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Xylene

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
   3.4 Other characteristics
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. TOXICOLOGY
   7.1 Mode of Action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI) and other guideline levels
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses and other investigations
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures and symptomatic treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES
    CHEMICAL SUBSTANCES
    1. NAME
     1.1 Substance
       Xylene
     1.2 Group
       Aromatic Hydrocarbons
     1.3 Synonyms
       1,2-, 1,3-, 1,4- dimethyl benzene
       ortho-, meta-, para-xylol
     1.4 Identification numbers
       1.4.1 CAS number
             1330-20-7
       1.4.2 Other numbers
             106-42-3
             108-38-3
             95-47-6
             NCI   C55232
             UN No, 1307
             ZE2190000
             ZE2275000
             ZE2450000
             ZE2625000
     1.5 Brand names, Trade names
       Acrylic Reducer (Shell)
       All Purpose Thinner (Shell)
       Andrew Lees Commercial Brush Cleaner
       ASA-3 (Shell)
       Basecoat Thinner (Dulux)
       Bergers Commercial Brush Cleaner
       Bourne Glift (Lawson Product)
       Brush Cleaner
       C3 Lacquer Thinner
     1.6 Manufacturers, Importers
       No data available.
    2. SUMMARY
     2.1 Main risks and target organs
       The major risk from xylene involves the relatively uncommon 
       situation of very high level exposures causing progressive 
       inhibition of nervous system function, culminating in coma, 
       respiratory depression and ultimately death from cerebral 
       anoxia.  There is danger also of life-threatening cardiac 
       arrythmia.
       
       Although experience with xylene specifically is more limited, 
       moderate-to-high exposures to solvent mixtures including 
       xylene or very similar compounds (e.g. toluene) may affect a 
       number of organ systems.  This has been observed most 
       commonly in solvent abusers.  There may be disturbances in 
       renal function, fluid and electrolyte balance and skeletal 
       muscle, which can be inter-related.  Non-specific irritation 
       of the respiratory and gastrointestinal tracts can also occur,
        and occasionally adverse hepatic effects.
       
       The major target organ is the nervous system.  At lower levels,
        around and somewhat above the TLV, reversible 
       neurobehavioural effects are the first to be observed.  These 

       can be of concern as some, e.g. impaired balance and reaction 
       time, may confer a greater risk of work-related injury.
     2.2 Summary of clinical effects
       In the most usual situation of workplace exposures to 
       concentrations below the TLV, some effects may occur, 
       particularly with mixed exposures.   Mild cases may show
       eye, nose and throat irritation, nausea, headache, 
       irritability, lassitude, possibly impaired reaction time and 
       impaired short-term memory.  With moderate exposures there 
       may be dizziness, weakness, tremor, increasing confusion, 
       corneal vacuolization, and possibly asymptomatic effects on 
       renal function and haematological parameters.
       
       With severe exposure, xylene causes gradually progressing coma 
       with respiratory depression and associated anoxia, and 
       increasingly disturbed renal function and hepatic
       damage.  Death may arise from anoxia secondary to respiratory 
       depression, although cardiac sensitization may play a 
       significant role.
       
       Adverse effects on cardiac function have only rarely been 
       reported.  It is likely however that high exposures do 
       constitute a risk for cardiac arrythmia, as has been observed 
       in toluene abusers.  Hypokalaemia may be a contributory 
       factor.  The most consistent effects are, however, on the 
       nervous system, with high levels resulting in progressive 
       drowsiness, coma and death probably from respiratory failure.
     2.3 Diagnosis
       Mild exposure is associated with eye, nose and throat 
       irritation, nausea, headache, irritability, lassitude, 
       possibly impaired reaction time and impaired short-term 
       memory.  
       
       With moderate exposures there may be dizziness, weakness, 
       tremor, increasing confusion, and corneal vacuolization.
       
       With severe exposure, xylene causes gradually progressing coma 
       with respiratory depression and associated anoxia, and 
       increasingly disturbed renal function and hepatic
       damage.  Death may arise from anoxia secondary to respiratory 
       depression, although cardiac sensitization may play a 
       significant role.
     2.4 First-aid measures and management principles
       Uncommonly, spontaneous respiration may be sufficiently 
       depressed to require emergency intubation and artificial 
       ventilation as a life-saving procedure. Cardiac arrhythmias 
       require monitoring and a defibrillator may be necessary.  
       Noradrenaline and other sympathomimetics are generally 
       considered contraindicated but may be required for cardiac 
       asystole.  Oxygen should be administered.  When the patient is 
        stabilized, monitor acid-base balance and fluid and 
       electrolyte status.   Intravenous bicarbonate or potassium 
       replacement therapy may be required.  With severe symptoms 
       and/or prolonged recovery, assessment of hepatic, renal, and 
       neurolocomotor function is necessary.
    3. PHYSICO-CHEMICAL PROPERTIES

