Fort Environmental Laboratories (United States)

The impact of the brominated flame-retardant mixture, DE-71, on gonadal steroidogenesis during sexual differentiation in Silurana tropicalis was examined. A partial lifecycle study exposing S. tropicalis to varying concentrations of DE-71 (0.0, 0.65, 1.3, 2.5, and 5.0 μg/l [nominal]) was conducted from early gastrula-stage embryo to 150 days postmetamorphosis (dpm). Exposure of S. tropicalis to DE-71 induced liver necrosis and induced abnormal ovary development characterized by previtellogenic oocyte necrosis and arrested development of vitellogenic oocytes in females in a concentration-dependent manner. Decreased mean plasma dihydrotestosterone (DHT) and T, gonad T, and increased mean plasma E2 levels were found in 150 dpm DE-71-treated male S. tropicalis compared to controls. Plasma E2 levels in females were not significantly altered compared to control S. tropicalis, although lower plasma and gonad T were detected. Mean gonadal CYP 19 aromatase activity in both male and female S. tropicalis exposed to DE-71 was not appreciably affected. Decreased mean male 5α-reductase and CYP17 activities in both male and females were observed compared to control frogs. Overall, these studies suggested that PBDE exposure induced liver necrosis and abnormal ovary development; and reduced circulating and gonadal androgens resulting in a phenotypic skew in sex ratio toward the female sex in S. tropicalis.

The impact of the perfluoro-chemical, perfluorooctanesulfonate (PFOS), on gonadal steroidogenesis during sexual differentiation in Silurana tropicalis was examined because of its ubiquity in the environment, bioaccumulative nature and potential to disturb endocrine activity. A partial life cycle study exposing S. tropicalis to varying concentrations of PFOS 0.06, 0.13, 0.25, 0.50 and 1.0mg PFOS/L [nominal]) was conducted. Gonad and plasma samples were collected from juvenile control specimens and organisms exposed to PFOS from early embryo through 150days post-metamorphosis. Gonad CYP17, aromatase and 5α-reductase activities were measured. Plasma estradiol, testosterone, dihydrotestosterone (DHT) and gonadal testosterone were measured in both males and females. Increased plasma DHT and gonadal testosterone were found in PFOS-treated juvenile male S. tropicalis compared to controls. Decreased plasma estradiol, but not testosterone, was detected in PFOS-treated female S. tropicalis compared to controls. Plasma DHT was not detected and an increase in gonadal testosterone was detected in PFOS-treated female frogs. Female S. tropicalis exposed to PFOS exhibited a concentration-related decrease in the mean aromatase activity, but not 5α-reductase. PFOS exposure in male frogs induced a concentration-related increase in 5α-reductase activity, but did not alter aromatase activity compared to control frogs. A concentration-related increase in CYP 17,20-lyase activity, but not 17-hydroxylase activity, was found in both female and male S. tropicalis exposed to PFOS.

The primary objective of this protocol is to provide alternative developmental toxicity data using the frog embryo teratogenesis assay-Xenopus (FETAX) model for preclinical safety assessment. FETAX is most useful in the prioritization of developmental toxicity hazard for sets of discovery-level compounds. Assessment of teratogenic potential is based on teratogenic indices (TI), which measure the teratogenic potential of a given test material. The relative hazard ranking is based on a set of weighted endpoints that include developmental toxicity potency, teratogenic potential, and growth inhibition. Because of the importance of potency and teratogenic potential in determining relative hazard, these endpoints are weighted 2×. Growth inhibition is weighted 1×. These data determine a generic ranking. The generic hazard rank is based on numerical endpoint data derived from an assessment of potency, teratogenic potential as determined by the TI value, and concentration at which growth inhibition is detected when expressed as a proportion of the 4-d LC50 value. With the generic rank, the lower the generic hazard ranking the greater the developmental toxicity hazard relative to the other materials evaluated. However, the relative severity of the malformation syndromes induced is not incorporated into the generic ranking process. An objective evaluation of the severity of the deformities induced is an important process in the evaluation of FETAX results; therefore, a final definitive ranking process is used. A final definitive ranking is determined using the generic rank and the severity of the malformations induced (weighted 5×).

ADVERTISEMENT RETURN TO ISSUEPREVCorrespondence/Rebut...Correspondence/RebuttalNEXTComment on "Effects of Triclocarban, Triclosan, and Methyl Triclosan on Thyroid Hormone Action and Stress in Frog and Mammalian Culture Systems"Paul DeLeo, Ph.D.*, Sascha Pawlowski, Ph.D., Charles Barton, Ph.D., DABT, and Douglas J. Fort, Ph.D.View Author Information American Cleaning Institute BASF SE Georgia-Pacific LLC Fort Environmental LaboratoriesE-mail: [email protected]Cite this: Environ. Sci. Technol. 2011, 45, 23, 10283–10284Publication Date (Web):October 7, 2011Publication History Published online1 November 2011Published inissue 1 December 2011https://pubs.acs.org/doi/10.1021/es202937qhttps://doi.org/10.1021/es202937qarticle-commentaryACS PublicationsCopyright © 2011 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views896Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (645 KB) Get e-AlertscloseSUBJECTS:Assays,Bacteria,Cell signaling,Enthalpy,Stress Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVCorrespondence/Rebut...Correspondence/RebuttalNEXTComment on "Effects of Triclocarban, Triclosan, And Methyl Triclosan on Thyroid Hormone Action and Stress in Frog and Mammalian Culture Systems"Douglas J. Fort*, Michael Mathis, and Sascha PawlowskiView Author Information Fort Environmental Laboratories, Inc. Fort Environmental Laboratories, Inc. Department of Product Safety, BASF SEE-mail: [email protected]Cite this: Environ. Sci. Technol. 2011, 45, 17, 7602Publication Date (Web):July 25, 2011Publication History Published online12 August 2011Published inissue 1 September 2011https://pubs.acs.org/doi/10.1021/es2021582https://doi.org/10.1021/es2021582article-commentaryACS PublicationsCopyright © 2011 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views693Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (624 KB) Get e-AlertscloseSUBJECTS:Alkyls,Morphology,Physical and chemical processes,Serum,Stress Get e-Alerts

Potential mechanisms of trichloroethylene-induced developmental toxicity were evaluated using FETAX (Frog Embryo Teratogenesis Assay--Xenopus). Early Xenopus laevis embryos were exposed to trichloroethylene for 96 h in two separate definitive concentration-response assays with and without an exogenous metabolic activation system (MAS) and inhibited MAS. The MAS was treated with either carbon monoxide or cyclohexene oxide to modulate mixed-function oxidase (MFO) or epoxide hydrolase activity, respectively. Trichloroethylene metabolites: dichloroacetic acid, trichloroacetic acid, trichloroethanol, and oxalic acid were also evaluated in two separate definitive, static renewal tests. Addition of the MAS decreased the 96 h LC50 and EC50 (malformation) of trichloroethylene 1.8-fold and 3.8-fold, respectively. Addition of the carbon monoxide inhibited MAS decreased the developmental toxicity of activated trichloroethylene to levels approximating that of the parent compound. Cyclohexene oxide-inhibited MAS substantially increased the developmental toxicity of trichloroethylene. In addition, each of the metabolites tested were significantly less developmental toxic than the parent compound, trichloroethylene. Results indicate that a highly embryotoxic epoxide intermediate, trichloroethylene oxide, formed as the results of MFO mediated metabolism may play a significant role in the developmental toxicity of trichloroethylene in vitro.