenham, E.W., van Schalkwijk, D.J. Phytopathology 1992, 82, 353-357. Caldas, E.D., Jones, A.D., Ward, B., Winter, C.K., Gilchrist, D.G. Agric. Food Chem. 1994, 42, 327-333. Caldas, E.D., Jones, A.D., Winter, C.K., Ward, B., Gilchrist, D.G. Anal. Chem. 1995, 67, 196-207. Dalcero, Α., Combina, M., Etcheverry, M., Chulze, S., Rodriguez, M.I. Food Additives and Contaminants 1996, 13, 315-320. Chourasia, H.K. Nat. Acad. Sci. Letters (India) 1992, 15, 243-246. El-Kady, I.A., El-Maraghy, S.S.M., Abdel-Mallek, A.Y., Hasan, H.A.H. Zentralbl.Mikrobiol.1993, 148, 549-557. Arino, A.A., Bullerman, L.B. J. FoodProt. 1993, 56, 718-721. Calori-Domingues, M.A., Fonseca, H. Food Additives and Contaminants 1995, 12, 347-350. Omar, S.A., Hahmoud, A.L.E. Mycoses 1995, 38, 93-96. Widstrom, N.W. J. Environ. Qual. 1979, 8, 5-11. Gianessi, L.P. Crop Protection Issues Paper #1, National Center for Food and Agricultural Policy, Washington, D.C., 1997. El-Morshedy, M.M.F., Aziz, N.H. Bull. Environ. Contam. Toxicol. 1995, 54, 514-518. Gareis, M., Ceynowa, J. Z. Lebensm. Unters. Forsch. 1994, 198, 244-248. Trumble, J.T., Millar, J.G., Ott, D.E., Carson, W.C. J. Agric. Food Chem. 1992, 40, 1501-1506. Nigg, H.N., Strandberg, J.O., Beier, R.C., Petersen, H.D., Harrison, J.M. J. Agric. Food Chem. 1997, 45, 1430-1436. Komives, T., Casida, J.E. J. Agric. Food Chem. 1983, 31, 751-755.


Pesticides and Human Health: The Influence of Pesticides on Levels

Recommend Documents