Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

This information was not available. Testing proposal for extendended one-generation study has been submitted.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available (further information necessary)
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

No reproductive study on bitumen has been performed. However, based on the results from repeated-dose toxicity studies, dermal exposure to bitumen at doses up to 2000 mg/kg did not show any treatment related effects on reproductive organ weights and histopathology.

Table 1. Summaries of data on reproductive organs from subchronic studies with bitumen

         (Robust study summaries are provided in Section 7.5 Repeated Dose Toxicity)

Test Material

Route, Species, Doses, Exposure Regimen

Endpoints

Results

Reference

Vacuum residuum

(API 81-13)

Dermal. Rabbit.

0, 200, 1000, 2000 mg/kg, applied on a gauze pad and wrapped for 6 hr, 3 d/wk for 4 wk

Weights of testes and ovaries.

Histopathology of seminal vesicles, testes, epididymides, prostate, ovaries, uterus, and vagina

No treatment-related effect on reproductive organs noted.

API, 1983a

Vacuum residuum

(API 81-14)

Dermal. Rabbit.

0, 200, 1000, 2000 mg/kg, applied on a gauze pad and wrapped for 6 hr, 3 d/wk for 4 wk

Weights of testes and ovaries.

Histopathology of seminal vesicles, testes, epididymides, prostate, ovaries, uterus, and vagina

No treatment-related effect on reproductive organs noted.

API, 1983b

The need for an extended one-generation reproductive toxicity study with bitumen is considered questionable based on the following observations.

1) No effects were seen in weights of testes or ovaries or in the histopathology of seminal vesicles, testes, epididymides, prostate, ovaries, uterus, or vagina in two 4-week dermal studies in rabbits with bitumen at doses up to 2000 mg/kg.

2) Additional supporting evidence comes from separate dermal screening-level fertility studies of syntower bottoms in males and females. The NOAEL was ≥ 250 mg/kg/day. Although not in the bitumen category, this test substance contains significantly higher levels of PACs than bitumen and is one of the more toxic petroleum streams.

 

Nonetheless, there is a clear data gap with respect to the REACH Annex X testing requirements for an extended one-generation reproductive toxicity study. Therefore an OECD guideline 443 study is proposed.

 

Short description of key information:

No reproductive study on bitumen has been performed. However, some indication of the likely effect of a test substance on reproductive organs can be gained from the results of repeated-dose toxicity studies where the weights and histopathology of reproductive organs were not affected following dermal exposure to bitumen at doses up to 2000 mg/kg.

Effects on developmental toxicity

Description of key information

Note on choice of exposure route:

A developmental inhalation study on bitumen has been performed. Bitumen is a (semi) solid material, therefore it is considered that any potential exposure is solely to the fumes that may arise during occupational handling of the material at elevated temperatures. This study was therefore performed via the inhalation route as this is considered the only relevant route of human exposure, which means that sufficient Bitumen and OA fumes, collected as condensates, were generated before the studies can be conducted.

An additional complexity with applying this approach is that the composition of the condensate is influenced by the occupational conditions, mainly the temperature at which the Bitumen is heated when applied. Thus, Concawe has validated the composition of the condensate collected at the manufacturing site against actual workplace fume samples through a workplace monitoring campaign to ensure that the tested material is representative of real-life exposures.

Full reports of fume collection and validation, as well as workplace monitoring campaigns and fume condensate comparisons, are available from Concawe upon request.

Brief summary of results:

The maternal NOAEL was determined to be the low dose group, 50 mg/m³.  Observations at 500 mg/m³ included effects on body weight, food consumption, lung weight and histopathological changes in the lung and larynx.  At 150 mg/m³ observations were restricted to histopathological changes in the larynx.

The developmental NOAEL was the medium dose group, 150 mg/m³, due to reduced fetal weight at 500 mg/m³.

Importantly, nose-only exposure to bitumen fumes in concentrations up to 500 mg/m³ from p.c days 1 to 19, did not induce any fetal anomalies.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
150 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
A single study study was conducted on a worst case test sample representing the category members. This category approach is further supported with additional historical data on the substances (available in this IUCLID dossier and the Category Justification Document), as well as ongoing mechanistic work to further support the worst case approach (see mechanism of action field below)
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Concawe initiated a multi-year research project in 2015 to generate further proof for the mechanistic basis underpinning the hypothesis that developmental toxicity is related to (3-7 ring) PAHs, supporting selection of the test sample with highest PAH content as a worst case representative and further supporting read across between the substances in the Concawe Bitumen category. Initial results are presented in the publication: Prenatal developmental toxicity testing of petroleum substances: Application of the mouse embryonic stem cell test (EST) to compare in vitro potencies with potencies observed in vivo; Lenny Kamelia, Jochem Louisse, Laura de Haan, Ivonne M.C.M. Rietjens, Peter J. Boogaard; To appear in: Toxicology in Vitro; Accepted date: 19 July 2017.

Justification for classification or non-classification

Currently available data do not raise concern with regard to classification of bitumen as toxic for reproduction or development under CLP Regulation, (EC)1272/2008.