Biomonitoring Summary

Substituted Urea Herbicides

General Information

The substituted urea herbicides (SUHs) are a large group of non-selective herbicidal agents. Some were introduced in the 1960s, and other SUHs have been introduced as recently as 2003. The SUHs are often applied for nuisance broadleaf weed and grass control in such noncrop areas as roadsides and drainage ditches, but many also have registered pre- and post-emergence applications for certain crops. Most SUHs bind to soils and are taken up by plant roots. Substitution of phenyl or sulfonyl chemical groups onto the urea structure identifies the two of the main types of SUHs. The phenylureas act by inhibiting photosynthesis. Chemicals in this class of SUHs have been available since the 1960's. The sulfonylurea herbicides are a relatively newer class of SUHs. Sulfonylureas inhibit the plant enzyme, acetolactate synthase, resulting in impaired branch chain amino acid synthesis, and are generally more potent herbicides than the phenylureas. An attractive feature of sulfonylureas is that they can be applied at relatively low application rates. The sulfonylureas have greater activity against broad-leaf weeds, but resistance has developed in some plant types.

Most SUHs are resistant to hydrolysis and oxidation under environmental conditions but are only moderately persistent because they are degraded by soil microorganisms. Phenylureas remain active in soil for several months, with half-lives that range from a few months up to a year. In contrast, sulfonylureas are less persistent with soil half-lives ranging from a few days to a few months (Kamrin, 1997). Most SUHs have low volatility, are mobile in soil, and are slightly to moderately soluble in water, so they can leach into runoff and can affect wild aquatic plant growth (Wauchope et al., 1992). In a 1998 survey, nicosulfuron was detected in 67% of 130 Midwestern streams and rivers (Battaglin et al., 2000). Many newer SUHs are nontoxic to slightly toxic to birds and aquatic insects and vertebrates, although with massive accidental spills into rivers, fish kills have been reported. Most of the newer SUHs (e.g., sulfonylureas) have very low mammalian toxicity (Kamrin, 1997).

Sulfonylurea Herbicides

General Information

The first sulfonylurea herbicides were introduced in 1982 and have been used for control of nuisance broadleaf weeds and grasses. They can be divided into the pyrimidinylsulfonylureas and the triazinylsulfonylureas. These herbicides are taken up by the roots and foliage and act by disrupting protein synthesis. The sulfonylureas have soil half-lives that range from a few days to two months, and they are degraded by soil microbes and chemical hydrolysis, depending on soil conditions (Sarmah and Sabadie, 2002). These herbicides are generally only slightly toxic to freshwater fish and invertebrates, and practically nontoxic to wildfowl and other mammals. Numerous sulfonylureas are currently registered with the U.S. EPA, and the 17 measured for the National Report on Human Exposure to Environmental Chemicals are shown in the Table:

Sulfonylurea Herbicides	CAS number
Bensulfuron methyl	83055-99-6
Chlorsulfuron	64902-72-3
Ethametsulfuron methyl	97780-06-8
Foramsulfuron	173159-57-4
Halosulfuron	135397-30-7
Mesosulfuron methyl	208465-21-8
Metsulfuron methyl	74223-64-6
Nicosulfuron	111991-09-4
Oxasulfuron	144651-06-9
Primisulfuron methyl	86209-51-0
Prosulfuron	94125-34-5
Rimsulfuron	122931-48-0
Sulfometuron methyl	74222-97-2
Sulfosulfuron	141776-32-1
Thifensulfuron methyl	79277-27-3
Triasulfuron	82097-50-5
Triflusulfuron methyl	126535-15-7

General population exposure to sulfonylurea herbicides is likely to be uncommon because of the low application rates of these herbicides. Potential routes of human exposure include consumption of foods grown in soil to which the sulfonylureas were applied or drinking contaminated water. Tolerances or acceptable concentrations have been established for various edible food crops to which several of these herbicides may be applied (U.S. EPA, 2002, 2004a, and 2004b). Estimated human intakes associated with registered uses have been below recommended limits (U.S. EPA, 2002, 2004a, 2004b, and 2008). Information on the toxicokinetics of the sulfonylureas is limited, but rapid metabolism and excretion into both feces and urine in animals was reported for several sulfonylureas, except for primisulfuron, which was not absorbed in the intestine and was eliminated unchanged in the feces (Kamrin, 1997).

