Solvent naphtha (coal), xylene-styrene cut

Endpoint summary

Description of key information

The available data indicate that mixed xylenes (comprising mixed xylene isomers and ethylbenzene) should be considered to be irritating to skin, eyes and the respiratory tract.

Data on the specific components benzene, toluene and styrene also indicate some irritation following dermal contact with effects sufficiently severe to warrant labelling. Data on benzene and styrene indicate that instillation of liquid test substance into the eye induce evidence of eye irritation of a severity sufficient to warrant labelling.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Mixed xylene (CAS 1330-20-7) comprises individual xylene isomers (m-xylene, o-xylene, p-xylene) and ethylbenzene. Data for these substances and the specific component substances benzene, toluene and styrene have been considered in this summary.

Skin irritation/corrosion

Non-human information

Mild-moderate skin irritation was noted in rats and rabbits treated topically with mixed xylenes or the xylene isomers. The extent of the irritation appeared to increase with duration of exposure; the most severe dermal irritation ratings were obtained in the longest exposures of 10-days (Hine, 1970).

The effects of short-term occlusive and repeated non-occlusive dermal exposure to m-xylene was investigated in the hairless rat using erythema, transepidermal water loss and skin moisture content as indicators of dermal irritation (Chatterjee, 2005). M-xylene was found to be mildly irritating to skin following single occluded exposure and repeated non-occluded contact and to damage the barrier function of the skin. 

Skin corrosion potential was determined in one study and this study evaluated p-xylene (Chevron Chemical Company, 1973). The intact skin of six rabbits was exposed to p-xylene for four hours. The sites of application were not destroyed or changed irreversibly during or after the exposure and p-xylene was considered not to be corrosive to the intact skin of rabbits.

As reported in the RAR (2008), after single exposure ethylbenzene is moderately irritating to the skin of rabbits. Repeated exposure results in erythema and oedema with superficial necrosis giving a "chapped" appearance and exfoliation of large patches of skin. 

Human information

There is little human information available for ethylbenzene and xylene, but the ATSDR (2007) reports that dermal exposure of humans to xylene causes skin irritation, dryness and scaling of the skin, and vasodilation.

Toluene (Classification: EU -Harmful Xi, R38; GHS/CLP - Category 2 H315): No data on skin irritation have been found. The EU RAR (2003) stated “it is well known that toluene has a degreasing effect on the skin. After repeated exposures, toxic contact dermatitis may develop. ”

Eye irritation/corrosion

Non-human information

Moderate eye irritation was observed in rabbits treated with mixed xylenes. Primary irritation studies in rabbits using the washed and unwashed eye (HLA, 1983) demonstrated transient eye irritation (conjunctival redness and oedema) following exposure to o-xylene.  No corneal effects were reported in either study.

Ethylbenzene caused irritation in the eyes of rabbits and guinea pigs (latter exposed to 5000 and 10000 ppm of ethylbenzene vapour) (RAR, 2008). 

Human information

No obvious irritation of the eye was reported in volunteer studies where individuals were exposed to 442 mg/m³ (SCOEL, 1992) mixed xylene for 15-30 minutes (Carpenter, 1975; Hastings, 1984).

High concentrations of ethylbenzene vapours are irritating to mucous membranes of the eyes (RAR, 2008).

There is evidence from human volunteer studies that styrene vapour causes irritation of the eyes at a dose level of 375 ppm. Data suggests NOAEC values of 216 ppm for 1 hour and of 100 ppm for 7 hours (Stewart, 1968).

There are no data from direct exposure of human eyes to liquid toluene. A number of human experimental studies in volunteers have investigated reports of eye “irritation” resulting from exposures to toluene in ambient air. These studies indicate that toluene produces subjective sensations of eye irritation at concentrations ≥ 75 ppm (EU RAR, 2003). In a recent study, Muttray et al (2005) exposed twenty healthy men to a constant level of 50 ppm toluene. Acute symptoms related to eye irritation were assessed with the Swedish Performance Evaluation System (SPES) self-assessment questionnaire, once before and 3 times during exposure. Values obtained during exposure were related to pre-exposure values. There was no effect of toluene exposure on "irritation to the eye", "watering eyes" or "blurred vision”. 50 ppm (188 mg/m³) toluene is a NOAEC for eye irritation in humans.

Respiratory irritation

Non-human information

A respiratory tract irritancy study in mice (HLA, 1983a) reported that exposure to o-xylene at a nominal concentration of 9480 mg/m3 via air inhalation resulted in very slight to slight depressions in respiratory rates indicative of very slight to slight respiratory irritation. For p-xylene at a nominal concentration of 11580 mg/m³, slight to severe depressions in respiratory rates indicative of slight to severe respiratory irritation were reported (HLA, 1983b).

A sensory irritation study in mice (De Ceaurriz, 1981) reported a decrease in respiratory rate during a 5 minute period of exposure of mice to the vapour of o-xylene with an RD50 value of 6370 mg/m³.

For ethylbenzene RD50 values of 1432 or 4060 ppm (6215 to 17620 mg/m³) for sensory irritation were determined in different strains of mice (RAR, 2008).

Human information

Mild irritation of the upper respiratory tract was reported in volunteer studies where individuals were exposed to 442 mg/m³ xylene for 15-30 minutes (Carpenter, 1975; Hastings, 1984).

No symptoms of nose or throat irritation have been reported in volunteers exposed to mixed xylenes up to 400 ppm (UK HSC, 2001).

The RAR (2008) reports that high concentrations of ethylbenzene vapours are irritating to the nose and respiratory tract.

There is evidence from human volunteer studies that styrene vapour causes irritation of the eyes and respiratory tract (throat, nasal passages) at a dose level of 375 ppm. Data suggests NOAEC values of 216 ppm for 1 hour and of 100 ppm for 7 hours (Stewart, 1968).

References

EU RAR (2003). European Union Risk Assessment Report for Toluene. EC Joint Research centre. http://ecb.jrc.ec.europa.eu/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/toluenereport032.pdf

UK HSC (2001): European Commission Directive 2000/39/EC establishing a First List of Indicative Occupational Exposure Limit Values at European Community level in implementation of council directive 98/24/EC on the protection of the health and safety of workers from the risks related to chemical agents at work: Consultative Document

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Mixed xylenes are classified as skin irritants under Annex I of the DSD (Xi, R38) and therefore H315 (skin irritant Cat 2) applies under Annex VI of the CLP regulation. Specific components styrene and benzene are classified as irritating to the skin and eyes and toluene is classified as irritating to the skin.

Mixed xylene streams that contain ≥ 12.5% styrene are classified as irritating to the eyes under Annex I of the DSD (Xi, R38). This corresponds with a classification of Cat 2 (H319) for streams containing ≥10% styrene under CLP.

Mixed xylenes are considered to be irritating to the eyes and should be self classified under DSD (Xi, R36) which corresponds with a Cat 2 (H319) classification under CLP: induces reversible eye irritation (conjunctival redness and oedema).

Mixed xylenes are considered to be irritating to the respiratory system based on the occurrence of reversible irritant effects in animal studies and should therefore be self classified Xi, R37 Irritating to the respiratory system under DSD and category 3 (H335) for specific target organ toxicity - single exposure (STOT-SE) under CLP.