Aldicarb

1.1.1. Synonyms, structural and molecular data

• Chem. Abstr. Serv. Reg. No.: 116-06-3
• Chem. Abstr. Name: 2-Methyl-2-(methylthio)propanal, O-[(methylamino)carbonylloxime
• IUPAC Systematic Name: 2-Methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime

1.1.2. Chemical and physical properties

1. Description: Colourless crystals (Worthing & Walker, 1987)
2. Boiling-point: Decomposes (Rhone-Poulenc Ag Co., 1987)
3. Melting-point: 98–100°C (Worthing & Walker, 1987)
4. Spectroscopy data: Infrared spectroscopy data have been reported (US Environmental Protection Agency, 1976).
5. Solubility: Slightly soluble in water (6 g/l at 20°C); soluble in most organic solvents: at 25 °C, acetone, 350 g/kg; dichloromethane, 300 g/kg; benzene, 150 g/kg; xylene, 50 g/kg; practically insoluble in heptane (Worthing & Walker, 1987)
6. Volatility: Vapour pressure, 9.75 × 10⁻⁵ mm Hg [1.3 × 10⁻⁵ Pal at 25°C (Worthing & Walker, 1987)
7. Stability: Stable in neutral, acidic and weakly alkaline media; hydrolysed by concentrated alkalis; decomposes above 100°C; rapidly converted by oxidizing agents to the sulfoxide, which is more slowly oxidized to the sulfone (Worthing & Walker, 1987; Royal Society of Chemistry, 1989)
8. Conversion factor for airborne concentrations¹: mg/m³ = 7.78 × ppm

1.1.3. Trade names, technical products and impurities

Some common trade names are AI3-27 093, Aldicarb, ENT 27 093, OMS 771, Temik and UC 21149.

Aldicarb is available in the USA as a technical grade product with a purity of 98% (minimum) (Rhone-Poulenc Ag Co., 1987).

It is formulated in the USA and Europe as a granular product with the concentration of active ingredient ranging from 5 to 15%; some formulated products also contain gypsum and dichloromethane (Royal Society of Chemistry, 1986; Rhone-Poulenc Ag Co., 1990a,b; see IARC, 1987a). Aldicarb is also formulated as mixtures with pentachloronitrobenzene (see IARC, 1974,1987b), 5-ethoxy-3-(trichloromethyl)-l,2,4-thiadiazole and lindane (see IARC, 1987c) (Royal Society of Chemistry, 1986; Rhone-Poulenc Ag Co., 1990c). The granular carrier material is impregnated with aldicarb and a bonding agent which helps prevent dustiness that may be caused by abrasion during shipping; dust is also removed during the manufacturing process to minimize inhalation exposure and hazards of direct handling (Baron & Merriam, 1988).

1.1.4. Analysis

Selected methods for the analysis of aldicarb in various matrices are given in Table 1. Several more methods and the environmental fate and transport of aldicarb and its metabolites have been reviewed (Moye & Miles, 1988).

1.2.1. Production

Aldicarb was first prepared by Payne and Weiden (1965) and was first made available as a commercial product in 1970, following its registration in the USA for use on cotton (Romine, 1974).

Aldicarb is synthesized by reacting nitrosyl chloride with isobutylene to obtain 2-chloro-2-methyl-1-nitrosopropane dimer, which is further reacted with methyl mercaptan and sodium hydroxide to obtain 2-methyl-2-(methylthio)propionaldoxime. Aldicarb is obtained by reaction of the oxime with methyl isocyanate (Romine, 1974).

Aldicarb is currently produced in the USA and in France (Meister, 1990). Production in the USA in 1979–81 was estimated at 2000 tonnes per annum (US Environmental Protection Agency, 1987).

1.2.2. Use

Aldicarb acts as a systemic insecticide, acaricide and nematicide and is applied to soil under cotton, potatoes, sugar beets, peanuts, soya beans, ornamental plants, sweet potatoes, pecans, citrus (grapefruit, lemons, limes and oranges only), dry beans, sorghum and sugar-cane (Rhone-Poulenc Ag Co., 1989; Meister, 1990). In the USA during 1979–81, annual usage of aldicarb (active ingredient) was estimated as follows (tonnes;%): cotton, 520 (29%); potatoes, 430 (25%); peanuts, 250 (14%); soya beans, 205 (12%); pecans, 180 (10%); ornamental plants (lilies, roses, holly), 45 (3%); sugar beets, 45 (3%); citrus, 34 (2%); sweet potatoes, 22 (< 1%); and tobacco, 6 (< 1%) (Holtorf, 1982). In Finland, 132 kg aldicarb (active ingredient) were sold in 1988 (Hynninen & Blomqvist, 1989). In the USA in 1989, about 1000–1500 tonnes aldicarb are believed to have been used. Aldicarb use is restricted in certain areas in various parts of the world, usually because of its potential to leach to groundwater (IRPTC/UNEP, 1990).