Human health effects from the sulfonylurea herbicides at low environmental doses or at biomonitored levels from low environmental exposures are unknown. The sulfonylurea herbicides are generally of low toxicity in mammalian studies. Animal studies showed low acute toxicity and little chronic, reproductive, or developmental toxicity or teratogenic effects. Developmental or teratogenic effects tended only to occur at high or maternally toxic doses. At high sublethal, chronic oral doses, such nonspecific effects as weight loss and anemia were observed. Some chemical-specific effects were noted at high doses in animals. Primisulfuron-methyl produced chronic nephritis, testicular atrophy, tooth and bone growth disorders (EXTOXNET, 1996; Kamrin, 1997); halosulfuron and halosulfuron-methyl produced reproductive toxicity and fetotoxic malformations of central nervous system (U.S. EPA, 1999a and 2001); sulfosulfuron produced urinary calculi and bladder tumors (U.S. EPA, 1999b); and triflusulfuron-methyl produced interstitial cell hyperplasia and adenomas (U.S. EPA, 1996). Sulfonylurea herbicides were not mutagenic in vitro and most were not carcinogenic in animals. IARC and NTP have not classified the sulfonylurea herbicides with respect to human carcinogenicity. U.S.EPA considers the sulfonylureas not classifiable, not rated, or noncarcinogenic, with the exception of sulfosulfuron, classified as a likely human carcinogen, and triflusulfuron-methyl classified as a possible human carcinogen. Additional information about external exposure (i.e., environmental levels) is available from U.S. EPA web site at: https://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of the sulfonylurea herbicides reflect recent exposure. There is very limited information on the biomonitoring of sulfonylurea herbicides or their metabolites. Detection of the metabolites may reflect exposure to more than one particular sulfonylurea herbicide or from exposure to environmental degradation products. The urinary metabolites dimethoxypyrimidine and dimethylpyrimidine can be used as non-specific markers of exposure to the pyrimidinylsulfonylureas, a group that includes bensulfuron-methyl, halosulfuron, primisulfuron-methyl, and sulfosulfon. The urinary metabolite methoxymethyl triazine can be used as a non-specific marker of exposure to the triazinylsulfonylureas, a group that includes chlorosulfuron, prosulfuron, and triasulfuron.

Finding a measurable amount of a sulfonylurea herbicide or metabolites in the urine does not imply that the levels of sulfonylurea herbicide or metabolites cause an adverse health effect. Biomonitoring studies on levels of sulfonylurea herbicides provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of sulfonylurea herbicides 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.

E X T O X N E T/Extension Toxicology Network; Pesticide Information Profiles. Primisulfuron-Methyl. Revised June, 1996. Available at URL: http://ace.ace.orst.edu/info/extoxnet/pips/primisul.htm. 2/1/13

Kamrin, Michael (editor). Pesticide Profiles-Toxicity, Environmental Impact, and Fact. CRC-Lewis Publishers, Boca Raton (FL), 1997, pp. 377-409.

Sarmah AK, Sabadie J. Hydrolysis of sulfonylurea herbicides in soils and aqueous solutions: a review. J Agric Food Chem 2002;50:6253-65.

U.S. Environmental Protection Agency (U.S. EPA). Federal Register Environmental Documents. Halosulfuron; pesticide tolerance. May 12, 1999a. Available at URL: https://www.epa.gov/EPA-PEST/1999/May/Day-12/p11835.htm. 2/1/13

U.S. Environmental Protection Agency (U.S. EPA). Federal Register Environmental Documents. Halosulfuron-methyl; pesticide tolerances for emergency exemptions. December 27, 2001. Available at URL: https://www.epa.gov/fedrgstr/EPA-PEST/2001/December/Day-27/p31800.htm. 2/1/13

U.S. Environmental Protection Agency (U.S. EPA). Federal Register Environmental Documents. Sulfosulfuron; pesticide tolerance. May 19, 1999b, Available at URL: https://www.epa.gov/fedrgstr/EPA-PEST/1999/May/Day-19/p12247.htm. 2/1/13

U.S. Environmental Protection Agency (U.S. EPA). Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Chlorimuron Ethyl. [online] September 22, 2004a. Available at URL: https://www.epa.gov/pesticides/reregistration/REDs/chlorimuronethyl_tred.pdf. 2/1/13

U.S. Environmental Protection Agency (U.S. EPA). Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Nicosulfuron. [online] December 2004b. Available at URL: https://www.epa.gov/oppsrrd1/reregistration/REDs/nicosulfuron_tred.pdf. 2/1/13

U.S. Environmental Protection Agency (U.S. EPA). Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Primisulfuron-methyl. [online] July 23, 2002. Available at URL: https://www.epa.gov/pesticides/reregistration/REDs/primisulfuron_tred.pdf. 2/1/13

U.S. Environmental Protection Agency (U.S. EPA). Reregistration Eligibility Decision (RED) Sulfometuron Methyl. September 2008. Available at URL: https://www.epa.gov/pesticides/reregistration/REDs/sulfometuron_methyl_red.pdf. 2/1/13

Wauchope RD, Buttler TM, Hornsby AG, Augustijn-Beckers PW, Burt JP. The SCS/ARS/CES pesticide properties database for environmental decision-making. Rev Environ Contam Toxicol 1992;123:1-155.