Lack of (Anti-) Androgenic or Estrogenic Effects of Three Pyrethroids (Esfenvalerate, Fenvalerate, and Permethrin) in the Hershberger and Uterotrophic Assays

Kunimatsu, Takeshi; Yamada, Tomoya; Ose, Keiko; Sunami, Osamu; Kamita, Yusuke; Okuno, Yasuyoshi; Seki, Takaki; Nakatsuka, Iwao

doi:10.1006/rtph.2001.1527

Cited by 49 publications

(24 citation statements)

References 28 publications

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“…These data indicate that permethrin has antiandrogenic activity, but it does not have androgenic activity. On the other hand, Kunimatsu et al reported that permethrin has no androgenic and antiandrogenic effects in the Hershberger assay [25]. However, there are basic differences in assay protocols of the Hershberger assay used by Kunimatsu et al [25] and the assay used in the present study.…”

Section: Discussionmentioning

confidence: 65%

“…But the uterine weights increased by permethrin were reduced by co-treatment with ICI 182,780, an antiestrogen, thus indicating the estrogenic activity of permethrin. Kunimatsu et al assessed the estrogenic activity of permethrin using an uterotrophic assay, and reported the lack of an estrogenic effect for permethrin based on the absence of no increases in the weights of uteri [25]. I n t h i s u t e r o t r o p h i c a s s a y , 8 -w e e k -o l d ovariectomized Sprague-Dawley rats were used, and permethrin (37.5, 75 or 150 mg/kg/day) was administered by oral gavage for 3 days.…”

Section: Discussionmentioning

confidence: 99%

“…Many pesticides have been reported to possess estrogenic or androgenic activities [15][16][17][18][19][20][21][22], and thus are classified as endocrine disruptors. However, relatively few studies have reported on the estrogenic and androgenic activities of permethrin [3,[23][24][25][26], and the results of the studies are in some respects contradictory. Accordingly, more investigation is needed to clarify the estrogenic and androgenic activities of permethrin.…”

mentioning

confidence: 99%

“…In the uterotrophic assay, the test protocols involve an immature rat uterotrophic assay, whereby chemicals are subcutaneously administered to immature female rats for three consecutive days. The Hershberger assay has been commonly used to determine the androgenic and antiandrogenic activities of certain chemicals [19,20,25,31,32]. In this study, we examined the potential estrogenic a c t i v i t y o f p e r m e t h r i n b y i m m a t u r e r a t uterotrophic assay, and the uterine CaBP-9k gene expression assay.…”

mentioning

confidence: 99%

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Potential Estrogenic and Antiandrogenic Effects of Permethrin in Rats

Kim

Lee

Lim

et al. 2005

Journal of Reproduction and Development

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Abstract. Many environmental chemicals including pesticides have been reported to possess hormonal activities, and thus are classified as endocrine disruptors. Permethrin, a synthetic pyrethroid insecticide, is used worldwide, which provides potential environmental exposure. However, relatively few studies have reported on hormonal activities, particularly estrogenic and androgenic activities of permethrin, and the results of these studies are in some respects contradictory. Therefore, this study investigated the potential estrogenic and androgenic activities of permethrin in vitro and in vivo. We conducted an uterine Calbindin-D9k (CaBP-9k) gene expression assay and an uterotrophic assay for estrogenic activity, and a Hershberger assay for androgenic activity. The CaBP9k gene, one of the intracellular calcium binding proteins, is estrogen-responsive in the uterus. The rat uterotrophic and Hershberger assays are generally used as in vivo short-term screening assays for detecting the estrogenic and androgenic activities of chemicals, although these assays are still being validated by the Organization for Economic Cooperation and Development (OECD). Northern blot analysis showed the induction of uterine CaBP-9k mRNA level in response to permethrin as well as co-administration of permethrin with E2. In the uterotrophic assay using 18-day-old female rats, subcutaneous treatments with permethrin (10 to 800 mg/kg) for three days increased relative uterine wet weights, and E2-induced uterine weights. These effects were statistically significant at 800 and 200 mg/kg, respectively. Moreover, permethrin-induced uterine weights were inhibited by the coadministration of ICI 182,780, an antiestrogen. In the Hershberger assay, the administration of permethrin orally to testosterone propionate-treated castrated male rats led to statistically significant reductions in androgen-dependent sex accessory tissue (ventral prostate, seminal vesicles, levator ani and bulbocavernosus muscles, Cowper's gland and glans penis) weights at all doses tested (10, 50 and 100 mg/kg). These results suggest that permethrin might have estrogen-like effects on female rats, but antiandrogen-like effects on males.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Potential Estrogenic and Antiandrogenic Effects of Permethrin in Rats

