A critical review of the scientific literature on potential endocrine-mediated effects in fish and wildlife.

A rigorous approach to evaluating the reliability and relevance of experimental methods and results is critical for making appropriate, scientifically sound decisions. A literature evaluation framework was modified and adapted based on criteria described by Klimisch et al. (H. J. Klimisch, M. Andrae, and U. Tillman, 1997, Reg. Tox. Pharm. 25, 1-5) and requirements of the USEPA High Product Volume Challenge Program. This simple framework was used to evaluate an appropriate selection of peer-reviewed references to assign a Study Reliability "score" to the study design, endpoints, and conclusions compared to established data quality guidelines. Subsequently, the interpretation of the data was evaluated and assigned a Relevance Index based on the overall strength of evidence of endocrine modulation potential, which was evaluated based on the Weybridge (European Commission (1996). European workshop on the impact of endocrine disrupters on human health and wildlife. Report of proceedings from a workshop held in Weybridge, UK, 2-4 December 1996. Report reference EUR 17549, European Commission, DGXII, Brussels, Belgium.) definition. This report describes the evaluation of 50 peer-reviewed primary publications. The vast majority of studies reviewed were published in the period from 1996 to the present and most examined in vivo responses of fish to natural hormones, organochlorines, or alkylphenolic compounds. Of the studies reviewed, approximately 40% received a score of "2-Reliable with Restrictions," while approximately 60% received a score of "3-Not Reliable," where reliability was interpreted to include scientific integrity, technical credibility, endpoint relevance, and regulatory compliance. The most common deficiencies were inadequate methods, lack of suitable controls, exceeding aqueous solubility, inappropriate statistics, and unsupported conclusions. Based on the Relevance Index, few of the studies examined attained the level of quality necessary to identify the study results as providing an acceptable basis for evaluation of endocrine modulation potential directly resulting from identified deficiencies in meeting the established study reliability criteria.

Oxidant, mixed-function oxidase and peroxisomal responses in channel catfish exposed to a bleached kraft mill effluent.

Channel catfish (Ictalarus punctatus) were exposed to 0, 10, 20, and 40% bleached kraft pulp and paper mill effluent (BKME) for up to two weeks. Fish were sacrificed on days 1, 3, 7, and 14 of exposure. Blood, liver, and gill tissues were assayed for biochemical responses associated with oxidative stress (superoxide dismutase, catalase, and glutathione peroxidase activities and methemoglobin, reduced glutathione, and malondialdehyde concentrations), peroxisome proliferation (palmitoyl-CoA oxidase and lauroyl-CoA oxidase activities) and the mixed-function oxidase system (cytochrome P-450 difference spectra and ethoxyresorufin O-deethylase activities). There were significant dose-related increases in hepatic catalase and ethoxyresorufin O-deethylase activities and significant decreases in hepatic reduced glutathione concentrations. There were also significant increases in lauroyl-CoA oxidase and palmitoyl-CoA oxidases activities, both components of the fatty acid beta-oxidation system and located in peroxisomes. No statistically significant changes were seen in the other components studied. The increases in catalase and the fatty-acid oxidase activities suggest that BKME exposure may have resulted in peroxisome proliferation in catfish hepatic tissue.

Ecological toxicology and human health effects of heptachlor.

The chlorinated cyclodiene heptachlor was registered in 1952 as an agricultural and domestic insecticide. By early 1984, registration for all purposes, except subterranean termite control and for limited use in the control of fire ants, had been cancelled. This restriction of use arose primarily from concerns over the environmental persistance and bioaccumulation potential of the organochlorine pesticides. Currently, sale of heptachlor has been voluntarily suspended over questions about its carcinogenic potential, and the absence of safe and effective application methods. As a persistent organochlorine pesticide, heptachlor residues are detected in all components of the environment. In historical use, heptachlor was directly applied to terrestrial systems, while air and water were secondarily contaminated via volatilization and land run-off, respectively. Within each environmental compartment, heptachlor undergoes a variety of metabolic and abiotic transformations. In vivo studies indicate that heptachlor epoxide is the predominant metabolite, formed as a product of the mixed-function oxidase system, while 1-hydroxychlordene is the major soil metabolite. For quantification, heptachlor and its metabolites are extracted from air, soil and sediment, water, or biological materials using various organic solvents and analyzed by gas chromatography or thin-layer chromatography. Residue reports comprise most of the literature concerning the effects of heptachlor on the biota. In many such reports, toxic effects cannot be conclusively attributed to heptachlor exposure. Toxicity to organisms seems more dependent on acute exposure, while the chronic effects of low level exposure to heptachlor are poorly defined. Maximal terrestrial residues coincide with temporal and spatial proximity to application; peak residues in aquatic systems on the other hand, correlate to periods of maximum run-off. The lipophilic nature of both heptachlor and heptachlor epoxide results in the potential for significant bioaccumulation in all lipid-type compartments in the environment. The toxic effects of heptachlor are not specific for any one organ system. The liver and the central nervous system are most significantly affected by heptachlor, although effects can also be seen in the reproductive, hematopoietic, immune, and renal systems. An important consideration is the relation of relevant environmental exposure levels to toxicity. The concentrations necessary to elicit results in laboratory experiments do not translate directly to the same results upon environmental exposure, nor do experimental laboratory animal models absolutely equate with native-state organisms or with humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Antioxidant enzyme activities and malondialdehyde, glutathione and methemoglobin concentrations in channel catfish exposed to DEF and n-butyl mercaptan.

Indicators of free-radical or oxidant-mediated responses were quantified in channel catfish, Ictalurus punctatus, exposed to the organophosphorus herbicide DEF and its metabolite, n-butyl mercaptan (nBM). The activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase did not vary significantly with toxicant or dose. The concentrations of reduced glutathione (GSH) and malondialdehyde (MDA) did not vary significantly with toxicant or dose. The percentage of methemoglobin increased in the nBM-exposed fish with dose, up to 16.5% of total hemoglobin. The DEF-exposed catfish had no significant increases in methemoglobin compared to controls.