     3.1 Origin of the substance
       Synthetic, derived from distillation of petroleum principally 
       and, to a lesser extent, from coal.
     3.2 Chemical structure
       Dimethyl benzene
       
       Molecular weight  106.16
       
       Formula  CH3C6H4CH3
     3.3 Physical properties
                                          Xylene isomer
                                     ortho          meta     para
       
                 Boiling point:      144C          139C    138C
                 Melting point:      -25C          -47C    13.4C
                 Flash point:        34.4C         30.6C   30.0C
                 Vapour pressure:    0.91kPa        1.12kPa  1.118kPa
                 Relative molecular 
                 mass:               0.876          0.860    0.857
       
                 Autoignition temperature:     about 500C
                 Relative vapour density:      3.7
                 Explosive limits:             LEL 1%
                                               UEL 7%
                 Solubility     water:         practically insoluble
                              alcohol:         completely miscible
                                ether:         completely miscible
                 pH:                           not applicable
     3.4 Other characteristics
       -                                          colourless liquid
       -    odour threshold 0.2-2 ppm
       -    vapour denser than air and may travel considerable
            distances to source of ignition and flashback
       -    flammable
       -    can form explosive mixtures in air
       -    combustion/decomposition products include carbon
            monoxide, carbon dioxide
       -    no reaction with moisture
       -    reacts with oxidizing agents and strong acids, with
            generation of heat
       -    low electrical conductivity - can generate electrostatic
            charges as a result of flow, agitation
       -    aquatic toxicity high - harmful in low concentration:
            22 ppm/96hr/bluegill/TLm/fresh water B.O.D.
            016/16 5 days 
       
       
       For spills; evacuate area, shut off all sources of ignition, 
       cover with activated carbon absorbent or sand (or 
       alternatively carbon dioxide, dry chemical powder, alcohol or 
       polymer foam), or place in closed lined containers.  Transfer 
       for burial or controlled atmospheric evaporation.   Wear 
       rubber boots, gloves and self-contained breathing apparatus.  
       Ventilate area to evaporate remaining liquid.  Prevent liquid 
       entering drains or water sources.
    4. USES/CIRCUMSTANCES OF POISONING

     4.1 Uses
       Technical (industrial) xylene is a mixture of the 3 
       isomers plus ethylbenzene (6-15%) and occasionally 
       toluene, trimethyl benzene and other trace components.  
       It is widely used as a solvent and thinner for paints 
       and varnishes, often in combination with other organic 
       compounds and as a solvent in glues and printing inks.
       
       It is used as a process chemical in the rubber and 
       leather industries, in the formulation of pesticides, as 
       an intermediate in the manufacture of certain polymers, 
       in petroleum distillation, and in histology 
       laboratories.
     4.2 High risk circumstance of poisoning
       Most common uses and exposures are in the manufacture and 
       application of paints, varnishes, printing inks.  Of great 
       significance also is the intentional abuse of solvents 
       containing xylene, e.g. "glue-sniffing".
     4.3 Occupationally exposed populations
       -    Paint, varnish, ink, glue manufacturers and applicators
       -    Pesticide formulators and sprayers
       -    Histology laboratory workers
       -    Rubber, leather, petroleum and some other chemical
            industry workers
    5. ROUTES OF ENTRY
     5.1 Oral
       Accidental or suicidal ingestion.  This has occurred only 
       rarely.
     5.2 Inhalation
       Common for several occupational groups.
       Potentially significant for solvent abusers.
     5.3 Dermal
       Skin absorption is not rapid but this is a potentially 
       significant route due to the frequency of manual work in these 
       occupations.
     5.4 Eye
       This is not likely to be a significant route of entry.
     5.5 Parenteral
       Not relevant.
     5.6 Others
       Not relevant.
    6. KINETICS
     6.1 Absorption by route of exposure
       Oral
       
       Gut absorption is prompt: Bergman (1979) found that peak blood 
       levels occurred 1 to 2 hours after ingestion.
       
       Inhalation
       
       Pulmonary retention or absorption was found to be around 63.6 
       + 4.2% by Sedivec and Fleck (1976), differing little between 
       individuals and depending very little on level and duration of 
       exposure.
        
       This estimate is in agreement with that of about 60% by 

       Riihimaki et al.  (1979); although their subject numbers were 
       small, they also found a fairly constant uptake over time.
       
       Bergman (1979) found that peak blood levels occurred 15 to 30 
       minutes after inhalation.
       
