2,4-dichlorophenol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Method similar to OECD 471 except certain E. coli strains missing.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

E. col wpA2 strains not included

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dichlorophenol

EC Number:

204-429-6

EC Name:

2,4-dichlorophenol

Cas Number:

120-83-2

Molecular formula:

C6H4Cl2O

IUPAC Name:

2,4-dichlorophenol

Details on test material:

Received as coded aliquots from Radian Corporation, Texas, USA

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

S9 fraction from Syrian hamster or Sprague Dawley rat Aroclor 1254 induced liver

Test concentrations with justification for top dose:

0, 3.3, 10, 33, 100, 333 µg/plate

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

2-aminoanthracene, 4-nitro-o-phenylediamine, sodium azide

Details on test system and experimental conditions:

2,4-DCP in addition to the solvent and positive controls were tested in the presence or absence of S-9 mix. 3 replicates were used. The experiment was repeated no less than 1 week after completion of the initial test. Liver S9 fraction were prepared from male Sprague Dawley rats and Syrian hamster that were induced with Aroclor 1254 5 days before sacrifice.

Evaluation criteria:

A positive repsonse was defined as a reproducible, dose related increase in histidine-independent (revertant) colonies in any one strain/activation combination. An equivocal response was defined as an increase in revertants which was not dose related, not reproducible, or of insufficient magnitude to support a determination of mutagenicity. A reponse was considered negative when no increase in revertant colonies was observed after chemical treatment.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

ambiguous

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Slight toxicity seen at highest dose tested (333 µg/plate)

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at highest dose tested 333 µg/plate

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium, other: TA 1537, TA98 and TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at highest dose tested (333 µg/plate)

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The equivocal or ambiguous result see with metabolic activation in TA 1535 was seen in the presence of Hamster derived S9 only and NOT with rat derived S9.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
ambiguous with metabolic activation Strain 1535 gave equivocal results in the presence of hamster derived S9 only (and not rat derived S9)).

2,4 dichlorophenol gave an ambiguous result in strain TA 1535 in the presence of Hamster derived S9 only. Results obtained in all other scenarios examined were negative.

Executive summary:

In a reverse gene mutation assay in bacteria, strains TA 98, TA 100, TA 1535, TA1537 of S. typhimurium were exposed to 2,4-dichlorophenol, at concentrations of 0, 3.3, 10, 33, 100, 333 µg/plate (co-incubation) in the presence and absence of mammalian metabolic activation derived from both Aroclor 1254 induced Sprague Dawley rat and Syrian hamster liver.

2,4-dichlorophenol was tested up to cytotoxic concentrations (300 µg/plate). The positive controls induced the appropriate responses in the corresponding strains.  There was some evidence of induced mutant colonies over background (2 fold) for strain TA 1535 at the top dose (i.e. in the presence of cytotoxity) in the presence of Syrian hamster S9 but not rat S9.

This study is classified as acceptable and satisfies the requirement of Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data with the exception that certain E. coli strains were missing.