CAS No. 333-41-5
The chemical 2-isopropyl-4-methyl-6-hydroxypyrimidine is a metabolite of diazinon, an organophosphorus insecticide that is used to control insects on nuts, fruits, vegetable, and forage crops. It is also used for cattle ear tag applications to control flies and ticks and, in the past, in some pest strips. Most granular formulations, aerial, seed and foliar applications are planned to be phased out (U.S.EPA, 2004). Prior to 2000, diazinon was widely used in residential and garden application, but these uses have been phased out; since 2004, diazinon cannot be sold for residential use. Before these restrictions, about 13 million pounds of diazinon were used annually on agricultural sites in the United States. Diazinon is biologically and chemically degraded in soils with a half-life of about a few weeks. It has been infrequently detected in general groundwater sampling but has been detected in streams receiving runoff from application sites (IPCS, 1998; USGS, 2007). It is toxic to birds, and particularly when it was ingested in granular form, diazinon produced wild bird kills before use restrictions were in place. Fish and aquatic invertebrates show modest degrees of bioconcentration and are very sensitive to toxic effects.
Human exposure to diazinon from dietary sources is expected to be low due to its limited applications to food crops and due to its rapid degradation. Estimated intakes from diet and water do not exceed recommended intake limits (U.S.EPA, 2004). Inhalational and dermal routes of exposure can be significant for pesticide applicators. Diazinon is not well-absorbed through the skin, but is rapidly absorbed orally (IPCS, 1998). Once absorbed, phosphorothioates such as diazinon are metabolically activated to the "oxon" form which has greater toxicity. Metabolic hydrolysis leads to the formation of 2-isopropyl-4-methyl-6-hydroxypyrimidine, dialkyl phosphate metabolites, and other metabolites. Experimental diazinon exposure in people has demonstrated its rapid elimination into urine, as inferred from dialkyl phosphate metabolite excretion (Garfitt et al., 2002). In animals, diazinon does not accumulate in tissues (IPCS, 1998). In addition to being a human metabolite of diazinon, 2-isopropyl-4-methyl-6-hydroxypyrimidine can also occur in the environment from the breakdown of the parent compound. Thus, detection of 2-isopropyl-4-methyl-6-hydroxypyrimidine in a person's urine may reflect exposure to the environmental degradate.
Human health effects from diazinon at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Diazinon has moderate acute toxicity in animal studies. At high doses, diazinon and other organophosphorus insecticides share a 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. Intoxications in humans from intentional overdose, agricultural, and indoor applications have been documented. There has been only limited study of diazinon at systemically non-toxic doses that do not result in cholinergic signs (Anthony et al., 1986 Rajendra et al., 1986; Seifert and Pewnim, 1992). Diazinon is not considered to be a mutagen, animal carcinogen, teratogen, or reproductive toxicant (IPCS, 1998). The U.S.EPA considers diazinon unlikely to be carcinogenic in humans. Additional information about external exposure (i.e., environmental levels) and health effects is available from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp and from U.S. EPA at https://www.epa.gov/pesticides/.
Urinary levels of 2-isopropyl-4-methyl-6-hydroxypyrimidine reflect recent exposure. In two nonrandom samples of United States adults and children, 2-isopropyl-4-methyl-6-hydroxypyrimidine was detectable in 57% and 43% of the 130 and 140 participants, respectively (Baker et al., 2000; Olsson et al., 2003). In the U.S. subsamples of NHANES 1999-2000 and 2001-2002, most of the measurements of 2-isopropyl-4-methyl-6-hydroxypyrimidine in urine were below the limit of detection, although the 95th percentiles for children 6-11 years old and for non-Hispanic blacks were 1.45 and 1.49 μg/L, respectively, in the 2001-2002 subsample (CDC, 2009). In 23 children, urinary 2-isopropyl-4-methyl-6-hydroxypyrimidine was detected in less than 14% of multiple samples collected during varied diets (Lu et al., 2006). In a small number of men visiting fertility clinics in Missouri and Minnesota, Swan et al. (2003) found that 2-isopropyl-4-methyl-6-hydroxypyrimidine was detectable in 96% and 58% of the subjects. In 54 Canadian greenhouse workers, urinary 2-isopropyl-4-methyl-6-hydroxypyrimidine levels were below the limit of detection (Bouchard et al., 2006).
Finding a measurable amount of 2-isopropyl-4-methyl-6-hydroxypyrimidine in urine does not imply that the level causes an adverse health effect. Biomonitoring studies of 2-isopropyl-4-methyl-6-hydroxypyrimidine provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of diazinon than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
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