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Biomonitoring Summary

Atrazine

CAS No. 1912-24-9

General Information

Atrazine is a widely used chlorotriazine herbicide active against broadleaf and grassy weeds. Related chlorotriazine herbicides include simazine, propazine, and cyanazine, all which act by inhibiting plant photosynthesis. Atrazine is applied pre- and post-emergence to agricultural land for crops such as corn and sorghum. It is also used as a non-selective herbicide. Atrazine was first registered as an herbicide in 1958. More than 70 million pounds have been applied annually in recent years, with about 75% of corn cropland receiving treatment. Atrazine has limited water solubility and is not tightly bound to soil, but is leachable in to ground and surface waters. In regions where atrazine is used, it is one of the more commonly detected pesticides in surface and ground waters (USGS, 2007). In soils, atrazine is slowly degraded to dealkylated products, which have half-lives of several months. Bacteria and plants can metabolize atrazine to hydroxyatrazine. Atrazine does not bioaccumulate. It has little toxicity in birds and moderate toxicity in some fish and aquatic invertebrates. Atrazine may alter the sexual development of frogs at environmental levels (Gammon et al., 2005; Hayes et al., 2002; U.S.EPA, 2003a).

For the general population, drinking water is an infrequent source of atrazine exposure, but estimates of seasonal intakes from drinking water in a small number of communities have exceeded the recommended limits (U.S.EPA, 2003b). As a result, atrazine use has progressively been restricted in an effort to reduce surface and ground water contamination. Applicators of atrazine may be exposed dermally and by inhalation. Atrazine is well absorbed orally, metabolized, and then eliminated in the urine over a few days (Bradway et al., 1982; Catenacci et al., 1993; Timchalk et al, 1990). In animals and humans, glutathione conjugation appeared to be the major route of biotransformation, resulting in atrazine mercapturate and N-dealkylation (IPCS, 1996; U.S.EPA, 2003b). Atrazine mercapturate accounted for a major proportion of human urinary metabolites (Lucas et al., 1993). The dealkylated chloroatrazine metabolites, particularly diaminochloroatrazine (the main dealkylated product), may mediate some effects of atrazine (Laws et al., 2003). Dealkylated metabolites from atrazine can result also result from metabolism of other chlorotriazine pesticides, including simazine, propazine, and cyanazine. In addition being human metabolites of atrazine, the dealkylated atrazine metabolites and hydroxyatrazine can occur in the environment from the breakdown of the parent chemical. Thus, detection of these dealkylated metabolites in a person's urine may also reflect exposure to these degradates in the environment.

Human health effects of atrazine at environmental doses or at biomonitored levels from environmental exposure are unknown. In mammalian studies, atrazine is rated as having low acute toxicity. Atrazine product formulations can be mild skin sensitizers and irritants. Chronic high dose toxicity observed in animals have demonstrated decreased body weight, myocardial muscle degeneration, liver toxicity, developmental ossification defects, impaired fertility, altered estrus cycles, increased pituitary weight, delayed onset of puberty, and reduced levels of luteinizing hormone, prolactin, and testosterone (Gillis et al., 1994; Laws et al., 2000 and 2003; Rayner et al., 2004; Stoker et al., 2000 and 2002; U.S.EPA, 2003b). Atrazine and the dealkylated chlorinated metabolites did not have estrogen receptor activity, but reduced the pituitary secretion of luteinizing hormone and prolactin and also inhibited aromatase at high doses in some mammalian species (Cooper et al., 2000; Eldridge et al., 1994 and 1999; Gammon et al., 2005; Sanderson et al., 2002; Stevens et al., 1999). Estimated human exposures are thousands of times lower than doses that caused effects in animals (Gammon et al., 2005). Some human ecologic and epidemiologic studies of reproductive and cancer outcomes have shown either positive or no associations, but are effects are difficult to attribute due to lack of exposure markers or due to mixed chemical or pesticide exposures (ATSDR, 2003; Gammon et al., 2005; Sathiakumar and Delzell, 1997). Atrazine is not considered genotoxic. IARC considers atrazine not classifiable with respect to human carcinogenicity, and U.S.EPA considers atrazine unlikely to be a human carcinogen. Additional information is available from U.S. EPA at: http://www.epa.gov/pesticides/ and from ATSDR at: http://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Urinary levels of atrazine mercapturate reflect recent exposure. In the NHANES 1999-2002 subsamples, levels of atrazine mercapturate were generally not detectable (CDC, 2009). In small studies of Maryland residents in 1995-1996 (MacIntosh et al., 1999) and 83 Minnesota children with multiple urine collections during 1997 (Adgate et al., 2001), atrazine mercapturate was infrequently detected at the detection limit of < 1 µg/L. In a study of 60 farm worker children, atrazine was detected in only four children (Arcury et al., 2007). Using immunoassay atrazine equivalents (detected mostly as atrazine mercapturate), the urinary geometric mean levels for herbicide applicators in Ohio and Wisconsin were about 6 µg/L (Hines et al., 2003; Perry et al., 2000). The geometric mean of urinary atrazine mercapturate was 1.2 µg/L in 15 farmers studied several days after spraying the pesticide (Curwin et al., 2005). In a small number of field workers, urinary concentrations ranged from 5-1756 µg/L (Lucas et al., 1993).

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

References

Adgate JL, Barr DB, Clayton CA, Eberly LE, Freeman NC, Lioy PJ, et al. Measurement of children's exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample. Environ Health Perspect 2001;109(6):583-590.

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for atrazine. September 2003 [online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=338&tid=59. 10/16/12

Arcury TA, Grzywacz JG, Barr DB, Tapia J, Chen H, Quandt SA. Pesticide urinary metabolite levels of children in eastern North Carolina farmworker households. Environ Health Perspect 2007;115(8):1254-60.

