Biomonitoring Summary

2,4,5-Trichlorophenoxyacetic Acid

CAS No. 93-76-5

General Information

2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) is a chlorophenoxy acid herbicide that is no longer registered for use in the United States. Chlorophenoxy herbicides act as plant growth hormones. At low levels, these herbicides can enhance plant growth, but higher levels are herbicidal. 2,4,5-T was once applied as either an aqueous salt or as an oil-soluble ester. Ester forms of 2,4,5-T and 2,4-D were used as defoliants in the Vietnam War (e.g., Agent Orange) and concern about contamination with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) led to the discontinuation of 2,4,5-T use as a herbicide in 1985. The half-life of 2,4,5-T in soil varies with conditions, ranging from several weeks to many months. 2,4,5-T degrades to 2,4,5-trichlorophenol and other degradates. 2,4,5-T has been rarely detected in ground waters (USGS, 2007).

Given the unavailability of 2,4,5-T, the general population is unlikely to be exposed to 2,4,5-T. Although 2,4,5-T is rapidly absorbed via oral and inhalation routes, it is not well absorbed through the skin. Once absorbed into the body, 2,4,5-T is eliminated mostly unchanged in the urine, with an elimination half-life of approximately 19 hours (Arnold et al., 1989; Kohli et al., 1974).

Human health effects from 2,4,5-T at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Intentional overdoses and unintentional high dose occupational exposures to chlorophenoxy acid herbicides have resulted in weakness, headache, dizziness, nausea, abdominal pain, myotonia, hypotension, renal and hepatic injury, and delayed neuropathy (Bradberry et al, 2004). Teratogenic and developmental effects have been reported in studies of multiple rodent strains treated with high doses of technical grade 2,4,5-T (Holson et al., 1992; Mohammad and St. Omer, 1986; Nelson et al., 1992). Epidemiological studies have reported associations of several types of cancer, such as soft tissue sarcoma and non-Hodgkin's lymphoma, with the exposure to chlorophenoxy herbicides as defoliants or contaminated herbicides. It is unclear whether these associations are related to the chlorophenoxy herbicides, other exposures, or to contaminants in the herbicide formulations (specifically 2,3,7,8-tetrachlorodibenzo-p-dioxin) (Garabrant and Philbert, 2002; IOM, 2003; IPCS, 1996; Pearce and McLean, 2005). 2,4,5-T itself is not mutagenic. IARC considers the chlorophenoxyacetic acids group of chemicals as possibly carcinogenic to humans. Additional information is available from U.S.EPA at: https://www.epa.gov/pesticides/.

Biomonitoring Information

Urinary levels of 2,4,5-T reflect recent exposure. In the NHANES 1999-2000 and 2001-2002 subsamples (CDC, 2009), urinary levels of 2,4,5-T were generally below the limit of detection, similar to results of NHANES II (1976-1980), in which urinary levels of 2,4,5-T were below the limit of detection (Kutz et al., 1992). Mean urinary levels of 2,4,5-T measured after a day of exposure in a few asymptomatic herbicide applicators were 35,000 times higher than the detection limit for the NHANES 2001-2002 data (Kolmodin-Hedman and Erne, 1980).

Finding a measurable amount of does not imply that the level of the 2,4,5-T will result in an adverse health effect. Biomonitoring studies on 2,4,5-T in urine also provide physicians and public health officials with reference values so that they can determine whether other people have been exposed to higher levels of 2,4,5-T than levels found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Arnold EK, Beasley VR. The pharmacokinetics of chlorinated phenoxy acid herbicides: a literature. Vet Hum Toxicol 1989;31(2):121-5.

Bradberry SM, Proudfoot AT, Vale JA. Poisoning due to chlorophenoxy herbicides. Toxicol Rev. 2004;23(2):65-73.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. 2009. [online] Available at URL: https://www.cdc.gov/exposurereport/. 10/1512

Garabrant DH, Philbert MA. Review of 2,4-dichlorophenoxyacetic acid (2,4-D) epidemiology and toxicology. Crit Rev Toxicol 2002;32(4):233-57.

Holson JF, Gaines TB, Nelson CJ, LaBorde JB, Gaylor DW, Sheehan DM, et al. Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). I. Multireplicated dose-response studies in four inbred strains and one outbred stock of mice. Fundam Appl Toxicol 1992;19(2):286-97.

International Programme on Chemical Safety-INCHEM (IPCS). Pesticides residues in food: 1996 evaluations Part II Toxicology. 914. Dichlorophenoxyacetic acid, 2,4-. Available at URL: http://www.inchem.org/documents/jmpr/jmpmono/v96pr04.htm. 3/17/09

Institute of Medicine (IOM). Board on Health Promotion and Disease Prevention. Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Fourth Biennial Update. Veterans and Agent Orange: update 2002. Washington (DC): National Academies Press; 2003. Available at URL: http://www.nap.edu/catalog.php?record_id=10603. 3/17/09

Kohli JD, Khanna RN, Gupta BN, Dhar MM, Tandon JS, Sircar KP. Absorption and excretion of 2,4,5-trichlorophenoxy acetic acid in man. Arch Int Pharmacodyn Ther 1974; 210:250-5.

Kolmodin-Hedman B, Erne K. Estimation of occupational exposure to phenoxy acids (2,4-D and 2,4,5-T). Arch Toxicol Suppl 1980;4:318-21.

Kutz FW, Cook BT, Carter-Pokras OD, Brody D, Murphy RS. Selected pesticide residues and metabolites in urine from a survey of the U.S. general population. J Toxicol Environ Health 1992;37(2):277-91.

Mohammad FK, St Omer VE. Behavioral and developmental effects in rats following in utero exposure to 2,4-D/2,4,5-t mixture. Neurobehav Toxicol Teratol 1986;8(5):551-60.

Nelson CJ, Holson JF, Gaines TB, LaBorde JB, McCallum WF, Wolff GL, et al. Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). II. Multireplicated dose-response studies with technical and analytical grades of 2,4,5-T in four-way outcross mice. Fundam Appl Toxicol 1992;19(2):298-306.

Pearce N, McLean D. Agricultural exposures and non-Hodgkin's lymphoma. Scand J Work Environ Health 2005;31 Suppl 1:18-25; discussion 5-7.