Environmental degradation of the insect growth regulator methoprene(isopropyl(2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate).  I.  Metabolism by alfalfa and rice

Quistad, Gary B.; Staiger, Luana E.; Schooley, David A.

doi:10.1021/jf60194a022

“…For example, in our test system, the parent molecule was relatively unstable, with more than 95% of the methoprene disappearing over the course of 48 h during the static-renewal phase of the assay. This behavior is consistent with the fate of methoprene in the environment, where various studies have shown relatively rapid degradation of the parent chemical, in particular, in the presence of sunlight [22,28,56,57]. In any case, because of this instability, it is impossible from our data to calculate meaningful effect and no-effect methoprene concentrations.…”

Section: Effects Of Methoprenesupporting

confidence: 86%

Effects of Ultraviolet Light and Methoprene on Survival and Development of Rana Pipiens

Ankley¹,

Tietge²,

DeFoe³

et al. 1998

Environ Toxicol Chem

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Abstract-Recently a suite of relatively specific hindlimb deformities have been observed in several anuran species in North America. These deformities include ectopic and supernumerary limbs and missing limbs, limb segments, or digits. The objective of this study was to assess two stressors hypothesized as responsible for limb malformations in amphibians: methoprene, an insect growth regulator that, through interaction with the retinoic acid signaling system, could possibly cause limb deformities, and ultraviolet (UV) light. Northern leopard frogs (Rana pipiens) were exposed to several different concentrations of methoprene both in the absence and presence of UV light designed to mimic the UV wavelength spectrum present in sunlight. Exposures were initiated at early embryonic stages (newly fertilized eggs) and continued through emergence of the forelimbs of the frogs. At the highest methoprene concentration tested, both in the absence and presence of UV light, severe developmental effects were observed, with all organisms dying within 12 to 16 d of test initiation. However, exposure to the pesticide did not cause limb malformations. Irrespective of methoprene treatment, a very high percentage (ϳ50%) of animals held under the UV light for 24 d developed hindlimb malformations. These malformations usually were bilateral and sometimes completely symmetrical, and consisted of missing limb segments and missing or reduced digits. A complete proximal to distal representation of the deficiencies occurred, ranging from missing or malformed femurs to the absence of single digits or digit segments. The developmental period of greatest sensitivity to UV light occurred during very early limb bud development, corresponding with formation of the apical ectodermal ridge. The significance of these findings in terms of deformed frogs in the field is uncertain. Although the deformity types observed (i.e., missing limb segments and digits) were similar to those seen in some field specimens, the UV light treatment did not cause the full range of malformations observed in animals from the field (e.g., supernumerary limbs, nonbilateral deformities). Furthermore, although the artificial light spectrum utilized mimicked the relative UV spectrum present in sunlight, it did not match full sunlight intensity, and did not accurately mimic visible wavelengths. Finally, the relationship of the UV light dose used in the laboratory to that actually experienced by amphibians in the field is uncertain. Despite these questions, our findings suggest that UV light should be further considered as a plausible factor contributing to amphibian malformations in field settings.

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“…The ability of methoprene to activate but not bind RXR suggests that the ester is metabolically converted to the active acid form in cells. This hypothesis is supported by previous studies showing that methoprene is metabolized within cells to several products and that one of the major forms is the methoxy acid derivative, methoprene acid (22). Esterases that may facilitate this conversion are found in many cell types; organs and cells that display high levels of esterase activity include the pancreas, liver, and macrophages.…”

Section: Resultssupporting

confidence: 67%

Activation of mammalian retinoid X receptors by the insect growth regulator methoprene.