Bradway DE, Moseman RF. Determination of urinary residue levels of the N-dealkyl metabolites of triazine herbicides. J Agric Food Chem 1982;30(2):244-7.

Catenacci G, Barbieri F, Bersani M, Ferioli A, Cottica D, Maroni M. Biological monitoring of human exposure to atrazine. Toxicol Lett 1993;69(2):217-22.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Atlanta (GA). 2009 [online]. Available at URL: www.cdc.gov/exposurereport. 10/16/12

Cooper RL, Stoker TE, Tyrey L, Goldman JM, McElroy WK. Atrazine disrupts the

hypothalamic control of pituitary-ovarian function. Toxicol Sci 2000;53(2):297-307.

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

Eldridge JC, Wetzel LT, Stevens JT, Simpkins JW. The mammary tumor response in triazine-treated female rats: a threshold-mediated interaction with strain and species-specific reproductive senescence. Steroids 1999;64(9):672-8.

Eldridge JC, Fleenor-Heyser DG, Extrom PC, Wetzel LT, Breckenridge CB, Gillis

JH, et al. Short-term effects of chlorotriazines on estrus in female Sprague-Dawley and Fischer 344 rats. J Toxicol Environ Health 1994;43(2):155-67.

Gammon DW, Aldous CN, Carr WC Jr, Sanborn JR, Pfeifer KF. A risk assessment of atrazine use in California: human health and ecological aspects. Pest Manag Sci 2005;61(4):331-355.

Gillis JH, et al. Short-term effects of chlorotriazines on estrus in female Sprague-Dawley and Fischer 344 rats. J Toxicol Environ Health 1994;43(2):155-67.

Hayes TB, Collins A, Lee M, Mendoza M, Noriega N, Stuart AA, Vonk A. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proc Natl Acad Sci USA 2002;99(8):5476-80.

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.

International Programme on Chemical Safety (IPCS). WHO/FAO Data Sheets on Pesticides. No. 82. ATRAZINE. World Health Organization, Geneva, July 1996. Available at URL: http://www.inchem.org/documents/pds/pds/pest82_e.htm. 10/16/12

Laws SC, Ferrell JM, Stoker TE, Cooper RL. Pubertal development in female Wistar rats following exposure to propazine and atrazine biotransformation by-products, diamino-S-chlorotriazine and hydroxyatrazine. Toxicol Sci 2003;76(1):190-200.

Laws SC, Ferrell JM, Stoker TE, Schmid J, Cooper RL. The effects of atrazine on female wistar rats: an evaluation of the protocol for assessing pubertal development and thyroid function. Toxicol Sci 2000;58(2):366-76.

Lucas AD, Jones AD, Goodrow MH, Saiz SG, Blewett C, Seiber JN, et al. Determination of atrazine metabolites in human urine: development of a biomarker of exposure. Chem Res Toxicol 1993;6(1):107-16.

MacIntosh DL, Needham LL, Hammerstrom KA, Ryan PB. A longitudinal investigation of selected pesticide metabolites in urine. J Expo Anal Environ Epidemiol 1999;9(5):494-501.

Perry M, Christiani D, Dagenhart D, Tortorelli J, Singzoni B. Urinary biomarkers of atrazine exposure among farm pesticide applicators. Ann Epidemiol 2000;10(7):479.

Rayner JL, Wood C, Fenton SE. Exposure parameters necessary for delayed puberty and mammary gland development in Long-Evans rats exposed in utero to atrazine. Toxicol Appl Pharmacol 2004;195(1):23-34.

Sanderson JT, Boerma J, Lansbergen GW, van den Berg M. Induction and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicol Appl Pharmacol 2002;182(1):44-54.

Sathiakumar N, Delzell E. A review of epidemiologic studies of triazine herbicides and cancer. Crit Rev Toxicol 1997;27(6):599-612.

Stevens JT, Breckenridge CB, Wetzel L. A risk characterization for atrazine: oncogenicity profile. J Toxicol Environ Health A 1999;56(2):69-109.

Stoker TE, Laws SC, Guidici DL, Cooper RL. The effect of atrazine on puberty in male wistar rats: an evaluation in the protocol for the assessment of pubertal development and thyroid function. Toxicol Sci 2000;58(1):50-9.

Stoker TE, Guidici DL, Laws SC, Cooper RL. The effects of atrazine metabolites on puberty and thyroid function in the male Wistar rat. Toxicol Sci 2002;67(2):198-206.

Timchalk C, Dryzga MD, Langvardt PW, Kastl PE, Osborne DW. Determination of the effect of tridiphane on the pharmacokinetics of [14C]-atrazine following oral administration to male Fischer 344 rats. Toxicology 1990;61(1):27-40.

U.S. Environmental Protection Agency (U.S. EPA). Office of Prevention, Pesticides and Toxic Substances, EPA Office of Pesticide Programs, Environmental Fate and Effects Division. White paper on potential developmental effects of atrazine on amphibians. Washington (DC). May 2003a. Available at URL: http://www.epa.gov/scipoly/sap/meetings/2003/june/finaljune2002telconfreport.pdf. 10/16/12

U.S. Environmental Protection Agency (U.S. EPA). Interim Reregistration Eligibility Decision For Atrazine. Case No. 0062. 2003b. Available at URL: http://www.epa.gov/oppsrrd1/REDs/atrazine_ired.pdf. 10/16/12

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: http://water.usgs.gov/nawqa/pnsp/pubs/circ1291/supporting_info.php. 10/16/12


 
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