Structural basis of the induction of unscheduled DNA synthesis in rat hepatocytes

Zhang, Ying Ping; Praagh, Andrew Van; Klopman, Gilles; Rosenkranz, Herbert S.

doi:10.1093/mutage/9.2.141

Cited by 25 publications

(3 citation statements)

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“…The validated SAR models used for these studies have been described previously: binding to the Ah receptor (12); mutagenicity in Salmonella (13,14); SOS DNA repair (Chromotest; 15,16); carcinogenicity in rodents (combination of results of bioassays conducted by the US National Toxicology Program [17] and of those assessed in the Carcinogenic Potency Database [9,10,[18][19][20][21][22]); developmental toxicity in hamsters (23); induction of unscheduled DNA synthesis (UDS) in rat hepatocytes (24); and induction of micronuclei in vivo (25). Determination of lethality in rats (LD50) was based on data on 1411 orally administered chemicals extracted from the Registry of Toxic Effects of Chemical Substances (RTECS).…”

Section: Structure-activity Relationship Modelsmentioning

confidence: 99%

The High Production Volume Chemical Challenge Program: The Rodent LD50 and its Possible Replacement

Rosenkranz

Cunningham

2000

Altern Lab Anim

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The High Production Volume Chemical Challenge Program provides an opportunity to re-examine the usefulness and informational value of tests currently used to obtain preliminary hazard identification data. With a view to assessing the mechanistic information provided by the rodent LD50 test and to ascertain the possibility of replacing it with other “more acceptable” assays, we used a recently developed approach to determine the relationship of the LD50 assay to other toxicological protocols. Our analyses indicate that, of the assays examined, the LD50 was significantly related to toxicity in cultured cells and to binding at the Ah receptor.

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Section: Structure-activity Relationship Modelsmentioning

confidence: 99%

The High Production Volume Chemical Challenge Program: The Rodent LD50 and its Possible Replacement

Rosenkranz

Cunningham

2000

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“…The October 1999 agreement specifically calls for the use of internationally accepted in vitro tests for genotoxicity -which include the Ames/bacterial reverse-mutation test, as well as in vitro tests for chromosomal aberration, cell gene mutation, and sister chromatid exchanges (OECD Test Guidelines 471, 473, 476 and 479, respectively; 4). The use of these assays, alone or in combination, has been found to be highly sensitive to the detection of genotoxicants (11)(12). Despite the scientific and ethical considerations favouring the use of in vitro methods for this endpoint, numerous in vivo genetic toxicity tests have been proposed by companies and endorsed by the EPA (10).…”

Section: Genetic Toxicitymentioning

confidence: 99%

An Evaluation of the US High Production Volume (HPV) Chemical-testing Programme: A Study in (Ir)Relevance, Redundancy and Retro Thinking

Nicholson¹,

Sandler²,

Seidle³

2004

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Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines issued by the EPA in October 1999. Our review found major and recurring flaws in the programme's execution, as well as in its fundamental design. Approximately 75% of the test plans reviewed violated fundamental terms of the programme. Many participating companies failed to conduct comprehensive analyses of available data and instead proposed superfluous and meaningless tests. The US HPV programme's exclusion of human health and exposure data has led to numerous examples of irrelevant experiments that will not affect how a chemical substance is used or handled. Contrary to claims by both the EPA and Environmental Defense that few new animal tests are being performed, an estimated 100,000 animals have already died in this US Government-sponsored animal-testing programme.

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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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Structural basis of the induction of unscheduled DNA synthesis in rat hepatocytes

Cited by 25 publications

References 0 publications

The High Production Volume Chemical Challenge Program: The Rodent LD50 and its Possible Replacement

The High Production Volume Chemical Challenge Program: The Rodent LD50 and its Possible Replacement

An Evaluation of the US High Production Volume (HPV) Chemical-testing Programme: A Study in (Ir)Relevance, Redundancy and Retro Thinking

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

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