Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
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
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted in accordance with general scientific principles.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Lack of mutagenic activity of white spirit
Author:
Gochet B., de Meester C., Leonard A., Deknudt G.
Year:
1984
Bibliographic source:
International Archives of Occupational and Environmental Health 53: 359-364

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
white spirit
boiling temperature: 120-190 deg C

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
male/female
Details on test animals and environmental conditions:
The animals weighed 30 ± 3 g

Administration / exposure

Route of administration:
other: i.p. and inhalation
Vehicle:
none
Details on exposure:
The animals were sacrified 30 h after i.p. injection of 0.l, 0.05 or 0.01 ml of white spirit. In addition, male animals were allowed to inhale 50 g/m3 of white spirit, during 5 periods of 5 min spaced by intervals of 5min. According to Carpenter et al. (1975) 50 g/m3 represents about 50 times the limit of toxicity. Animals given 200 mg cyclophosphamide per kg b.w. were used as positive controls.

Carpenter C. P., Kinkead E. R., Geary, Jr. D. L., Sullivan L. J., and King J. M. Petroleum Hydrocarbon Toxicity Studies. Ill. Animal and Human Response to Vapors of Stoddard Solvent. 1975. Toxicology and Applied Pharmacology. 32: 282-297.20 ani
Duration of treatment / exposure:
Experiment #1 - 30 h after i.p. injection of 0.l, 0.05 or 0.01 ml of white spirit
Experiment #2 - male animals were allowed to inhale 50 g/m3 of white spirit, during 5 periods of 5 min spaced by intervals of 5min
Frequency of treatment:
Experiment #1 - once, animals were sacrificed 30 h after i.p. injection
Experiment #2 - 5 periods of 5 min spaced by intervals of 5min
Post exposure period:
none
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.l, 0.05, or 0.01 ml
Basis:
other: i.p. injection
Remarks:
Doses / Concentrations:
0, 50 g/m3
Basis:
nominal conc.
inhalation
No. of animals per sex per dose:
20 animals
Control animals:
yes, sham-exposed
Positive control(s):
Animals given 200 mg cyclophosphamide per kg b.w. were used as positive controls.

Examinations

Tissues and cell types examined:
micronucleus test; 3000 cells examined per dose
Details of tissue and slide preparation:
no data
Evaluation criteria:
micronuclei
Statistics:
Mann Whitney U-test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
see table

Any other information on results incl. tables

Treatment

Cells with micronuclei (%)
  Male Female

Negative controls

3.8 4.3

Cyclophosphamide (200 mg/kg)

36

31

White Spirit (0.01mL i.p.)

4.4 3.7

White Spirit (0.05mL i.p.)

4.2 4.1

White Spirit (0.1mL i.p.)

4 4

White Spirit (50g/m3 by inhalation)

4.1 N/A

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
White spirit did not produce chromosomal aberrations in vivo.
Executive summary:

The ability of white spirit to produce chromosomal aberrations in vivo in mammalian somatic cells was studied by examining eight-week-old BALB/c male and female mice for the presence of micronuclei in the polychromatic erythrocytes from bone marrow.

The animals were sacrified 30 h after i.p. injection of 0.l, 0.05 or 0.01 ml of white spirit. In addition, male animals were allowed to inhale 50 g/m3 of white spirit, during 5 periods of 5 min spaced by intervals of 5min. According to Carpenter et al. (1975) 50 g/m3 represents about 50 times the limit of toxicity. Animals given 200 mg cyclophosphamide per kg b.w. were used as positive controls. When compared to control animals, it was concluded that white spirits are not mutagenic or clastogenic.

 

Carpenter C. P., Kinkead E. R., Geary, Jr. D. L., Sullivan L. J., and King J. M. Petroleum Hydrocarbon Toxicity Studies.Animal and Human Response to Vapors of Stoddard Solvent. 1975. Toxicology and Applied Pharmacology. 32: 282-297.