Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-09-19 - 1995-09-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Study owner prepared study while seeking authorisation of the substance as active incredient for medical treatment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
other: in vivo micronucleus test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Type:
impurity
Test material form:
solid: bulk
Details on test material:
This composition is the usual techical grade of AlzChem AG. It will be used when test substance has this composition (or is very closed) or no specific information is available

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
Caging: Macrolon cages, type II

Animals per cage: 1

Bedding: Animal bedding softwood garnulation HW 300/500W

Diet: Standard diet ad libitum

Water: ad libitum

Room temperature: 21.0 - 22.0 °C
Relative humidity: 48 - 52 %
Room lighting: 6:00 - 18:00 (cet) artificial lighting
18:00 - 6:00 (cet) darknes

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Frequency of treatment:
single administration
Post exposure period:
24 h and 48 h
Doses / concentrations
Dose / conc.:
825 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Negative control: 12 m + 12 f
Positive control: 6 m + 6 f
Test material group: 19 m + 17 f
Control animals:
yes
Positive control(s):
Cyclophosphamid

Examinations

Tissues and cell types examined:
Bone marrow cells from both femurs.
Polychromatic erythrocytes
Details of tissue and slide preparation:
Bone marrow was suspended in approx. 1.5 ml FCS and centrifuged at 180 g for 5 min.
Supernatand was discarded and cells were suspended in FCS.
Small drop of this suspension was smeared on a slide and dried overnight.
Statistics:
POISSON test

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
ten test material group animals died
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
yes

Applicant's summary and conclusion

Conclusions:
Thioctic acid, racemate, at 825 mg/kg body weight (males and females, single oral administration) is non-genotoxic in the mouse micronucleus test under the described conditions.
Executive summary:

Ten (10) test mateial group animals died.

After a singele oral admission of the test material à 825 mg/kg b. w. no statistically significant test material-related increase im micronucleated PCEs was observed in both, male and female animals, respectively males and females combined, when compared with corresponding negative control group animals at 24 h or 48 h after administration. No reduction in PCE/NCE ratio was present in test material group animals, when compared to the corresponding control group animals.

The positive control group animals, wich recieved cyclophosphamide, exhibited a significant increase in the number of micronucleated polychromatic erythrocytes and thus validated the test system.