1.3.1. Air

Few studies are available on the stability or migration of aldicarb in air over or near treated fields. Laboratory studies with ¹⁴C-labelled aldicarb in various soil types resulted in its loss, which could be explained only on the grounds that aldicarb or its decomposition products had been transferred to the vapour phase. Subsequent experiments showed that transfer of radioactivity to the atmosphere was inversely proportional to the depth of application in the soil (Coppedge et al., 1977). Little aldicarb was released from a clay soil treated with this pesticide and placed in a volatilizer (Supak et al., 1977).

1.3.2. Water

Aldicarb has been detected in ground- and drinking-water in 15 states in the USA at levels ranging from traces to 500 µg/kg (WHO, 1991).

It was detected in water in Suffolk County, NY, in August 1979: a monitoring programme for aldicarb in water indicated that 1121 (13.5%) of 8404 wells examined exceeded the State recommended guideline of 7 µg/1. Of the contaminated wells, 52% contained between 8 and 30 µg/l, 32% between 31 and 75 µg/l and 16% contained more than 75 µg/l (Zaki et al., 1982). Following the banning of aldicarb in Suffolk County in 1979, approximately 74% of all wells sampled in the County in 1981 contained no detectable level of aldicarb. Of the 27% of wells (2054 samples) that did, residue levels were 1–10 µg/l in 56%, 11–100 µg/l in 40% and > 100 µg/l in 4% (US Environmental Protection Agency, 1988). Data derived from monitoring of all drinking-water wells in Suffolk County in which contamination had occurred are shown in Table 2.

Extensive monitoring studies in the USA have mostly been related to potato and citrus production. Relatively high percentages (5-> 50%) of positive findings occurred in Wisconsin and north-eastern states (New York, Massachusetts, Rhode Island, Connecticut, Maine). There was substantial evidence for leaching to shallow groundwater associated with citrus production in Florida (US Environmental Protection Agency, 1988; WHO, 1991).

1.3.3. Soil

Numerous studies have been carried out with aldicarb under field and laboratory conditions to study its translocation, persistence and degradation (WHO 1991) It has a half-time in soil of approximately 30 days; this can vary depending on microbial populations, soil composition, moisture, temperature and farming practices (Meister, 1990) Its half-time in the root zone varied from one week to over two months. The primary mode of degradation in this zone is oxidative metabolism by microorganisms, although some hydrolysis may occur. Warm soil temperatures, high moisture content and high organic contents may result in more rapid degradation (US Environmental Protection Agency, 1988; WHO, 1991).

Aldicarb is mobile in most types of soil, with adsorption coefficients typically of < 1.0 and often 0.1. Incidents of groundwater contamination have primarily been associated with sandy soils, to which aldicarb residues are poorly bound (US Environmental Protection Agency, 1988).

Aldicarb has been used extensively since 1979–80 to control cotton whitefly in the Sudan, reaching a maximum of nearly 84 000 ha in 1984–85. When uptake and distribution were studied and the maximum uptake recorded two weeks after application of aqueous treatments and four weeks after application of granular formulations, no aldicarb or its sulfoxide or sulfone metabolites were detected in plant tissues or in soil at harvest (El-Zorgani et al., 1988).

1.3.4. Food

In a market-basket survey carried out in the USA in 1983–85 on 491 samples of raw agricultural commodities, 76 (72 of white potatoes, two of sweet potatoes, one peach and one collard green) contained aldicarb residues. The mean residue level in potato samples taken in 1984 and 1985 was 200 µg/kg, while that taken in 1983 was 720 µg/kg (US Environmental Protection Agency, 1988).

In 1984–85 to 1988–89 in Canada, aldicarb residues were found in 13 of 30 samples of potatoes, at 0.02–0.78 mg/kg (mean, 0.13 mg/kg). No residue was detected in samples of bananas, oranges, cucumbers or wine (Government of Canada, 1990).

