1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 1992 - April 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

GLP study from 1993, some deviations from current updated guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Version / remarks:

1984

Deviations:

yes

Remarks:

deviations according to updated guideline, such as number of cells; no purity indicated

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol

EC Number:

204-137-9

EC Name:

1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol

Cas Number:

116-37-0

Molecular formula:

C21H28O4

IUPAC Name:

1-(4-{2-[4-(2-hydroxypropoxy)phenyl]propan-2-yl}phenoxy)propan-2-ol

Test material form:

solid

Details on test material:

Batch number: 299203720100
CAS number : 116-37-0
EC number : 204-137-9

To the best of knowledge, the sample used are representative to the boundary composition shared and agreed by each registrant.

Method

Target gene:

HGPRT locus

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

first assay: -S9: 0, 10, 25, 50, 75, 100, 150 µg/mL; +S9: 0, 10, 20, 40, 80, 100 µg/mL
second assay: -S9: 0, 25, 50, 75, 100, 125 µg/mL; +S9: 0, 25, 50, 75, 100, 125, 150 µg/mL
supplementary assay: -S9: 0, 130, 140, 150 µg/mL; +S9: 0, 160, 180, 200 µg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

Migrated to IUCLID6: 7,12-dimethylbenzanthracene (DMBA)

Details on test system and experimental conditions:

DURATION
- Preincubation period: 24h
- Exposure duration: 3h
- Expression time (cells in growth medium): 7 days

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 100 cells/plate, 3 plates

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency

Evaluation criteria:

Mutant frequency per 10E5 survivors = (no. of cells plated for PE/mean no. of PE colonies) x mean no. of 6-TG-r colonies. A comparison is made between the mutation frequency of the treated plaets and control plates. Statistical analysis is not applied.
The study is considered valid if:
solvent control data are acceptable and if positive control data are acceptable.
The test is considered positive if increases in mutation frequencies and/or mutatant colony numbers are consistently observed in each if the two assays. The significant elevantion of mutation frequency at only one concentration or in isolated single cultures at more than one concentration will be analysed on a case-by-case basis.

Statistics:

Statistical analysis is not applied.

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 130 µg/mL onwards -S9, from 160 µg/mL onwards +S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: cloudiness was obserbed at 200 µg/mL


RANGE-FINDING/SCREENING STUDIES: included

Any other information on results incl. tables

In the first mutation assay no cytotoxicity was apparent at concentrations up to and including 100 µg/mL; total cell death was observed at 150 µg/mL (-S9). In the second test, no cytotoxicity was observed up to and including 150 µg/mL. In the supplementary assay, reduced plating efficiency was observed at and above 130 µg/mL (-S9); in the presense of S9 toxicity was observed at and above 160 µg/mL.

No increases in mutation frequencies (or mutant colony numbers) were observed in Dianol 320 treated culteres, both in the absence and presence of S9.

Applicant's summary and conclusion

Conclusions:

Under the test conditions, 4,4’-Isopropylidenediphenol, propoxylated (BPA+2PO) did not show mutagenic activity at the HGPRT gene locus, both in the absence and in the presence of metabolic activating system.

Executive summary:

4,4’-Isopropylidenediphenol, propoxylated (BPA+2PO) was examined for mutagenic potential by measuring its ability to induce mutation in Chinese hamster (V79) cells at the hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) locus. Under the experimental conditions of the test, 4,4’-Isopropylidenediphenol, propoxylated (BPA+2PO) showed no evidence of mutagenic activity at the HGPRT gene locus, when cells were treated in the absence or presence of S-9 mix. The sensibility of the assay system was proven by the observed responses to known mutagens.