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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 1
CCOHS Chemical Name: Xylene (mixed isomers)

Synonyms:
Dimethylbenzene
Methyltoluene
Xylol
Xylene (non-specific name)

Chemical Name French: Xylène (mélange d'isomères)
Chemical Name Spanish: Xileno (mezcla de isómeros)
CAS Registry Number: 1330-20-7
UN/NA Number(s): 1307
RTECS Number(s): ZE2100000
EU EINECS/ELINCS Number: 215-535-7
Chemical Family: Aromatic hydrocarbon / alkylbenzene / dialkylbenzene
Molecular Formula: C8-H10
Structural Formula: CH3-C6H4-CH3

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless liquid with a characteristic odour

Odour Threshold:
1 ppm (detection) (2); 20 ppm (detection) (10); 40 ppm (recognition).(10)

Warning Properties:
GOOD - TLV is more than 10 times the odour threshold.

Composition/Purity:
There are three chemical forms (isomers) of xylene, ortho-xylene, meta-xylene and para-xylene. Commercial xylene, generally referred to as xylene (mixed isomers) or technical xylene, is a mixture of widely varying proportions of these three isomers (with m-xylene predominating), together with ethylbenzene (6-20%) and smaller amounts of toluene, trimethylbenzene, phenol, thiophene, pyridine and non-aromatic hydrocarbons.(4,5) The information presented in this CHEMINFO record is given for xylene (mixed isomers) where possible.

Uses and Occurrences:
Commercial xylene is produced from petroleum and coal tar. The mixture of xylene isomers also occurs naturally in small quantities in petroleum stocks, coal tar and natural gas, and is formed during forest fires.(4,5) Xylene is used as a solvent in paint, printing, rubber and leather industries; as a solvent for gums and resins, rubber, castor and linseed oils and dibenzylcellulose; as a constituent of paints, lacquers, varnishes, inks, dyes, adhesives and cleaning fluids; as a carrier in production of epoxy resins; as a degreaser and cleaning agent; as a constituent of motor and aviation fuels; in chemical synthesis; and in the manufacture of quartz crystal oscillators, perfumes and insect repellents.


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Clear, colourless liquid with a characteristic aromatic odour. FLAMMABLE LIQUID AND VAPOUR. Liquid can accumulate static charge by flow or agitation. Vapour is heavier than air and may spread long distances. Distant ignition and flashback are possible. Liquid can float on water and may travel to distant locations and/or spread fire. Can decompose at high temperature forming toxic gases. Closed containers may rupture and explode in heat of fire. May cause lung injury -- effects may be delayed. Central nervous system depressant. High vapour concentrations may cause headache, nausea, dizziness, drowsiness, confusion and incoordination. Causes skin irritation. Aspiration hazard. Swallowing or vomiting of the liquid may result in aspiration into the lungs. POSSIBLE REPRODUCTIVE HAZARD - may cause fetotoxicity, based on animal information.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
The main effect of inhaling xylene vapour is depression of the central nervous system (CNS), with symptoms such as headache, dizziness, nausea and vomiting. Volunteers have tolerated 100 ppm, but higher concentrations become objectionable. Irritation of the nose and throat can occur at approximately 200 ppm after 3 to 5 minutes. Exposures estimated at 700 ppm have caused nausea and vomiting. Extremely high concentrations (approximately 10000 ppm) could cause incoordination, loss of consciousness, respiratory failure and death. In some cases, a potentially fatal accumulation of fluid in the lungs (pulmonary edema) may result. Symptoms of pulmonary edema, such as shortness of breath and difficulty breathing, may be delayed several hours after exposure. However, these effects are rarely seen since xylene is irritating and identifiable by odour at much lower concentrations.(1,3) The only reported death resulted from exposure to xylenes (unspecified isomer composition and unknown concentration) in a confined space.(4,6) Reversible liver and kidney damage has been reported in cases of severe xylene exposure.(5,6)
Results of short-term studies on human volunteers indicate that xylenes can cause neurobehavioural effects such as impaired short-term memory and reaction time (300 ppm mixed xylenes, with exercise) and alterations in body balance (65 to 400 ppm m-xylene). Exposure to 300 or 400 ppm mixed xylenes or 65 to 150 ppm p-xylene have not had similar effects. This variation in results is probably due to differences in the effects being studied, exposure conditions, development of tolerance and total xylene uptake (which increases during exercise).(4,16)

Skin Contact:
Xylene (mixed isomers) liquid is a moderate skin irritant based on animal information.
Studies with xylene isomers have shown irritation, redness and a burning sensation can result from contact. These effects are reversible shortly (usually within 1 hour) after the contact stops.(1,3,6) Repeated or prolonged exposure to xylene can defat the skin resulting in dermatitis (red, dry, itchy skin).(6)
Xylene liquid or vapour can be absorbed through the skin, but not as readily as when inhaled or ingested.(1,16) Significant harmful effects are not expected by this route of exposure.