In 1978, national monitoring of potatoes treated at 3 kg/ha active ingredient in the Netherlands found total residues (expressed as the sulfone) in 23 samples, ranging from < 0.03 to 0.38 mg/kg, 100–205 days after broadcast application (mean, 0.11 mg/kg). Monitoring in 1982 of potatoes treated similarly showed residues of < 0.03–0.25 mg/kg (mean, 0.06 mg/kg) (FAO/WHO, 1986).

In a total diet study in 1986–88, 3737 domestic and imported food samples were analysed in the USA. Of these, 3656 (98%) contained no detectable residue. Potatoes (312) were included and residues found in 18% of samples, the highest level being 0.71 mg/kg No residue was found in 98% of bananas sampled (55); one sample contained 0.12 mg/kg (US Food and Drug Administration, 1989b).

4.1.1. Humans

Most carbamate insecticides are readily absorbed from the gastrointestinal tract They may also be absorbed to varying degrees through skin (Feldman & Maibach, 1970; Sterling, 1983).

Reports on the toxicity of aldicarb in humans (section 4.2.1) suggest that it enters the human body following skin contact, inhalation and ingestion. It is metabolized to aldicarb sulfoxide and aldicarb sulfone. Aldicarb derivatives (aldicarb, aldicarb sulfoxide and aldicarb sulfone) were found in the tissues of a 20-year-old man run over by a tractor following overexposure for about 2 h without adequate protection. The levels found were 482 µg/l in blood, 187 µg/kg in liver, 683 µg/kg in kidney and 823 µg/kg in skin from the hand Aldicarb itself was not detected in blood, but aldicarb sulfoxide was present at 108 ppb [µg/l] and aldicarb sulfone at 374 ppb [µg/l], indicating an almost complete two-step oxidation process. The same trend was seen in the liver and kidney, while aldicarb occurred at the highest level in the skin. The total body burden of aldicarb was estimated at 18.2 mg (equivalent to 0.275 mg/kg bw) (Lee & Ransdell, 1984).

4.1.2. Experimental systems

Aldicarb is readily absorbed through the gut in rats and cows and through the skin in rats and rabbits. It is rapidly metabolized and excreted within 24 h of exposure, almost all of the toxic and nontoxic metabolites being excreted in urine (Risher et al., 1987) Signs of poisoning were reported to occur only a few minutes after administration of higher doses in rats given aldicarb at up to 0.1 mg/kg bw by intubation (Cambon et al., 1979) In rats administered radiolabelled aldicarb orally, 80% of the label was excreted in the urine within 24 h; less than 0.4% consisted of unchanged aldicarb (Andrawes et al., 1967) Almost complete absorption via the gut was observed in cows (Dorough & Ivie, 1968; Dorough et al.,1970).

Analysis of tissue samples taken from rats one to four days following oral administration of radiolabelled aldicarb indicated general distribution and elimination (Andrawes et al., 1967)

The metabolism of aldicarb in rats involves both hydrolysis of the carbamate ester and oxidation of the sulfur to the sulfoxide and sulfone derivatives (Andrawes et al., 1967). While the hydrolysis results m compounds with little or no insecticidal activity or toxicity to other organisms, the sulfoxide and sulfone metabolites are active cholinesterase inhibitors (Bull et al., 1967; Risher et al., 1987). In rats, the sulfoxide and the oxime sulfoxide constitute the major urinary metabolites, at 40% and 30%, respectively (Knaak et al., 1966).

4.2.1. Humans

Aldicarb is one of the most toxic pesticides known (Marshall, 1985). Its toxicity is based on a transient inhibition of acetylcholinesterase. Carbamates form unstable complexes with chlolinesterases by carbamoylation of the active sites of the enzymes (Done 1979; Mortensen, 1986). Unlike the relatively irreversible anticholinesterase activity of the organophosphorus insecticides, the carbamoylation process which produces the esterase inhibition is quickly reversible.

Several reports on the acute and chronic toxicity of aldicarb are summarized in Table 4 In most exposure situations, the clinical symptoms observed were consistent with the known mechanism of action (inhibition of acetylcholinesterase). In some of the studies, the dose has been estimated. chlolinesterases measurements have been of additional use in characterizing dose or extent of exposure.

