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Increasing use of pyrethroids in Canadian households: should we be concerned?

Pyrethroid insecticides and naturally occurring pyrethrins are commonly used for insect control in households and in agriculture. (1) Reasons for this are increasing restrictions in the use of organophosphate and organochlorine insecticides, the greater selectivity of pyrethroids for certain target species, (2) their moderate acute oral toxicity in vertebrates and humans, (3) and relatively low levels of environmental residues due to rapid degradation outdoors. (1) While pyrethroids have received both scientific (2) and regulatory (4,5) attention, questions remain as to their safety, especially for residential applications.

What are pyrethroids?

Natural pyrethrins are present in pyrethrum extracts obtained from flowers of some species of chrysanthemum. Because pyrethrins degrade easily under the influence of water and sunlight, more stable alternatives--the synthetic pyrethroids--have been developed, allowing for longer intervals between applications. (1) Pyrethroids and pyrethrins act on the nervous system of flying insects by disrupting the function of sodium channels. They delay the closing of these channels, which results in repetitive firing of neurons, causing paralysis and death. (1,2) Pyrethroids produce toxicity in non-target species such as mammals in a similar manner. (1,6,7)

Synthetic pyrethroids are generally classified into two types, based on toxicological and physical-chemical properties. "Type-I"-like pyrethroids include allethrin, bifenthrin, permethrin, phenothrin, resmethrin, tefluthrin and tetramethrin. Examples of "Type-II" pyrethroids are cyfluthrin, cyhalothrin, cypermethrin and deltamethrin. (1) In Canada, the natural pyrethrins and the synthetic pyrethroids permethrin, allethrin, tetramethrin, phenothrin and resmethrin are registered for residential use. (8) More than 600 of 2,144 pesticide products currently registered for residential pest control in Canada contain one or more of these substances. (8)

In humans, pyrethroids are rapidly metabolized and excreted in urine. The identification of primary metabolites in urine is of little utility in distinguishing exposure to specific pyrethroids: metabolic pathways for different parent compounds produce the same breakdown products. For example, 3-phenoxybenzoic acid (3-PBA) is a common metabolite of cyhalothrin, cypermethrin, deltamethrin, fenpropathrin, permethrin and tralomethrin. The cis and trans configurations of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (i.e., cis-DCCA and trans-DCCA) are the metabolic products of the cis and trans isomers of cypermethrin, cyfluthrin or permethrin, respectively. (1) Thus, the specific pyrethroid to which an individual was exposed, and its source (e.g., diet or residential use), cannot be readily determined only by analyzing urine. (9)

To what degree are pyrethroids used?

To the best of our knowledge, there are no Canadian residential use data. In the US, 2 million pounds of permethrin, the most common pyrethroid used, are applied annually in agricultural and residential settings. The majority of permethrin, over 70%, is applied in non-agricultural settings. (10) Again in the US, permethrin residues were found in 89% of homes in a representative sample in 2005-2006. (11) In general, pyrethroids registered for home pest control are assumed to degrade rapidly in the environment under the influence of water and sunlight, thus limiting the potential for household exposure. However, when applied indoors, they may not degrade as rapidly and may possibly accumulate in homes, creating a potential for repeated and long-term exposure through contact with floors and other surfaces.

How toxic are pyrethroids?

Structural differences between pyrethroid compounds result in large variations in toxicity (as expressed in acute toxicity experimentation in small rodents). (1,6,7) There are also other determinants of toxicity in mammals. For instance, formulated commercial products may differ in toxicity from technical grade products, and the toxicological profile of the formulated product is not necessarily identical to that of the pure active ingredient. The ratio of cis and trans configurations in commercial products is also an important determinant of pyrethroid toxicity in mammals, with cis isomers generally being more potent. (1,12) Finally, commercial pest control products are up to 99% composed of "inert" ingredients, such as synergists (piperonyl butoxide, sulfoxide, sesamex) and solvents. These are relatively non-toxic chemicals, but co-administered in sufficient amounts with active ingredients, they can decrease the threshold doses for pyrethroid toxicity in humans. (1)

