Gases (petroleum), catalytic-cracked gas oil depropanizer bottoms, C4-rich acid-free

Genetic toxicity: in vivo

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 based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: For this endpoint, GLP compliant guideline animal experimental study, published in peer reviewed literature, fully adequate for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Remarks:

Exposures and micronucleus test to GLP

Type of assay:

micronucleus assay

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:

purity of 99.75%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

inhalation: gas

Duration of treatment / exposure:

Up to 20 days

Frequency of treatment:

6 hours/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 200, 2000 and 10,000 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

8

Control animals:

yes

Positive control(s):

- A 2 mg/mL solution of CP (in Milli-Q water) was prepared immediately prior to dosing. CP was administered to eight male rats (MN-positive control) by a single oral intubation using a dose volume of 10 mL/kg, yielding a dosage of 20 mg/kg.
- On inhalation exposure day 19, a separate group of eight untreated, male rats (Hprt-positive control) received a single oral intubation of the positive control agent CP (20 mg/kg in water).

Examinations

Statistics:

Statistics were calculated on exposure concentration and environmental conditions data and CE determinations. The individual rat was generally the experimental unit of analysis. Body weight and cell proliferation (expressed as ULLI) data were tested for lack of trend, and if not significant, then sequential application of the Jonckheere-Terpstra trend test or one-way ANOVA followed with Dunnett's test was performed. Results were statistically analysed for significance using the Pearson product-moment correlation for CE data and the Mann-Whitney rank sum test for Hprt mutation frequency data.

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

 No propene-related statistically significant changes in mean bodyweights or mean bodyweight gain was observed in any exposure group. No statistically significant differences in food consumption or food efficiency were observed in any exposure group. No mortality or clinical signs of toxicity were observed in any dose group during the study.

No effects on micronuclei frequencies were observed in the bone marrow at any exposure level. No toxic effects in rat bone marrow cells (decreased polychromatic/normochromatic ratio) were observed at any exposure level. The positive control, cyclophosphamide, induced a significant increase in the frequency of micronucleated PCEs (p 0.05 by Dunn's test). However, no toxic effects in the bone marrow cells were observed.

Micronucleus evaluation of rats (F344, male) following 20-day exposure to propene by inhalation

(Table based on Pottenger et al, Toxicological Sciences 97(2), 336-347 (2007), Table 5)

	Propene concentration in air 0 ppm	Propene concentration in air 200ppm	Propene concentration in air 2000ppm	Propene concentration in air 10000ppm	Positive control: 20 mg/kg CP
Micronucleated poly-chromatic erythrocytes /2000 PCEs	1.8±1.3	2.5±1.9	2.3±1.6	1.1±1.1	15.0±6.0*
PCE/NCE ratio	0.577±0.155	0.573±0.267	0.749±0.290	0.692±0.211	0.715±0.437
PCE/NCE ratio = mean of the PCE/NCE for the individual animals per 1000 erythrocytes scored *Stat sig p<0.05 by Dunn’s test

Applicant's summary and conclusion

Conclusions:

Propene did not induce a statistically significant increase in micronucleated polychromatic erythrocytes in rat bone marrow when evaluated after a total of 20 exposures. The highest exposure level was 10,000 ppm. Therefore, the test substance was negative in this in vivo assay.