Comparison of multiple parameters of rodent carcinogenicity and in vitro genetic toxicity

Tennant, Raymond W.; Stasiewicz, Stanley; Spalding, Judson W.

doi:10.1002/em.2860080204

Cited by 51 publications

(16 citation statements)

References 29 publications

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“…Recently, Ashby and Tennant, expanding upon and corrobor ating the work ofTennant et al (154), found that the distribution of tumor sites for agents mutagenic to Salmonella is different from those which are not (76). They examined 222 carcinogens which had been tested by the NCI/NTP in both mice and rats.…”

Section: Genotoxic Versus Nongenotoxic Agents and The Rodent Bioassaymentioning

confidence: 94%

Predicting the Carcinogenicity of Chemicals in Humans from Rodent Bioassay Data

Goodman¹,

Wilson²

1991

Environmental Health Perspectives

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Regulatory agencies currently rely on rodent carcinogenicity bioassay data to predict whether or not a given chemical poses a carcinogenic threat to humans. We argue that it is always more useful to know a chemical's carcinogenic potency (with confidence limits) than to be able to say only qualitatively that it has been found to be a carcinogen. In a typical bioassay, a chemical is administered to groups of 50 to 100 rodents at the highest feasible level (the maximum tolerated dose) and rarely at less than 1/10 this dose in order to maximize the statistical significance ofany increase in tumors that might result. Recently, much experimental work has focused on the mechani by which site-specific toxicity arising from chronic administration at the maximum tolerated dose may lead to carcinogencity. Extrapolation ofhigh-dose results to low doses does not take into consideration the possibility ofa threshold dose, below which the carcuiogenic potency is much lower or even zero. Threshold dose-response phenomena may be much more relevant to the etiology of cancer in the rodent bioassays than was earlier realized; if so, there is an even greater need for establishing dose-dependent potency estimates. The emphasis of this review is on the interspecies comparison of high-dose potencies. The qualitative and quantitative comparison ofcarcinogenicities between mice and rts and between rodents and humans isreviewed and discussed.We conclude that there is a good qualitative (yes/no) correlation for both the rat/mouse and the rodent/human comparison. There is also a good correlation of the carcinogenic potencies between rats and mice, and the upper limits on potencies in humans are consistent with rodent potencies for those chemicals for which human exposure data are available. For the rodent/human comparison, the best estimate ofthe interspecies potency factor is lognormally distributed around 1 when the potencies in both species are measured in units of (mg/kg-day) -'.

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Section: Genotoxic Versus Nongenotoxic Agents and The Rodent Bioassaymentioning

confidence: 94%

Predicting the Carcinogenicity of Chemicals in Humans from Rodent Bioassay Data

Goodman¹,

Wilson²

1991

Environmental Health Perspectives

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“…In TA1537 and TA100, mutagenicity was also found without metabolic activation [14]. The metabolite, N-acetyl-4,4'-oxydianiline, was mutagenic in the presence of S9 mix in the strains TA98 and TA100; N,N'-diacetyl-4,4'-oxydianiline was not mutagenic [2].…”

Section: Genotoxicitymentioning

confidence: 97%

“…In L5178Y mouse lymphoma cells, 4,4'-oxydianiline (concentrations not specified) was mutagenic with and without S9 mix [14,16]. In another L5178Y mouse lymphoma test, positive results were obtained without metabolic activation with 4,4'-oxydianiline concentrations from 50 to about 250 µ g/ml.…”

Section: Genotoxicitymentioning

confidence: 99%

“…Higher concentrations were cytotoxic [17]. Initially, unscheduled DNA synthesis (UDS) could not be demonstrated in rat hepatocytes treated with 4,4'-oxydianiline either in vitro or in vivo [14,18]. However, when hepatocytes from rats pretreated with Aroclor-1254 were used, exposure of the cells to 4,4'-oxydianiline in vitro resulted in a concentration-dependent increase in UDS.…”

Section: Genotoxicitymentioning

confidence: 99%

See 1 more Smart Citation

4,4′‐Oxydianiline [MAK Value Documentation, 1993]

2012

The MAK‐Collection for Occupational Health and Safety

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Published in the series Occupational Toxicants , Vol. 6 (1993) The article contains sections titled: Toxic Effects and Modes of Action Pharmacokinetics Effects in Man Effects on Animals Acute toxicity Dermal toxicity Subchronic and chronic toxicity Sensitization tests Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