We have little knowledge of long-term effects

Effects of acute exposure to high levels of pyrethroids are well-known and documented. In general, chemicals are tested at high-effective doses and safe levels are established based on downward extrapolation of the lowest observed adverse effect level (LOAEL) or the no observed adverse effect level (NOAEL) obtained from examining a few endpoints in a limited number of animals. However, this approach may not be appropriate, as post-marketing surveillance has shown adverse effects at levels of exposure considered non-toxic at the time of chemical registration. Further, current assumptions of the safety of long-term exposures in humans are not based on empirical assessments using realistic scenarios of repeated low-dose uptake of multiple pyrethroid compounds. Concerns for effects of long-term exposure include endocrine disruption, (2,13) functional alterations in reproductive organs, (2,13) and effects on neurologic development. (7,14)

In its Endocrine Disruptor Screening Program (EDSP), the U.S. Environmental Protection Agency will be testing a number of pesticide active ingredients and high production volume chemicals for their effects on the endocrine system. Permethrin is on the list of chemicals that will be screened first because of its occurrence in three of four exposure pathways as defined by the EPA: drinking water, food, residential use and occupational exposure. (15) Endocrine disruption is of great importance because chemicals targeting endocrinological domains can have effects at low doses that are not predicted by effects at higher doses. (16)

Both animal studies and studies in non-occupationally exposed humans indicate that pyrethroid exposure can affect sperm concentration, motility and morphology. For example, significant positive associations were found between pyrethroid metabolites in urine and FSH (follicle-stimulating hormone) and LH (luteinizing hormone) levels in serum in non-occupationally exposed men. (2) Elevated levels of FSH are highly predictive of poor semen quality. Associations were also found between sperm quality parameters (concentration, motility, sperm DNA damage and DNA fragmentation) and pyrethroid metabolites in urine. (2,13) Although most study subjects were recruited from infertility clinics, men with the highest levels of pyrethroid metabolites in their urine had lower semen quality, higher levels of sperm DNA damage and higher levels of DNA fragmentation. (2)

Since pyrethroids primarily act on the nervous system of insects and mammals, (14) there is also concern for neurological and neuropsychological effects of pyrethroid exposure, such as effects on behaviour, learning and motor performance. (7) So far, this has only been studied in small rodents. Preliminary evidence indicates that there are age-related differences in neurotoxicity, with neonatal rats being up to one order of magnitude more sensitive to the acute effects of deltamethrin, cypermethrin and permethrin than adult animals when middle-to-high effective doses are administered by the oral route: (14) this may have important implications for the safety of pyrethroids in babies and small children.

Combined exposure to pyrethroids and other chemicals is relevant to realistic exposure scenarios. The effects of repeated exposure to multiple pyrethroids at environmentally relevant levels may differ qualitatively and quantitatively from the acute or subacute effects of clinically effective doses of single compounds. For example, oral administration of a combination of 11 pyrethroids to rats resulted in locomotor effects at levels that were well below the threshold levels for the individual test compounds. (17) Also, there is limited evidence that combined administration of pyrethroids with insect repellents such as DEET and some organophosphates might have additive or synergistic effects on the nervous system. (1)

Why should we be concerned?

There are several reasons to be concerned about pyrethroids. First, household use of pyrethroid appears to be common: 89% of US homes had detectable levels of permethrin. (11) Although 15% of Canadian households are reported to use pesticide products indoors, (18) no Canadian data are available on the presence of pyrethroid residues in homes. Pyrethroids are the active ingredients of many insecticidal products, including sprays, pet shampoos against ticks and lice, foams, mosquito coils, and powders that appear to be ubiquitous in households. For example, permethrin is used to control bed bugs; its widespread use has likely contributed to the recently documented greater resistance of bed bugs and subsequent increase in infestation rates. (19) Pyrethroids may be applied excessively, which may result in health effects: in a recent US study, pyrethroids, pyrethrins, or both were implicated in 89% of illnesses from insecticides used to control bed bugs. (20)

Second, pyrethroids do not remain in the air but deposit onto surfaces and may accumulate in house dust (21) due to their low vapour pressure. (1) They may not degrade as rapidly in indoor environments as previously thought. It has been stated that household exposure contributes little to the overall uptake of pyrethroids, and that diet is the most significant source of the body burden. (1) Recent research shows that household use may actually contribute more to overall pyrethroid exposure than diet, especially for small children (who crawl on the floor and practice hand-to-mouth behaviour). (9,22) Multi-day measurements strongly suggest that the variation in levels of pyrethroid metabolites can be attributed to pest control product applications at home, (9,23) and that peaks following household use of insecticide products may be more relevant for long-term health risks than food consumption, especially when exaggerated or improper application is practiced.