       Dermal
       
       Under conditions of heavy dermal exposure, such as constant 
       immersion, pure liquid m-xylene penetrated the intact skin of 
       the hands at a rate of about 2 g/cm2/min (Engstrom et al., 
       1977).  This calculation was based on an estimate of 35 mg 
       xylene being absorbed over 15 mins.  Other experiments on 
       volunteers (Dutkiewicz & Tyras, 1968) indicated that liquid 
       xylene is absorbed through the skin at 4.5 - 9.6 mg/cm2/hr (75 
       - 160 g/cm2/min), which is a considerably higher estimate.
     6.2 Distribution by route of exposure
       Xylene distributes to a wide range of tissues. These have been 
       divided into 3 major groups by Riihimaki and Savolainen 
       (1980) on the basis of different values for the combination 
       of perfusion and partition coefficients.  Relatively well 
       perfused tissues, such as vessel-rich parenchymal organs with 
       distribution coefficients ranging from approximately 1.7 to 3.3,
       reach equilibrium within minutes; muscles equilibrate only
       after a few hours, largely because of the significantly lower 
       perfusion per unit volume of muscle tissue; adipose tissue 
       equilibrium is reached only after several working days 
       of continuous exposure due to the combination of greatly 
       increased tissue affinity, and hence capacity, and low 
       perfusion per unit volume (Riihimaki and Savolainen, 1980).
     6.3 Biological half-life by route of exposure
       The biological half-life as assessed by urinary metabolite 
       excretion after termination of inhalational exposure was 1.5 
       hours (Senczuk and Orlowski, 1978).
     6.4 Metabolism
       Over 95% of metabolism involves a pathway of oxidation to 
       methylbenzyl alcohol and subsequent reduction, via alcohol 
       dehydrogenase by aldehyde dehydrogenase, to methyl 
       benzaldehyde and methyl benzoic (or toluic) acid 
       respectively. The latter is excreted in different forms, but 
       predominantly conjugated with glycine as toluric or 
       methylhippuric acid.   With the o-isomer, however, o-toluic 
       acid is excreted in the free form (Sedivec and Fleck, 1976).
       
       A minor pathway (at least in animals) involves microsomal 
       oxidation with hydroxylation of the aromatic ring to form 
       xylenol, followed by conjugation with sulphate or glucuronic 
       acid.
       
       Urinary methylhippuric acid levels follow closely the time 
       course of xylene elimination from the blood.
     6.5 Elimination by route of exposure
       Only about 5% of xylene absorbed via the respiratory route is 
       exhaled unchanged (Astrand et al., 1978), about 95% being 
       excreted as urinary metabolites.  By far the most significant 
       compound is methylhippuric (or toluric) acid, formed by the 

       conjugation with glycine of methylbenzoic (toluic) acid, the 
       major metabolite of xylene (Riikimaki et al., 1979).   Thus 
       Sedivec and Flek (1976) estimated that toluric acid 
       represented 97.1%, 99.2% and 95.1% of excreted ortho-, meta- 
       and para-xylene respectively, while the metabolite xylenol 
       represented only 0.86%, 1.98% and 0.05% respectively.  
       Studies in volunteers by Ogata et al., (1970) indicated 
       efficient elimination, with about 72% of retained m-xylene 
       being excreted within 26 hours of exposure as m-toluric acid. 
       10 - 20% of absorbed xylene is distributed into adipose 
       tissue (Riihimaki and Savolainen, 1980) with an elimination 
       half-life from fat of 58hrs (Engstrom and Riihimaki, 1979).  
       As a consequence, some accumulation in adipose tissue will 
       occur over a few weeks after repeated daily exposure.
       
       Xylene in adipose tissue is eliminated much more slowly due to 
       its high fat/blood partition coefficient (about 100). By 
       contrast, the elimination half-life in most tissue is about 
       0.5-1 hr. Some accumulation does occur when exposure occurs 
       at levels around 3.9 mmol/m3 for 5 consecutive days for 6 
       hours per day (Riihimaki et al., 1979).
    7. TOXICOLOGY
     7.1 Mode of Action
       Little is known of the underlying mechanisms; both the 
       irritant and anaesthetic effects are probably mediated by non-
       specific mechanisms.
     7.2 Toxicity
       7.2.1 Human data
             7.2.1.1 Adults
                     Odour threshold 1 ppm.
                     
                     Inhalation
                     
                     TClo 200 ppm (870 mg/m3) Irritant effects e.g.
                                              conjunctivitis;
                                              eyes, nose, and
                                              throat irritation.   
                     
