Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 11 JAN 1995 to 24 MAR 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to guidelines with a full study report available

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
Deviations:
no
Principles of method if other than guideline:
Reports also mentions the study follows TSCA and FIFRA guidelines and the Japanese Ministry of International Trade and Industry Guidelines
GLP compliance:
yes (incl. certificate)
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Physical state: Clear colourless liquid
- Analytical purity: No data
- Lot/batch No.: C1527-04-5
- Storage condition of test material: Room temperature

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Manston, Kent
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 20 to 27g males and 20 to 24g females.
- Assigned to test groups randomly: Yes
- Fasting period before study: No
- Housing: In groups of up to 5 by sex in steel mesh bottom polypropylene cages suspended above absorbent paper.
- Diet (e.g. ad libitum): Rat and Mouse Expanded Diet No. 1 Special Diets Services Limited, Witham, Essex, UK. Ad libitum.
- Water (e.g. ad libitum):Mains drinking water. Ad libitum.
- Acclimation period: Minimum 7 days before randomisation.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 51-57
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: Arachis oil
- Justification for choice of solvent/vehicle: None given
- Concentration of test material in vehicle: For the purpose of this study the test material was freshly prepared as required as a solution at the appropriate concentration in arachis oil. No concentration provided.
- Lot/batch no. (if required): 014316, Lab serial number Co/877
Details on exposure:
Intraperitoneal injection. Volume administered to each animal was calculated according to its bodyweight at 10ml/kg.
Duration of treatment / exposure:
Single dose
Frequency of treatment:
Once
Post exposure period:
Dose range finding study: Animals observed 1 hour after dosing and subsequently once daily for 3 days.
Micronucleus study: See attached table with experimental design. All animals were observed for signs of overt toxicity and death one hour after dosing and then once daily as applicable.
Doses / concentrations
Remarks:
Doses / Concentrations:

Basis:
nominal conc.
No. of animals per sex per dose:
Dose range finding study: At 1250mg/kg and 2500mg/kg, N(m/f)=1/1; At 5000mg/kg, N(m/f)=3/3
Micronucleus study: Each dose three groups of N(m/f)=5/5
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): material known to produce micronuclei under the conditions of the test
- Route of administration: oral
- Doses / concentrations: 50mg/kg

Examinations

Tissues and cell types examined:
Bone marrow erythrocytes
Details of tissue and slide preparation:
Immediately following sacrifice one femur was dissected from each animal, aspirated with foetal calf serum and bone marrow smears prepared, air-dried, and fixed in absolute methanol and stained in May-Grunwald/Giemsa.
Evaluation criteria:
Comparison made between number of micronucleated polychromatic erythrocytes occurring in each of the three test material groups and the number occurring in the corresponding vehicle control groups.
Positive mutagenic response is demonstrated when a statistically significant and dose-related increase is observed for either 24, 48 or 72-hour when compared to their corresponding control group.
A positive response for bone marrow toxicity is demonstrated when the dose group mean polychromatic to normochromatic ration is shown to be statistically significantly lower than the concurrent vehicle group.
Statistics:
Methods as recommended by the UKEMS Sub-committee on Guidelines for Mutagenicity Testing Report, Part III (1989).
Data analysed by two-tailed Student's t-test and any significant results confirmed using the one way analysis of variance.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: No premature deaths or clinical observations seen in animals dose up to the maximum recommended dose level of 5000mg/kg.


RESULTS OF DEFINITIVE STUDY
There were no premature deaths recorded and no clinical observations seen.
- Induction of micronuclei (for Micronucleus assay): No significant increases compared to concurrent vehicle control group
- Ratio of PCE/NCE (for Micronucleus assay): No statistically significant change.
- Appropriateness of dose levels and route: Positive control group showed a marked increase in the incidence of micronucleated PCE.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The tested substance was considered to be non-genotoxic under the conditions of the test
Executive summary:

The potential of a C30 -72 hydrogenated polyalphaolefin to produce damage to chromosomes or aneuploidy when administered intraperitoneally to mice was studied. There was no evidence of bone marrow toxicity, or of a statistically significant increase in the incidence of micronucleated polychromatic erythrocytes in animals dosed with test material at the maximum recommended level of 5000mg/kg when compared to the concurrent vehicle control group. This result can be read across to the C28 -C80 hydrogenated polyalphaolefin "Pentadecane, 7-methylene mixed with 1-tetradecene, dimers and trimers, hydrogenated."