Pyrethroids are assumed to metabolize rapidly in mammals, but a recent study shows that pyrethroids bioaccumulate in dolphins and are transferred from mother to calf through breast milk. (24) A body burden of pyrethroids has also been found in humans: metabolite levels found in urine samples in the Canadian population are similar to those observed in the US population. (25,26) Although measurable levels of pyrethroid metabolites do not necessarily mean that adverse health effects will occur, (3) the fact that they are detected in the general population indicates that the alleged high metabolic capacity for pyrethroids in mammals, including humans, may not be optimal and that exposure is likely to be ongoing.

Implications for public health

No reliable data on use and exposure are available for Canada, but public health professionals should be aware that pyrethroids are almost certainly ubiquitous in Canadian households. Education is needed because occupants may not realize that many of the products they use contain pyrethroids.

Public health practitioners may also help lobby for better labelling of pyrethroid products. For example, information on the ratio of cis and trans isomers, which greatly affects toxicity, is often not included on Material Safety Data Sheets. Also, it is known that people often do not understand the technical information and application instructions included on pesticide labels, (27) which may result in improper use and sometimes higher application rates than those recommended on the label. (28)

Pyrethroids may be perceived as safe because they are wrongly thought to be "natural". People may equate natural pyrethrins with synthetic pyrethroids, and deem both natural and safe. Modern synthetic pyrethroids certainly are not natural but rather manmade chemicals that were designed to optimize the insecticidal attributes of natural pyrethrins. Further, natural does not necessarily mean harmless.

A handful of reports unequivocally indicate that exposure to pyrethroids may lead to alterations in the neurological, endocrine and reproductive domains at doses near and below previously proposed toxic thresholds in laboratory animals. At present, it is unclear to what extent these findings can be extrapolated to humans. Few human studies are available, but preliminary results seem to point in the same direction. (2,13) Currently, empirical evidence is lacking to produce well-informed decisions on health protection from long-term exposure to pyrethroid insecticides.

Acknowledgement: The authors thank Michele Wiens for bibliographical support.

Conflict of Interest: None to declare.

Received: July 19, 2012 Accepted: September 20, 2012

REFERENCES

(1.) Todd GD, Wohlers D, Citra M. Toxicological profile for pyrethrins and pyrethroids. Atlanta, GA: Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, 2003. Available at: http://www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=787&tid=153 (Accessed July 11, 2012).

(2.) Koureas M, Tsakalof A, Tsatsakis A, Hadjichristodoulou C. Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes. Toxicol Lett 2011;210(2):155-68.

(3.) Centers for Disease Control and Prevention. Fourth National Report on Human Exposure to Environmental Chemicals, 2009. Atlanta: U.S. Department of Health and Human Services, 2009. Available at: http://www.cdc.gov/exposurereport/ (Accessed July 11, 2012).

(4.) Health Canada. Re-evaluation Note REV2011-05, Re-evaluation of Pyrethroids, Pyrethrins and Related Active Ingredients. Ottawa, ON: Health Canada, 2011. Available at: http://www.hc-sc.gc.ca/cps-spc/pubs/pest/_decisions/rev2011-05/index-eng.php (Accessed July 11, 2012).

(5.) U.S. Environmental Protection Agency. EPA's Reevaluation of Pyrethrins, Pyrethroids and Synergists. Washington, DC: EPA, 2012. Available at: http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html#epa (Accessed July 11, 2012).

(6.) Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, Sargent D, et al. Mechanisms of pyrethroid neurotoxicity: Implications for cumulative risk assessment. Toxicology 2002;171(1):3.

(7.) Wolansky MJ, Harrill JA. Neurobehavioral toxicology of pyrethroid insecticides in adult animals: A critical review. Neurotoxicol Teratol 2008;30(2):55-78.

(8.) Pest Management Regulatory Agency. Pesticide Label Search. Ottawa: Health Canada. Available at: http://www.hc-sc.gc.ca/cps-spc/pest/registranttitulaire/tools-outils/label-etiq-eng.php (Accessed December 20, 2010).

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(10.) U.S. Environmental Protection Agency. Permethrin facts. Washington: EPA, 2009. Available at: http://www.epa.gov/pesticides/reregistration/permethrin/ (Accessed July 11, 2012).

