Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in mammalian cells
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
yes
Type of assay:
other: thymidine kinase locus
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Test concentrations with justification for top dose:
5, 6, 7, 8, 9, and 10 mM (without S9, Experiments 1 and 2)
0.313, 0.625, 1.25, 2.5, 5 and 10 mM (with S9 Experiment 1)
5, 6, 7, 8, 9 and 10 mM (with S9 Experiment 2)
Vehicle / solvent:
The test item was dissolved in dimethylsulfoxide (DMSO).
Negative solvent / vehicle controls:
yes
Remarks:
Dimethylsulfoxide (DMSO
Positive controls:
yes
Remarks:
Methylmethane sulfonate (MMS); cyclophosphamide (CPA)
Details on test system and experimental conditions:
Type: other: thymidine kinase locus
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Positive controls validity:
not specified
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Positive controls validity:
not specified

Preliminary Toxicity Study: Without S9:  Following the 3-hour treatment without S9 mix, a moderate to marked toxicity was noted at dose-levels = 1 mM (50-75% decrease in adjusted relative suspension growth (Adj. RSG) and up to 50-69% decrease in adjusted relative total growth (Adj. RTG)).

Main study:
 
Without S9:
  In both experiments, a moderate to marked toxicity was noted at all dose-levels as shown by 54-76% decrease in Adj. RSG and 46-83% decrease in Adj. RTG.
Noteworthy increases in the mutation frequency (up to 4.8-fold the vehicle control value) were observed following the 3-hour treatment in both experiments.

With S9:

A slight to marked toxicity was observed at dose-levels = 5 mM, as shown by 30-78% decrease in Adj. RSG and 28-65% decrease in Adj. RTG

In the First experiment:
  a slight increase in the mutation frequency was noted at the dose-level of 10 mM. Since this very slight increase which did not reach the 2-fold level was neither dose-related nor reproducible in the second experiment, it was not considered as biologically relevant.

Conclusions:
Interpretation of results: positive

Under these experimental conditions, Resorcinol (A011) induced mutagenic activity in the mouse lymphoma assay, without metabolic activation (S9 mix)
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.
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
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
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
Key result
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

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.

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).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo insect germ cell study: gene mutation
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study; No data regarding GLP
Principles of method if other than guideline:
Method: other: Zimmering et al (1985)
GLP compliance:
not specified
Type of assay:
Drosophila SLRL assay
Species:
Drosophila melanogaster
Strain:
other: Canton-s wild type
Sex:
male
Route of administration:
other: feed (diet)
Duration of treatment / exposure:
72 hours
Remarks:
Doses / Concentrations:
11,000 ppm
Basis:

Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
Lethality measured as part of the test protocol

Resorcinol (11,000 ppm) was negative for induction of sex-linked recessive lethal mutations in germ cells of male Drosophila melangaster when administered to adult flies by feeding.

Conclusions:
Interpretation of results (migrated information): negative
Endpoint:
in vivo insect germ cell study: gene mutation
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study; No data regarding GLP
Principles of method if other than guideline:
Method: other: Zimmering et al (1985)
GLP compliance:
not specified
Type of assay:
Drosophila SLRL assay
Species:
Drosophila melanogaster
Strain:
other: Canton-s wild type
Sex:
male
Route of administration:
other: injection
Duration of treatment / exposure:
72 hours
Remarks:
Doses / Concentrations:
11,940 ppm
Basis:

Statistics:
Recessive lethal data were analyzed by the normal approximation to the binomial test (Margolin et al., 1983). A test result was considered to be
positive if the P value was less than 0.01 and the mutation frequency in the tested group was greater that 0.10%, or if the P value was less than 0.05
and the frequency in the treatment group was greater than 0.15%. A test was considered to be inconclusive if (a) the P value was between 0.05 and
0.01 but the frequency in the treatment group was between 0.10% and 0.15%, or (b) the P value was between 0.10 and 0.05 but the frequency in the
treatment group was greater than 0.10%. A result was considered to be negative if the P value was greater than 0.10 or if the frequency in the
treatment group.
Key result
Sex:
male
Genotoxicity:
ambiguous
Toxicity:
yes
Remarks:
Lethality measured as part of the test protocol

Administration of the test substance (11,940) by injection yielded an increase in mutations which was equivocal (P=0.06 and mutation frequency of 0.12% in the treated group).

Conclusions:
Interpretation of results (migrated information): ambiguous
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Resorcinol generally showed no evidence of activity in bacterial mutation assays. In mammalian cells in culture, it induced chromosome aberrations (breaks and micronuclei), but no SCE effects. In an in vitro Unscheduled Synthesis Assay in rat hepatocytes, resorcinol is negative. In an OECD TG 476 (in vitro thymidine kinase locus) under GLP conditions, resorcinol is positive without activation in the L5178Y mouse lymphoma cells; however, the observed induction of small colony mutants is associated with chromosome aberrations. A repeat of this study was conducted in 2009 with two experiments within the same study. Resorcinol was negative in the mouse lymphoma cells L5178Y, tested up to the limit concentration (1101 ug/mL), gave 37% and 26% relative survival with and without S-9 metabolic activation, respectively. In an OECD TG 487 (in vitro Micronucleus assay) under GLP conditions, resorcinol is positive with and without activation in female human lymphocytes. In an in vitro Syrian hamster embryo cell morphological transformation assay following OECD, FDA and MHLW guidelines under GLP conditions, resorcinol is negative. Several in vivo studies suggest that it does not induce micronuclei or SCE in mammals. Resorcinol was negative for inducing micronuclei in six in vivo micronucleus assays in which one study was conducted following OECD TG 474 under GLP conditions. In one of two NTP in vivo micronucleus assays, resorcinol was positive for inducing micronuclei. Resorcinol was negative in three sister chromatid exchange assays. In a transgenic mouse model, resorcinol was negative for activating RasH2. In studies to evaluate the effectiveness of the transgenic mouse model, resorcinol was negative in p53+/- while positive in Tg.AC. While resorcinol appears to induce chromosome aberrations in vitro, based on the weight of evidence, these findings suggest that resorcinol is not genotoxic in vivo. 


Short description of key information:
While resorcinol appears to induce chromosome aberrations in vitro, based on the weight of evidence, these findings suggest that resorcinol is not genotoxic in vivo.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

While resorcinol appears to induce chromosome aberrations in vitro, based on the weight of evidence, these findings suggest that resorcinol is not genotoxic in vivo.