Eye Contact:
Xylene (mixed isomers) liquid is a very mild irritant, based on animal information.
Eye irritation has been reported at vapour levels as low as 200 ppm.(3,16) Corneal vacuoles (pockets of fluid or air in the cornea) have also been reported following exposure to undefined vapour concentrations. This effect was reversible within 8 to 11 days for 7 of 8 workers.(1,3)

Ingestion:
Based on animal information, xylene is only slightly toxic by ingestion. Ingestion of large amounts is likely to cause CNS effects such as dizziness, nausea and vomiting. In one case, ingestion of food probably contaminated with xylene caused pulmonary edema, liver impairment and coma. The man recovered within 2 hours after treatment.(6) Ingestion is not a common route of occupational exposure.
Although there are no case reports, xylene may be aspirated, based on its physical properties (viscosity and surface tension). Aspiration is the inhalation of a material into the lungs during ingestion or vomiting. Severe lung irritation, damage to the lung tissues and death may result.

Effects of Long-Term (Chronic) Exposure

SKIN: Repeated contact can produce dermatitis (dryness and cracking) due to degreasing action.

SKIN SENSITIZATION: Skin sensitization was not produced in any of 24 volunteers.(1,3,6) There is one case report of a person developing an allergic skin reaction (contact urticaria) following exposure to xylene (unspecified composition) vapour. The person subsequently tested positive in a patch test. No information was provided regarding previous history of allergies.(9) No conclusions can be drawn regarding the potential for xylene to produce allergic skin reactions, based on this single case report.

NERVOUS SYSTEM EFFECTS: Long-term xylene exposure may cause harmful effects on the nervous system, but there is not enough information available to draw firm conclusions. Symptoms such as headaches, irritability, depression, insomnia, agitation, extreme tiredness, tremors, and impaired concentration and short-term memory have been reported following long-term occupational exposure to xylene and other solvents. This condition is sometimes generally referred to as "organic solvent syndrome". Unfortunately, there is very little information available which isolates xylenes from other solvent exposures in the examination of these effects. Other study deficiencies include inadequate reporting on the duration of exposure and the exposure levels, and poor matching of controls.(3,4,6,16)
In a recent study, 175 employees were exposed to an average xylene concentration of 21 ppm for an average of 7 years. Subjective symptoms such as anxiety, forgetfulness, inability to concentrate and dizziness were reported. Xylenes accounted for greater than 70% of the total exposure.(22) This study is also limited by factors such those described above.

BLOOD EFFECTS: Historical reports sometimes associate xylene exposure with certain blood effects, including leukemia, which are now known to be caused by benzene. Uncontaminated xylene is not known to cause these effects.(1,4,6) Reduced blood platelet counts were observed in 12 of 27 men exposed to mixed xylene (unspecified composition) at a level up to 200 ppm. When exposure stopped, platelet counts returned to normal.(3) There is insufficient information to draw any conclusions from this study.

LIVER AND KIDNEY EFFECTS: A number of case reports and occupational studies have suggested that liver and kidney damage may result from long-term occupational exposure to xylene. However, it is not possible to attribute these effects directly to xylene exposure because generally there was exposure to other chemicals at the same time, particularly other solvents, and there was no information provided on the exposure levels or duration of exposure.(3,4,16)
In a recent study, 175 employees were exposed to a mean xylene concentration of 21 ppm for an average of 7 years. Liver and kidney effects were not reported. Xylenes accounted for greater than 70% of the total exposure.(22)

Carcinogenicity:

Xylene has been mentioned as an exposure in 4 case-control studies. Cancers at most sites were not significantly associated with xylene exposure in any study. Most results were based on small numbers, most studies involved exposure to other potentially harmful substances, and the consistency of findings is weak. Therefore, the International Agency for Research on Cancer (IARC) has determined that there is inadequate evidence for the carcinogenicity of xylene in humans. No conclusions can be drawn from the available animal information.(5,24)

The International Agency for Research on Cancer (IARC) has concluded that this chemical is not classifiable as to its carcinogenicity to humans (Group 3).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as not classifiable as a human carcinogen (A4).

