Biomonitoring Summary

Metolachlor

CAS No. 93-76-5

General Information

Metolachlor is a chloroacetanilide type herbicide that is applied for preemergent control of grasses and broadleaf weeds on agricultural crop land, including corn, soybeans, sorghum and other crops, and on non-crop land for general weed control. It is absorbed by plants and inhibits plant protein synthesis. Metolachlor has a soil half-life of a few weeks to three months and is degraded microbiologically and photochemically to at least five different products. Metolachlor or its degradates can leach from soils and have been detected in watersheds of agricultural land, in both ground and surface waters (Battaglin et al., 1999; Gilliom, 2007; Hladik et al., 2005; Kolpin et al., 2000; USGS, 2007; WHO, 2003). Occasionally in the past, metolachlor levels in water have exceeded lifetime human health advisory levels (U.S.EPA, 1995). Metolachlor shows little potential to bioaccumulate but is moderately toxic to fish.

General population exposure may occur through the consumption of contaminated food or drinking water. Estimated human intakes have been below recommended limits (U.S.EPA, 1995). Metolachlor is well absorbed dermally, so applicators, formulators, and field workers may have significant exposures via this route. In animal studies, metolachlor was quickly absorbed after dermal or oral doses, and eliminated in urine and feces over two to three days (WHO, 2003). In animals, mercapturate conjugates were the predominant metabolites, but another metabolic pathway can produce 2-methyl-6-ethylaniline and its reactive metabolite which may account for observed effects (Coleman et al., 2000; Davison et al., 1994; Feng and Wratten, 1989; Jefferies et al., 1998). People exposed to metolachlor will excrete metolachlor mercapturate in their urine. This metabolite is not a marker of exposure to either plant metabolites or environmental degradates of metolachlor which can be present in the environment.

Human health effects from metolachlor at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Metolachlor has low potential for acute toxicity (U.S. EPA, 1995). Salivation, lacrimation, and convulsions were observed at lethal doses in animal studies. Metolachlor did not show developmental or reproductive toxicity in chronic animal studies, and it was not mutagenic in mammalian cells (U.S.EPA, 1995; WHO, 2003). U.S.EPA considers metolachlor to be a possible human carcinogen; NTP and IARC do not have ratings regarding human carcinogenicity. Additional information is available from U.S. EPA at: https://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of metolachlor mercapturate reflect recent exposure. Urinary levels of metolachlor mercapturate were generally not detectable in the NHANES 2001-2002 subsample, though the 95th percentile for males and non-Hispanic whites was at the limit of detection, 0.200 μg/L (CDC, 2009). The geometric mean urinary metolachlor mercapturate concentration was 4.7 μg/L in farmers after they had sprayed metolachlor (Curwin et al., 2005). Hines et al. (2003) showed that 2.2% of a small reference population had detectable metolachlor equivalents by immunoassay in their urine, whereas 60% of applicators had detectable amounts.

Finding measurable amounts of metolachlor mercapturate in the urine does not imply that the levels of metolachlor mercapturate cause an adverse health effect. Biomonitoring studies on levels of metolachlor mercapturate provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels metolachlor 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.

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/. 1/24/13

Coleman S, Linderman R, Hodgson E, Rose RL. Comparative metabolism of chloroacetamide herbicides and selected metabolites in human and rat liver microsomes. Environ Health Perspect 2000;108(12):1151-7.

Curwin BD, Hein MJ, Sanderson WT, Barr DB, Heederik D, Reynolds SJ, Ward EM, Alavanja MC. Urinary and hand wipe pesticide levels among farmers and nonfarmers in Iowa. J Expo Anal Environ Epidemiol 2005;15(6):500-8.

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

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.

Gillion, R. Pesticides in U.S. streams and groundwater. Environ Sci Technol 2007;41:3409-3414. Available at URL: https://water.usgs.gov/nawqa/pnsp/pubs/files/051507.ESTfeature_gilliom.pdf. 1/24/13

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.

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.

U.S. Environmental Protection Agency (U.S. EPA). Reregistration Eligibility Decision (RED) Metolachlor. April 1995. EPA 738-R-95-006. Available at URL: https://www.epa.gov/oppsrrd1/REDs/0001.pdf. 1/24/13.

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. 1/24/13

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/text.html. 1/24/13

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). Metolachlor 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/metolachlor.pdf. 1/24/13