                     LC 10,000 ppm (6-18.5 hr) Estimated levels and
                                               duration (Morley et
                                               al., 1970)
                     
                     LC   6,125 ppm (12 hr)    (RTECS, 1990)
                     
                     o-xylene
                     
                     TClo 300 ppm (1350 mg/m3) 
                     (70 min)            Impairment of reaction
                                         times and short-term
                                         memory (Gamberale, 1978)
                     
                     TClo 100 ppm (435 mg/m3) 
                     (6 hours)           Impairment of reaction
                                         time and short-term
                                         memory.  Increased body
                                         sway (worse with exercise)

                     
                     Oral
                     
                     LDlo 50 mg/kg       (RTECS, 1990)
             7.2.1.2 Children
                     No data
       7.2.2 Relevant animal data
             LC50 (rat)  6,350 ppm/4hr (Hine and Zuidema, 1970)
             LC50 (rat)  6,700 ppm/4hr (Carpenter et al., 1975)
             LC (cat)    9,500 ppm/2hr (Carpenter et al., 1975)
             TC (mouse)  2,300-3500 ppm (narcosis)
                         3,500-4,600 ppm (narcosis)
             LC (mouse)  6,920 ppm (Smyth et al., 1962)
             
             Oral
             
             LD50 (rat)  4.3 g/kg (Wolf et al., 1956)
             LD50 (rat)  2.5 ml/kg (lethality between 30-70%) 
             (Gerarde, 1959)
             
             Dermal
             
             Rabbit (undiluted)  Moderate to marked irritation
             (Wolf et al., 1956)
             
             Eye
             
             Cat (undiluted)     Corneal vacuoles resembling 
             "polisher's keratitis" (Gerarde, 1956)
             
             Chronic Inhalation Effects
             
             Rat, beagle    - 180 ppm: No statistically significant
             effects (Browning, 1965)
             
             Rat, beagle - 180 ppm, 460 ppm, 810 ppm 6hr/day for 5
             days/week for 13 weeks: No statistically significant
             effects (Browning et al., 1965)
       7.2.3 Relevant in vitro data
             No data available.
       7.2.4 Workplace standards
             ACGIH Threshold Limit Values:
             
             TLV-TWA   100 ppm (435 mg/m3)
             TLV-STEL  150 ppm (655 mg/m3)
       7.2.5 Acceptable daily intake (ADI) and other guideline levels
             Not established.
     7.3 Carcinogenicity
       There is no direct evidence of carcinogenicity in humans 
       although this has not been studied epidemiologically.  
       Certainly there is no evidence of carcinogenicity in test 
       animals, nor genotoxicity in in vitro studies.  (See Section 
       7.5)  Xylene has not been the subject of an IARC review.
     7.4 Teratogenicity
       Animal Data
       

       Foetal malformations (e.g. cleft palate) have been described 
       in rodents (Hood and Ottley, 1985), but largely toxic to the 
       dams.  At 435 and 1737 mg/m3, xylene caused no significant 
       increase in malformations or weight gain but at the highest 
       exposure level there was a significant increase in retarded 
       skeletal ossification (Litton Bionetics, 1978).  Mirkova et 
       al., (1983) investigated three airborne exposure levels in 
       pregnant rats for 6 hours per day, 5 days per week, until 21 
       days gestation.  There appeared to be a significant increase 
       in delayed ossification, post-implantation losses, and 
       inhibition of weight gain at both 53 mg/m3 and 468 mg/m3 
       There also appeared to be an increased incidence of foetal 
       haemorrhage.  This study differed from previous ones in 
       describing adverse effects at under 100 mg/m3, but there was 
       some evidence that the health of the test animals may have 
       been compromised and the precise xylene mixture was not 
       specified (Hood and Ottley, 1985). Mirkova et al (1979) also 
       investigated dermal exposure at 100, 200 and 2000 mg/kg/day: 
       no comments were made on adverse reproductive outcomes.
     7.5 Mutagenicity
       Chromosome alterations and sister-chromatid exchanges (SCEs) 
       were measured among 17 of the most heavily exposed workers in 
       paint manufacturing plants, where the predominant chemicals 
       were xylene and toluene (Haglund et al., 1980).  This 
       controlled study showed no increased frequency of chromosome 
       abnormalities or SCE.  Human lymphocytes exposed in vitro to 
       xylene also showed no increases in SCE or structural 
       chromosome aberrations (Gerner-Smidt and Friedrich, 1978).  
       Bos et al (1981) tested all xylene isomers as well as some 
       metabolites (or suspected metabolites of o-xylene in the rat) 
       in the AMES test, with and without metabolic activation.  All 
       results were negative. No clastogen effects were observed in 
       bone marrow smears from rats exposed to 300 ppm mixed with 
       xylenes for up to 18 weeks (Donner et al., 1980).  The 
       majority of evidence suggests that xylene is not genotoxic.
     7.6 Interactions
       Studies in volunteers of xylene and ethanol exposures, alone 
       in combination, were not inconclusive (Savolainen, 1980).  
       Two groups of five subjects each were exposed in cross-over 
       fashion to two different levels of xylene (150 ppm, 290 ppm), 
       or ethanol (0.4 g/kg, 0.8 g/kg), and then both agents 
       together at the higher dose of ethanol.  The effect of xylene 
       alone was less than that of ethanol.  With combined exposure 
       there appeared to be an additive effect on nervous system 
       function as measured by choice reaction times.  This 
       interaction was considered possibly both pharmacodynamic and 
       pharmacokinetic because ethanol increases blood concentrations 
       of xylene, and Riihimaki et al., (1982) have shown that a 
       moderate dose of ethanol can inhibit xylene metabolism.  
       However, there was no strong dose-response relationship and 
       there was less disturbance in body sway and reaction time 
       than with ethanol alone.  The authors suggested that xylene 
       and ethanol may have different actions on the vestibular 
       system which are more opposite than additive.
       
