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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: gene mutation
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP, animal experimental study, adequate for assessment

Data source

Reference
Reference Type:
publication
Title:
Hprt mutant frequencies in splenic T-cells of male F344 rats exposed by inhalation to propylene
Author:
Walker DM, Seilkop SK, Scott BR and Walker VE
Year:
2004
Bibliographic source:
Environ. Mol. Mutagen. 2004 Vol 43 (4) 265-272

Materials and methods

Principles of method if other than guideline:
Hprt mutant frequencies in T-lymphocytes isolated and cultured from spleens of male F344 rats exposed to propene at 200, 2000, or 10,000 ppm for 20 days.
GLP compliance:
no
Remarks:
Animal exposures to GLP conditions
Type of assay:
other: Hprt mutant frequencies in splenic T-lymphocytes

Test material

Constituent 1
Chemical structure
Reference substance name:
Propene
EC Number:
204-062-1
EC Name:
Propene
Cas Number:
115-07-1
Molecular formula:
C3H6
IUPAC Name:
propene
Constituent 2
Reference substance name:
propylene
IUPAC Name:
propylene
Details on test material:
- Name of test material (as cited in study report): propene
- Physical state: gas
- Analytical purity: 99.5%

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories (Raleigh, NC, USA)
- Age at study initiation: 6 weeks
- Assigned to test groups randomly: yes
- Housing: In groups of 4 in standard polycarbonate rat cages suspended on racks.
- Diet: Certified rodent chow (#2025C, purchased from Harlan Tetdad) ad libitum
- Water: Filtered tap water ad libitum
- Acclimation period: quarantined for 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 72 ± 4° F
- Humidity: 50% ± 10%
- Air changes (per hr): not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: not reported

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
Vehicle used: air
Details on exposure:
TYPE OF INHALATION EXPOSURE: whole body
Duration of treatment / exposure:
20 days
Frequency of treatment:
6 hours/day, 5 days/week for 4 weeks
Post exposure period:
8 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 200, 2000, 10000 ppm
Basis:
nominal conc.
No. of animals per sex per dose:
8
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide monohydrate (CPP)
- Route of administration: i.p. injection
- Dose: 20mg/kg bw

Examinations

Tissues and cell types examined:
Splenic T-lymphocytes
Evaluation criteria:
The frequency of Hprt mutant T-cells among the total population of lymphocytes isolated from the spleen of individual rats, the percentage of cells that grew under nonselection culture conditions, or the cloning efficiency (CE) of the cells were determined.
Statistics:
Statistical significance of the differences in Hprt Mf values between controls and each treatment group was determined using the Mann-Whitney Rank Sum Test. A P-value <0.05 was considered significant.

Results and discussion

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

Any other information on results incl. tables

Hprt mutant frequencies in T-lymphocytes isolated and cultured from spleens of male F344 rats exposed to propene at 200, 2000, or 10,000 ppm for 20 days, as well as negative (air only) and positive (cyclophosphamide) controls were measured.

Mean Hprt mutant frequencies were significantly increased over control values (mean Mf = 5.24±1.55 x 10-6) in CPP-treated rats (10.37 ± 4.30 x 10-6, p = 0.007). However, Hprt mutant frequencies in propene-exposed rats were not significantly increased over background, with mean Mfs of 4.90 ± 1.84 x 10-6(p = 0.152), 5.05 ± 3.70 x 10-6(p = 0.895), and 5.95 ± 2.49 x 10-6(P = 0.500) for animals exposed to 200, 2000, or 10000 ppm propene, respectively. These findings support the conclusion that inhalation exposure of rats to propene does not cause mutations or cancer.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Propene did not produce an increase in Hprt mutant frequencies in splenic T-lymphocytes; the NOAEL was 10000 ppm, which about half the lower explosion limit of this substance.