Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
Three read-across in-vivo and two in-vitro assays were identified for a structurally related material. There was no evidence of genotoxic activity in-vitro, in a modified Ames test and a mouse lymphoma assay. In a dominant lethal assay in male mice there was no evidence of heritable genotoxic effects. In a well conducted bone marrow chromosomal aberration assay by the oral route there was no evidence of genotoxic activity. In a further bone marrow chromosomal aberration study by the intraperitoneal route weak activity was observed. Effects were only seen at high dose levels (2.0 and 6.0 ml/kg) and the magnitude of effect was small and restricted to chromosomal fragments.
Link to relevant study records
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because, though it does not follow a prescribed guideline, it is well conducted and reported.
Justification for type of information:
See read-across justification provided in section 13.
equivalent or similar to
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Principles of method if other than guideline:
No specific GLP guideline was followed. The study is well conducted and reported.
GLP compliance:
Type of assay:
micronucleus assay
Route of administration:
oral: gavage
corn oil
Doses / Concentrations:
1.0, 2,5, 5,0 g/kg
no data
No. of animals per sex per dose:
15 male 15 female / dose level
Tissues and cell types examined:
bone marrow erythrocytes
Details of tissue and slide preparation:
bone marrow smears harvested at 24, 48, 72 hrs post exposure
no effects
Vehicle controls validity:
Negative controls validity:
not examined
Positive controls validity:
Interpretation of results (migrated information): negative
The study authors concluded that home heating oil did not exhibit a positive response when tested for micronucleus induction.
Executive summary:

In a micronucleus assay, fifteen male and female CD-1 mice were treated with 1.0, 2.5, or 5.0 g/kg of home heating oil dissolved in corn oil via oral gavage. A concurrent control group received only corn oil, while another group served as positive control and was treated with 0.04 g/kg cyclophosphamide.

Five male and female mice from each dose group were sacrificed 24, 48 or 72 hours after test material administration. Bone marrows were removed and examined for the presence of micronuclei. Mice treated with cyclophosphamide were sacrificed 24 hours after administration. The micronucleus assay was conducted using the Schmid method. Erythrocytes numbering 1,000, were counted for each animal bone marrow slide and the number of polychromatic (PCE) and normochromatic (NCE) erythrocytes were tabulated. Frequency of micronucleus induction was determined by examining the number of micronuclei per 1,000 PCEs. 

There was no increase in the frequency of micronuclei for the test material. In addition, there was no evidence of bone marrow depression. Cyclophosphamide, the positive control, exhibited appropriate results and the vehicle control result was within the normal range. Based on these results the study authors concluded home heating oil did not exhibit a positive response. 

This study received a Klimisch rating of “reliable with restrictions” because, though it does not follow a prescribed guideline, it is well conducted and reported.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

Based on read-across to data on structurally related materials, the substance is not considered to be genotoxic. There was no evidence of activity in two in-vitro assays and two out of three in-vivo studies. In one chromosomal aberration study, weak activity was seen following intraperitoneal treatment at high doses. The magnitude of effects was small and was restricted to small increases in chromosomal fragments.

Justification for selection of genetic toxicity endpoint
key in-vivo study, selected from 2 in-vitro and 3 in-vivo assays.

Justification for classification or non-classification

Some oil products containing relatively high concentrations of polycyclic aromatic compounds (PAC) are considered genotoxic carcinogens, and, consequently, are classified and labelled as carcinogenic, Cat. 1A or 1B (H350) or Cat. 2 (H351) according to the EU CLP Regulation (EC) 1272/2008. This classification as carcinogenic does not automatically imply that these substances need also to be classified as mutagenic as defined by the CLP Regulation. The EU legislation aims primarily to classify substances as mutagenic if there is evidence of producing heritable genetic damage, i.e. evidence of producing mutations that are transmitted to the progeny or evidence of producing somatic mutations in combination with evidence of the substance or relevant metabolite reaching the germ line cells in the reproductive organs. The PAC in oil products are poorly bioavailable due to their physico-chemical properties (low water solubility and high molecular weight), making it unlikely that the genotoxic constituents can reach and cause damage to germ cells (Roy, 2007; Potter, 1999). Considering their poor bioavailability, oil products which have been classified as carcinogenic do not need to be classified as mutagenic unless there is clear evidence that germ cells are affected by exposure, consistent with the CLP Regulation. For example, based on in vivo micronucleus tests on home heating oil as well as for read-across substances that were all negative for genotoxicity, vacuum distillate fuels are not classified as mutagens according to the EU CLP Regulation (EC) 1272/2008.