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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

ATBC was tested in valid in vitro test systems and in all of these tests negative results were obtained.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: S. typhimurium TA1535, TA1537, TA1538, TA98 and TA100
Metabolic activation:
without
Test concentrations with justification for top dose:
9 - 495 ug/plate
Vehicle / solvent:
DMSO
Untreated negative controls:
yes
Remarks:
only one group
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
other: Nitrofluorene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)
Statistics:
no data
Species / strain:
other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative without metabolic activation

ATBC gave no indication for mutagenic activity
Executive summary:

ATBC was tested in an Ames test similar to OECD Guideline 471 with limited test conditions. The test substance gave no indication for mutagenic activity in S. typhimurium TA1535, TA1537, TA1538, TA98 and TA100 when tested without S9 mix.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

ATBC was tested in valid in vivo test systems and negative results were obtained.

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
chromosome aberration assay
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
Vehicle(s)/solvent(s) used: polyethylene glycol
Amount of vehicle (if gavage or dermal): 10 mL/kg bw
Purity: PEG 400
Duration of treatment / exposure:
24 and 48 hours after treatment, the bone marrow cells were collected for chromosome aberration analysis
Frequency of treatment:
One single oral treatment
Post exposure period:
24 and 48 hours
Remarks:
Doses / Concentrations:
2000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
10 animals (6 male and 6 female rats, 5 of each sex were evaluated)
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (CPA)
- Justification for choice of positive control(s): CPA is known to induce a distinct increase in induction of aberration frequency
- Route of administration: Once oral by gavage
- Dose: 15 mg/kg bw
Tissues and cell types examined:
Bone marrow: at least 100 well spread metaphases per animals were scored for cytogenetic damage
Evaluation criteria:
The test item is classified as mutagenic if it induces either a dose-related increase in the number of structural chromosomal aberrations and a reproducible statistically significant positive response for at least one of the test points.
Statistics:
non-parametric Mann-Whitney test
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
A single dose was administered at 2000 mg/kg bw to 4 animals (2 males/2 females)
Solubility: Formulated in PEG 400
Clinical signs of toxicity in test animals: Signs recorded 1 - 48 h post-treatment. All animals showed reduction of spontaneous activity at all time points.
Evidence of cytotoxicity in tissue analyzed: The mitotic indices were slightly reduced at 2000 mg/kg bw in the main study indicating that the test item had a slight cytotoxic effect to the bone marrow
Rationale for exposure: 2000 mg/kg bw was the highest dose as required by regulatory Guidelines and expresses the MTD

RESULTS OF DEFINITIVE STUDY
Types of structural aberrations for significant dose levels: No enhancement of the aberrations frequencies
Appropriateness of dose levels and route: The single dose selected of 2000 mg/kg bw was appropriate, as it reflected the MTD and had a slight cytotoxic effect to the bone marrow after 24 h
Statistical evaluation: No significant differences for the test item as compared to the control group

Table: Experimental results

Experimental group

Dose
mg/kg bw

Preparation hours post administra-tion

Number of cells scored

% aberrant cells

Incl. Gaps Excl. gaps

Mean mitotic index (%)

PEG 400

0

24

1000

0.3

0.3

4.87

o-Acetytributyl citrate

2000

24

1000

0.6

0.6

3.52

Cyclophosphamide

15

24

1000

12.1***

11.8***

3.09

o-Acetytributyl citrate

2000

48

1000

0.3

0.3

5.30

 

*** = p<0.0001

 

Conclusions:
Interpretation of results (migrated information): negative
O-Acetyltributyl citrate did not induce chromosomal aberration in the rat in vivo
Executive summary:

A chromosomal aberration study according to OECD 475 was performed in rats in vivo after a single dose of 2000 mg/kg bw. Five animals per sex and group, i.e. one vehicle control group, two test item groups and one positive control group were employed for the study. The test item was formulated in PEG 400. 24 and 48 h post-treatment, bone marrow cells were collected and 100 well-spread metaphases/animal were scored for chromosomal aberrations. Test item-treated animals showed reduction of spontaneous activity.

The mitotic index was slightly reduced after 24 h, but the test substance did not induce chromosomal aberrations at any time point investigated.

In contrast, the positive control substance induced a highly significant effect documenting the sensitivity of the test system.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro and vivo:

In vitro studies:

Ames test similar to OECD Guideline 471 (S. typhimurium TA1535, TA1537, TA1538, TA98 and TA100): negative (San & Wagner, 1991)

Ames test similar to OECD Guideline 471 (S. typhimurium TA1535, TA1537, TA1538, TA98 and TA100): negative (Heath & Reilly, 1982)

Mammalian cell forward mutation assay with L5178Y TK+/- mouse lymphoma cells comparable to OECD Guideline 476: negative (Bigger & Harbell, 1991)

Ames test according to OECD Guideline 471 and 472 (S. typhimurium TA1535, TA1537, TA98 and TA100 and E.coli Wp2uvrA): negative (Nite 2001)

Chromosome aberration test according to OECD Guideline 473 (CHL/IU cells): negative (Nite 2001)

In vivo studies:

Chromosomal aberration study according to OECD Guideline 475 in rats: negative (Honarvar, 2002)


Justification for selection of genetic toxicity endpoint
GLP and guideline study conducted with mammalian cells.

Justification for classification or non-classification

ATBC was tested in valid in vitro and in vivo test systems and in all of these tests negative results were obtained. Therefore, there is no need for classification.