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
Mixed xylenes are considered fetotoxic in humans, based on observations of reduced fetal weight, delayed ossification and persistent behavioural effects in animal studies in the absence of maternal toxicity. Other developmental effects have been observed in animal studies in the presence of maternal toxicity.
Several human population studies have suggested a link between exposure to organic solvents (including xylene) and increased occurrence of miscarriages or birth defects in children. However, in the majority of cases, there was exposure to a variety of solvents at the same time, exposures were ill-defined, and the number of cases examined was small.(3-6,16) Overall, no conclusions can be made on the effects of exposure to xylenes on the unborn child because of the inadequacy of the available information.

Reproductive Toxicity:
An increase in menstrual disorders has been reported in women exposed to organic solvents such as benzene, toluene and xylenes.(6) It is not possible to attribute these effects to xylenes in particular. The limited animal information available suggests that xylenes do not cause reproductive effects.

Mutagenicity:
There have been a few studies investigating the mutagenic potential of mixed xylenes (undefined composition) in workers exposed occupationally. In one study, xylene contained ethylbenzene, and in the other there was co-exposure to other solvents including benzene. These studies (induction of sister chromatid exchanges and chromosomal aberrations in human lymphocytes (white blood cells)) were negative. Negative results were also obtain in a study where volunteers were exposed to 40 ppm mixed xylenes over two weeks. However, no conclusions can be drawn because of limitations such as small study populations and exposure to other chemicals at the same time.(3,4,5,16,24) There were no increases in chromosome aberrations and sister chromatid exchanges without metabolic activation, in cultured human lymphocytes.(3,4)

Toxicologically Synergistic Materials:
Exposure to related solvents, such as benzene, toluene and ethanol (alcohol) slows the rate of clearance of xylenes from the body, thus enhancing its toxic effects.(4) Exposure to xylene in combination with other solvents has had an additive effect with respect to harming the hearing of rats.(21)

Potential for Accumulation:
The three xylene isomers are readily absorbed by inhalation and ingestion and are widely distributed throughout the body. A small amount may be absorbed through the skin. Xylenes are largely broken down by the liver and most of the absorbed material is rapidly excreted in the urine as breakdown products. Smaller amounts are eliminated unchanged in the exhaled air.(1,3,4,16) There is low potential for accumulation.


SECTION 4. FIRST AID MEASURES

Inhalation:
This product is flammable and a possible reproductive hazard. Take proper precautions (e.g. remove any sources of ignition, wear appropriate protective equipment). Remove source of contamination or move victim to fresh air. If breathing is difficult, oxygen may be beneficial if administered by trained personnel, preferably on a doctor's advice. DO NOT allow the victim to move about unnecessarily. Symptoms of pulmonary edema can be delayed up to 48 hours after exposure. Immediately transport victim to an emergency care facility.

Skin Contact:
Avoid direct contact, wear chemical resistant protective clothing. As quickly as possible, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Quickly and gently blot or brush away excess chemical. Wash gently and thoroughly with water and non-abrasive soap for at least 20 minutes or until chemical is removed. Obtain medical advice immediately. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Quickly and gently blot or brush away excess chemical. Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes or until the chemical is removed, while holding the eyelid(s) open. Obtain medical attention immediately.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or is convulsing. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 ozs) of water to dilute material in stomach. If vomiting occurs naturally, have victim lean forward to reduce risk of aspiration. Repeat administration of water. Obtain medical attention immediately.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest). Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
Some recommendations in the above sections may be considered medical acts in some jurisdictions. These recommendations should be reviewed with a doctor and appropriate delegation of authority obtained, as required.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
17-25 deg C (62.6-77 deg F) (closed cup) (4)

Lower Flammable (Explosive) Limit (LFL/LEL):
1% by volume (4)

Upper Flammable (Explosive) Limit (UFL/UEL):
7% by volume (4)

Autoignition (Ignition) Temperature:
464 deg C (867 deg F) (4)

Sensitivity to Mechanical Impact:
Probably not sensitive. Stable material.

