Aldicarb By Caroline Cox pulses across the junctions between nerves. (given over a one-year period). The high- This causes loss of muscular coordination, est dose at which no adverse effects were In 1966, four years before the insecticide convulsions, and ultimately death.5 The observed (called the NOEL) was 0.02 mg/ 11 aldicarb was registered for use in the United AChE inhibition is said to be reversible be- kg/day, about one-tenth of the LD50. States, researchers were using the chemical cause the aldicarb disassociates from the There is evidence that people may suf- on an experimental basis.1 One researcher AChE within several hours. This occurs even fer acute symptoms when exposed to even brought a small amount home and his wife if death has occurred. Organophosphate in- lower levels of aldicarb. In humans who applied it to the soil under a backyard rose secticides (malathion and diazinon, for ex- consumed aldicarb-contaminated water- bush. Over three weeks later she ate a sprig ample) have the same mode of action ex- melons, clinical signs of aldicarb poison- of mint from a plant growing nearby. Within cept that the AChE inhibition is not as ing were found in individuals consuming half an hour she was suffering from vomit- readily reversible.7 as little as 0.002 mg/kg of the aldicarb ing, diarrhea, and involuntary urination. Her Aldicarb is a systemic insecticide. It is metabolite aldicarb sulfoxide. This pupils closed to pinpoints, her muscles applied as granules below the soil surface amount is one-tenth the NOEL in the twitched, and her breathing was difficult. and is then absorbed by plant roots and beagle study.12 After hospitalization and treatment with the translocated throughout the plant, killing in- Chronic Neurotoxicity antidote atropine, she recovered. However, sects and mites that feed on three grams of the same mint plant was the plant.8 In addition to its sufficient to kill a rabbit.1 While it might Figure 1 acute toxicity to animals’ seem that a pesticide that caused this kind Acute Toxicity Aldicarb and Acetylcholine nervous systems, aldicarb of incident is a poor candidate for managing can also have long-term Aldicarb is “one of the CH3 O - pests on food crops, aldicarb has been ex- most acutely toxic pesticides = delayed behavioral ef- CH3S-C-CH=N-OCNHCH3 tensively used for over 20 years on both - registered” according to CH fects. Two studies of 4 3 food and nonfood crops. EPA. The oral LD50 (the aldicarb-exposed chicks, Aldicarb, 2-methyl-2-(methylthio)- dose required to kill 50 per- aldicarb one in which chicks were propionaldehyde O-methylcarbamoyloxime cent of a population of test exposed during the first (see Figure 1), is currently manufactured in animals) is between 0.3 and CH3 O week after hatching and = the U.S. by Rhone-Poulenc Company and - one in which chicks were 0.9 milligrams per kilogram CH3N-CH2CH2OCCH3 sold under the trade name Temik. It is reg- 9 - (mg/kg) of body weight. If CH exposed before hatching, istered for use on citrus, cotton, beans, sor- humans are equally sensitive, 3 showed that aldicarb acetylcholine: ghum, soybeans, sugarbeets, and sweet po- less than a thousandth of an the neurotransmitter caused changes in the tatoes.2,3 The U.S. Environmental Protec- ounce of aldicarb would be mimicked by aldicarb chicks’ gait.13,14 The tion Agency (EPA) estimated that between sufficient to kill a typical (60 5.2 and 5.6 million pounds of aldicarb were kg) adult. 4 Figure 2 used nationwide in 1988. Use of aldicarb In humans, signs of Use of Aldicarb in California During 1990 during 1990 (totalling almost half a million aldicarb poisoning include (pounds) pounds) in California is shown in Figure 2. dizziness, salivation, excessive sweating, nausea, abdominal Ornamentals Mode of Action 2,472 Beans Sugarbeets cramps, vomiting, diarrhea, 4,518 29,844 Aldicarb is a carbamate insecticide and blurred vision, pinpoint pu- Other acaricide (pesticide used to kill mites). Like pils, difficult breathing, and 988 all members of this chemical family, it in- muscle twitching. Death fol- Cotton hibits the action of an enzyme that is an lows if exposure has been Cotton Sugarbeets essential component of both insect and high enough.10 435,481 Beans mammal nervous systems. The enzyme, ace- A sensitive sign of tylcholinesterase (AChE), controls the chemi- aldicarb poisoning is mea- Ornamentals cal reaction that transforms acetylcholine, a surement of AChE activ- Other neurotransmitter, into choline.5 (Aldicarb and ity. This can be done by acetylcholine have similar chemical struc- laboratory analysis of blood tures.6 See Figure 1.) Without functioning and other tissue samples. In AChE, acetylcholine accumulates and pre- laboratory animals vents the smooth transmission of nerve im- (beagles), AChE inhibition Source: State of California. Environmental Protection Agency. has been observed at doses Department of Pesticide Regulation. Information Services Branch. Caroline Cox is JPR’s editor. as low