CAS No. 121-75-5
Malathion dicarboxylic acid is a metabolite of malathion, which is an organophosphorus insecticide that is used on a wide variety of agricultural crops, as well as lawns, gardens, ornamental trees, shrubs, and plants. It is registered for use in public health mosquito control, in fruit fly control, and in government programs such as the USDA's Boll Weevil Eradication Program. Most of the estimated 15 million pounds used annually are applied to cotton (U.S.EPA, 2006). When malathion is used on food or feed crops, usually only a small fraction of the crop is treated. It has a short half-life in soils and water and is not considered persistent in the environment. Malathion is infrequently detected in groundwater sampling (USGS, 2007). It is moderately to highly toxic to fish, depending on the species. It is highly toxic to aquatic invertebrates and rare fish kills have been reported from wide area applications onto surface waters and runoff into waters. Malathion is also used medically in lotion form (0. 5%) to kill body lice.
Limited general population exposure occurs through the diet. Estimated intakes for the general population have not exceeded recommended intake limits. Pesticide applicators and agricultural workers can have higher exposures via dermal, inhalational, or oral routes (U.S.EPA, 2006). Malathion is slowly absorbed through the skin, but is more rapidly and efficiently absorbed via ingestion. Once they are absorbed, phosphorothioates such as malathion are metabolically activated to the "oxon" forms which have greater toxicity than the parent insecticide. Metabolism of malathion leads to the formation of malathion monocarboxylic acid, malathion dicarboxylic acid, dialkyl phosphate metabolites, and other metabolites. Malathion is rapidly eliminated from the body within 12-24 hours (Bouchard et al., 2003). About 31-35% of oral doses of malathion are excreted in the urine as malathion monocarboxylic acid (Krieger and Dinoff, 2000). In addition to being a metabolite of malathion, malathion dicarboxylic acid can also occur in the environment from the breakdown of the parent compound. Thus, the detection of malathion dicarboxylic acid in a person's urine may also reflect exposure to the environmental degradate.
Human health effects from malathion at low environmental doses or at biomonitored levels from low environmental exposures are unknown. At high doses, malathion and other organophosphorus insecticides share a common mechanism of toxicity: inhibition of the activity of acetylcholinesterase enzymes in the nervous system, resulting in excess acetylcholine at nerve terminals, and producing acute symptoms such as nausea, vomiting, cholinergic effects, weakness, paralysis, and seizures. Compared with other organophosphorus insecticides, malathion has low acute toxicity. Severe toxicity or deaths have been reported from direct ingestion of agricultural strength solutions. Toxicity from unprotected bystander exposure during applications is rare (U.S.EPA, 2006). Human studies of single oral doses between 0.5 and 5.0 mg/kg/day have shown no acetylcholinesterase inhibition or other short term effects (IPCS, 2003). Malathion does not appear to produce human reproductive or teratogenic effects at environmental levels of exposure (Grether et al., 1987; Thomas et al., 1990), and it is not considered an animal teratogen or a reproductive toxicant. Malathion itself has not been considered genotoxic (U.S.EPA, 2006), but isomalathion, a malaoxon metabolite and a technical grade impurity, tested positive in some chromosomal tests (Blasiak et al., 1999; Flessel et al., 1993; Giri et al., 2002; Pluth et al., 1996). IARC considers malathion not classifiable as a human carcinogen. Additional information about external exposure (i.e., environmental levels) and health effects is available from ATSDR at http://www.atsdr.cdc.gov/toxprofiles/index.asp and from U.S. EPA at http://www.epa.gov/pesticides/.
