Xylene

Endpoint summary

Description of key information

The available data indicate that mixed xylene and the individual isomers (m-, o- and p-xylene) should be considered to be irritating to skin, eyes and the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-guideline study, GLP status not known, animal experimental study, limitations in design and/or reporting but otherwise adequate for assessment.

Justification for type of information:

N/A

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

7 day observation period

Principles of method if other than guideline:

0.5 mL of the undiluted compound was applied to an intact and to an abraded site on the backs of six rabbits. The sites were covered with a gauze patch. After a 4 h exposure period the patch and any excess material remaining were removed. 4 h, 24 h, 48 h, 72 h and seven-day scorings of irritation were made using the method of Draize.

GLP compliance:

not specified

Specific details on test material used for the study:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Male rabbits
- Food and water available ad libitum
- Housing: The rabbits were housed individually in hanging wire bottom cages
- no further details

ENVIRONMENTAL CONDITIONS
- In an air-conditioned room where the temperature was maintained at approximately 70°F
- no further details

IN-LIFE DATES: no data

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL of the undiluted material

Duration of treatment / exposure:

4 h

Observation period:

Up to 7 days

Number of animals:

6

Details on study design:

The rabbits were clipped on the day prior to testing. 0.5 mL of the undiluted compound was applied to an intact and to an abraded site on the backs of six rabbits. The epidermal abrasions were made with a hypodermic needle. The application sites were covered with a gauze patch. The trunk of each animal was then loosely wrapped in a plastic sheet followed by a wrapping of paper towels to prevent tearing of the plastic sheet. After a 4 h exposure period the wrappings and any excess material remaining were removed. 4 h, 24 h, 48 h, 72 h and seven day scorings of irritation were made using the method of Draize.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hr

Score:

3

Reversibility:

not specified

Remarks on result:

other: score is the summation of the average erythema and oedema for 24 and 72 hours divided by 4.

Irritation parameter:

erythema score

Basis:

other: not specified

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

other: not specified

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

In general, well-defined erythema and barely perceptible to slight oedema were observed throughout the seven-day observation period on intact skin. Similar irritation was observed on abraded application sites.

Other effects:

Primary Irritation Score: 3.0

Interpretation of results:

other: moderately irritating; not corrosive

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

CHEVRON PARAXYLENE 99% was not corrosive to the intact skin of the rabbits tested.

Executive summary:

The skin corrosion potential was determined by exposing the intact skin of six rabbits to p-xylene for four hours. The sites of application were not destroyed or changed irreversibly during or after the exposure. CHEVRON PARAXYLENE 99% was considered not to be corrosive to the intact skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-guideline study, GLP status not known, animal experimental study, limitations in design and/or reporting but otherwise adequate for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

unwashed eye

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no further details

Vehicle:

not specified

Controls:

not required

Amount / concentration applied:

no data

Duration of treatment / exposure:

1 h (not confirmed)

Observation period (in vivo):

1, 24, 48 and 72 hours, 4 and 7 days post instillation

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

no further details

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1 hour

Score:

6

Max. score:

10

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Conjunctival redness (vessels definitely injected above normal to more diffuse, deeper crimson red, individual vessels not easily discernible) was noted in all 6 rabbits at 1 h post instillation of o-xylene. Conjunctival chemosis (swelling above normal) and conjunctival discharge (any amount above normal) were noted in 5 rabbits at 1 h post instillation. Phonation at instillation was noted in 4 rabbits. No corneal opacity or iritis was noted in any of the 6 rabbits. All ocular lesions had cleared by Day 7.

Eye Irritation Score Ranges and Means with Standard Deviations

Observation	Hours				Days
	1	24	48	72	4	7
Cornea
Mean	0.0	0.0	0.0	0.0	0.0	0.0
S.D.	0.0	0.0	0.0	0.0	0.0	0.0
Range	-	-	-	-	-	-
Iris
Mean	0.0	0.0	0.0	0.0	0.0	0.0
S.D.	0.0	0.0	0.0	0.0	0.0	0.0
Range	-	-	-	-	-	-
Conjunctivae
Mean	6.0	1.7	1.3	1.3	1.0	0.0
S.D.	2.2	0.8	1.6	1.6	1.1	0.0
Range	2-8	0-2	0-4	0-4	0-2	-
Total Score
Mean	6.0	1.7	1.3	1.3	1.0	0.0
S.D.	2.2	0.8	1.6	1.6	1.1	0.0
Range	2-8	0-2	0-4	0-4	0-2	-

Means based on six observations.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: not specified

Executive summary:

Conjunctival redness (vessels definitely injected above normal to more diffuse, deeper crimson red, individual vessels not easily discernible) was noted in all 6 rabbits at 1 h post instillation of o-xylene. Conjunctival chemosis (swelling above normal) and conjunctival discharge (any amount above normal) were noted in 5 rabbits at 1 h post instillation. Phonation at instillation was noted in 4 rabbits. No corneal opacity or iritis was noted in any of the 6 rabbits. All ocular lesions had cleared by Day 7.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

The irritation/corrosion of mixed xylene and the xylene isomers was reviewed and reported in the ATSDR (2007). Some additional relevant data from proprietary studies has been sourced.

 

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 although by exception, Smyth (1962) found m-xylene to be non-irritating after non-occluded application to rabbit skin. 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. The histological and molecular changes in rodent skin caused by brief topical occluded exposure to m-xylene were also investigated (Gunasekar, 2003) and epidermal-dermal separation and granulocyte infiltration and increases in IL-1α and iNOS protein expression were observed.

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.

Human information

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

 

Eye irritation/corrosion

Non-human information

Moderate eye irritation was observed in rabbits treated with mixed xylenes although Smyth (1962) found m-xylene to be non-irritating.  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.

Human information

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

Respiratory irritation

Non-human information

A respiratory tract irritancy study in mice (HLA, 1983) 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, 1983).

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.

Human information

Mild irritation of the upper respiratory tract was reported in volunteer studies where individuals were exposed to 442 mg/m³ mixed 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). Reference 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

Justification for selection of skin irritation / corrosion endpoint:
Mild-moderate skin irritation was reported in rats and rabbits treated topically with mixed xylenes or xylene isomers. The extent of the irritation appeared to increase with duration of exposure, however the severity of the response did not appear sufficient to require classification.
Note: Although xylene isomers (including mixed xylenes) are classified H315 - Skin irritant Cat 2 according to the CLP regulation, the rationale for this is not clear since the available data indicate a potential to cause no more than mild-moderate skin irritation.

Justification for selection of eye irritation endpoint:
Xylene isomers (including mixed xylenes) are considered to be irritating to the eyes and warrant classification H319 - Eye irritant Cat 2.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Xylene isomers are classified as skin irritants under CLP (H315 - skin irritant Cat 2) . They are considered to be irritating to the eyes and warrant classification under CLP classification (H319 - Cat 2): induces serious eye irritation. Xylene isomers are considered to be irritating to the respiratory system based on the occurrence of reversible irritant effects in animal studies and should therefore be classified category 3 (H335) for specific target organ toxicity - single exposure (STOT-SE) under CLP.