Registration Dossier

Administrative data

Description of key information

Key acute oral (OECD 401), dermal (OECD 402), and inhalation (OECD 403) studies were identified.

• The oral LD50 was > 5000 mg/kg bw in male and female rats for two petroleum vacuum residues.

• The dermal LD50 was > 2000 mg/kg bw in male and female rabbits for two petroleum vacuum residues.

• The LC50 was > 94.4 mg/m3 in male and female rats for fumes from oxidized (air-rectified) asphalt.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
Three studies gave similar results

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
94.4 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Two studies available showing similar results

Additional information

At ambient temperature bitumens are solid or semi-solid. For most applications, materials are handled at elevated temperatures which makes thermal burns the greatest acute hazard. Guideline oral and dermal toxicity studies have been conducted on samples of vacuum residue (straight-run bitumen) to assess the acute hazard. No acute inhalation toxicity data are available for straight-run bitumen but a study has been performed on a sample of oxidized (air-rectified) asphalt, which is used for read across. For all of these endpoints bitumen is not acutely toxic. Read across of oxidized asphalt to straight run bitumen is considered valid since mild oxidation is not expected to change the composition or acute toxicity of the material. Additionally repeated dose toxicity studies on bitumen and oxidized asphalt support that bitumens are not acutely hazardous. Therefore bitumens are not classified as acutely toxic under CLP (EC 1272/2008) criteria.

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Acute Oral Toxicity

One key and a supporting study (Klimisch score=2) were identified, in which two petroleum vacuum residues (CAS# 64741-56-6) were tested by API for acute oral toxicity in rats using a method similar to OECD 401 (API, 1982a,b). The materials were dispersed in corn oil and administered by gavage (20 mL/kg) to 5 male and 5 female rats at a single dose of 5000 mg/kg body weight. No mortalities were observed and the LD50 for oral exposure was reported as > 5000 mg/kg for both residues. Clinical observations included hypoactivity, diarrhoea, dark brown / black staining of the anal region for both samples.

 

Additional data supports that bitumen is not an acute oral toxicant (ARCO, 1973a). This information is presented in the dossier.

The results of these studies indicate that bitumen is not acutely toxic by the oral exposure route and, since the available data do not meet the EU criteria for classification and labelling (CLP EC 1272/2008) for this endpoint, a DNEL is not required.

 

Acute Inhalation Toxicity

It is important to recognize that toxicity studies involving exposure to bitumen fumes represent only the volatile fraction of the whole material.

In a ‘read across’acute inhalation toxicity study, fume from an oxidized (air-rectified) asphalt was tested in an OECD 403 study under GLP conditions (Fraunhofer, 2000). The fumes were collected from hot storage tanks, condensed and regenerated in the laboratory under well defined conditions. Wistar rats (5 males and 5 females) were exposed, nose-only, to regenerated fume or clean air for 4.5 h (half an hour longer than the standard 4 h to achieve the desired exposure concentration during 4 h) and subsequently housed individually for 2 weeks. The exposure concentration was 94.4±7.7 mg/m3 as total hydrocarbon with a number median aerodynamic diameter (NMAD) as measured with the SMPS - system (scanning mobility particle seizer) of 85 nm. All animals were observed for clinical and behavioural signs during the exposure, several times after the termination of exposure on the day of exposure and daily on all the subsequent days. Body weights were recorded on day 0, 3, 7 and 14. At the end of the study the animals were sacrificed and subject to gross pathology. No clinical signs of intoxication were observed at any time. No effects on any of the reflexes tested were observed at any time. Also no differences in body weight were observed between exposed and controls nor were any gross abnormalities found upon necropsy. The only difference observed between exposed and controls, was a slight decrease in body temperature in the exposed animals (35.6 and 36.6°C in males and females, respectively) compared with the controls (37.3 and 37.7°C in males and females, respectively). The LC50 was found to be > 94.4 mg/m3 (4 hours).

 

The results of this study indicate that bitumen is not acutely toxic by inhalation and, since the available data do not meet the EU criteria for classification and labelling (CLP EC 1272/2008) for this endpoint, a DNEL is not required.

Regulatory classification and labelling for aspiration toxicity relies on the measured or calculated kinematic viscosity of a substance at 40°C rather than results from toxicological studies with animals. Inherent in the classification process is the likelihood that a substance could be aspirated following oral exposure.  Measured or calculated data for kinematic viscosity of bitumen are greater than the threshold criteria for classification as an aspiration hazard underCLP EC 1272/2008 and hence bitumens do not pose an aspiration hazard. 

 

Acute Dermal Toxicity

For acute dermal toxicity, the same petroleum vacuum residues (CAS# 64741-56-6) that were tested for acute oral toxicity were also tested according to a protocol similar to OECD 402 (API, 1982a,b; Klimisch score=1). The vacuum residues were warmed overnight in a water bath to lower the viscosity and were subsequently applied in a single dose of 2000 mg/kg body weight to the shaved skin of 4 male and 4 female white rabbits. The skin of 2 male and 2 female rabbits was abraded before the material was applied whereas the skin of the other animals was kept intact. After 24 hours the material was wiped (not washed) off. The animals were observed for 14 days and then sacrificed. No toxicity was observed in the animals with intact skin, or in the animals with abraded skin. The LD50 for dermal exposure was reported as > 2000 mg/kg. Clinical observations during the study and pathology after sacrifice revealed no abnormalities. Mild diarrhoea was observed in a single female in the study with sample 81-13 which was considered not to be substance-related (API, 1982a).

 

The results of these studies indicate that bitumen is not acutely toxic by the dermal exposure route and, since the available data do not meet the EU criteria for classification and labelling (CLP EC 1272/2008) for this endpoint, a DNEL is not required.

 

Justification for selection of acute toxicity – oral endpoint

Based on similar results in one key  and two supporting studies

Justification for selection of acute toxicity – inhalation endpoint

only one acute read-across inhalation study available

Justification for selection of acute toxicity – dermal endpoint

Based on similar results in two studies (one key and one supporting)

Justification for classification or non-classification

Based on evaluation of all the acute toxicity data available, bitumens do not meet the criteria for classification as acute oral, inhalation or dermal toxicants under the CLP Regulation, (EC)1272/2008, because the LD50/LC50 values are greater than the limits for classification defined in the criteria.

Based on measured or calculated kinematic viscosities, bitumens are not classified for aspiration hazard.