Kim

Lee

Lim

et al. 2005

Journal of Reproduction and Development

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“…Moreover, four pyrethroid insecticides (permethrin, cypermethrin, fenvalerate, and phenothrin) did not induce estrogenic activity in an in vitro luciferase reporter gene assay using the metabolic activation system [12]. These results were confirmed with a uterotrophic assay in which none of the pyrethroid insecticides tested (esfenvalerate, fenvalerate, and permethrin) exhibited any estrogenic activity [13]. Although in vitro combination assays have indicated that certain pyrethroid insecticides have weak estrogenic activity, their estrogenic mechanisms of action are not understood and little is known about their associations with the ERs.…”

mentioning

confidence: 74%

Assessing Estrogenic Activity of Pyrethroid Insecticides Using In Vitro Combination Assays

et al. 2004

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Abstract. Pyrethroid insecticides are among the most commonly used classes of insecticides worldwide, but their endocrine disrupting activities remain unclear. Therefore, in the present study, we examined the estrogenic activities of pyrethroid insecticides in E-screen and competition binding assays. In addition, we measured estrogen receptor (ER) protein and pS2 mRNA levels in human breast cancer cells (MCF-7 BUS) to clarify the mechanism of their estrogenicity. Seven pyrethroid insecticides (bioallethrine, cypermethrin, deltamethrin, fenvalerate, permethrin, sumithrin, and tetramethrin) were tested because of their worldwide usage. In addition, 17β-estradiol was tested as a positive control. As expected, 17β-estradiol significantly increased MCF-7 BUS cell proliferation at concentrations of 10 -11 M and above. Of the pyrethroid insecticides tested, only sumithrin increased MCF-7 BUS cell proliferation in a dose-dependent manner; the maximum induction of cell proliferation was observed at a dose of 10 -5 M. In the anti-estrogenic activity test, bioallethrin, fenvalerate, and permethrin significantly inhibited 17β-estradiol-induced MCF-7 BUS cell proliferation at 10 -6 M, a concentration comparable to the effective dose (10 -9 M) of ICI 182,780, a pure ER antagonist. However, none of the pyrethroid insecticides competitively inhibited the binding of [ 3 H]estradiol to rat uterus ERs in competition binding assays. Both 17β-estradiol (10 -10 M) and sumithrin (10 -5 M) decreased the levels of cytosolic ERα and ERβ protein expression significantly as compared with the vehicle control. In addition, 17β-estradiol (10 -10 M) increased pS2 mRNA expression markedly, and sumithrin significantly increased pS2 mRNA levels in a dose-dependent manner. The other six compounds tested in the present study did not affect ER protein levels or pS2 mRNA levels. These results suggest that certain pyrethroid insecticides may be considered to be estrogen-like chemicals that act through pathways other than direct ER binding, and may function as endocrine modulators in both wildlife and humans.

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Environmental Endocrine Toxicology

Bjerregaard

2009

General, Applied and Systems Toxicology

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Disorders in sexual development have increased in frequency in certain geographical regions during the latter half of the 20th century. In humans, this is expressed as elevated prevalence of testicular cancer, cryptorchidism and hypospadias and decreased sperm counts, collectively termed the ‘Testicular Dysgenesis Syndrome’ (TDS). A fairly large number of chemicals in widespread use (i.e. alkylphenols, phthalates, bisphenol, PCBs, pesticides) have been shown to interfere with the synthesis and/or the function of sex hormones, and exposure to some of these chemicals (individually or in mixtures) compromises normal sexual development in animals in tests in the laboratory. The occurrence of TDS in humans seems to be associated with general life style factors, but although associations between TDS and exposure to certain chemicals (e.g. PCBs, phthalates, pesticides) have been demonstrated, firm causal relationships have not yet been established. In nature, effects caused by exposure to discharged hormones or chemicals with endocrine disrupting properties have been firmly documented among snails, fish, amphibians, reptiles, birds and mammals: The anti‐fouling biocide tributyltin masculinizes female snails, synthetic p‐pill estrogens and natural estrogens feminize male fish downstream discharges from sewage treatment plants, effluents from pulp and paper mills masculinize female fish and various chlorinated hydrocarbons have feminized higher vertebrates such as alligators and birds.

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Lack of (Anti-) Androgenic or Estrogenic Effects of Three Pyrethroids (Esfenvalerate, Fenvalerate, and Permethrin) in the Hershberger and Uterotrophic Assays

Cited by 49 publications

References 28 publications

Potential Estrogenic and Antiandrogenic Effects of Permethrin in Rats

Potential Estrogenic and Antiandrogenic Effects of Permethrin in Rats

Assessing Estrogenic Activity of Pyrethroid Insecticides Using In Vitro Combination Assays

Environmental Endocrine Toxicology

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