Sensitivity to Static Charge:
Specific information is not available. Can accumulate static charge by flow or agitation.(13) Vapour can be ignited by static discharge.

Combustion and Thermal Decomposition Products:
Carbon monoxide, carbon dioxide, reactive hydrocarbons, aldehydes.

Fire Hazard Summary:
Flammable liquid. Can release vapours that form explosive mixtures with air at, or above, 17 deg C. Liquid can accumulate static charge by flow or agitation. Vapour can be ignited by a static charge. Vapour is heavier than air and may travel a considerable distance to a source of ignition and flash back to a leak or open container. Liquid can float on water and may travel to distant locations and/or spread fire. During a fire, irritating/toxic gases may be generated. Can accumulate in confined spaces, resulting in a toxicity and flammability hazard. Containers may explode in heat of fire.

Extinguishing Media:
Carbon dioxide, dry chemical powder, foam, water spray or fog. Water may be ineffective since it may not cool xylene below its flash point.(13) Firefighting foams are the extinguishing agent of choice for most flammable liquid fires.

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products.
Stop leak before attempting to put out the fire. If the leak cannot be stopped, and if there is no risk to the surrounding area, let the fire burn itself out. If the flames are extinguished without stopping the leak, vapours could form explosive mixtures with air and reignite.
Water can extinguish the fire if used under favourable conditions and when hose streams are applied by experienced firefighters trained in fighting all types of flammable liquid fires. If possible, isolate materials not yet involved in the fire, and move containers from fire area if this can be done without risk, and protect personnel. Otherwise, fire-exposed containers or tanks should be cooled by application of hose streams and this should begin as soon as possible and should concentrate on any unwetted portions of the container. If this is not possible, used unmanned monitor nozzles and immediately evacuate the area. If a leak or spill has not ignited, use water spray in large quantities to disperse the vapours and to protect personnel attempting to stop the leak. Water spray can be used to flush spills away from ignition sources. Solid streams of water may be ineffective and spread the material.
For a massive fire in a large area, use unmanned hose holder or monitor nozzles. If this is not possible, withdraw from fire area and allow fire to burn. Stay away from ends of tanks. Be aware that flying material from ruptured tanks can travel in any direction. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire.
Xylene (mixed isomers) is a possible reproductive hazard. Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. Chemical resistant clothing (e.g. chemical splash suit) and positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 2 - Intense or continued (but not chronic) exposure could cause temporary incapacitation or possible residual injury.
NFPA - Flammability: 3 - Liquids and solids that can be ignited under almost all ambient temperature conditions.
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 106.16

Conversion Factor:
1 ppm = 4.33 mg/m3; 1 mg/m3 = 0.23 ppm at 25 deg C (calculated)

Physical State: Liquid
Melting Point: Variable depending on isomer composition. No data reported.
Boiling Point: Variable boiling ranges depending on isomer composition; 137- 140 deg C (279-284 deg F) (4); 129-150 deg C (264-302 deg F).(1)
Relative Density (Specific Gravity): 0.86 at 20 deg C (4) (water = 1) (4)
Solubility in Water: Practically insoluble (130 mg/L at 25 deg C) (4)
Solubility in Other Liquids: Soluble in all proportions in absolute alcohol, diethyl ether and other organic compounds; very soluble in ethanol.(4)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 3.12-3.20 (4)
pH Value: Not applicable
Viscosity-Dynamic: Specific information is not available for xylene (mixed isomers). Individual isomers fall in range 0.620-0.076 centipoises (0.620-0.076 mPa.s) at 20 deg C.
Viscosity-Kinematic: Specific information is not available for xylene (mixed isomers). Individual isomers fall in the range 0.717-0.864 m2/s (0.717-0.864 centistokes) at 20 deg C (calculated)
Surface Tension: No information available for xylene (mixed isomers). Individual isomers fall in range 28.3-29.76 mN/m (28.3-29.76 dynes/cm) at 20 deg C.
Vapour Density: 3.7 (air = 1)
Vapour Pressure: Approximately 0.8-0.867 kPa (6-6.5 mm Hg) at 20 deg C (4)
Saturation Vapour Concentration: Variable - approximately 7900-8550 ppm (0.79-0.86%) at 20 deg C (calculated)
Evaporation Rate: Approximately 0.7 (n-butyl acetate = 1)

SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable to heat, light and air.

