Asphalt

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study planned

Study period:

Subject to approval following ECHA/MSCA review of this testing proposal

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS

[Please provide information for all of the points below. The information should be specific to the endpoint for which testing is proposed. Note that for testing proposals addressing testing on vertebrate animals under the REACH Regulation this document will be published on the ECHA website along with the third-party consultation on the testing proposal(s).]

NON-CONFIDENTIAL NAME OF SUBSTANCE:
These tests are proposed to be conducted on one member of the Bitumen category, with the results then read-across to other category members. Brief justification is given below, with additional support for the category given in the category justification document (attached to the category object and to Section 13 of the dossier) and in the document "Bitumen read-across justification April 2023 " also attached in Section 13.

Name of the substance on which testing is proposed to be carried out:
- EC 232-490-9 (Asphalt)

In addition, it is anticipated that the result will allow read-across to the to the following substances:
- EC 265-057-8 /CAS 64741-56-6 Residues (petroleum), vacuum
- EC 295-518-9 /CAS 92062-05-0 Residues (petroleum), thermal cracked vacuum

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:

- Available GLP studies:

For compliance with all other regulatory regimes, petroleum substances (PS) have been tested via the dermal and/or inhalation route as this is the route of human exposure; this is also an objective of REACH which states that tests should be done by the ‘most appropriate route of administration, having regard to the likely route of human exposure’. This has allowed successful risk management of these substances and avoids the uncertainty of route-to route extrapolation which is required if the oral route is used.

No repeat-dose oral studies on bitumen have been identified. Two studies involving repeated dermal exposure are available. Repeat dose inhalation studies are available on fumes from bitumen (90-day repeat dose toxicity in rat) and air-rectified (partially oxidized) asphalt (2-year carcinogenicity in rat). In addition, a combined repeat dose/reproductive screening study is available for oxidized asphalt.

- Available non-GLP studies

There are no studies available to fulfil this endpoint.

- Historical human/control data

No relevant human health data are available.

- (Q)SAR

There are no QSAR’s which are adequate to fully evaluate a UVCB substance (for more detailed explanation on [the complexity of] petroleum UVCBs is referred to section 2).

- In vitro methods

There are no validated in vitro methods that fulfil this endpoint.

- Weight of evidence

There is insufficient oral data at this point to build a weight of evidence argument to address the repeated dose endpoint for this EC number. The information from the proposed study will be part of the data which will support grouping and read across, this data will be used in weight of evidence arguments for remaining Bitumens in this category.

- Grouping and read-across

The ongoing Concawe state-of-the-art analytical program of Bitumen as outlined in the Read-across Justification aims to demonstrating chemical similarities to underpin read-across of data applicable to registrations of substances covering the EC numbers in this category. It is the intention that the 90-day data from the proposed study will be applied to the remaining Bitumen category members therefore reducing the need for animal tests.

- Substance-tailored exposure driven testing

The study may use the dietary route or gavage depending on the choice of the available Contract Laboratory Organisation. There are too few oral studies available to draw conclusions on the most appropriate administration regimen. Practical issues like possibility to formulate rat feed containing bitumen and the palatability need to be evaluated if a dietary route is most appropriate. If gavage is investigated the solubility of bitumen in eg corn oil and its dilution series need to be assessed. In addition, it is known that Bitumen contains mainly long hydrocarbon chains (>>C25) which could be assumed to have limited bioavailability and would most probably pass through the gastrointestinal tract with little absorption as suggested by Borrowman et al (1989)[1]. The bioaccessibility of non-soluble PAH is also dependant on the feed intake, including the amount of fibres and fats[2].

- Approaches in addition to above [if applicable]

- Other reasons [if applicable]

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:

Adaptation options as defined in Annexes VII to X were not applicable for this category and this endpoint. Regarding the column 2 rules for adaption, the data base was fully evaluated according to ‘Guidance on information requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance’.

[1] James A. Barrowman, Anisur Rahman, Mats B. Lindstrom, Bengt Borgstrom, Intestinal absorption and metabolism of hydrocarbons, Progress in Lipid Research, Volume 28, Issue 3, 1989, Pages 189-203, ISSN 0163-7827, https://doi.org/10.1016/0163-7827(89)90012-X.
[2] Kelly L Harris, Leah D Banks, Jane A Mantey, Ashley C Huderson & Aramandla Ramesh (2013) Bioaccessibility of polycyclic aromatic hydrocarbons: relevance to toxicity and carcinogenesis, Expert Opinion on Drug Metabolism & Toxicology, 9:11, 1465-1480, DOI: 10.1517/17425255.2013.823157

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Test material

Test material information

Constituent 1

Reference substance name:

Asphalt

EC Number:

232-490-9

EC Name:

Asphalt

Cas Number:

8052-42-4

Molecular formula:

Not applicable (i.e., UVCB substance)

IUPAC Name:

Asphalt

Specific details on test material used for the study:

Test material is an example of one of the substances expected to be used in the planned studies.

Test animals

Species:

rat

Strain:

Wistar

Details on species / strain selection:

The species of rat is commonly used in repeated dose testing.