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Evaluation of the reproductive effects of tamoxifen citrate in partial and full life‐cycle studies using fathead minnows ( Pimephales Promelas )
Author(s) -
Williams Tim D.,
Caunter John E.,
Lillicrap Adam D.,
Hutchinson Thomas H.,
Gillings Edward G.,
Duffell Stephen
Publication year - 2007
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1897/05-646r1.1
Subject(s) - biology , vitellogenin , pimephales promelas , gonad , reproduction , cyprinidae , population , toxicology , andrology , medicine , endocrinology , fish <actinopterygii> , ecology , minnow , fishery , environmental health
Laboratory studies were conducted to investigate potential adverse effects on development, growth, reproduction and biomarker responses (vitellogenin [VTG] and gonad histology) in fathead minnows ( Pimephales promelas ) exposed to tamoxifen citrate. Based on the results of a partial life cycle study (nominal [mean measured] concentrations ranged from 0.18 [0.11] to 18 [15.74] μg/L), a 284‐d fish full life‐cycle (FFLC) flow‐through study was conducted using newly fertilized embryos (<24 h postfertilization) exposed to nominal (mean measured) concentrations of 14 C‐tamoxifen citrate that ranged from 0.01 (0.007) to 5.12 (4.08) μg/L. Triethylene glycol (2.0 μl/L) was used as a solvent carrier, with 17β‐estradiol (E2) as a positive control (nominal 0.1 μg/L). Among the biomarkers measured, significant effects on VTG and gonad histology were observed, although these results required care in their interpretation. Among important population‐relevant endpoints, no effects on reproduction were observed at nominal concentrations ≤5.12 μg/L. Effects on growth (length and weight) were observed in some treatments; however, some of these showed irregular concentration‐response relationships, which made interpretation uncertain, or were deemed transient in nature (e.g., reduction in growth of F1 28‐d posthatch larval fish at nominal concentrations of 0.08, 0.64, and 5.12 μg/L) and judged not to be biologically significant. Interpretation of results from fish chronic studies is challenging and frequently calls for scientific judgement about statistical and biological significance and what constitutes an adverse effect. Using the principles used in mammalian toxicology studies, data from partial and FFLC studies were evaluated from both statistical and biological perspectives in order to determine no‐observed‐adverse effect concentrations (expressed as adverse NOEC) for use in environmental risk assessment. Careful consideration of both biological and statistical outcomes from these studies suggested overall adverse NOEC concentration and lowest‐observed‐effect concentration ( adverse LOEC) values for tamoxifen citrate of 5.12 μg/L and 5.6 μg/L, respectively.