Petroleum gases, liquefied, sweetened, C4 fraction

Endpoint summary

Description of key information

Members of Other Petroleum Gases category are flammable gases at room temperature. Therefore, in accordance with section 2 of REACH Annex XI, neither skin nor eye irritation studies need be conducted. There are no indications that main constituents of the Other Petroleum Gases category are skin or eye irritants, but direct skin or mucous membrane contact with liquid forms of C1- C4 alkane gases may cause burns and frostbite due to the extreme cold of the liquid. Mild rhinitis has only been reported following lifetime exposure to high concentrations of propene gas. Data are also available on Butadiene Concentrate (approximately 67% 1,3-butadiene, 30% butenes, 2% 1,2-butadiene) and indicate that the irritation potential is low.

Streams containing <1% benzene will not trigger classification for irritation, however, streams containing >10% benzene will trigger classification..

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In accordance with Section 2 of REACH Annex XI, studies on skin and eye irritation do not need to be conducted as members of the Other Petroleum Gases category are flammable gases at room temperature.

Category streams that contain <1% benzene are not expected to be irritating and this is confirmed by pre-guideline rabbit skin and eye irritation studies on formulations although these data cannot be relied upon since there are insufficient details on how the test materials (as gases) were applied (Anon, 1982. Final report of the safety assessment of isobutane, isopentane, n-butane and propane, J American College of Toxicology, Volume 1, Number 4, 127-142).

 

Skin

Non-human information

No guideline studies available. 

Butadiene Concentrate (CAS no. 68955-28-2) was not irritating to rabbit skin or eyes (Mobil 1985). The available data on one of the constituents,1,3-butadiene, also indicates that it is not irritating (EU RAR, 2002). Humans exposed to1,3-butadiene at 2000 ppm (4425 mg/m³) and 4000 ppm (8851 mg/m³) described slight smarting of the eyes and difficulty in focusing although at 8000 ppm (17,702 mg/m³) no subjective symptoms were reported (Carpenter et al, 1944). Rapid evaporation following application of these substances is likely so the value of these studies is questionable. No data are available on the other constituents (butene isomers and butane), but based on physical chemical properties, the liquid gases may cause burns and frostbite due to the extreme cold of the liquid. There are no indications of irritation from repeat dose inhalation studies.

Human information

Very slight and transient erythema occurred randomly among the subjects following repeated applications of aerosol products, containing a mixture of isobutane and propane at 64.5% and 70% by weight, respectively. The reactions were reported to be negligible. Both isobutane and propane were considered practically non irritant to human skin (Anon 1982).

Direct skin contact with liquid forms of C1- C4 alkane gases may cause burns and frostbite due to the extreme cold of the liquid (rapid evaporation lowers the skin temperature causing frost injuries) (Cavender 1994).

Although propene has been used in humans at concentrations sufficient to induce anaesthesia, there is only one literature report of potential adverse irritation effects associated with repeated induction of anaesthesia in one volunteer “after the first few breaths, there was usually slight reddening of the eyelids with some lacrimation and flushing of the eyes. Sometimes coughing would occur from pharyngeal irritation.” In this study, to efficiently induce anaesthesia, very high concentrations (688,000 – 861,000 mg/m3) of propene were rapidly introduced (Kahn and Riggs LK, 1931). This information is not considered useful in assessment of the irritation potential of propene gas, with its lower explosive limit of (34,000 mg/m3).

 

Eye

Non-human information

No guideline studies available.

 

Human information

Direct mucous membrane contact with liquid forms of C1- C4 alkane gases may cause burns and frostbite due to the extreme cold of the liquid (Cavender 1994).

 

Respiratory tract

Non-human information

No data exist for the C1-C4 alkanes. There are no indications of irritation from repeat dose inhalation studies.

 

Mild rhinitis (mild nasal inflammation) was reported in rats following lifetime exposure to high concentrations of propene gas, a main constituent in the category (NTP,1985) & (Harkema 2002). However, any irritant properties in rodents were mild in nature, lacking a clear dose-response relationship and reported only when high concentrations of propene gas were maintained throughout lifetime exposure.

 

 

Human information

Berzins et al (1995) reported human exposure to propane at 100000 ppm (180 mg/L) caused slight dizziness but no mucosal irritation of nose, eyes or respiratory tract was observed.

Although propene has been used in humans at concentrations sufficient to induce anaesthesia, there is only one literature report (Kahn and Riggs, 1931) of potential adverse irritation effects associated with repeated induction of anaesthesia in one volunteer. Since very high concentrations of propene were used (688,000 – 861,000 mg/m3), this information is not considered useful in assessment of the irritation potential of propene gas, with its lower explosive limit of 34,000 m/m3.

Justification for selection of skin irritation / corrosion endpoint:
These streams are gases at room temperature, hence testing for skin irritation potential is not technically feasible.

Justification for selection of eye irritation endpoint:
These streams are gases at room temperature, hence testing for eye irritation potential is not technically feasible.

Streams containing >1% benzene:

Non-human information

Skin irritation

The irritation potential of benzene was assessed on the skins of six shaved rabbits exposed to neat benzene for 4 hours, using an exposure chamber of 6 cm²(Jacobs. 1991). One hour after exposure oedema grade 2 and erythema grade 1 were documented. No oedema, but mean scores of 2.0/2.2/2.4 for erythema were recorded at 24, 48, and 72 hours after the end of exposure. Erythema increased to a mean of grade 3 at 6 days. A second study (Wolf et al, 1956) examined skin irritation potential of benzene following repeated applications. Undiluted benzene was applied 10 -20 times over 2-4 weeks to the ear and shaved abdomen of white rabbits (abdomen bandaged). Perceptible to definite erythema, oedema and superficial necrosis were documented. These effects resulted in a "chapped" appearance and exfoliation of large patches of skin. Although the design and reporting are not compliant with regulatory guidelines the results are consistent with benzene being irritating to rabbit skin.

Eye irritation

The key study is considered to be Wolf et al (1956). Instillation of benzene into the rabbit eye caused moderate conjunctival irritation and very slight, transient corneal injury.

Human information

Skin irritation

Liquid benzene on direct contact with the skin may cause erythema and blistering. Skin contact with benzene removes fat from the tissue which may result in the development of a dry, scaly dermatitis if exposure is repeated or prolonged.

Eye irritation

High concentrations of benzene vapours are irritating to the mucous membranes of the eyes, nose, and respiratory tract (EU RAR, 2008).

Justification for selection of skin irritation / corrosion endpoint:
Liquid benzene is irritating to rabbit skin, and removes fat from the tissue which may result in the development of a dry, scaly dermatitis if exposure is repeated or prolonged.

Justification for selection of eye irritation endpoint:
Liquid benzene is irritating to rabbit eye, causing moderate conjunctival irritation and very slight, transient corneal injury.

Effects on skin irritation/corrosion:irritating

Effects on eye irritation:irritating

Justification for classification or non-classification

There is no evidence that members of this category are irritating to skin, eyes or respiratory tract. 

Any propene-induced rhinitis has been reported as mild in nature, occurring in rodents only after lifetime exposure to high concentrations (5,000ppm & 10,000ppm (8,600 and 17,200 mg/m3) of propene gas.

Streams containing >10% benzene:

It is concluded that benzene is irritating to rabbit skin and should be classified as Category 2, H315, under CLP. Benzene is irritating to rabbit eye and should be classified Category2, H319, under CLP.