Identity, physical and chemical properties: Carbendazim, a white crystalline solid, is a systemic fungicide belonging to the benzimidazole family. It melts at approximately 250 C and has a vapour pressure of I x 10-7 Pa (I x 10-9 mbar) at 20 C. Carbendazim is essentially insoluble in water (8 mg/litre solubility) at pH 7 and 20 C. It is stable under normal storage conditions. Environmental transport, distribution and transformation: Benomyl is rapidly converted to carbendazim in the environment, with half-lives of 2 and 19 h in water and in soil, respectively. Data from studies on both benomyl and carbendazim are therefore relevant for the evaluation of environmental effects. Carbendazim is decomposed in the environment with half-lives of 6 to 12 months on bare soil, 3 to 6 months on turf, and halflives in water of 2 and 25 months under aerobic and anaerobic conditions, respectively. Carbendazim is mainly decomposed by microorganisms; 2-aminobenzimidazole (2-AB) is the major degradation product and is further decomposed by microbial activity. When phenyl-14C-labelled benomyl was decomposed, only 9% of the 14C label was evolved in CO2 during I year of incubation, the remaining 14C being recovered mainly as carbendazim and bound residues. The fate of a possible degradation product (1,2-diaminobenzene) may shed further light on the degradation pathway of benzimidazole fungicides in the environment. Field and column studies have shown that carbendazim remains in the soil surface layer. No determination of carbendazim adsorption in soil is available, but it is likely to be as strongly adsorbed to soil as benomyl (Koc values ranking from 1000 to 3600). Log Kow values for benomyl and carbendazim are 1.36 and 1.49, respectively. A risk of leaching was not apparent when this was evaluated in a screening model based on adsorption and persistence data. This statement is supported by analysis of well water in the USA, where carbendazim has not been found in any of 212 wells (limit of detection not available). Surface run-off of benomyl and carbendazim is expected to consist only of fungicide adsorbed to soil particles, and the fungicides are likely to be strongly adsorbed to sediments in the aqueous environment. Carbendazim is hydrolysed to 2-AB. This is also the primary metabolite in soil and plants. In animal systems, carbendazim is metabolized to (5-hydroxy-lH-benzimidazol-2-yl)-carbamate (5-HBC) and other polar metabolites, which are rapidly excreted. Carbendazim has not been observed to accumulate in any biological system. In a bioaccumulationstudy with the bluegill sunfish a BCF of 27 was obtained. Environmental levels: There appear to be no environmental monitoring data for carbendazim. However, the following can be summarized from environmental fate studies. Due to the fact that they are stable for several weeks on plant material, benomyl and carbendazim may become accessible to organisms feeding on leaf litter. Soil and sediments may contain residues of carbendazim for up to 3 years. However, the strong adsorption of carbendazim to soil and sediment particles reduces the exposure for terrestrial and aquatic organisms. Effects on laboratory mammals and in vitro test systems: Single exposure. Carbendazim has low acute toxicity. The LD50 values range from 2000 to 15000 mg/kg in a wide variety of test animals and routes of administration. However, significant adverse reproductive effects have been noted following a single exposure. Short-term exposure. Dietary administration of carbendazim for up to 90 days produced slight effects on liver weight in female rats exposed to 360 mg/kg body weight per day. In a 90-day gavage study in the rat, the NOEL was 16 mg/kg per day based on hepatotoxicity. Short-term feeding studies on dogs were not adequate for establishing a NOEL. A 10-day dermal study in the rabbit revealed no systemic toxicity at the only dose tested (200 mg/kg). Skin and eye irritation and sensitization. Application to the skin of the rabbit and guinea-pig produced no irritation or skin sensitization. Application to the eyes of rabbits produced moderate or mild conjunctival irritation. Long-term exposure. Male and female rats fed 2500 mg/kg diet showed reduced erythrocyte count and haemoglobin and haematocrit values. No liver-related toxicity was noted. Male rats fed 2500 mg/kg diet or more presented a marginal increase in diffuse testicular atrophy and prostatitis. The NOEL in the rat is 500 mg/kg diet. Elevated serum cholesterol and alkaline phosphatase activity and other indications of hepatotoxicity were observed in dogs fed a diet containing 500 mg carbendazim/kg for I year or longer. The NOEL in the dog is 300 mg/kg diet. Male and female mice fed 5000 mg/kg diet showed increased absolute liver weight. There was also significant centrilobular hypertrophy, necrosis and swelling of the liver in male mice fed 1500 