Hazardous Chemical Information System (HCIS)

Xylene (o-, m-, p-isomers)

Exposure standards first adopted in 1990

Documentation notice: National Occupational Health and Safety Commission documentation available for these values.

No standard should be applied without reference to Guidance on the interpretation of Workplace exposure standards for airborne contaminants.

1. IDENTITY

2. CHEMICAL AND PHYSICAL PROPERTIES

Xylene can exist in three isomeric forms . These three isomers possess similar properties . Commercial xylene is a mixture of these three isomers: ortho, meta and para , with the meta form usually the principal component (45-70%) . Ethyl benzene may also be present in a concentration of 6-10% ⁽¹⁾ . Xylene is a clear, flammable liquid with an aromatic hydrocarbon odour . Its chemical and physical properties include:

*50% response value

3. MAJOR INDUSTRIAL USES

Xylene is present in petrol and many petroleum solvents . It is widely used as a thinner, and as a solvent for ink, rubber, gums, resins, adhesives and lacquers . o-Xylene is used in the synthesis of plasticisers; p-xylene in the manufacture of polyester fibres and films; and m-xylene in the production of isophthalic acid.

4. METABOLISM

Xylene is absorbed mainly through inhalation . About 60% of inhaled xylene is absorbed into the systemic circulation ⁽¹⁾ . Exercise increases the absorption of xylene . About 95% of absorbed xylene is metabolised rapidly in the liver and excreted in urine as methyl hippuric acid . Biological exposure indices have been developed for xylene ⁽⁴⁾.

5. ANIMAL STUDIES

The effects of xylene to animals have been reviewed ^{(5 ,6,7,8,9 )}.

5.1 Toxic Effects

An oral LD₅₀ of 10mL/kg ( similar or equal to 8.6g/kg) body weight in rats was reported for the three xylene isomers mixed with ethyl benzene ⁽¹⁰⁾ . The corresponding four-hour inhalation LC₅₀ in rats is 6350ppm ⁽¹⁰⁾.

Carpenter et al ⁽²⁾ exposed groups of rats and dogs to 180, 460 or 810ppm mixed xylenes (p-xylene, 8%; m-xylene, 65%; o-xylene, 8%; ethyl benzene, 19%) for 6 hours/day, 5 days/week for 13 weeks . No significant adverse effects were observed . In another inhalation study ⁽¹¹⁾ when rats were exposed to 300ppm xylene vapour for 18 weeks, the researchers did not find any significant adverse effects.

Jenkins et al ⁽¹²⁾ exposed rats, guinea pigs, squirrel monkeys and beagle dogs to o-xylene at 770ppm intermittently, or 77ppm continuously, for 90 days . No haematological changes or other effects were found.

5.2 Teratogenic Effects

Continuous exposure of rats to 230ppm mixed xylenes (10% o-xylene; 50% m-xylene; 20% p-xylene; 20% ethyl benzene) on days 9-14 of gestation did not show any significant teratogenic effects ⁽¹³⁾.

Shigeta et al ⁽¹⁴⁾ exposed mice to 500, 1000, 2000 or 4000ppm xylene vapour 6 hours/day on days 6-12 of gestation . Decreased foetal weights and delayed skeletal ossification was found only at 2000 and 4000ppm.

In an inhalation study ⁽¹⁵⁾, groups of rats were exposed continuously to 35, 350 or 700ppm of each of the three xylene isomers on days 7-14 of gestation . Mean foetal weight was significantly reduced following exposure to all three isomers at the 700ppm concentration . Litters from dams exposed to p-xylene at 700ppm showed significantly increased foetal loss . Skeletal retardation occurred in foetuses from dams exposed to 700ppm o-xylene and all p-xylene-exposed groups.

5.3 Carcinogenicity

Following a 2-year gavage study of mixed xylenes , the mixture was found to be non-carcinogenic to mouse strain B6C3F or to rat strain F3441N ⁽¹⁶⁾.

6. HUMAN STUDIES

In 1943, Nelson et al ⁽¹⁷⁾ exposed 10 unacclimatised human subjects to xylene vapour in a test chamber for 3-5 minutes . Irritation of the eyes, nose and throat was experienced at 200ppm . A majority of the subjects estimated that 100ppm would be a satisfactory exposure level for eight hours.

Carpenter et al ⁽²⁾ exposed human volunteers to 105, 230 or 460ppm xylene vapour for 15 minutes . Slight lightheadedness was reported at 230ppm from one out of seven subjects.

In a study ⁽¹⁸⁾ where 23 male volunteers were exposed to 100 and 200ppm for 3-7 hours, no effects on critical flicker fusion rate, reaction time, pulse rate or blood pressure were observed.

Olson et al ⁽¹⁹⁾ studied the effects of xylene in 16 male subjects on performance in tests of simple reaction time, short-term memory and choice reaction time . The subjects were exposed to 70ppm for four hours . The results indicated that the performance on the tests was not affected by the exposure.

Gamberale et al ⁽²⁰⁾ have also made an experimental study of the effects of exposure to xylene . With exposures up to 300ppm for 70 minutes at rest, performance in reaction time and memory tests was not affected . However, when respiratory uptake was increased by light physical exercise, impaired performances were observed.

