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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
AY23 - Testing of 24 Food, Drug, Cosmetic, and Fabric Dyes in the In Vitro and the In Vivo/ In Vitro Rat Hepatocyte Primary Culture/ DNA Repair Assays
Author:
Douglas Kornbrust and Thomas Barfknecht
Year:
1984
Bibliographic source:
Environmental Mutagenesis 7:lOl-120 (1985)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
Deviations:
not specified
GLP compliance:
not specified
Type of assay:
other: HPC/DN repair assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
No data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
cesarean-derived
Sex:
male
Details on test animals and environmental conditions:
Male Sprague Dawley cesarean-derived (Crl: COBS@ CD@ [SD] BR) rats (Charles River Breeding Laboratories, Inc., Kingston, NY), weighing 200-300 g, were used for all in vivo/in vitro HPC/DR assays, and also served as the source of hepatocytes for the in vitro HPC/DR assays. Prior to use, the animals were housed in humidity- and temperature-controlled rooms with 12-hr light/dark cycles, and allowed access to food and water ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration of treatment / exposure:
single application
Doses / concentrations
Dose / conc.:
500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
not specified
Control animals:
other: Negative control: Acid Red 14 (Carmoisine)
Positive control(s):
Solvent Yellow 3 (0-aminoazotoluene)

Examinations

Evaluation criteria:
Consistent with the criteria employed by other investigators [Williams, 1977; Bermudez et al, 1979; Probst et al, 19811, average net nuclear grain counts of 5 or greater were assumed to constitute a positive response, since these differed from the control net nuclear counts by greater than 2 SD. On a historical basis in this laboratory, control incubations have invariably yielded an average value for net nuclear grains of less than zero. In the present study, NNG counts ranged from -0.6 to -2.8 and from -0.9 to -2.1 for no-solvent and 1% DMSO control incubations, respectively. In addition, the proportion of cells with 2 5 NNG was 6 8% for all control incubations [4.1 f 2.6% (mean -t standard deviation), n = 17). Therefore, net nuclear grain counts below zero were considered negative responses. For those dyes that produced responses between zero and 5 average net nuclear grains, it was generally not possible to demonstrate a statistically significant difference from the control value within a given experiment. Therefore, these responses were judged to be equivocal, unless, in addition to an average net nuclear grain count between zero and 5, at least 25% of the cells examined contained 2 5 net nuclear grains, in which case the response was considered weakly positive. Concentrations of the dyes that produced approximately 90% or greater detachment of the hepatocytes from the coverslips (as assessed visually by comparing to control slides) were assumed to be toxic and were not counted.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Not mutagenic
Executive summary:

The tested substance showed negative results in the in vivo HPC/DR assay.