Modeling the mouse lymphoma forward mutational assay: the Gene-Tox program database

Grant, Stephen G.; Zhang, Ying Ping; Klopman, Gilles; Rosenkranz, Herbert S.

doi:10.1016/s1383-5718(99)00186-2

Cited by 25 publications

(7 citation statements)

References 51 publications

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“…Since the aetiology of cancer in rodents includes genomic and chromosomal events as well as tumour promotion, it is noteworthy that phenomena associated with these events (for example, the in vivo induction of micronuclei and SCEs which involve chromosomal and genomic effects [68]), and iGJIC which is associated with tumour promotion (52), are also significantly associated with acute toxicity in minnows (Tables 3 and 4: Analysis 11). Interestingly, toxicity in fish exhibits associations with other toxicological effects (for example, Analyses 6, 7, 13-16, Tables 3 and 4).…”

Section: Resultsmentioning

confidence: 99%

Lack of Predictivity of the Rat Lethality (LD50) Test for Ecological and Human Health Effects

Rosenkranz

Cunningham

2005

Altern Lab Anim

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The relationship between acute toxicity in rats (LD50 values) and indicators of potential health hazards in humans was investigated, based on a chemical population-based paradigm (i.e. the “chemical diversity approach”). These structure–activity relationship-based analyses indicate that high toxicity in rats (i.e. a low LD50 value) is not a good predictor of health effects in humans. In fact, it was found that high acute toxicity to minnows, as well as toxicity to cultured cells, showed significantly greater associations with the potential for health effects than rat LD50 values.

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Section: Resultsmentioning

confidence: 99%

Lack of Predictivity of the Rat Lethality (LD50) Test for Ecological and Human Health Effects

Rosenkranz

Cunningham

2005

Altern Lab Anim

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“…SAR models based on subsets of that database have been described (24)(25)(26). SAR models of the ability to induce error-prone DNA repair in Escherichia coli (SOS Chromotest; EBPI, Brampton, Ontario, Canada) (27,28), mutations in cultured mouse lymphoma cells (29), sister chromatid exchanges (SCEs), chromosomal aberrations in cultured Chinese hamster ovary (CHO) cells (30), and unscheduled DNA synthesis in primary rat hepatocytes (31) have been described previously, as have models of the potentials for inducing SCEs (32) and micronuclei in vivo (33).…”

Section: Hpv Chemical Selection a Sample Of 200mentioning

confidence: 99%

Estimating the Extent of the Health Hazard Posed by High-Production Volume Chemicals

Cunningham¹,

Rosenkranz²

2001

Environmental Health Perspectives

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the goal of providing a humane, economical, and efficient method of collecting basic toxicologic data for HPV chemicals (2-4). For this purpose, HPV chemicals are defined as those produced or imported into the United States in quantities greater than 1 million pounds per year. The program asks chemical producers and importers to voluntarily provide basic toxicologic data on HPV chemicals (5). These chemicals were identified under the Toxic Substance Control Act 1990 Inventory Update Rule (6). Overall, the HPV Chemical Challenge Program list contains 2,800 chemicals (7). The Screening Information Data Set (SIDS) of the Organization for Economic Cooperation and Development was selected as the toxicologic criteria needed to meet the goals of the HPV Chemical Challenge Program (8). SIDS includes tests for genotoxicity, acute and chronic toxicity, reproductive toxicity, ecotoxicity, and environmental fate. One of the challenges, as part of the TestSmart Program, was to assess the overall magnitude of the health hazards posed by HPV chemicals based on structure-activity relationship (SAR) modeling. The U.S. EPA will consider test result submission for the HPV Program based on SAR models that are scientifically justifiable (9). As part of this program we undertook an analysis of a random set of 200 HPV chemicals and predicted the probability of each to induce a variety of toxic effects including genotoxicity, carcinogenicity, developmental toxicity, and systemic

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Section: Hpv Chemical Selectionmentioning

confidence: 99%

Estimating the extent of the health hazard posed by high-production volume chemicals.

Cunningham

Rosenkranz

2001

Environ Health Perspect

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We used structure-activity relationship modeling to estimate the number of toxic chemicals among the high-production volume (HPV) group. We selected 200 chemicals from among the HPV chemical list and predicted the potential of each for its ability to induce a variety of adverse effects including genotoxicity, carcinogenicity, developmental, and systemic toxicity. We found a significantly less than expected proportion of toxic chemicals among the HPV sample when compared to a reference set of 10,000 chemicals representative of the universe of chemicals.

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Modeling the mouse lymphoma forward mutational assay: the Gene-Tox program database

Cited by 25 publications

References 51 publications

Lack of Predictivity of the Rat Lethality (LD50) Test for Ecological and Human Health Effects

Lack of Predictivity of the Rat Lethality (LD50) Test for Ecological and Human Health Effects

Estimating the Extent of the Health Hazard Posed by High-Production Volume Chemicals

Estimating the extent of the health hazard posed by high-production volume chemicals.

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