Biomonitoring Summary

Pyrethroid Pesticides Overview

Pyrethroid pesticides are synthetic analogues of pyrethrins, which are natural chemicals found in chrysanthemum flowers. Pyrethroid pesticides are used to control a wide range of insects in public and commercial buildings, animal facilities, warehouses, agricultural fields, and greenhouses. They are also applied on livestock to control insects. In agriculture, cypermethrin, cyfluthrin, and deltamethrin have been used frequently on cotton. Pyrethroid insecticides are the most common active ingredient in commercially available insect sprays and are also used as structural termiticides. Certain pyrethroid insecticides (such as permethrin, resmethrin, and sumithrin) are also registered for use in mosquito-control programs in the United States. Outside the U.S., deltamethrin has been used for indoor protection against mosquitoes that carry malaria, in some situations replacing the use of DDT. About two million pounds of permethrin and one million pounds of cypermethrin have been applied annually (U.S. EPA, 2006a, 2006b). Permethrin is also used in skin lotions and shampoos as medical treatments for lice and scabies. Pyrethroid pesticides are generally formulated as complex mixtures of different chemical isomers, solvent oils, and synergists, such as piperonyl butoxide. Pyrethroid pesticides have low volatility, bind to soils, and are rarely detected in ground waters (USGS, 2007). Generally, they are not persistent in the environment due to their rapid degradation within days to several months. This class of pesticides has low toxicity in birds and mammals, but pyrethroids are highly toxic to fish and some aquatic invertebrates, so usage is restricted near water (U.S.EPA, 2012).

The general population may be exposed to pyrethroid insecticides primarily from the ingestion of food or from residential use. Estimated intakes from diet and drinking water are below recommended limits. Dermal exposure with the potential for inadvertent ingestion may occur when lotions or shampoos are applied to treat lice or scabies. Pesticide applicators can be exposed to pyrethroid pesticides via dermal and inhalation routes from powders and liquid formulations. Pyrethroids are not well absorbed through the skin (ATSDR, 2003; Woollen et al., 1992). After absorption from inhalation or ingestion, pyrethroids are rapidly metabolized, by either ester hydrolysis or hydroxylation, followed by conjugation, and then eliminated over several days in urine and bile (Kuhn et al., 1999; Leng et al., 1997; Soderlund et al., 2002; Woollen et al., 1992). Unmetabolized pyrethroids have been measured in breast milk, but may be poorly transferred across the placenta (ATSDR, 2003; WHO, 2005).

Human health effects from pyrethroid pesticides at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Compared with other classes of insecticides such as organochlorines, organophosphorus, or carbamate pesticides, pyrethroid pesticides have less acute toxicity in animals and people. They are ranked as having moderate acute oral toxicity. Adverse effects from large doses are related to the action of pyrethroids on the nervous system, where these chemicals prolong sodium channel opening when a nerve cell is depolarized (Shafer et al., 2005; Soderlund et al., 2002). Possible other additional actions on neuroreceptors and other ion channels may also explain some pyrethroid effects. Human cases of systemic poisoning are rare and usually result from accidental exposure or intentional ingestion of pyrethroid insecticides. Signs and symptoms of acute pyrethroid poisoning after massive ingestions include agitation, hypersensitivity, tremor, salivation, choreoathetosis, and seizures (ATSDR, 2003; Ray et al., 2000; Soderlund et al., 2002). Concomitant exposure to organophosphorus insecticides may increase pyrethroid toxicity by slowing metabolic clearance of the pyrethroid. In California, cyfluthrin was the most frequent pyrethroid associated with symptomatic effects (irritant respiratory and dermal effects, paresthesias) reported in agricultural workers from 1996 to 2002 (Spencer and O'Malley, 2006). Transient dermal paresthesias have been reported among pesticide applicators after direct contact with certain types of pyrethroid pesticides. No relationship of indoor air or housedust concentrations of permethrin and irritant symptoms was found in a study of urban residents in 80 private homes (Berger-Preiss et al., 2002).

In developing rodents, neurochemical changes in cholinergic, dopaminergic, and catecholaminergic pathways and behavioral changes have been demonstrated at subacute and subchronic doses for some pyrethroid pesticides (Aziz et al., 2001; Elwan et al., 2006; Eriksson and Fredriksson, 1991; Lazarini et al., 2001; Shafer, et al., 2005). The pyrethroids in general use are not considered teratogenic or to have significant reproductive toxicity (ATSDR, 2003; WHO, 2005), though a few pyrethroid pesticides and some metabolites have shown weak or inconsistent estrogenic effects on standardized assays (ATSDR, 2003; Garey and Wolff, 1998; Go et al., 1999; Hu et al., 2003; Kim et al., 2004; Kunimatsu et al., 2002; McCarthy et al., 2006; Moniz et al., 2005). Generally, the pyrethroids are not considered genotoxic in in vitro testing or carcinogenic in animal testing (WHO, 2005). IARC considers deltamethrin and permethrin as not classifiable as to their human carcinogenicity. Additional information about pesticides is available from U.S. EPA at https://www.epa.gov/pesticides and from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp#H.

