Petrolatum

Genetic toxicity: in vivo

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:

1987-03-03 to 1987-10-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restriction because it was conducted according to or similar to guideline study OECD TG 475.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

64742-04-7

Cas Number:

64742-04-7

IUPAC Name:

64742-04-7

Constituent 2

Reference substance name:

318 Isthmus Furfural

IUPAC Name:

318 Isthmus Furfural

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): Furfural extract (Distillate Aromatic Extract)

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data reported.

Administration / exposure

Route of administration:

dermal

Vehicle:

- Vehicle(s)/solvent(s) used: None

Details on exposure:

TEST SITE
- Area of exposure: Back

Duration of treatment / exposure:

Not reported

Frequency of treatment:

5 days a week over 90 days

Post exposure period:

Not reported

Doses / concentrations

Remarks:

Doses / Concentrations:
30, 125, 500, and 1250 mg/kg/day
Basis:
other: prepared according to animal body weight

No. of animals per sex per dose:

10 males and 10 females per dose were dermally exposed however several animals were sacrificed before the schedule completion date. See Table 1 below.

Control animals:

yes, concurrent no treatment

Positive control(s):

No data

Examinations

Tissues and cell types examined:

Bone marrow was collected. Mature (normochromatic erythrocytes) and immature (polychromatic erythrocytes) red blood cells were examined.

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: Not reported

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Bone marrow was harvested at the scheduled completion data, femurs were taken from five animals per sex from the remaining dose group. See Table 1 below.

DETAILS OF SLIDE PREPARATION: Three slides were prepared for each animal. Details of slide preparation was not provided.

METHOD OF ANALYSIS:
Using fluorescence microscopy normochromatic erythrocytes and polychromatic erythrocytes were counted.

Evaluation criteria:

A ratio of the number of polychromatic erythrocytes (PCE) and normochromatic erythrocyte (NCE) was calculated. If the ratio did not differ from controls, it was determined that cytotoxicity was not a factor in the evaluation of the cytogenetic effects.

Statistics:

Data was collected and analysed by SAS ANOVA and SAS GLM. The SAS Analysis of Variance method was used to compare mean square values relative to their expected values under a null hypothesis. The ANOVA F test determined if the test means were significantly different from one another. If the null hypothesis is rejected, the sample means have to be compared. The statistical analysis compared test values to negative control data; a significant increase in micronuclei is an indication of clastogenic activity by the test agent.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Based on statistical analysis (General Linear Model) there was no difference between the observed responses and the negative controls. The ANOVA F test found no significant difference in the number of micronucleated PCEs of the 318 Isthmus Furfural Extract-treated animals in comparison to each other or to the negative controls. 318 Isthmus Furfural Extract was not cytotoxic to red blood cell formation nor did it induce significant increase in the formation of micronucleated PCEs or NCEs in bone marrow of treated rats. 318 Isthmus Furfural Extract does not cause chromosome damage to rats dermally exposed.

Executive summary:

Read across justification

This compound is an untreated distillate aromatic extract and provides a worst case scenario for petrolatum (carcinogenic or unknown feed-stock) due to the concentration effect of the solvent extraction process.

In a mammalian cell micronucleus assay rats were dermally exposed to 30, 125, or 500 mg/kg/day of 318 Isthmus Furfural Extract for 90 days. The micronucleus test was performed to determined if 318 Isthmus Furfural Extract caused a significant increased in micronucleated red blood cells harvested from bone marrow when rats are dermally exposed.

Based on statistical analysis (general linear model) there was no difference between the observed responses and the negative controls. The ANOVA F test found no significant difference in the number of micronucleated PCEs of the 318 Isthmus Furfural Extract-treated animals in comparison to each other or to the negative controls. 318 Isthmus Furfural Extract was not cytotoxic to red blood cell formation nor did it induce significant increase in the formation of micronucleated PCEs or NCEs in bone marrow of treated rats. 318 Isthmus Furfural Extract does not cause chromosome damage to rats dermally exposed.

This study received a Klimisch score of one and is classified as reliable without restriction because it was conducted according to or similar to guideline study OECD TG 475.