       Campbell et al., (1988) demonstrated a mutual inhibition of

       metabolism between m-xylene (100 ppm) and aspirin (1500 mg)
       over 4 hours, as evidenced by reduced rate of excretion of
       their respective glycine conjugates during this period.  This
       may be due to competition between the two compounds for the
       conjugating mechanisms.
    8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
     8.1 Material sampling plan
       8.1.1 Sampling and specimen collection
             8.1.1.1 Toxicological analyses
             8.1.1.2 Biomedical analyses
             8.1.1.3 Arterial blood gas analysis
             8.1.1.4 Haematological analyses
             8.1.1.5 Other (unspecified) analyses
       8.1.2 Storage of laboratory samples and specimens
             8.1.2.1 Toxicological analyses
             8.1.2.2 Biomedical analyses
             8.1.2.3 Arterial blood gas analysis
             8.1.2.4 Haematological analyses
             8.1.2.5 Other (unspecified) analyses
       8.1.3 Transport of laboratory samples and specimens
             8.1.3.1 Toxicological analyses
             8.1.3.2 Biomedical analyses
             8.1.3.3 Arterial blood gas analysis
             8.1.3.4 Haematological analyses
             8.1.3.5 Other (unspecified) analyses
     8.2 Toxicological Analyses and Their Interpretation
       8.2.1 Tests on toxic ingredient(s) of material
             8.2.1.1 Simple Qualitative Test(s)
             8.2.1.2 Advanced Qualitative Confirmation Test(s)
             8.2.1.3 Simple Quantitative Method(s)
             8.2.1.4 Advanced Quantitative Method(s)
       8.2.2 Tests for biological specimens
             8.2.2.1 Simple Qualitative Test(s)
             8.2.2.2 Advanced Qualitative Confirmation Test(s)
             8.2.2.3 Simple Quantitative Method(s)
             8.2.2.4 Advanced Quantitative Method(s)
                     Gas chromatography can be used to measure xylene 
                      specifically in biological fluids using 
                     headspace methods (Engstrom et al., 1976). Gas 
                     chromatography has also been used to measure 
                     methylhippuric acids in urine, as their methyl 
                     (Caperos and Fernandez, 1977) or
                     trimethylsilyl derivatives (Engstrom et al., 
                     1976); Van Roosmalen and Drummond, 1978).
             8.2.2.5 Other Dedicated Method(s)
                     No data available.
       8.2.3 Interpretation of toxicological analyses
             In three fatalities due to the ingestion of gasoline or 
             other xylene-containing products, blood xylene 
             concentrations ranged from 2-40 mg/l (average 21), and 
             liver concentrations in all three cases were around 1 
             mg/kg (Bonnichsen et al., 1966).  Blood concentrations 
             over 3 mg/l (produced by exposures of 300-400 ppm) 
             caused significant impairment of equilibrium 
             (Savolainen et al., 1979).
     8.3 Biomedical investigations and their interpretation

       8.3.1 Biochemical analysis
             8.3.1.1 Blood, plasma or serum
             8.3.1.2 Urine
             8.3.1.3 Other fluids
       8.3.2 Arterial blood gas analyses
             No data available.
       8.3.3 Haematological analyses
             No data available.
       8.3.4 Interpretation of biomedical investigations
             No data available.
     8.4 Other biomedical (diagnostic) investigations and their 
       interpretation
       No data available.
     8.5 Overall Interpretation of all toxicological analyses and 
       toxicological investigations
     8.6 References
    9. CLINICAL EFFECTS
     9.1 Acute poisoning
       9.1.1 Ingestion
             Severe gastrointestinal signs and symptoms.
             