There are about 30 different pyrethroid pesticides in use. The table shows the urinary pyrethroid metabolites measured in the National Biomonitoring Program.

Phthalates and Urinary Metabolites Measured in the National Biomonitoring Program

Table of Phthalates and Urinary Metabolites Measured in the National Biomonitoring Program
Pyrethroid (CAS number)	Urinary metabolite (CAS number)
Cyfluthrin (68359-37-5)	4-Fluoro-3-phenoxybenzoic acid (77279-89-1)
Cypermethrin (52315-07-8) Cyfluthrin (68359-37-5) Permethrin (52645-53-1)	cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (63597-73-9) trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (59042-50-1)
Deltamethrin (52918-63-5)	cis-3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (59042-49-8)
Cyhalothrin (68359-37-5) Cypermethrin (52315-07-8) Deltamethrin (52918-63-5) Fenpropathrin (39515-41-8) Permethrin (52645-53-1) Tralomethrin (66841-25-6)	3-Phenoxybenzoic acid (3739-38-6)

Cyfluthrin

CAS No. 68359-37-5

Cypermethrin

CAS No. 52315-07-8

Permethrin

CAS No. 52645-53-1

General Information

Several pyrethroid pesticides are formulated as a mixture of cis– and trans-isomers. In the body, cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid is a metabolite formed from cis-permethrin, cis-cypermethrin and cis-cyfluthrin. The chemical trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid is a metabolite formed from trans-permethrin, trans-cypermethrin and trans-cyfluthrin. The cis-isomer of permethrin has more potent insecticidal activity than trans-permethrin. Generally, more of the trans-metabolite than the cis-metabolite is found in the urine.

The presence of cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid in urine not only reflects the metabolic transformation of any of the three pesticides, cis-permethrin, cis-cypermethrin, and cis-cyfluthrin, but it can also reflect exposure to cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid that is formed in the environment from the degradation of these pesticides (George, 1985; Kuhn et al., 1999). Similarly, the presence oftrans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid in urine not only reflects the metabolic transformation of any of the three pesticides, trans-permethrin, trans-cypermethrin, and trans-cyfluthrin, but can also reflect exposure to trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid formed in the environment from the degradation of these pesticides (George, 1985; Kuhn et al., 1999).

Biomonitoring Information

Urinary levels of cis– or trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid reflect recent exposure to either their parent pyrethroid pesticides or their environmental degradates. Studies in Germany of 396 children and adolescents (Becker et al., 2006) and 1177 urban adults and children (Heudorf et al., 2001) showed urinary levels of cis– and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acids at the 95th percentile that were similar or slightly less than the 95th percentiles in the U.S. representative NHANES 2001-2002 subsample (CDC, 2009). Urinary levels of the two chemicals in adults were similar to those in children in these studies (Heudorf et al., 2001, 2006). Estimated daily pyrethroid intakes based on urinary levels in the German children were below the acceptable daily tolerances (Heudorf et al., 2004). These studies indicated that intake is mainly from the diet and that dermal absorption contributes little to intake (Heudorf et al., 2004, 2006; Schettgen et al., 2002). Other studies have provided evidence that urinary levels of cis– and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acids in children were related to residential pesticide use and house dust levels (Becker et al., 2006; Lu et al., 2006).

In a study of urban residents in Germany (Berger-Preiss et al., 2002), urinary levels of cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid at the 95th percentile were about halfthe 95th percentile in the NHANES 2001-2002 subsample (CDC, 2009). In the same residents, urinary trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid levels at the 95th percentile were about one-third of the 95th percentile in the NHANES 2001-2002 subsample (CDC, 2009). In a study of volunteers, the median and 95th percentile of urinary levels of cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid did not increase at 24-72 hours after exposure to nearby pest control operations (Leng et al., 2003); the levels at 24-72 hours were slightly less than the 95th percentile in the NHANES 2001-2002 subsample (CDC, 2009). In these volunteers, median urinary levels of trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid did not increase, though the 95th percentile levels increased several fold after exposure to nearby pest control operations (Leng et al., 2003); the levels at 24-72 hours were slightly less than the 95th percentile in the NHANES 2001-2002 subsample (CDC, 2009).

In a small group of indoor pest-control operators, post-application median urinary levels of summed cis– and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (Hardt and Angerer, 2003) were similar to the 95th percentiles for adults in the NHANES 2001-2002 subsample (CDC, 2009). The maximum post-application urinary levels, however, were up to 27 times higher than the 95th percentile for adults in the NHANES 2001-2002 subsample (CDC, 2009).

Finding a measurable amount of cis– or trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid in urine does not imply that the level causes an adverse health effect. Biomonitoring studies on urinary levels of cis– or trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of pyrethroid pesticides than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

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Content source: Centers for Disease Control and Prevention