Chlorpyrifos, Part 1: Toxicology
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JOURNAL OF PESTICIDE REFORM/ WINTER 1994 • VOL.14, NO. 4 ■ INSECTICIDE FACTSHEET CHLORPYRIFOS, PART 1: TOXICOLOGY The broad spectrum organophosphate insecticide chlorpyrifos is the most widely used insecticide in the U.S. Total use is estimated at almost 30 million pounds per year. Like all organophosphate insecticides, chlorpyrifos affects the nervous system by inhibiting an enzyme that is important in the transmission of nerve impulses. Symptoms of acute poisoning include headache, nausea, muscle twitching, and convulsions. Chlorpyrifos poisonings are reported to state and federal agencies more often than poisonings of almost every other insecticide. In both laboratory animals and humans, chlorpyrifos can also cause delayed effects on the nervous system. Some effects have been measured years after exposure. Human birth defects have been associated with exposure to chlorpyrifos products. In pregnant laboratory animals, chlorpyrifos exposure caused fetal death. Pups that did survive were smaller pups and did not survive as well as pups from unexposed mothers. Chlorpyrifos also affects the male reproductive system; exposure to a chlorpyrifos product has caused death of cells in male rat testes and a decrease in sperm production in cattle. Chlorpyrifos has caused genetic damage in human blood and lymph cells, mice spleen cells, and hamster bone marrow cells. Immune system abnormalities have been reported from patients exposed to chlorpyrifos. Many individuals report developing sensitivities to a broad array of substances following chlorpyrifos exposure. The second part of this factsheet will discuss human exposure to chlorpyrifos and the ecological effects of chlorpyrifos. BY CAROLINE COX mary agricultural uses are for oranges, al- plications are made annually. Over 17 per- monds, and walnuts.4 Structural pest con- cent of U.S. households use chlorpyrifos. trol uses much more chlorpyrifos than does Most of the chlorpyrifos products are used hlorpyrifos (see Figure 1) is the any single agricultural crop. (See Figure 4.) in the kitchen, bathroom, and other living C 5 most widely used insecticide in the United In American homes, lawns, and gardens, spaces. (See Figure 5.) States, both in crop production and in over two hundred million chlorpyrifos ap- Chlorpyrifos has been registered in the 6 nonagricultural applications.1 Its non- U.S. since 1965, and is manufactured by agricultural use in the United States is esti- DowElanco, formerly the Dow Chemical Company. Common brand names are mated at between 9 and 12 million pounds Figure 1 per year.1 Agricultural use estimates vary: Chlorpyrifos and Chlorpyrifos-oxon Dursban (for household products) and 3 the U.S. Environmental Protection Agency Lorsban (for agricultural products). Cl (EPA) estimates that between 10 and 15 S Mode of Action 1 CH CH O million pounds are used annually, while the P-O- -Cl U.S. Department of Agriculture (USDA) CH CH O Chlorpyrifos is an organophosphate in- N secticide. Investigations of this family of estimates agricultural uses at 21 million Cl pounds per year.2 (See Figure 2 for details.) chlorpyrifos chemicals began during World War II when 7 Chlorpyrifos is a broad spectrum insec- chemists studied their use as nerve gases. 3 Chlorpyrifos is directly toxic to the ner- ticide and has many uses. Nationwide, Cl USDA estimates show that the primary ag- CH CH O O vous system. In addition, it is transformed 8,9 ricultural uses are on corn, alfalfa, and cot- P-O- -Cl inside animals to chlorpyrifos-oxon (see 2 CH CH O Figure 1) which is about 3000 times as ton. (See Figure 3 for details.) In Califor- N nia, where pesticide use reporting is more Cl potent against the nervous system as 10 comprehensive than in other states, the pri- chlorpyrifos-oxon chlorpyrifos itself. Like all organophos- phates, chlorpyrifos and chlorpyrifos-oxon Chlorpyrifos is transformed in animals to chlorpyrifos-oxon, a much more potent neuro- kill insects and other animals, including Caroline Co x is JPR’s editor. toxin. humans, because of this toxicity to the ner- NORTHWEST COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP P. O. BOX 1393, EUGENE, OREGON 97440 / (503)344-5044 15 JOURNAL OF PESTICIDE REFORM/ WINTER 1994 • VOL.14, NO. 4 Figure 2 Figure 3 Agricultural Chlorpyrifos Use in the United States Crops on which Chlorpyrifos Is Used in the U.S. wheat citrus 1.0 million 0.9 million pounds pounds soybeans other 1.1 million 4.1 million pounds pounds peanuts 1.1 million pounds cotton 1.4 million pounds alfalfa 1.8 million pounds field corn 9.6 million pounds Source: U.S. Dept. of Agriculture. National Agricultural Pesticide Impact Assessment Program. 1994. The biologic and economic assessment of Pounds per year Sources: the field crop usage of chlorpyrifos: Briefing paper. U.S. Dept. of Agriculture. National Agricultural Statistics Service. Economic Washington, D.C. (April.) Not reported Research Service. 