             If aspiration occurs, chemical pneumonitis and pulmonary 
             oedema may develop.
             
             Reversible hepatotoxicity and glycosuria have been 
             described with one relatively small ingestion 
             (Ghislandi and Fabiani, 1957).
       9.1.2 Inhalation
             Initially symptoms of eye, nose and throat irritation 
             followed by mild dizziness and lightheadedness, 
             associated with disturbed short-term memory and 
             prolonged reaction time, drowsiness, fatigue, headache, 
             nausea.  Some tolerance can develop.  In severe 
             exposures, respiratory distress, elevated serum 
             transaminases, abnormal hepatic histology, reversible 
             renal damage with albuminuria, pyuria and haematuria, 
             and possibly cardiac involvement.  Progressive nervous 
             system depression with confusion and coma.  In extreme 
             cases, death arising from anoxic respiratory depression 
             with possibly cardiac arrythmia as a contributory factor 
              in some cases.
       9.1.3 Skin exposure
             Hand immersion causes erythema and a burning sensation
             (Riihimaki, 1979).
       9.1.4 Eye contact
             Direct contact can result in conjunctivitis and corneal 
             burns.
       9.1.5 Parenteral exposure
             Not relevant.
       9.1.6 Other
             Not relevant.
     9.2 Chronic poisoning
       9.2.1 Ingestion
             Not relevant.
       9.2.2 Inhalation
             Many reports of chronic effects have involved mixed 

             solvent exposures and knowledge regarding the specific 
             toxicity of xylene is more limited, particularly as 
             regards dose-response relationships.  However, 
             volunteers studies have shed light on the effects at 
             low levels.  Apart from local effects such as dryness 
             and irritation of the eyes, nose and throat, as well as 
             nausea and anorexia, the most frequent concern relates 
             to the nervous system with effects such as headaches, 
             tiredness, irritability, and impaired performance in 
             tests of simple reaction time, perceptual speed, and 
             short-term memory.  Clinical neurological examination 
             and EEG in such subjects have generally been normal 
             although ENMG has been affected, even at concentrations 
             below the mixture TLV (Anshelm Olson, 1982).  Other 
             controlled studies of long-term exposure to solvent 
             mixtures (Elofsson S et al., 1980) suggest that 
             neurological symptoms and signs such as headache, 
             insomnia and irritability, as well as psychological and 
             neurophysiological changes, may also occur.  An initial 
             nervous excitation with apprehension and tremors has 
             been described.  Paraesthesia, weakness and vertigo have 
             also been described.
             
             Renal effects, specifically proliferative 
             glomerulonephritis, may occur.  There are conflicting 
             results in epidemiological studies although most suggest 
             some increased risk.  However, the role of xylene 
             specifically in these generally diverse exposures is 
             difficult to assess.  For example controlled studies in 
             painters exposed predominantly to xylene and toluene 
             suggested increased urinary albumin and blood cells 
             (Askergren, 1981).  A further study (Franchini et al., 
             1983) suggested possibly slight tubular effects, even 
             at relatively low concentrations, on the basis of 
             increased urinary beta-glucuronidase and lysozyme.
             
             There is little evidence of hepatotoxicity at commonly 
             encountered workplace levels: in one controlled study, 
             no increased incidence of abnormal liver function tests 
             was found in workers exposed to various solvents 
             including xylene (Kurppa and Husman, 1982).  Adverse 
             hepatic effects can occur at very high exposure levels 
             (Morley, 1970).
             
             There are no reports of bone marrow toxicity in man 
             induced exclusively by xylene.
       9.2.3 Skin exposure
             Prolonged skin contact will result in some absorption 
             and the potential for causing or exacerbating mild 
             systemic effects. In addition repeated contact causes 
             defatting and irritation of the skin with dryness, 
             cracking and blistering (Von Oettingen, 1940).
       9.2.4 Eye contact
             Exposure to a mix of solvents including xylene was 
             associated with eye irritation and photophobia.  Corneal 
             vacuoles were demonstrated and these lesions were also 

             seen when xylene was the major component in the mixture 
             (Schmid, 1956).  Nelson et al., (1943) observed eye 
             irritation at 200 ppm.
       9.2.5 Parenteral exposure
             Not relevant.
       9.2.6 Other
             Not relevant.
     9.3 Course, prognosis, cause of death
       Some effects may occur in the most usual situation of 
       workplace exposures below the TLV, particularly with mixed 
       exposures.  Thus mild cases may show eye, nose and throat 
       irritation, nausea, headache, irritability, lassitude, and 
       possibly impaired reaction time and impaired short-term 
       memory.  With moderate exposures there may be dizziness, 
       weakness, vertigo, tremor, increasing confusion, corneal 
       vacuolization, and possibly asymptomatic effects on renal 
       function and haematological parameters.
       
