Genetic activity profiles in the testing and evaluation of chemical mixtures

Waters, Michael D.; Claxton, Larry D.; Stack, H.Frank; Brady, Ann L.; Graedel, T. E.

doi:10.1002/tcm.1770100211

Cited by 8 publications

(4 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This information can be used to select bioassay systems that may be used to detect known or suspect components of mixtures that may possess genotoxic potential. (39)…”

Section: Mutagenicity Testsmentioning

confidence: 99%

Carcinogenic Mixtures

Krewski

Thomas

1992

Risk Analysis

View full text Add to dashboard Cite

Human populations are generally exposed simultaneously to a number of toxicants present in the environment, including complex mixtures of unknown and variable origin. While scientific methods for evaluating the potential carcinogenic risks of pure compounds are relatively well established, methods for assessing the risks of complex mixtures are somewhat less developed. This article provides a report of a recent workshop on carcinogenic mixtures sponsored by the Committee on Toxicology of the U.S. National Research Council, in which toxicological, epidemiological, and statistical approaches to carcinogenic risk assessment for mixtures were discussed. Complex mixtures, such as diesel emissions and tobacco smoke, have been shown to have carcinogenic potential. Bioassay-directed fractionation based on short-term screening test for genotoxicity has also been used in identifying carcinogenic components of mixtures. Both toxicological and epidemiological studies have identified clear interactions between chemical carcinogens, including synergistic effects at moderate to high doses. To date, laboratory studies have demonstrated over 900 interactions involving nearly 200 chemical carcinogens. At lower doses, theoretical arguments suggest that risks may be near additive. Thus, additivity at low doses has been invoked as as a working hypothesis by regulatory authorities in the absence of evidence to the contrary. Future studies of the joint effects of carcinogenic agents may serve to elucidate the mechanisms by which interactions occur at higher doses.

show abstract

“…This information can be used to select bioassay systems that may be used to detect known or suspect components of mixtures that may possess genotoxic potential. (39)…”

Section: Mutagenicity Testsmentioning

confidence: 99%

Carcinogenic Mixtures

Krewski

Thomas

1992

Risk Analysis

View full text Add to dashboard Cite

show abstract

“…A recent application ofGAPs is in testing and evaluating complex mixtures (22). Some knowledge ofthe potential genetic activity of a complex environmental mixture may be gained from assessing the genetic activity of its component chemicals.…”

Section: Testing and Evaluating Complex Mixturesmentioning

confidence: 99%

The Genetic Activity Profile Database

Waters¹,

Stack²,

Garrett³

et al. 1991

Environmental Health Perspectives

Self Cite

View full text Add to dashboard Cite

A graphic approach termed a Genetic Activity Profile (GAP) has been developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose (LED) or highest ineffective dose (HID) is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for the production and evaluation of GAPs has been developed in colaboration with the International Agency for Research on Cancer. Data on individual chemicals have been compiled by LARC and by the U.S. Environmental Protection Agency. Data are available on 299 compounds selected from volumes 1-50 ofthe LARC Monogmphs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors.Structurally similar compounds frequently display qualitatively and quantitatively similar GAPs. By eamning the patterns of GAPs of pairs and groups ofchemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluating chemical analogs. GAPs have provided useful data for the development of weightof-evidence hazard ranking schemes. Also, some knowledge ofthe potential genetic activity ofcomple environmental mixtures may be gained from assessing the GAPs ofcomponent chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines.

show abstract

“…A recent application ofGAPs is in testing and evaluating complex mixtures (22 (27). The evaluative approach selected by ICPEMC Committee 1 is based on a '"weighted test" scoring system that provides a relative ranking of genotoxic potential.…”

Section: Testing and Evaluating Complex Mixturesmentioning

confidence: 99%