1991. Agricultural chemical use: 1991 Fruits and nuts summary. Washington, D.C. (June.) Less than 250,000 U.S. Dept. of Agriculture. National Agricultural Statistics Service. Economic Research Service. 1993. Agricultural chemical usage - vegetables: 1992 Almost half of the chlorpyrifos used in U.S. ag- 250,000-500,000 summary. Washington, D.C. (June.) riculture is used on corn. U.S. Dept. of Agriculture. National Agricultural Statistics Service. Economic 500,000-750,000 Research Service. 1994. Agricultural chemical use: 1993 Field crops summary. Washington, D.C. (March.) 750,000-1,000,000 California Environmental Protection Agency. Dept. of Pesticide Regulation. could be sufficient to kill an average-sized Information Services Branch. 1994. Pesticide use report: Annual 1992. (60 kg) adult human. Over 1,000,000 Indexed by chemical. Sacramento, CA. (February.) Based on the LD50, inhalation of for- Agricultural production in California, Iowa, and Indiana uses over a million pounds of chlorpyrifos mulated chlorpyrifos is more toxic to mice 15 annually. and rats than is oral ingestion. Dermal (skin) exposure in laboratory animals is less vous system. They inhibit an enzyme, ace- ing in humans include headache, nausea, toxic than ingestion.14 However, dermal tylcholinesterase (AChE), that breaks down dizziness, muscle twitching, weakness, in- exposure causes skin irritation, and also al- acetylcholine, a chemical involves in trans- creased sweating and salivation, and fluid- lows the body to absorb chlorpyrifos. This mitting nerve impulses across the junctions filled lungs. These symptoms are common is especially true if the skin is cut or between nerves. Without functioning to all organophosphate insecticides. Un- scratched. Therefore, the Cooperative Ex- AChE, acetylcholine accumulates, produc- consciousness, convulsions, and death can tension Service warns that “dermal contact ing rapid twitching of involuntary muscles, result with sufficient exposure.13 should be avoided.”14 convulsions, paralysis, and ultimately death.7 A variety of different kinds of exposure Inhibition of AChE activity has been Chlorpyrifos exposure has also been to chlorpyrifos can cause acute toxicity. Di- measured at doses that are much smaller shown to inhibit enzymes other than AChE. rect skin contact with the insecticide, either than the LD50. For example, AChE inhi- It impedes respiration (production of en- as a solid or in water can be toxic. Inges- bition in female rats was measured at doses ergy within a cell) in the livers of laboratory tion, breathing of vapors, or contact with of 0.1 mg/kg/day (less than 1 percent of animals. This results from the effect of chlorpyrifos-treated soil is also toxic.3 the LD50) and in beagle dogs at 3.3 mg/ chlorpyrifos on the activity of ATPase, an The acute oral median lethal dose kg/day (less than 5 percent of the LD50).14 enzyme important in cellular respiration.11 (LD50; the dose required to kill half of a The inhibition of AChE activity caused Chlorpyrifos-oxon inhibits the enzyme population of laboratory test animals) for by chlorpyrifos is more persistent than that cholesterol ester hydrolase; inhibition of this chlorpyrifos is between 82 and 270 milli- caused by other organophosphates, with enzyme in rats eliminates one of their nor- grams per kilogram (mg/kg) of body weight measurable inhibition two weeks after ex- mal reactions to stress.12 in rats.14 If it is assumed that humans are posure in one study,8 one month after ex- equally as sensitive as rats (usually a more posure in another study,16 and six weeks in Acute Toxicity conservative assumption should be made), other studies.17-18 Researchers believe that Symptoms of acute chlorpyrifos poison- then a dose of less than one-fifth of a ounce this is because chlorpyrifos is lipophilic (at- NORTHWEST COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP 16 P. O. BOX 1393, EUGENE, OREGON 97440 / (503)344-5044 JOURNAL OF PESTICIDE REFORM/ WINTER 1994 • VOL.14, NO. 4 Figure 4 Figure 5 Chlorpyrifos Uses in California (1992) Use of Chlorpyrifos by U.S. Households other pets structural pest control (1.5 million uses other outdoor uses annually) (5.0 million uses) oranges kitchens (5.5 million almonds uses annually) walnuts alfalfa lawns sugarbeets (2.5 million cotton uses) broccoli bathrooms lemons other indoor (3.5 million uses uses (3.8 million landscape maintenance annually) uses) bedrooms, living rooms cauliflower (3.8 millions uses annually) apples Source: Whitmore, R.W., J.E. Kelly, and P.L. Reading. 1992. National home and garden plums pesticide use survey. Final report, Vol. 1: Executive summary, results, and peaches recommendations. Research Triangle Park, NC: Research Triangle Institute. corn brussels sprouts Household use of chlorpyrifos is divided ap- proximately equally between indoor and out- nectarines door applications. cabbages 0 200,000 400,000 600,000 800,000 1,000,000 tivity, some organophosphates cause a “less (pounds per year) common but potentially more devastating Note: Total use of chlorpyrifos in California in 1992 was 2.6 million pounds. syndrome” called delayed neuropathy.