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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
(adopted 1997); EEC Annex 4D Test B13/14 (2000); UKEMS Guidelines (1990) and ICH Harmonised Tripartite Guideline (1997).
Deviations:
yes
Remarks:
minor deviations detailed in sections below
Principles of method if other than guideline:
This study was performed according to the protocol, with the exception of minor deviations detailed below, none of which in any way prejudiced the
validity of this study.

Deviations from Protocol:
Subject Deviation Analysis of Results Acceptance criteria Following Experiment 2, the mean solvent control value for TA1537 in the presence of S-9
was above the laboratory's historical range. However, counts were considered comparable to the range and data was accepted as valid. Materials Test
Article The crude test compound was not stored under nitrogen as stated in the protocol. Following discussions with the sponsor this deviation was
not considered to affect stability of the test compound and therefore the study integrity was not affected.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Resorcinol
EC Number:
203-585-2
EC Name:
Resorcinol
Cas Number:
108-46-3
Molecular formula:
C6H6O2
IUPAC Name:
benzene-1,3-diol
Details on test material:
Resorcinol >95%

Method

Species / strain
Species / strain / cell type:
S. typhimurium, other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA102
Metabolic activation:
with and without
Metabolic activation system:
rat liver metabolic activation system (S-9).
Test concentrations with justification for top dose:
up to 5000 µg/plate
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Details on test system and experimental conditions:
Ames Test
Statistics:
Dunnett's Test

Results and discussion

Test results
Species / strain:
S. typhimurium, other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
5000 ug/plate
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

In the range finding study, TA100, evidence of toxicity was observed at the highest dose level in the absence and presence of S-9 and was manifest as a marked decrease in revertant numbers. These results were considered to be acceptable for mutation assessment and are used to comprise
the TA100 mutagenicity data for Experiment 1. Treatments of the remaining test strains (TA98, TA1535 and TA102) in Experiment 1 retained the same test doses employed for the range-finder experiment treatments. Following these treatments, no evidence of toxicity was observed.

In experiment 2, evidence of toxicity in the form of a marked decrease in revertant numbers and/or a thinning of the background lawn was observed at the highest test dose for strains TA98 and TA1535 in the absence of S-9 and strains TA98 and TA102 in the presence of S-9.

Stastical significance:
  Following Experiment 1 a statistically significant increase in revertants was observed at a single dose level for strains TA1537 and TA102 in the absence of S-9 when data were analysed at the 1% level using Dunnett's test. However, these increases showed
no evidence of a dose response, and were not reproducible in Experiment 2. Therefore it is considered that the increases in revertant numbers were due to a chance event and not indicative of Resorcinol (AO11) mutagenic activity.

No statistically significant, dose-related and reproducible increases in revertant numbers were observed following any other strain treatments in the absence or presence of metabolic activation, and therefore this study was considered to have provided no clear evidence of any
Resorcinol (AO11) mutagenic activity.

Controls:
  Negative (solvent) and positive control treatments were included for all strains in both experiments. The mean numbers of revertant colonies on negative control plates all fell within acceptable ranges, and were significantly elevated by positive control treatments.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

It was concluded that Resorcinol (AO11) did not induce mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of
Salmonella typhimurium when tested under the conditions of this study. These conditions included treatments at concentrations up to
5000 mg/plate, in the absence and in the presence of a rat liver metabolic activation system (S-9).