title: Test concentration setting for fish in vivo endocrine screening assays.
abstract: Fish in vivo screening methods to detect endocrine active substances, specifically interacting with the hypothalamic-pituitary-gonadal axis, have been developed by both the Organization for Economic Co-operation and Development (OECD) and United States Environmental Protection Agency (US-EPA). In application of these methods, i.e. regulatory testing, this paper provides a proposal on the setting of test concentrations using all available acute and chronic data and also discusses the importance of avoiding the confounding effects of systemic toxicity on endocrine endpoints. This guidance is aimed at reducing the number of false positives and subsequently the number of inappropriate definitive vertebrate studies potentially triggered by effects consequent to systemic, rather than endocrine, toxicity. At the same time it provides a pragmatic approach that maximizes the probability of detecting an effect, if it exists, thus limiting the potential for false negative outcomes.
authors.affiliation: Syngenta Environmental Safety, Jealott's Hill International Research Centre, Bracknell, Berkshire RG42 6EY, United Kingdom. James.Wheeler@Syngenta.com
authors.forename: James R
authors.initials: JR
authors.lastname: Wheeler
authors.forename: Grace H
authors.initials: GH
authors.lastname: Panter
authors.forename: Lennart
authors.initials: L
authors.lastname: Weltje
authors.forename: Karen L
authors.initials: KL
authors.lastname: Thorpe
mesh_terms: D000735:Androstenedione / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity*; D005026:Ethylene Glycols / Q000737:chemistry / Q000633:toxicity; D005399:Fishes; D005485:Flutamide / Q000737:chemistry / Q000633:toxicity; D007093:Imidazoles / Q000737:chemistry / Q000633:toxicity; D007654:Ketoconazole / Q000737:chemistry / Q000633:toxicity; D020714:Maximum Tolerated Dose; D000442:Octanols / Q000737:chemistry / Q000633:toxicity; D010636:Phenols / Q000737:chemistry / Q000633:toxicity; D011196:Potassium Permanganate / Q000737:chemistry / Q000633:toxicity; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000633:toxicity
chemical_list: D052244:Endocrine Disruptors; D005026:Ethylene Glycols; D007093:Imidazoles; D000442:Octanols; D010636:Phenols; D011196:Potassium Permanganate; D012967:Sodium Dodecyl Sulfate; D000735:Androstenedione; C019566:p-tert-amylphenol; D005485:Flutamide; C045362:prochloraz; C005219:methyl cellosolve; C105260:4-tert-octylphenol; D007654:Ketoconazole
keywords: Concentration setting; Endocrine; Fish; Maximum Tolerated Concentration; Screening assay; Systemic toxicity