       After severe exposure, the effects are gradually progressing 
       coma with respiratory depression and associated anoxia, and 
       increasingly disturbed renal function and hepatic damage.  
       Death may arise from anoxia secondary to respiratory 
       depression although cardiac sensitization may play a 
       significant role.
     9.4 Systematic description of clinical effects
       9.4.1 Cardiovascular
             There is little direct evidence that xylene is 
             cardiotoxic in humans but it is probable that effects 
             will occur at very high levels.  The closely related 
             toluene, at high doses, resulted in cardiac arrhythmias,
              multifocal premature ventricular contractions or 
             supraventricular tachycardia in 5 of 25 adults 
             hospitalized after paint sniffing (Streicher et al., 
             1981).  Hypokalaemia may have been a contributory 
             factor.   Toluene is one of the solvents implicated in 
             sudden sniffing death (Bass, 1970) and as this effect 
             may depend on the physicochemical characteristics of 
             solvents rather than a specific chemical structure 
             (Clark and Tinston, 1973), it is likely that all 
             solvents have this potential, at least to some degree 
             at large doses.  Sensitization of the myocardium to 
             adrenaline, as demonstrated by Reinhardt et al (1973) 
             for some solvents, may be a significant factor.
             
             Damage to the myocardium itself has also been described 
             in severe poisoning (Sikora and Gala, 1967), and 
             Tomaszewdki et al., (1978) described a patient who 
             developed junctional cardiac rhythm.
             
             Cutaneous vasodilation with local flushing, and a 
             feeling of increased body heat has been described 
             (Gerarde, 1960).
       9.4.2 Respiratory
             Repeated exposure may produce dryness of the nose and 
             throat and irritant effects have been noticed at about 
             460 ppm (Carpenter et al., 1975).  Joyner and Pegues 

             (1961) described upper respiratory tract irritation in 
             6 of 8 workers inhaling waste vapours containing 
             xylene.  In the fatal exposure described by Morley et 
             al., (1970) there was focal intra-alveolar haemorrhage, 
             severe congestion and acute pulmonary oedema.  Vapour 
             levels were estimated in retrospect to be about 10,000 
             ppm.  Reported cases of ingestion are few and 
             subsequent pulmonary aspiration of liquid appears not 
             well documented.  However Gerarde (1960), on the basis 
             of animal experiments, states that a few ml of liquid 
             xylene on direct contact could be expected to cause 
             chemical pneumonitis, with pulmonary haemorrhage and 
             oedema.  Xylene has been classified as a cilia toxin 
             and mucus coagulating agent (Searle, 1976).
       9.4.3 Neurological
             9.4.3.1 CNS
                     Central nervous system effects are the most 
                     consistent manifestations of systemic toxicity.  
                     The effects of xylene specifically have been 
                     studied systemically at relatively low levels 
                     in volunteers.   Gamberale et al., (1978) 
                     exposed groups of 5 healthy subjects in a three-
                     way cross-over study to xylene at 
                     concentrations of 435 and 1300 mg/m3 
                     respectively for 70 minutes.  The taste and 
                     smell of the vapour was disguised.  Part of the 
                     purpose was to assess psychomotor and cognitive 
                     functions bearing in mind that the TLV of 435 
                     mg/m3 was based on levels causing irritation. 
                     Eight of the 15 subjects were then observed at 
                     the higher exposure level with half the study 
                     time spent under moderately heavy exercise.  In 
                     the initial study involving non-exercising 
                     subjects, an analysis of variance revealed only 
                     slight and statistically non-significant changes 
                     in simple addition and choice reaction times, 
                     short-term memory and critical flicker fusion. 
                     However, significant differences were observed 
                     in the addition reaction time and short-term 
                     memory with exercise at a concentration of 1300 
                     mg/m3, equivalent to three times the TLV.
                     
