Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Guideline:
other: Micronucleus analysis in NTP toxicity studies
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
Alpha-pinene
IUPAC Name:
Alpha-pinene
Constituent 2
Reference substance name:
Pin-2(3)-ene
EC Number:
201-291-9
EC Name:
Pin-2(3)-ene
Cas Number:
80-56-8
IUPAC Name:
2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
Details on test material:
Chemical name: alpha-pinene
CASRN: 80-56-8

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: aerosol
Vehicle:
Air
Details on exposure:
Start date: 2012/07/25 male
Start date: 2012/07/25 female
Sample collection time: 24hr
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
INHAL x 5
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 25, 50, 100, 200, 400 ppm
Basis:
other: inhalation
No. of animals per sex per dose:
5
Control animals:
yes

Examinations

Tissues and cell types examined:
Peripheral Blood
Statistics:
Official NTP Protocol

Data presented are the mean number of micronucleated cells per 1,000 cells for each treatment group. A positive trend test is one in which the P value is equal to or less than 0.025. For the slide-based micronucleus data, the micronucleus frequency in any dose group is considered significantly elevated over the control group if the P value is equal to or less than 0.025 divided by the number of chemical-treatment groups. Thus, if the number of treated groups is 3, then the required pairwise P value is 0.008. This adjustment in the pairwise P value is a correction for multiple comparisons of the same data.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Start Date Sample Collection Time Sex Cell Methodology Used Dosing Regimen Route Trend Test P-Value
07/25/2005 24 Hours Male NCE Slide Scoring INHAL x 5, 13 Weeks Inhalation 0.742
  Dose (ppm) Number of Animals Scored Mean MN-NCE/1000 NCE ± SEM Pairwise P
Vehicle Control Air  0          5 1.60 ± 0.33  
Test Chemical alpha-Pinene 25          5 1.80 ± 0.30 0.3657
50          5 1.90 ± 0.53 0.3059
100          5 2.10 ± 0.43 0.2053
200          5 1.90 ± 0.29 0.3059
400          5 1.40 ± 0.40 0.6426
A82162 - 2
Start Date Sample Collection Time Sex Cell Methodology Used Dosing Regimen Route Trend Test P-Value
07/26/2005 24 Hours Female NCE Slide Scoring INHAL x 5, 13 Weeks Inhalation 0.899
  Dose (ppm) Number of Animals Scored Mean MN-NCE/1000 NCE ± SEM Pairwise P
Vehicle Control Air  0          5 1.40 ± 0.19  
Test Chemical alpha-Pinene 25          5 2.10 ± 0.43 0.1182
50          5 1.80 ± 0.25 0.2396
100          5 1.70 ± 0.44 0.2949
200          5 1.70 ± 0.30 0.2949
400          5 1.10 ± 0.19 0.7259

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The Micronucleus peripheral blood study conducted on Alpha-pinene showed no genotoxicity under the conditions of this study.
Executive summary:

A Peripheral blood micronucleus test study test was conducted as part of a NTP 13 week inhalation study on B6C3F1 female and male mice.

At the end of the treatment period, blood sample 13-week exposure period a blood sample was obtained from male and female mice. Sample collection time was typically between 0 (in the case of continuous exposures) and 24 hours (in the case of single daily exposures). 1,000 to 10,000 mature erythrocytes (normochromatic erythrocytes or NCEs) were scored per animal for presence of micronuclei. The percent PCE (immature erythrocytes) was determined in the blood as a measure of chemical-induced toxicity to the bone marrow. All data are analyzed separately for male and female mice. The results of the study showed no genetic toxicity under the test conditions.