Assessing Toxicity of Mixtures: The Search for Economical Study Designs

Price, Bertram; Borgert, Christopher J.; Wells, Christopher S.; Simon, Glenn S.

doi:10.1080/20028091056935

Cited by 12 publications

(7 citation statements)

References 14 publications

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“…However, for DLERA, a weight of evidence approach incorporating contamination, toxicity, status of resident exposed biota and tissue concentrations is more appropriate (Borgmann et al 2001;Norwood et al 2003). Additionally, sequential toxicity tests to determine concentration or dose combinations that define the dose boundary for a specific acceptable risk level, can be used in DLERA to provide situation-specific experimental data (Price et al 2002).…”

Section: Risk Assessments Of Inorganic Metals and Metalloidsmentioning

confidence: 99%

Conducting Ecological Risk Assessments of Inorganic Metals and Metalloids: Current Status

Chapman¹,

Wang

Janssen

et al. 2003

Human and Ecological Risk Assessment: An International Journal

143

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Ecological risk assessment (ERA) of inorganic metals and metalloids (metals) must be specific to these substances and cannot be generic because most metals are naturally occurring, some are essential, speciation affects bioavailability, and bioavailability is determined by both external environmental conditions and organism physiological/biological characteristics. Key information required for ERA of metals includes: emissions, pathways, and movements in the environment (Do metals accumulate in biota above background concentrations?); the relationship between internal dose and/or external concentration (Are these metals bioreactive?); and the incidence and severity of any effects (Are bioreactive metals likely to result in adverse or, in the case of essential metals, beneficial effects?) -ground-truthed in contaminated areas by field observations. Specific requirements for metals ERA are delineated for each ERA component (Hazard Identification, Exposure Analysis, Effects Analysis, Risk Characterization), updating Chapman and Wang (2000). In addition, key specific information required for ERA is delineated by major information category (conceptual diagrams, bioavailability, predicted environmental concentration [PEC], predicted no effect concentration [PNEC], tolerance, application [uncertainty] factors, risk characterization) relative to three different tiered, iterative levels of ERA: Problem Formulation, Screening Level ERA (SLERA), and Detailed Level ERA (DLERA). Although data gaps remain, a great deal of progress has been made in the last three years, forming the basis for substantial improvements to ERA for metals.

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Section: Risk Assessments Of Inorganic Metals and Metalloidsmentioning

confidence: 99%

Conducting Ecological Risk Assessments of Inorganic Metals and Metalloids: Current Status

Chapman¹,

Wang

Janssen

et al. 2003

Human and Ecological Risk Assessment: An International Journal

143

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show abstract

“…Response addition would then be used for all other mixtures whose components follow different modes; rat studies using nine compounds with unrelated target sites or four nephrotoxins with different modes of action displayed response additivity (Cassee et al, 1998). However, there is no consensus or guidance on how strict the requirements for choosing dose or response addition have to be before applying either one (Altenburger et al, 2003;Price et al, 2002). Environmental mixtures of components with the same mode of action are the exception, not the rule (Cassee et al, 1998).…”

Section: Mixture Of Concern Proceduresmentioning

confidence: 99%

“…For a true assessment of mixture components using any of the three approaches, a dose-response curve for each chemical is needed (Price et al, 2002). This is due to the definition of "no interaction" and the dependent definitions of synergism and antagonism discussed previously (U.S. EPA, 2000).…”

Section: Mixture Of Concern Proceduresmentioning

confidence: 99%

The Toxicology of Chemical Mixtures Risk Assessment for Human and Ecological Receptors

Sterner¹,

Robinson²,

Mattie³

et al. 2005

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REPORT DOCUMENTATION PAGE ublic reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the lata needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing ,is burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently alid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2 I. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)kir Force Materiel Command*** HEPB SUPPLEMENTARY NOTES ABSTRACT4ixtures of chemicals represent a concern in all areas of toxicology and a challenge to risk Issessors as most sites with environmental contamination, including Department of Defense sites, involve simultaneous or sequential exposures of multiple chemicals to human or ýcological receptors.A major concern with mixtures is that they may lead to outcomes (health effects) or increased toxicity (synergism) not expected from the risk 'haracterization of individual chemicals at the site.The focus of this literature review is :o examine the principles used to determine toxicity in chemical mixtures risk assessment for luman and ecological receptors at hazardous waste sites.This review provides an overview of 'urrent practices useful to a remedial project manager or risk assessor prior to their first ",hemical mixtures risk assessment. 5.SUBJECTTERMS

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“…Therefore, we used sex‐steroid hormone production as an endpoint to investigate whether DDE and MCL may operate through a similar mode of action in fish gonads. Mechanistic similarity was assessed by classical interaction experiments that compared the results produced by dose combinations of these agents with a no‐interaction hypothesis based on Loewe additivity [10–12].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we used sex-steroid hormone production as an endpoint to investigate whether DDE and MCL may operate through a similar mode of action in fish gonads. Mechanistic similarity was assessed by classical interaction experiments that compared the results produced by dose combinations of these agents with a no-interaction hypothesis based on Loewe additivity [10][11][12]. The Loewe additivity model, which is sometimes called dose addition or concentration addition, is based on the concept that an agent cannot interact with itself in producing a specific response.…”

Section: Introductionmentioning

confidence: 99%

Interactive effects of p,p′‐dichlorodiphenyldichloroethylene and methoxychlor on hormone synthesis in largemouth bass ovarian cultures

Borgert

Gross

Guiney

et al. 2004

Enviro Toxic and Chemistry

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p,p'-Dichlorodiphenyldichloroethylene (DDE) and methoxychlor were tested alone and in combination to assess the similarity of their actions on hormone synthesis in gonadal tissue from largemouth bass (Micropterus salmoides floridanus), a species whose reproductive fitness has relevance to ecosystem health in Florida (USA). Gonads were harvested from adult female bass (age, two to three years) during the peak reproductive season (January-May), minced, and incubated in culture medium with or without test agents for 48 h. Duplicates of each treatment were performed in each of three experiments using tissue from a different female. Both 17beta-estradiol and testosterone were measured in aliquots of culture medium by validated radioimmunoassay procedures. Dose-response relationships of individual agents were characterized over a 6-log concentration range (1 X 10(-2) to 1 X 10(4) ppb). Both DDE and methoxychlor, tested individually, produced a dose-dependent decrease in testosterone levels. 17beta-Estradiol levels were unaffected. Mixtures of the agents were tested at all concentration combinations of 0.01, 1, 100, and 10,000 ppb in culture medium. Statistical tests indicated that of 16 dose combinations tested, 15 were antagonistic, and only 1 was additive based on the Loewe additivity model of no interaction. These results imply that methoxychlor and DDE inhibit testosterone production by different mechanisms in bass ovaries.

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Assessing Toxicity of Mixtures: The Search for Economical Study Designs

Cited by 12 publications

References 14 publications

Conducting Ecological Risk Assessments of Inorganic Metals and Metalloids: Current Status

Conducting Ecological Risk Assessments of Inorganic Metals and Metalloids: Current Status

The Toxicology of Chemical Mixtures Risk Assessment for Human and Ecological Receptors

Interactive effects of p,p′‐dichlorodiphenyldichloroethylene and methoxychlor on hormone synthesis in largemouth bass ovarian cultures

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