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“…According to TemaNord, no evidence for genotoxicity was found in a wide range of in vitro studies, such as Salmonella/microsome test, mouse lymphoma TK +/-assay, chromosome aberration/sister chromatid exchange test in Chinese hamster ovary cells, and rat hepatocyte/DNA repair assay (no further details on any of these studies were given) (Ashby et al, 1988;Benigni, 1989;Cameron et al, 1987;Gulati et al, 1989;Kornbrust and Barfknecht, 1985;McGregor et al, 1988;Mortelmans et al, 1986;Shelby and Stasiewics, 1984;Sweeney et al, 1994;Tennant et al, 1986Tennant et al, , 1987Zeiger, 1987).…”

Section: Genotoxicitymentioning

confidence: 99%

Scientific Opinion on the re-evaluation of Azorubine/Carmoisine (E 122) as a food additive

Aguilar¹,

Charrondière²,

Dusemund³

et al. 2009

EFSA Journal

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The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion re-evaluating the safety of Azorubine/Carmoisine (E 122). Azorubine/Carmoisine has previously been evaluated by JECFA in 1983 and the SCF in 1984. Both committees established an Acceptable Daily Intake (ADI) of 0-4 mg/kg bw/day. The Panel was not provided with a newly submitted dossier and based its evaluation on previous evaluations, additional literature that became available since then and the data available following a public call for data. New studies included a study reporting alterations in the morphology of somatic chromosomes in Secale cereale (rye), and a study by McCann et al. that concluded that exposure to mixtures including Azorubine/Carmoisine, resulted in increased hyperactivity in 3-years old and 8-to 9-years old children. The Panel notes that the study in rye was not a standard genotoxicity assay, and concluded, given that all other genotoxicity tests were negative and that Azorubine/Carmoisine does not contain a structural alert, that there is no concern with respect to genotoxicity. The Panel also concurs with the conclusion from a previous EFSA opinion on the McCann et al. study that the findings of the study cannot be used as a basis for altering the ADI. The Panel concludes that the present database does not give reason to revise the ADI of 4 mg/kg bw/day. The Panel also concludes that at the maximum reported levels of use, refined intake estimates are below the ADI, although in 1-to 10-year old children the high percentile of exposure (95 th ) can be slightly higher than the ADI at the upper end of the range. KEY WORDSAzorubine, Carmoisine, E 122, CAS 3567-69-9, CI Acid Red 14, CI Food Red 3, food colouring substance, EINECS number 222-657-4. The Panel noted that the specifications on the purity of Azorubine/Carmoisine permit concentrations of unidentified unsulphonated aromatic amines to be present in concentrations of up to 100 mg/kg Azorubine/Carmoisine. Although some aromatic amines may be associated with genotoxicity or even carcinogenicity, the Panel notes that Azorubine/Carmoisine was negative in in vitro genotoxicity studies and an in vivo genotoxicity study as well as in long-term carcinogenicity studies.The Panel concurs with the view expressed in previous evaluations by JECFA and TemaNord that the absorption of Azorubine/Carmoisine is limited, but that after reduction in the gastrointestinal tract, free sulphonated aromatic amines may reach the systemic circulation.The SCF and also the JECFA and TemaNord evaluations concluded, based on in vivo and in vitro studies available at that time, that Azorubine/Carmoisine does not show any genotoxic activity.In a more recent study, Zaharia and Pavel have tested four colourings, Tartrazine (E 102), Azorubine/Carmoisine (E 122), Patent Blue (E 131) and Acid Green 50 (E 142), on the frequency of divisional cells, mitotic index, mutagenic process, and the potential of these synthetic colourings to induce chromosomal modifications. Using cyt...

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Comparison of multiple parameters of rodent carcinogenicity and in vitro genetic toxicity

Cited by 51 publications

References 29 publications

Predicting the Carcinogenicity of Chemicals in Humans from Rodent Bioassay Data

Predicting the Carcinogenicity of Chemicals in Humans from Rodent Bioassay Data

4,4′‐Oxydianiline [MAK Value Documentation, 1993]

Scientific Opinion on the re-evaluation of Azorubine/Carmoisine (E 122) as a food additive

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