Tetra-n-butyl titanate, polymer with water

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / micronucleus study

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Though no guideline was followed the experiments performed and results presented can be considered reliable. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.

Data source

Reference

Reference Type:

publication

Title:

The in vitro micronucleus assay for detection of cytogenetic effects induced by mutagen-carcinogens: comparison with the in vitro sister-chromatid exchange assay

Author:

Lasne C., Gu Z., venegas W., Chouroulinkov I.

Year:

1984

Bibliographic source:

Mutation Reasearch, Vol 130, PN. 273-282

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The induction potential of micronuclei was analyzed after exposure of the chinese hamster lung (V79) cells to n-butanol.

GLP compliance:

no

Type of assay:

in vitro mammalian cell micronucleus test

Test material

Test material information

Constituent 1

Constituent 2

Reference substance name:

Butan-1-ol

EC Number:

200-751-6

EC Name:

Butan-1-ol

Cas Number:

71-36-3

Molecular formula:

C4H10O

IUPAC Name:

1-Butanol

Details on test material:

- Name of test material (as cited in study report): 1- butanol

Method

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: Eagles MEM supplemented with 10% foetal salf serum
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes/
- Periodically checked for karyotype stability: yes/
- Periodically "cleansed" against high spontaneous background: yes

Metabolic activation:

with and without

Test concentrations with justification for top dose:

50 µl/dish

Vehicle / solvent:

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

Controls

Negative solvent / vehicle controls:

yes

Remarks:

Medium, Acetone

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

methylmethanesulfonate

other: N-methyl-N'-nitro-N-nitrosoguanidine

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation; in suspension

DURATION
- Preincubation period:15-18 hrs
- Exposure duration: 1hr
-
SPINDLE INHIBITOR (cytogenetic assays): colchicine in sister chromatide exchange

STAIN (for cytogenetic assays):Fluroscent dye Hoechest 33258 (5 ug/ml)

NUMBER OF CELLS EVALUATED: 4000-7000 interphase cellswith visible cytoplasm were scored per treatment

Evaluation criteria:

The criteria used to score micronucleus included
(1)staining intensity equal to that of nucleus
(2) diameter less then one fifth that of the nucleus
(3) location in cytoplasm
(4) no contact with nucleus.

Statistics:

The dose response of V79 cells to chemical mutagen has been estimated by linear regression curves.

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not valid

Positive controls validity:

valid

Remarks on result:

other: strain/cell type:

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Read-across justifications and data matrices are presented in IUCLID section 13.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

This study evaluated genotoxicity potential of n-butanol using in vitro micronucleus assay. n-Butanol at concentration up to 50 µl/dish failed to induce micronuclei. Based on this result n-butanol can be concluded as non genotoxic.