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(12.) Wolansky MJ, Crofton KM, Romero DM, Tornero-Velez R. PS2109. Revisiting the impact of biological and experimental conditions of laboratory animal studies on estimations of risk of neurotoxicity by exposure to pesticides in humans: The pyrethroid case. 51st Annual Meeting and ToxExpo--Society of Toxicology Annual Conference, March 11-15, San Francisco, CA. Toxicologist 126(1), Oxford University Press; 2012;454.

(13.) Perry MJ. Effects of environmental and occupational pesticide exposure on human sperm: A systematic review. Hum Reprod Update 2008;14(3):233-42.

(14.) Shafer TJ, Meyer DA, Crofton KM. Developmental neurotoxicity of pyrethroid insecticides: Critical review and future research needs. Environ Health Perspect 2005;113(2):123-36.

(15.) U.S. Environmental Protection Agency. Endocrine disruptor screening program (EDSP). Washington: EPA, 2012. Available at: http://www.epa.gov/endo/ (Accessed July 4, 2012).

(16.) Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee D-H, et al. Hormones and endocrine-disrupting chemicals: Low-dose effects and non-monotonic dose responses. Endocr RevMarch 14, 2012, doi: 10.1210/er.2011 1050.

(17.) Wolansky MJ, Gennings C, DeVito MJ, Crofton KM. Evidence for dose-additive effects of pyrethroids on motor activity in rats. Environ Health Perspect 2009;117(10):1563-70.

(18.) Statistics Canada. Households and the environment 2007. Ottawa: Statistics Canada, 2009. Available at: http://www.statcan.gc.ca/pub/11-526-x/11-526x2009001-eng.pdf (Accessed July 11, 2012).

(19.) Davies TG, Field LM, Williamson MS. The re-emergence of the bed bug as a nuisance pest: Implications of resistance to the pyrethroid insecticides. Med Vet Entomol 2012;26(3):241-54.

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(21.) Quiros-Alcala L, Bradman A, Nishioka M, Harnly ME, Hubbard A, McKone TE, et al. Pesticides in house dust from urban and farmworker households in California: An observational measurement study. Environ Health 2011;10:19.

(22.) Tulve NS, Egeghy PP, Fortmann RC, Xue J, Evans J, Whitaker DA, et al. Methodologies for estimating cumulative human exposures to current-use pyrethroid pesticides. J Expo Sci Environ Epidemiol 2011;21(3):317-27.

(23.) Lu CS, Barr DB, Pearson M, Bartell S, Bravo R. A longitudinal approach to assessing urban and suburban children's exposure to pyrethroid pesticides. Environ Health Perspect 2006;114(9):1419-23.

(24.) Alonso MB, Feo ML, Corcellas C, Vidal LG, Bertozzi CP, Marigo J, et al. Pyrethroids: A new threat to marine mammals? Environ Int 2012;47:99-106.

(25.) Fortin M-C, Bouchard M, Carrier G, Dumas P. Biological monitoring of exposure to pyrethrins and pyrethroids in a metropolitan population of the Province of Quebec, Canada. Environ Res 2008;107(3):343-50.

(26.) Health Canada. Canadian Health Measures Survey: Summary of the Bio-monitoring Results and Government Actions. Ottawa: Health Canada, 2010.

(27.) Grey CNB, Nieuwenhuijsen MJ, Golding J. The use and disposal of household pesticides. Environ Res 2005;97(1):109-15.

(28.) Brimble S, Bacchus P, Caux PY. Pesticide utilization in Canada: A compilation of current sales and use data. Ottawa: Environment Canada, 2005.

Erna C. van Balen, MSc, MPhil, [1] Marcelo J. Wolansky, PhD, [2] Tom Kosatsky, MD, MPH [1,3]

Author Affiliations

[1.] National Collaborating Centre for Environmental Health, Vancouver, BC

[2.] University of Buenos Aires, Autonomous City of Buenos Aires, Argentina

[3.] British Columbia Centre for Disease Control, Vancouver, BC

Correspondence: Ms. Erna van Balen, Tel: 604-675-2582, E-mail: e.vanbalen@gmail.com
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Title Annotation:COMMENTARY
Author:van Balen, Erna C.; Wolansky, Marcelo J.; Kosatsky, Tom
Publication:Canadian Journal of Public Health
Article Type:Report
Geographic Code:1CANA
Date:Nov 1, 2012
Words:2883
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