Gases (petroleum), C3-5 olefinic-paraffinic alkylation feed

Genetic toxicity: in vivo

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

Test material information

Constituent 1

Reference substance name:

Propene

EC Number:

204-062-1

EC Name:

Propene

Cas Number:

115-07-1

Molecular formula:

C3H6

IUPAC Name:

prop-1-ene

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.