Levels of urinary malathion dicarboxylic acid reflect recent exposure. The 95th percentile urinary levels of malathion dicarboxylic acid in both urban and nonurban Minnesota children aged 3-13 years (adjusted for sociodemographic variables) in 1997 were several-fold higher than the analytical detection limits reported for children aged 6-11 years in the U.S. representative subsample from NHANES 1999-2000 (Adgate, 2001; CDC, 2009). Malathion dicarboxylic acid was infrequently detected in multiple samples from 80 Maryland residents in 1995-96 (MacIntosh et al., 1999). Of 382 pregnant women living in an agricultural community, 30% had detectable levels of malathion dicarboxylic acid at a detection limit about tenfold lower than the detection limit in the NHANES 1999-2000 analyses (Eskenazi et al., 2004). A study of 13 children from an agricultural region of Washington State reported median levels that were below the detection limit in the NHANES 1999-2000 subsample (Kissel et al., 2005). Replacing conventional diets with organic diets in 23 children led to a tenfold decrease in urinary levels of malathion dicarboxylic acid; median urinary levels on the conventional diet were similar to the detection limit in the NHANES 1999-2000 subsample (CDC, 2009; Lu et al., 2006). A study of agricultural workers reported preshift urinary levels of malathion dicarboxylic acid that were twofold to eightfold higher than detection limits in the NHANES 1999-2000 subsample (Krieger and Dinoff, 2000); some of the postshift urine levels in duster-applicators were thousands of times higher than the detection limits in the NHANES 1999-2000 subsample (CDC, 2009), but cholinesterase activity was not affected.
Finding a measurable amount of malathion dicarboxylic acid in urine does not imply that the level of malathion dicarboxylic acid causes an adverse health effect. Biomonitoring studies of malathion dicarboxylic acid provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of malathion than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
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.
Blasiak J, Jaloszynski P, Trzeciak A, Szyfter K. In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues. Mutat Res 1999;445(2):275-283.
Bouchard M, Gosselin NH, Brunet RC, Samuel O, Dumoulin MJ, Carrier G. A toxicokinetic model of malathion and its metabolites as a tool to assess human exposure and risk through measurements of urinary biomarkers. Toxicol Sci 2003;73(1):182-94. Erratum in: Toxicol Sci. 2003; Aug;74(2) following table of contents.
Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. 2009. [online] Available at URL: http://www.cdc.gov/exposurereport/. 1/24/13
Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, et al. Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environ Health Perspect 2004;112(10):1116-1124.
Flessel P, Quintana PJ, Hooper K. Genetic toxicity of malathion: a review. Environ Mol Mutagen 1993;22(1):7-17.
Giri S, Prasad SB, Giri A, Sharma GD. Genotoxic effects of malathion: an organophosphorus insecticide using three mammalian bioassays in vivo. Mutat Res 2002;514(1-2):223-231.
Grether JK, Harris JA, Neutra R, Kizer KW: Exposure to aerial malathion application and the occurrence of congenital anomalies and low birthweight. Am J Public Health 1987;77:1009-1010.
International Programme on Chemical Safety-INCHEM (IPCS). Pesticides residues in food: 2003 FAO/WHO Meeting on Pesticide Residues. Malathion (addendum). Available at URL: http://www.inchem.org/documents/jmpr/jmpmono/v2003pr06.htm. 1/24/13
Kissel JC, Curl CL, Kedan G, Lu C, Griffith W, Barr DB, et al. Comparison of organophosphorus pesticide metabolite levels in single and multiple daily urine samples collected from preschool children in Washington State. J Expo Anal Environ Epidemiol 2005;15(2):164-171.
Krieger RI, Dinoff TM. Malathion deposition, metabolite clearance, and cholinesterase status of date dusters and harvesters in California. Arch Environ Contam Toxicol 2000;38(4):546-553.
Lu C, Toepel K, Irish R, Fenske RA, Barr DB, Bravo R. Organic diets significantly lower children's dietary exposure to organophosphorus pesticides. Environ Health Perspect 2006;114(2):260-263.
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.
Pluth JM, Nicklas JA, O'Neill JP, Albertini RJ. Increased frequency of specific genomic deletions resulting from in vitro malathion exposure. Cancer Res 1996;56(10):2393-2399.
Thomas D, Goldhaber M, Petitti D, Swan SH, Rappaport E, Hertz-Picciotto I. Reproductive outcome in women exposed to malathion. Am J Epidemiol 1990;132(4):794-795.
U.S. Environmental Protection Agency (U.S. EPA). Reregistration eligibility decision (RED) Malathion. July 2006. EPA 738-R-06-030. Available at URL: http://www.epa.gov/oppsrrd1/REDs/malathion_red.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. March 2006, revised February 15, 2007 [online]. Available at URL: http://pubs.usgs.gov/circ/2005/1291/. 1/24/13