Biomonitoring Summary

Alachlor

CAS No. 15972-60-8

General Information

Alachlor is a chloroacetanilide type herbicide with restricted usage for preemergent control of grasses and broadleaf weeds on agricultural cropland, including corn, soybeans, peanuts and other crops, and on non-crop land for general weed control. Since the late 1980s alachlor use has been declining. In 1993-1995, about 20-25% of the U.S. corn cropland was treated with alachlor. It is absorbed by plants and inhibits plant protein synthesis. Alachlor has a soil half-life of a few weeks. It is both metabolized in plants and degraded microbiologically in agricultural soils into as many as 19 metabolites and degradates. Alachlor and its degradates are leachable from agricultural soils and have been detected in watersheds of agricultural land including ground and surface waters (Battaglin et al., 2000; Hladik et al., 2005; Kolpin et al., 2000; USGS, 1999 and 2007; WHO, 2003). Alachlor is highly toxic to freshwater fish and slightly toxic to birds and some invertebrates, but shows little bioaccumulation.

General population exposure to alachlor may occur through consumption of contaminated food or drinking water. Estimated human intakes have been below recommended limits (U.S.EPA, 1998). Because it can be absorbed through skin, the dermal exposure route is potentially significant for applicators, formulators, and field workers. In animal studies, alachlor is quickly absorbed after oral doses and mostly excreted as metabolites within a week (IPCS, 1996; U.S.EPA, 1998; WHO, 2003). In animals, mercapturate conjugates were predominant metabolites, but another metabolic pathway can produce 2,6-diethylaniline and its reactive metabolite; the latter may account for some observed tumor effects (Davison et al., 1994; Feng and Wratten, 1989; Jefferies et al., 1998). People exposed to alachlor will excrete alachlor mercapturate in their urine (Driskell et al., 1996), but this metabolite is not a marker of exposure to most plant metabolites or environmental degradates which are often more prevalent in the environment.

Human health effects from alachlor at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Alachlor has low potential for acute toxicity. In chronic animal testing, alachlor has demonstrated hepatotoxicity, hemosiderosis, and uveal degeneration, but has not shown developmental or reproductive toxicity in mammalian systems (U.S.EPA, 1998; WHO, 2003). Alachlor itself is not considered mutagenic, though positive genotoxic results are reported for several metabolites of alachlor (Brown et al., 1988; Hill et al., 1997; Tessier and Clark, 1995; U.S.EPA, 1998). Animal carcinogenicity studies have demonstrated tumors of the nasal turbinates, stomach, and thyroid only at either maximum tolerated doses or related to species-specific pathways (Heydens et al., 1999; IPCS, 1996; U.S.EPA, 1998; WHO, 2003). U.S.EPA considers alachlor to be a probable human carcinogen at high doses, but not likely at low doses. NTP and IARC do not have ratings regarding human carcinogenicity. Additional information about is available from U.S. EPA at: https://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of alachlor mercapturate reflect recent exposure. Urinary levels of alachlor mercapturate were generally not detectable in the NHANES 1999-2000 subsample (CDC, 2009). In a study of applicators and workers exposed to alachlor, mean values of urinary concentrations of alachlor metabolites, as measured through conversion to deethylamine, ranged from 0.1 to 1.1 mg/L at various collection times (Sanderson et al., 1995). Hines et al. (2003) showed that 2.2% of a reference population had detectable alachlor equivalents by immunoassay in their urine, whereas 60% of applicators had detectable amounts.

Finding measurable amounts of alachlor mercapturate in the urine does not imply that the levels of alachlor mercapturate cause an adverse health effect. Biomonitoring studies on levels of alachlor mercapturate provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of alachlor than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Battaglin WA, Furlong ET, Burkhardt MR, Peter CJ. Occurrence of sulfonylurea, sulfonamide, imidazolinone, and other herbicides in rivers, reservoirs and ground water in the Midwestern United States, 1998. Sci Total Environ 2000;248(2-3):123-33.

Brown MA, Kimmel EC, Casida JE. DNA adduct formation by alachlor metabolites. Life Sci 1988;43(25):2087-94. Erratum in: Life Sci 1989;44(18):1325.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Atlanta (GA). 2009. [online] Available at URL: https://www.cdc.gov/exposurereport/. 10/15/12

Davison KL, Larsen GL, Feil VJ. Comparative metabolism and elimination of acetanilide compounds by rat. Xenobiotica 1994;24(10):1003-12.

