Titanium tetrakis(2-ethylhexanolate)

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: see 'Remark'

Remarks:

Guideline study. 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:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Deviations:

no

Principles of method if other than guideline:

Reverse mutation; increase of histidine independent mutants

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexan-1-ol

EC Number:

203-234-3

EC Name:

2-ethylhexan-1-ol

Cas Number:

104-76-7

Molecular formula:

C8H18O

IUPAC Name:

2-ethylhexan-1-ol

Details on test material:

- Source: Wako Pure Chemcials Industries, Osaka,, Japan
- Purity 2-EH: 98%

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 2

Species / strain / cell type:

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

Additional strain / cell type characteristics:

other:

Metabolic activation:

with and without

Test concentrations with justification for top dose:

0, 1, 5, 10, 50, 100, 500, 1000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; preincubation;
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours
- Selection time (if incubation with a selection agent): 48 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 48 hours
SELECTION AGENT (mutation assays): histidine deficiency
SPINDLE INHIBITOR (cytogenetic assays): n.a.
STAIN (for cytogenetic assays): n.a.
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: n.a.
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: no data
OTHER EXAMINATIONS:
- Determination of polyploidy: no
- Determination of endoreplication: no

Evaluation criteria:

no data

Statistics:

no data

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:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 6

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS

ADDITIONAL INFORMATION ON CYTOTOXICITY: growth inhibition was noted in all test strains except TA1537 at 500 and 1000 µg/plate

Remarks on result:

other: other: Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538; E. coli (WP2 uvrA)

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Except for TA 1537 toxicity was observed at doses of 500 and 1000 µg/plate in all tester strains.

Mean number of revertants:

Dose (µg/plate)	TA100		TA1535		E. coli WP uvrA		TA98
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
0 water	149	161	28	15	32	33	29	39
0 DMSO	150	154	30	15	30	34	32	42
1	144	170	39	23	32	31	24	44
5	166	171	23	19	30	26	33	61
10	161	149	26	18	27	31	29	48
50	155	147	33	13	26	33	28	57
100	133	151	19	14	28	33	37	51
500	0*	0*	0*	0*	0*	0*	0*	0*
1000	0*	0*	0*	0*	0*	0*	0*	0*
Positive control	501	1084	1101	440	1082	359	278	809

 

Dose (µg/plate)	TA1537		TA1538
	-S9	+S9	-S9	+S9
0 water	16	21	21	28
0 DMSO	18	22	22	28
1	13	36	25	24
5	11	28	33	30
10	15	23	29	25
50	16	30	25	30
100	12	26	18	30
500	12	39	0*	0*
1000	16	28	0*	0*
Positive control	889	313	270	354

0* = growth inhibition

Applicant's summary and conclusion

Conclusions:

2-EH was not mutagenic in Salmonella typhimurium and E. coli with and without metabolic activation.

Executive summary:

The mutagenicity of 2 -EH was tested in bacterial test sytems (S. tyhimurium TA98, TA100, TA1535, TA1537, TA1538, and E. coli WP2 uvrA) according to OECD TG 471 and TG 472 both with and without metabolic activation in a dose range from 1 to 1000 µg/plate (Shimizu et al., 1985). 2 -EH did not increase the number of revertants in any of the test strains. Growth inhibition was seen at 500 and 1000 µg/plate. The negative and positive controls performed as expected. Therefore, 2 -EH was not mutagenic in baterial test systems in-vitro.