Hazardous Polymerization:
Does not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


STRONG OXIDIZING AGENTS - Increased risk of fire and explosion (14)
NITRIC ACID, DICHLOROHYDRANTOIN - Reaction can be explosive (14)

Hazardous Decomposition Products:
None reported.

Conditions to Avoid:
Static discharge, sparks, open flames, heat, other ignition sources.

Corrosivity to Metals:
Not corrosive to metals.

Stability and Reactivity Comments:
Xylene will attack some forms of plastics, rubber and coatings.


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (rat): 6350 ppm (4-hour exposure) (unspecified isomers and ethylbenzene) (1)
LC50 (rat): 6700 ppm (4-hour exposure) (65% m-xylene, 7.6% o-xylene, 7.8% p-xylene, 19.3% ethylbenzene) (2)

LD50 (oral, rat): 5400 mg/kg (52% m-, 19% o-, 24% p-) (1)
LD50 (oral, female mouse): 5251 mg/kg (60.2% m-, 9.1% o-, 14.6% p-, 17.0% ethylbenzene) (4)
LD50 (oral, male mouse): 5627 mg/kg (60.2% m-, 9.1% o-, 14.6% p-, 17.0% ethylbenzene) (4)

LD50 (dermal, rabbit): 12180 mg/kg (m-xylene); greater than 1700 mg/kg (mixed xylenes - undefined composition) (3)

Eye Irritation:

Xylene (mixed isomers) is a very mild eye irritant.

In 2 tests, application of 0.1 mL of 100% xylene (unspecified composition, 99% pure) caused very mild irritation in rabbits (modified maximum averages 1.5/110 and 9/110).(26) Application of 0.1 mL of xylene (unspecified composition) caused very mild irritation in rabbits. Average scores at 24, 48 and 72 hours were: corneal opacity: 0/4, 0/4, 0/4, 0/4, 0.33/4, 0.67/4; iris injury: all 0/2; redness: 2/3, 1.67/3, 1.33/3, 1.33/3, 1.33/3, 0.33/3; chemosis: all 0 or 0.33/4.(27). Application of 0.1 mL undiluted xylene (unspecified composition) caused very mild irritation in rabbits (averages score for 24, 48 and 72 hours: 5.44/110.(28) Application of xylene (52% m-, 24% p-, 19% o-) caused mild irritation and very slight, transient corneal damage in rabbits.(15) Vapour exposure (unknown concentration) to mixed xylenes (undefined composition) resulted in fine vacuoles in the corneas of cats which disappeared in 24 hours.(3)

Skin Irritation:

Xylene (mixed isomers) is a moderate skin irritant.

Application of 0.5 mL of xylene (unspecified composition), under a cover to intact skin for 4 hours, caused moderate irritation in rabbits. Average scores at 24, 48 and 72 hours for each of 6 rabbits were: erythema: 2.33/4, 2.33/4, 2.33/4, 2.33/4, 2/4, 2/4; edema: 2.3/4, 2/4, 2/4, 2/4, 2/4, 1.33/4.(27) Application of xylene (unspecified amount, probably 0.5 mL; unspecified composition) to intact and damaged skin for 24 hours caused irritation assessed as moderate in rabbits (average primary irritation score 2.21/8).(28) In a non-standard test, a single application of a disc soaked in xylene (amount and composition not specified) caused redness and skin permeability changes in rabbits. The redness disappeared after 3-5 days.(29) Repeated application, 10-20 times over a 2 to 4 week period, of mixed xylene (52% m-, 24% p-, 19% o-) to rabbit skin caused moderate to marked irritation, swelling and tissue death.(15)

Effects of Short-Term (Acute) Exposure:

Inhalation:
The major effect of xylene inhalation is on the central nervous system (CNS). There is initial excitation followed by depression, drowsiness, incoordination and unconsciousness at approximately 2000 ppm. Death at higher concentrations is from respiratory failure due to CNS depression and/or accumulation of fluid in the lungs (pulmonary edema).(4) Irritation of the respiratory tract, causing a decrease in the respiratory rate, has been reported.(3,4) The RD50, the concentration which produces a 50% decrease in the respiratory rate of mice, is 2440 ppm.(4) This concentration is expected to produce intolerable eye, nose and throat irritation (sensory irritation) in humans. Behavioural effects such as effects on learned behaviors and avoidance conditioning have been observed in animals following short-term inhalation.(3,4,16) Hearing loss, mainly at mid-frequencies, has been observed in rats following short-term exposures (800 ppm and above for 6 weeks or 1450 ppm for 3 days) to xylene (80% m-, 10% o-, 10% p-). A no-effect level was not determined and reversibility was not assessed.(3,4,16)

Effects of Long-Term (Chronic) Exposure:

In general, animal studies have provided little evidence of damage to the liver, kidney or lungs, nor any other significant long-term health effects following long-term inhalation. No effects were observed following exposure of rats or dogs to mixed xylenes (65.01% m-, 7.63% o-, 7.84% p-, 19.27% ethylbenzene) up to 810 ppm, 6 hours/day for 13 weeks.(3,6,16) Some studies have shown subtle, reversible blood effects at concentrations above 1000 ppm. However, xylenes have not been shown to cause benzene-like cancer of the blood.(1)

Ingestion:
No important findings were observed following oral administration of 1000 mg/kg (rats) and 2000 mg/kg (mice) of mixed xylenes (60.2% m-, 9.1% o-, 13.6% p-, 17% ethylbenzene) for 90 days.(3,16) Similarly, only reduced body weight was observed in male rats fed 500 mg/kg of the same mixed xylene for 103 weeks. No significant effects were noted in mice fed up to 1000 mg/kg for 103 weeks.(16)

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has determined that there is inadequate evidence for carcinogenicity of xylene in animals.(5,24)
Oral studies of mixed xylenes (60.2% m-, 9.1% o-, 13.6% p-, 17% ethylbenzene) in rats (up to 500 mg/kg for 103 weeks) and mice (up to 1000 mg/kg for 103 weeks) found no treatment-related increase in the incidence of tumours.(5) In another carcinogenicity study, xylene (unspecified composition) was administered to rats (up to 500 mg/kg for 104 weeks). The reporting of this study was so poor that it is not possible to evaluate the results. A number of studies have investigated whether exposure to xylenes causes skin cancer. The conduct and reporting of these studies do not allow any conclusions to be drawn.(3)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
Mixed xylenes are considered fetotoxic, based on observations of reduced fetal weight, delayed ossification and persistent behavioural effects in the absence of maternal toxicity. Other developmental effects have been observed in the presence of maternal toxicity.
In three studies, fetotoxic effects (delayed ossification and behavioural effects) were observed in the offspring of rats exposed by inhalation to 500 ppm mixed xylenes with up to 20% ethylbenzene.(17,18,19) In another study, fetotoxicity (decreased weight) was observed in the female offspring of rats exposed to up to 500 ppm of mixed xylenes (12.8% ethylbenzene).(6,20) No signs of maternal toxicity were observed in these studies. The offspring of rats exposed to 0, 100, 500, 1000 or 2000 ppm technical xylene (15.3% ethylbenzene, 21.3% o-xylene, 43.9% m-xylene, 19.4% p-xylene) from days 6-20 of pregnancy (6 hr/d) showed decreased fetal body weights at 500, 1000 and 2000 ppm. Maternal toxicity (reduced body weight gain and food consumption) was observed at 2000 ppm.(25) In other studies where rats and mice were exposed by inhalation or ingestion, harmful effects in the offspring (teratogenicity, embryotoxicity and/or fetotoxicity) were either not observed or were observed in the presence of significant harmful effects in the mothers. Some other studies have not been evaluated because of significant study design limitations for example, poor reporting of exposure details and/or effects, and inadequate evaluation of maternal toxicity.(3,4,6,16,20)

Reproductive Toxicity:
No harmful reproductive effects were noted in males or females when rats were exposed to up to 500 ppm mixed xylenes (44.2% m-, 20.4% o-, 20.3% p-, 12.8% ethylbenzene) in a single generation study.(3,4) No firm negative conclusions can be drawn from this study because the maximum tolerated dose may not have been achieved. Ingestion of mixed xylenes for up to 2 years caused no observable adverse effects in the reproductive organs of male and female rats (up to 500 mg/kg/day) or mice (up to 1000 mg/kg/day).(4)