as 0.05 mg/kg/day 1990. Pesticide use report. Sacramento, CA. JOURNAL OF PESTICIDE REFORM / SUMMER 1992 / VOL. 12, NO. 2 31 changes in locomotion persisted after monella typhimurium, a 24 Figure 3 AChE inhibition could no longer be mea- bacteria. Effects of Aldicarb on the Immune System sured, over 40 days after treatment.13,14 While chemicals that 1000 damage genes often also Suppression of the Immune System 900 cause cancer, aldicarb ex- Note that the 800 smallest aldicarb In 1986, epidemiologists in Wiscon- posure has not been as- dose had the largest effect. sin studied how well the immune system sociated with an increase 700 was functioning in women who were in cancer incidence in drinking water from wells that were con- tests conducted by the 600 taminated by low levels of aldicarb. They National Toxicology 500 25 found that consumption of aldicarb-con- Program. Even though 400 taminated water was associated with one carcinogenicity tests sub- 300 immune system abnormality (an increase mitted in support of in the number of T8 cells). This abnor- aldicarb’s registration do 200 mality could not be correlated with any not meet current stan- 100 clinical evidence of adverse health effects dards, California’s De- (Number of plaque forming cells in the spleen) 0 (self reported doctor visits, drug prescrip- partment of Pesticide 0 1 10 100 1000 Aldicarb Dose tions, illnesses, etc.). The researchers con- Regulation concluded in (Parts per billion in drinking water over a 34 day period) cluded that “the public health implica- 1987, “Although no one tions of continuing to expose large popu- study is unacceptable, the lations to potential immuno–modulating collective data from the 100 environmental contaminants warrants several studies provide 90 15 careful review.” sufficient evidence on the 80 The epidemiological study was lack of an oncogenic ef- 70 prompted by a study of the effects of fect.” Several unexpected aldicarb on the immune system of mice.16 tumors were observed in 60 In this study, consumption of water con- a reproduction study in 50 taminated with as little as 1 part per bil- rats completed in 1991; Immune System Function (averages with standard errors) 40 lion (ppb) of aldicarb affected one pa- Rhone-Poulenc has re- 30 rameter of immune function, the plaque ported to EPA that the forming cell response. Interestingly, the tumor findings “might 20 effect was strongest at the lowest concen- possibly reflect an adverse 10 23 of activity in untreated mice) percent tration (1 ppb). Three subsequent mouse effect….” Because very 0 (Stimulatory activity of macrophages as a studies found effects of aldicarb (at doses small doses of aldicarb 0 0.00001 0.00010.001 0.01 0.1 as low as 0.0001 micrograms of aldicarb cause death, it may be Aldicarb Dose per mouse) on another immune system very difficult to detect a (micrograms given in a single injection) 17-19 Sources: component, macrophage activity. (See carcinogenic effect in Olson, L.J. et al. 1987. Aldicarb immunomodulation in mice: an inverse dose-response to parts per billion levels in drinking water. Arch. Environ. Contam. Figure 3.) laboratory tests. Toxicol. 16:433-439. A recent follow-up study to the Wis- Dean, T.N. et al. 1990. Aldicarb treatment inhibits the stimulatory activity of N-Nitrosoaldicarb, macrophages without affecting the T-cell responses in the syngeneic mixed consin epidemiology study found that im- formed by a reaction be- lymphocyte reaction. Int. J. Immunopharm. 12(3):337-348. mune system abnormalities continued in tween aldicarb and so- women whose exposure to aldicarb con- dium nitrite (see Figure 4), is also muta- tinued.20 genic in Salmonella26 and causes sister- tion levels in drinking water wells, al- chromatid exchanges in human cells.27 In though the study was not sufficient to Mutagenicity and Carcinogenicity rats, consumption of N-nitrosoaldicarb conclude that aldicarb was the cause.30 In human cells, aldicarb causes an in- has been associated with an increased in- Aldicarb has also caused reproductive crease in the number of three different cidence of stomach cancers.28 problems in laboratory rats. Doses of kinds of chromosome abnormalities: sis- aldicarb as low as 0.001 mg/kg caused ter-chromatid exchanges, chromatid Effects on Reproduction inhibition of AChE in fetal brains and breaks, and chromosome breaks.21,22 and Development livers. This dose is a thousand times lower In other mammal cells, no evidence After over 1000 consumers of aldicarb- than the adult LD50. Doses of 0.01 mg/ was found linking aldicarb exposure to contaminated watermelon became ill in kg caused inhibition that continued for three types of genetic damage: mutation July 1985, stillbirths were reported by two 24 hours following exposure.31 Fetuses frequency of Chinese hamster ovary cells, women who had suffered acute symp- were more sensitive than their mothers to chromosome aberrations in mouse bone toms.29 In addition, epidemiological stud- aldicarb’s effects.