Harmon

¹

,

Boehm

²

,

Heyman

³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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We report that methoprene and its derivatives can stimulate gene transcription in vertebrates by acting through the retinoic acid-responsive transcription factors, the retinoid X receptors (RXRs). Methoprene is an insect growth regulator in domestic and agricultural use as a pesticide. At least one metabolite of methoprene, methoprene acid, directly binds to RXR and is a transcriptional activator in both insect and mammalian cells. Unlike the endogenous RXR ligand, 9-cis-retinoic acid, this activity is RXR-specific; the methoprene derivatives do not activate the retinoic acid receptor pathway. Methoprene is a juvenile hormone analog that acts to retain juvenile characteristics during insect growth, preventing metamorphosis into an adult, and it has been shown to have ovicidal properties in some insects. Thus, a pesticide that mimics the action ofjuvenile hormone in insects can also activate a mammalian retinoid-responsive pathway. This finding provides a basis through which the potential bioactivity of substances exposed to the environment may be reexamined and points the way for discovery of new receptor ligands in both insects and vertebrates.With the exception of their role in vision, the manner in which the retinoids exert their biological effects resides in their ability to regulate gene expression. Vitamin A metabolites-i.e., retinoids-play essential roles in many aspects of development, metabolism, and reproduction in vertebrates (1). Some of the end products of vitamin A metabolism have been identified as the molecules responsible for the action of retinoids. Retinol, the major circulating form of retinoid, is converted within cells to all-trans-retinoic acid and 9-cis-retinoic acid (9cRA) (2-4). The retinoic acids function through two classes of receptors: the retinoic acid receptors (RARs), which bind to both atRA and 9cRA, and the retinoid X receptors (RXRs), which bind only to 9cRA. These receptors modulate ligand-dependent gene expression by interacting as RXR/RAR heterodimers or RXR homodimers on specific target-gene DNA sequences known as hormone response elements. In addition to their role in retinoid signaling, RXRs also serve as heterodimeric partners of nuclear receptors for vitamin D, thyroid hormone, and peroxisome proliferators (reviewed in ref. 5).Although both RXR and RAR bind and respond to 9cRA, evolutionarily these receptors are quite distinct. RXR and RAR share only 27% amino acid identity in their ligandbinding domains (6). In addition, at least one homolog of RXR has been identified in insects, called ultraspiracle (7). Like RXR, ultraspiracle serves as a heterodimeric partner to other receptors. For example, the ecdysone receptor requires ultraspiracle as its coreceptor to bind and respond to its ligand, 20-hydroxyecdysone (8). Significantly, however, ultraspiracle does not respond to any of the known retinoids, including 9cRA. These results are consistent with the finding that insectsThe publication costs of this article were defrayed in part by page charge payment. This a...

show abstract

“…For example, in our test system, the parent molecule was relatively unstable, with more than 95% of the methoprene disappearing over the course of 48 h during the static‐renewal phase of the assay. This behavior is consistent with the fate of methoprene in the environment, where various studies have shown relatively rapid degradation of the parent chemical, in particular, in the presence of sunlight [22,28,56,57]. In any case, because of this instability, it is impossible from our data to calculate meaningful effect and no‐effect methoprene concentrations.…”

Section: Discussionsupporting

confidence: 83%

Effects of ultraviolet light and methoprene on survival and development ofRana pipiens

Ankley

¹

,

Tietge

²

,

DeFoe

³

et al. 1998

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Abstract-Recently a suite of relatively specific hindlimb deformities have been observed in several anuran species in North America. These deformities include ectopic and supernumerary limbs and missing limbs, limb segments, or digits. The objective of this study was to assess two stressors hypothesized as responsible for limb malformations in amphibians: methoprene, an insect growth regulator that, through interaction with the retinoic acid signaling system, could possibly cause limb deformities, and ultraviolet (UV) light. Northern leopard frogs (Rana pipiens) were exposed to several different concentrations of methoprene both in the absence and presence of UV light designed to mimic the UV wavelength spectrum present in sunlight. Exposures were initiated at early embryonic stages (newly fertilized eggs) and continued through emergence of the forelimbs of the frogs. At the highest methoprene concentration tested, both in the absence and presence of UV light, severe developmental effects were observed, with all organisms dying within 12 to 16 d of test initiation. However, exposure to the pesticide did not cause limb malformations. Irrespective of methoprene treatment, a very high percentage (ϳ50%) of animals held under the UV light for 24 d developed hindlimb malformations. These malformations usually were bilateral and sometimes completely symmetrical, and consisted of missing limb segments and missing or reduced digits. A complete proximal to distal representation of the deficiencies occurred, ranging from missing or malformed femurs to the absence of single digits or digit segments. The developmental period of greatest sensitivity to UV light occurred during very early limb bud development, corresponding with formation of the apical ectodermal ridge. The significance of these findings in terms of deformed frogs in the field is uncertain. Although the deformity types observed (i.e., missing limb segments and digits) were similar to those seen in some field specimens, the UV light treatment did not cause the full range of malformations observed in animals from the field (e.g., supernumerary limbs, nonbilateral deformities). Furthermore, although the artificial light spectrum utilized mimicked the relative UV spectrum present in sunlight, it did not match full sunlight intensity, and did not accurately mimic visible wavelengths. Finally, the relationship of the UV light dose used in the laboratory to that actually experienced by amphibians in the field is uncertain. Despite these questions, our findings suggest that UV light should be further considered as a plausible factor contributing to amphibian malformations in field settings.

show abstract

Environmental degradation of the insect growth regulator methoprene(isopropyl(2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate). I. Metabolism by alfalfa and rice

Cited by 36 publications

References 7 publications

Effects of Ultraviolet Light and Methoprene on Survival and Development of Rana Pipiens

Effects of Ultraviolet Light and Methoprene on Survival and Development of Rana Pipiens

Activation of mammalian retinoid X receptors by the insect growth regulator methoprene.

Effects of ultraviolet light and methoprene on survival and development ofRana pipiens

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