Mutagenicity:
Negative results have been consistently obtained in a variety of studies using live animals and cultured cells. Mixed xylenes (11.40% o-, 52.07% m-, 0.31% p-, 36.08% ethylbenzene, and undefined compositions) gave negative results in a number of bacterial assays, with and without metabolic activation. Negative results were obtained in a variety of tests live animals exposed by a number of exposure routes. Tests for chromosome damage in rats and mice (both bone-marrow cytogenetics and micronucleus) (by oral, injection and inhalation routes) were negative. Negative results were also obtained in dominant lethal assays in rats and mice following administration by injection of adequate maximum doses.(3,4,5,16,24)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Low, L.K., et al. Health effects of the alkylbenzenes. II. Xylenes. Toxicology and Industrial Health. Vol. 5, no. 1 (1989). p. 85-105
(2) Carpenter, C.P., et al. Petroleum hydrocarbon toxicity studies. V. animal and human response to vapors of mixed xylenes. Toxicology and Applied Pharmacology. Vol. 33 (1975). p. 543-558
(3) Bell, G.M., et al. Xylenes. Toxicity Review 26. UK Health and Safety Executive, 1992
(4) Agency for Toxic Substances and Disease Registry. Toxicological profile for total xylenes (update). US Department of Health and Human Services, 1995
(5) IARC Monographs on the evaluation of carcinogenic risks to humans. Vol. 47. World Health Organization, 1989. p. 125-156
(6) Xylenes. Joint assessment of commodity chemicals: no. 6. European Chemical Industry Ecology and Toxicology Centre, June 1986
(7) Marks, T.A., et al. Teratogenicity of a commercial xylene mixture in the mouse. Journal of Toxicology and Environmental Health. Vol. 9 (1982). p. 97-105
(8) HSDB database record for xylenes. Last revision date: 9706
(9) Palmer, K.T., et al. Occupational airborne contact urticaria due to xylene. Contact Dermatitis. Vol. 28, no. 1 (1993). p. 44
(10) Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, 1989. p. 30, 80
(11) NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety and Health, June 1997
(12) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(13) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 49
(14) Urben, P.G., ed. Bretherick's handbook of reactive chemical hazards. 5th ed. Vol. 1. Butterworth-Heinemann Ltd., 1995. p. 962
(15) Wolf, M.A. et al. Toxicological studies of certain alkylated benzenes and benzene. AMA Archives of Industrial Health. Vol. 14 (1956). p. 387-398
(16) International Programme on Chemical Safety (IPCS). Xylenes. Environmental Health Criteria 190. World Health Organization, 1997
(17) Hass, U., et al. Prenatal xylene toxicity of xylene inhalation in the rat: a teratogenicity and postnatal study. Pharmacology and Toxicology. Vol. 73, no. 1 (1993). p. 20-23
(18) Hass, U., et al. Effects of prenatal exposure to xylene on postnatal development and behavior in rats. Neurotoxicology and Teratology. Vol. 17, no. 3 (1995). p. 341-349
(19) Hass, U., et al. Long-lasting neurobehavioral effects of prenatal exposure to xylene in rats. NeuroToxicology. Vol. 18, no. 2 (1997). p. 547-552
(20) Hood, R.D., et al. Developmental effects associated with exposure to xylene: a review. Drug and Chemical Toxicology. Vol. 8, no. 4 (1985). p. 281- 297
(21) Rebert, C.S., et al. Combined effects of paired solvents on the rat's auditory system. Toxicology. Vol. 105, nos. 2/3 (1995). p. 345-354
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(29) Steele, R.H., et al. The inflammatory reaction in chemical injury . I . Increased vascular permeability and erythema induced by various chemicals. British Journal of Experimental Pathology. Vol. 47 (1966). p. 612-623

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 1998-03-23

Revision Indicators:
Carcinogenicity 1999-12-01
Mutagenicity 1999-12-01
TDG 2002-05-29
WHMIS disclosure list 2003-07-09
PEL transitional comments 2003-12-19
PEL-TWA final 2003-12-19
PEL-STEL final 2003-12-19
Resistance of materials for PPE 2004-04-06
Teratogenicity/embryotoxicity 2004-06-17
Bibliography 2006-02-17
Toxicological info 2006-02-21
Short-term skin contact 2006-02-21
Short-term eye contact 2006-02-21



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