Savolainen et al ^(11,21) found in human subjects that exposure to 100ppm xylene vapour for 5-6 hours caused changes in reaction time and slight impairment of body balance . The researchers found that physical exercise could antagonise these effects . At 200ppm (with 400ppm peak exposure), the EEG showed an increase in transient occipital slow waves.

7. OVERSEAS EXPOSURE STANDARD

8. CONCLUSION

There is inadequate evidence that the three xylene isomers differ significantly in toxicity.

Exposure to 200ppm xylene for 3-5 minutes caused irritation of the eyes, nose and throat . Exposure at 100ppm for 5-6 hours could cause some neurobehavioural effects.

A few studies suggested that relatively low concentrations (about 350-700ppm) of xylene might have teratogenic effects in rats . However, more evidence is required for evaluating the teratogenic effects of xylene.

9. RECOMMENDATION FOR EXPOSURE STANDARD

To minimise sensory irritation to most workers, the Exposure Standards Working Group recommends for xylene (o-, m-, p-isomers) a time-weighted average exposure standard of 80ppm and a STEL of 150ppm . These levels should also be low enough to protect the workers from narcotic and other chronic health effects.

REFERENCES

1. National Board of Occupational Safety and Health, Consensus report for xylene, Scientific Basis for Swedish Occupational Standards, Criteria Group for Occupational Standards, Solna , Sweden , p.46-51, 1981

2. Carpenter CP et al, "Petroleum hydrocarbon toxicity studies . V. Animal and human response to vapors of mixed xylenes ", Toxicol Appl Pharmacol , 33(3), 543-558, 1975

3. Verschueren K, Handbook of Environmental Data on Organic Chemicals pp.638-642, Van Nostrand -Reinhold, New York, 1977

4. American Conference of Governmental Industrial Hygienists ( ACGIH ), Documentation of Threshold Limit Values and Biological Exposure Indices, 5th edition, Ohio , 1986

5. Sandmeyer EE, Aromatic Hydrocarbons, In: Patty's Industrial Hygiene and Toxicology, ed. by Clayton GD & Clayton FE, 3rd rev. edition, Volume 2B, pp.3291-3300, 1981

6. (US) Environmental Protection Agency, Health Effects Assessment for Xylene, PB86-134178, EPA/540/1-86/006, Cincinnati , September 1984

7. Haley TJ , "Xylene", Dangerous Properties of Industrial Materials Report, VNR Information Services, 6(6), 1-11, Nov/Dec 1986

8. Jori A et al, " Ecotoxicological Profile of xylenes ", Ecotoxicology & Environ Safety, 11, 44-80, 1986

9. National Institute for Occupational Safety and Health (NIOSH), Criteria for a Recommended Standard - Occupational Exposure to Xylene, NIOSH 75-168, Cincinnati, Ohio, 1975

10. Hine CH & Zuidema HH , "The toxicological properties of hydrocarbon solvents", Ind Med Surg 39, 215-220, 1970

11. Savolainen K et al, " Neurochemical and behavioural effects of long-term intermittent inhalation of xylene vapor and simultaneous ethanol intake", Acta Pharamacol Toxicol , 44, 200-207, 1979

12. Jenkins LJ et al, "Long-term inhalation screening studies on benzene, toluene, o-xylene and cumene on experimental animals", Toxicol Appl Pharmacol , 16, 818-823, 1970

13. Hudak A & Ungvary G , " Embryotoxic effects of benzene and its methyl derivatives: toluene, xylene", Toxicology, 11, 55-63, 1978

14. Shigeta S et al, " Fetotoxicity of inhaled xylene in mice", Teratology, 28(1): 22A, 1983

15. Ungvary G et al, "Studies on the embryotoxic effects of ortho-, meta-, and para -xylene", Toxicology, 18, 65-74, 1980

16. Eastin WC, NTP Technical Report on the Toxicology and Carcinogenesis Studies of Xylene (mixed), NIH Publ No. 86-2583, NIH, NTP, Research Triangle Park , NC , 1986

17. Nelson KW et al, "Sensory response to certain industrial solvent vapours", J Ind Hyg Toxicol , 25, 282-285, 1943

18. Ogata M et al, "Urinary excretion of hippuric acid and m- or p- methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene as a test of exposure", Br J Ind Med, 27, 43-50, 1970

19. Olson BA et al, " Coexposure to toluene and p-xylene in man: central nervous functions", Br J Ind Med, 42, 117-122, 1985

20. Gamberale F et al, "Exposure to xylene and ethyl benzene: III . Effects on central nervous functions", Scand J Work Environ Health, 4, 204-211, 1978

21. Savolainen K et al, "Effect of short-term xylene exposure and physical exercise on the central nervous system", Int Arch Occup Environ Health, 45, 105-121, 1980

Footnotes:

Documentation notice: Entries carrying a notice for National Occupational Health and Safety Commission documentation indicate that these substances have been reviewed in detail by the Exposure Standards Expert Working Group and that documentation supporting the adopted national values is available in the National Commission's Documentation of the Exposure Standards [NOHSC:10003(1997)].