mg/kg diet. Reproduction, embryotoxicity and teratogenicity. Carbendazim was without adverse effects on reproduction when it was fed to rats in a three-generation reproduction study at levels up to and including 500 mg/kg diet. Male fertility was depressed in rats when carbendazim (200 mg/kg per day) was administered by gavage for 85 days. A dose of 50 mg/kg body weight per day in this study caused a significant decrease in epididymal sperm count. Following a single oral dose to rats, histological examination revealed early (0-2 days) disruption of spermatogenesis with occlusion of efferent ducts and increased testicular weights at 100 mg/kg body weight. No effect was observed at 50 mg/kg in this single dose study. These effects persisted until day 70 in rats treated with 400 mg/kg. Carbendazim caused an increase in malformations and anomalies in rats when administered at daily dose levels greater than 10 mg/kg on days 7-16 of gestation. There was a slightly decreased rate of implantation in rabbits administered 20 and 125 mg/kg per day on days 7- 19 of gestation and an increased incidence of resorption at 125 mg/kg per day. Maternal toxicity was observed at 20 mg/kg per day and 125 mg/kg per day in the rat and rabbit, respectively. In addition to decreased pregnancy rate and increased early resorptions in the rat, there were significant reductions in fetal weights at 20 and 90 mg/kg per day and a significant increase in fetal malformations at 90 mg/kg per day. These consisted primarily of hydrocephaly, microphthalmia, anophthalmia, malformed scapulea and axial skeletal malformations (vertebral, rib and sternebral fusions, exencephaly, hemivertebrae and rib hyperplasia). However, in the rabbit there were no significant malformations. Mutagenicity and related end-points. Assays in mammalian and non-mammalian systems in vitro and in vivo and in somatic cells as well as in germ cells show that carbendazim does not interact with DNA, induce point mutation or cause germ cell mutation. Carbendazim does, however, cause numerical chromosome aberrations (aneuploidy and/or polyploidy) in experimental systems, both in vitro and in vivo. Carcinogenicity. Benomyl and carbendazim feeding resulted in an increase in the incidence of hepatocellular tumours in CD- I and SPF Swiss mice. A carcinogenicity study of carbendazim using CD- I mice showed a statistically significant dose-related increase in the incidence of hepatocellular neoplasia in females. There was also statistically significant increase in the mid-dose (1500 mg/kg diet) males, but not in the high-dose males because of a high mortality rate. A carcinogenicity study of carbendazim in a genetically related mouse strain, SPF mice (Swiss random strain) at doses of 0, 150, 300 and 1000 mg/kg diet (increased to 5000 mg/kg during the study) showed an increase in the incidence of combined hepatocellular adenomas and carcinomas. A study carried out in NMRKf mice at dose levels of 0, 50, 150, 300 and 1000 mg/kg diet of carbendazim (increased to 5000 mg/kg during the study) showed no carcinogenic effects. Benomyl or carbendazim caused liver tumours in two strains of mice (CD-I and SPF), both of which have a high spontaneous rate of liver tumours. In contrast, carbendazim is not carcinogenic in NMRKf mice, which have a low spontaneous rate of such tumours. Carcinogenicity studies of both benomyl and carbendazim in rats were negative. Effects on humans. No adverse effects on human health have been reported. Effects on other organisms in the laboratory and field: Carbendazim has little effect on soil microbial activity at recommended application rates. Some adverse effects have been reported for groups of fungi. The 72-h EC50 based on total growth, for the green alga Selenastrum capricornutum was calculated to be 1.3 mg/litre; the NOEC was 0.5 mg/litre. In another study using Chlorella pyrenoidosa, the 48-h EC50 for growth inhibition was 0.54 mg/litre. The toxicity of carbendazim to aquatic invertebrates and fish varies widely, with 96-h LC50 values ranging from 0.007 mg/litre for the channel catfish to 5.5 mg/litre for the bluegill sunfish. The 96-h LC50-values for the rainbow trout ranged between 0.1 and 0.9 mg/litre. A 48-h LC50-value for the water flea (Daphnia magna) was 0.087 mg/l. In a 21-day test on Daphnia magna the onset of reproduction was significantly delayed at 0.025 mg/litre; the NOEC was 0.013 mg/litre. Carbendazim is toxic to earthworms in laboratory experiments at realistic exposure concentrations and from recommended use in the field. An LC50 of 5.7 mg a.i./kg soil and another of 9.3 mg/kg soil was calculated for Eisenia andrei and E. foetida, respectively. It is "relatively non-toxic" to honey-bees and of low toxicity to birds. The oral LC50 for bobwhite quail was 2250 mg/kg body weight. For the mallard duck the dietary 5-day LC50 was 10000 mg carbendazim/kg diet.