4.2.2. Experimental systems

The acute toxicity of alidcarb is high, with oral LD₅₀s in rats and mice generally below 1 mg/kg bw. Depression of cholinesterase activity has been reported in rats administered aldicarb, its sulfoxide or its sulfone. The relative order of inhibition of cholinesterase was plasma > red blood cells > brain (DePass et al., 1985; studies reported by Risher et al., 1987).

After a review of several studies, Risher et al. (1987) concluded there was no effect of subchronic and chronic oral feeding to rats of aldicarb at 0.3 mg/kg bw/day; of aldicarb sulfoxide at 0.3 mg/kg bw/day; of aldicarb sulfone at 2.4 mg/kg bw/day; or of 1:1 aldicarb sulfoxide:sulfone mixture at 0.6 mg/kg bw/day. The latter was tested owing to the observation that residues found in drinking-water are generally present as this mixture.

Suppressed humoral immune response (splenic plaque-forming cell assay) has been reported after exposure of mice to aldicarb in drinking-water for up to 34 days. Suppression on day 34 was significant, however, only at 1 ppb [µg/l] water and was less pronounced and not significant at 10, 100 or 1000 µg/l water (Olson et al., 1987). In a similar study in mice exposed to aldicarb in drinking-water at levels of 0.1–1000 ppb [µg/l] for 34 days using a variety of immunological endpoints including that used by Olson et al., no significant effect on the immunological system was noted (Thomas et al., 1987). Shirazi et al. (1990) however performed a follow-up experiment using the same assay and aldicarb at 0.01–1000 µg/l in drinking-water but prolonging the study time up to 180 days. After extensive statistical analysis, the authors concluded that there was a stimulatory effect at 30 and 60 days and an inhibitory effect at 90 and 180 days. Dean et al. (1990) reported that aldicarb given mtrapentoneally to mice at doses of 0.01–100 ng per mouse (0.1 ml of a 0.1, 1, 10, 100 or 1000 ppb solution) decreased the stimulatory function of macrophages without affecting T-lymphocyte function. There was no clear dose-response relationship.

4.3.1. Humans

No data were available to the Working Group.

4.3.2. Experimental systems

Few data are available on the reproductive and developmental effects of aldicarb. In two studies described in a review by Risher et al. (1987), there was reported to be no evidence of toxicity in the offspring of rats treated with aldicarb in the feed at doses as high as 1 mg/kg bw [near the LD50] throughout pregnancy and lactation, and offspring of rabbits treated with aldicarb by gavage at doses of up to 0.5 mg/kg bw on days 7–27 of gestation were reported to exhibit no developmental toxicity. Rats investigated in a three-generation study in which aldicarb was incorporated into the diet were also reported to exhibit no significant difference in any parameter assessed compared to control animals.

Cambon et al. (1979, 1980) evaluated the effects of administering a single dose of aldicarb (0–0.1 mg/kg bw) on gestation day 18 on acetylcholinesterase activity in maternal and fetal tissue of Sprague-Dawley rats. Maternal blood acetylcholinesterase activity was reduced at doses greater than 0.001 mg/kg, and fetal blood acetylcholinesterase activity was reduced at doses of 0.001 mg/kg and above in samples taken > 1 h after dosing. The effect persisted for up to 24 h at doses of 0.01 mg/kg and above. Tissues were stored overnight at 4°C before analysis. Acetylcholinesterase was assayed in maternal and fetal brain homogenates 1 h after administration of 0.1 mg/kg bw aldicarb, and isoenzymes were analysed using polyacrylamide electrophoresis. Both maternal and fetal brain acetylcholinesterase levels were decreased by aldicarb; the levels of two of three cholinesterase isozymes were decreased in fetal brain and that of only one of the cholinesterase isozymes was decreased in maternal brain.

4.4.1. Humans

No data were available to the Working Group.

4.4.2. Experimental systems

Aldicarb induced differential toxicity in Salmonella typhimurium but not in strains of Escherichia coli. Aldicarb was not mutagenic to bacteria, whereas mutations were induced in cultured mammalian cells. Gene mutation, sister chromatid exchange and chromosomal aberrations were induced by aldicarb in cultured human cells. In a single study, no DNA strand breakage was observed in human cells.

In vivo, aldicarb induced chromosomal aberrations in cells of rat bone marrow.

Overall evaluation

Aldicarb is not classifiable as to its carcinogenicity to humans (Group 3).