Driskell WJ, Hill RH Jr, Shealy DB, Hull RD, Hines CJ. Identification of a major human urinary metabolite of alachlor by LC-MS/MS. Bull Environ Contam Toxicol 1996;56(6):853-9.

Feng PCC, Wratten SJ. In vitro transformation of chloroacetanilide herbicides by rat liver enzymes: A comparative study of metolachlor and alachlor. J Agri Food Chem 1989;37(4):1088-93.

Heydens WF, Wilson AG, Kier LD, Lau H, Thake DC, Martens MA. An evaluation of the carcinogenic potential of the herbicide alachlor to man. Hum Exp Toxicol. 1999;18(6):363-91.

Hill AB, Jefferies PR, Quistad GB, Casida JE. Dialkylquinoneimine metabolites of chloroacetanilide herbicides induce sister chromatid exchanges in cultured human lymphocytes. Mutat Res. 1997;395(2-3):159-71.

Hines CJ, Deddens JA, Striley CA, Biagini RE, Shoemaker DA, Brown KK, et al. Biological monitoring for selected herbicide biomarkers in the urine of exposed custom applicators: application of mixed-effect models. Ann Occup Hyg 2003;47(6):503-17.

Hladik ML, Hsiao JJ, Roberts AL. Are neutral chloroacetamide herbicide degradates of potential environmental concern? Analysis and occurrence in the upper Chesapeake Bay. Environ Sci Technol 2005;39(17):6561-74.

International Programme on Chemical Safety (IPCS). WHO/FAO Data Sheets on Pesticides. No. 86. ALACHLOR. World Health Organization, Geneva, 1996. Available at URL: http://www.inchem.org/documents/pds/pds/pest86_e.htm. 10/15/12

Jefferies PR, Quistad GB, Casida JE. Dialkylquinonimines validated as in vivo metabolites of alachlor, acetochlor, and metolachlor herbicides in rats. Chem Res Toxicol 1998;11(4):353-9.

Kolpin DW, Thurman EM, Linhart SM. Finding minimal herbicide concentrations in ground water? Try looking for their degradates. Sci Total Environ 2000;248(2-3):115-22.

Sanderson WT, Biagini R, Tolos W, Henningsen G, MacKenzie B. Biological monitoring of commercial pesticide applicators for urine metabolites of the herbicide alachlor. Am Ind Hyg Assoc J 1995;56(9):883-9.

Tessier DM, Clark JM. Quantitative assessment of the mutagenic potential of environmental degradative products of alachlor. J Ag Food Chem 1995;43(9):2504-2512.

U.S. Environmental Protection Agency (U.S. EPA). Reregistration Eligibility Decision (RED) Alachlor. December 1998. EPA 738-R-98-020. Available at URL: https://www.epa.gov/oppsrrd1/REDs/0063.pdf. 10/15/12

U.S. Geological Survey (USGS). The Quality of Our Nation's Waters Pesticides in the Nation's Streams and Ground Water, 1992-2001. Circular 1291. Supplemental Technical Information (available on-line only). March 2006, revised February 15, 2007. Available at URL: https://water.usgs.gov/nawqa/pnsp/pubs/circ1291/supporting_info.php. 10/15/12

U.S. Geological Survey (USGS). Water-Resources Investigations Report: Distribution of Major Herbicides in Ground Water of the United States Water Resource Investigations Report No. 98-4245 (by Barbash JE, Thelin GP, Kolpin DW, Gilliom RJ). Sacramento, California, 1999. Available at URL: https://water.usgs.gov/nawqa/pnsp/pubs/wrir984245/ 10/15/12

Whyatt RM, Barr DB, Camann DE, Kinney PL, Barr JR, Andrews HF, et al. Contemporary-use pesticides in personal air samples during pregnancy and blood samples at delivery among urban minority mothers and newborns. Environ Health Perspect 2003;111(5):749-56.

World Health Organization (WHO). Alachlor in Drinking-water. Background document for development of WHO Guidelines for Drinking-water Quality. 2003. Available at URL: http://www.who.int/water_sanitation_health/dwq/chemicals/en/alachlor.pdf. 10/15/12