Bis(ethyl acetoacetato-O1',O3)bis(2-methylpropan-1-olato)titanium

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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: Study is performed according to Ames test with some deviation but with out GLP compliances.

Justification for type of information:

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 alcohols, ethyl acetoacetate and hydrated titanium dioxide. The half-life of hydrolysis is < 10 minutes @ 25 ˚C. This rapid hydrolysis 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 most hazardous degradation products released from the target substance. In addition, because of rapid hydrolysis the dermal effects of the target substance are similar to the irritating properties of the degradation products. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the mixture of particular alcohol and ethyl acetoacetate which might change the hazardous properties of the target substance compared to the properties of the pure alcohol and ethyl acetoacetate. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across from the most hazardous degradation products (alcohols) to evaluate irritation, sensitization and the short-term and long-term toxicological effects of the target substance.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Ministry of labor guidelines

Principles of method if other than guideline:

Test is performed by using 6 bacterial strains and based on the principle of Ames assay.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpropan-1-ol

EC Number:

201-148-0

EC Name:

2-methylpropan-1-ol

Cas Number:

78-83-1

Molecular formula:

C4H10O

IUPAC Name:

2-methylpropan-1-ol

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Iso butyl alcohol
- Physical state: liquid
- Analytical purity: 99%

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

S9 mix prepared from liver of male SD rat

Test concentrations with justification for top dose:

5,10,50,100,500,1000,5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Water
- Justification for choice of solvent/vehicle: No data

Controls

Untreated negative controls:

yes

Remarks:

DMSO and Aceton

Negative solvent / vehicle controls:

yes

Remarks:

Water

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: AF-2

Remarks:

See picture attached below

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation;

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 hours


NUMBER OF REPLICATIONS: 2

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

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

According to this study after examination through Ames assay, Isobutyl alcohol is found to be non-mutagenic in all salmonella typhimuriumspecies ( TA98,TA100,TA1535,TA1537,TA1538) and escherichia coli (WP2uvrA) in both with and with out microsomal activation media.