                     It was estimated that exercise had more than 
                     doubled the xylene uptake to about 1210 mg.  
                     The authors concluded that psychophysiological 
                     functions might begin to be affected at uptakes 
                     between 600-1000 mg but that the implications 
                     for setting an appropriate 8 hours standard 
                     were not clear due to uncertainties over the 
                     rate of metabolism. Savolainen et al., (1979, 
                     1980) performed a series of experimental 
                     studies with m-xylene to investigate the 
                     kinetics and psychophysiological effects, which 
                     they then attempted to interrelate (Riihimaki 
                     and Savolainen, 1980).  Healthy male subjects 
                     were exposed both to constant concentrations 

                     (100 ppm, 200 ppm) and to levels fluctuating up 
                     to hourly peaks of 100 ppm and 400 ppm, but
                     averaging out the same overall as previously. 
                     Exposures were for 6 hours per day and included 
                     a period of 5 successive days as well as 4 
                     episodes per day of 2 interrupted 5 minute 
                     sessions of exercise of 100W.  Three different 
                     studies were performed: sedentary subjects with 
                     exposure fluctuation; exercise periods under 
                     constant levels; and exercise sessions 
                     encompassing fluctuations of concentrations.  
                     There were statistically significant 
                     impairments in balance as measured by average 
                     and maximal body sway.  In the sedentary 
                     subjects these were noted only after the 400 
                     ppm peak, and in exercising subjects the 
                     impairment was "marked" only after this peak.  
                     For constant exposures some increase in sway 
                     was noticed at 100 ppm and above.  Impairment 
                     of simple and choice reaction times was also 
                     observed. The development of tolerance to both 
                     of these effects was noted, certainly by the 
                     fifth day, but the effects were again 
                     discernible after a two-day exposure-free 
                     interval. The effects on body balance were more 
                     related to blood levels than cumulative 
                     absorption.  The group showing the greatest 
                     effects (i.e. after the 400 ppm peaks) had blood 
                      concentrations of 29-93 mol/l.  It appeared 
                     however that the rate of rise in blood level 
                     rather than the level per se was the relevant 
                     factor in causing symptoms. Blood levels of 54 
                     mol/l achieved under exposure conditions were 
                     not associated with abnormality.  EEG changes 
                     suggestive of slightly lowered vigilance were 
                     also only observed after fluctuating levels. 
                     Body balance impairment occasionally persisted 
                     for half an hour beyond the end of exposure.  
                     The effects were less marked with xylene than 
                     ethanol, e.g. 4 hours of sedentary exposure at 
                     140 ppm and 280 ppm respectively had less 
                     effect than ingestions of 0.4 g/kg and 0.8 g/kg 
                     of ethanol.  However the molar concentrations 
                     of ethanol in blood under these conditions were 
                     more than 200 times greater than those of 
                     xylene.
                     
                     Anshelm Olson et al., (1985) studied the effects 
                     in men of four hours'exposure to 3.25 mmol/m3 
                     toluene (300 mg/m3 or 80 ppm), 2.84 mmol/m3 p-
                     xylene (300 mg/m3 or 69 ppm) or the combination 
                     of both (200 mg/3 and 100 mg/m3 respectively).  
                     No significant impairment was noted in simple 
                     or choice reaction times, or short term memory.  
                      These exposure conditions were at slightly 
                     lower levels and of shorter duration than those 

                     employed by Riihimaki and Savolainen (1980) and 
                     did not feature either exercise periods or 
                     exposure fluctuations.  The latter study, along 
                     with that of Gamberale et al., (1978) indicated 
                     that these two factors are significant 
                     determinants of the effects of xylene.  Anshelm 
                     Olson et al., (1985) noted that reaction times 
                     deteriorated both over and during experimental 
                     days, while on the other hand some aspects of 
                     memory function improved over successive days 
                     and during specific days. These findings point 
                     to the need for the effects on test performance 
                     of fatigue and learning to be taken into 
                     account in the design of such studies.
                     
                     The above studies indicated that the earliest 
                     manifestations of acute neurotoxicity include 
                     slowed reaction time, impaired memory, 
                     dizziness and drowsiness as well as headache. 
                     Increasing concentrations cause progressive CNS 
                     depression with confusion, coma and slowed 
                     respiration.
                     
                     Three subjects became comatose and one man died 
                     after exposure to xylene at estimated levels of 
                     10,000 ppm.   While this would seem to have 
                     occurred within the first 6 hours, it is not 
                     clear when the subjects became unconscious.  
                     This state persisted for at least 15 hours in 
                     the two survivors (Morley et al., 1970).
                     
                     Arthur and Curnock (1982) described a case where 
                     exposure to xylene-based glues during 
                     aeromodelling was associated 25 hours later 
                     with a grand mal convulsion as well as regular 
                     exacerbation of pre-existing petit mal in an 
                     adolescent boy; epileptic attacks did not 
                     develop with exposure to a MEK-based blue.  
                     Goldie (1960) also described a probable 
                     epileptic fit following exposure to xylene-
                     containing paint.  This is a well known 
                     consequence of toluene abuse.
                     
                     Neurobehavioural effects, similar to those 
                     observed in experimental xylene exposures, have 
                     been described in workforce populations exposed 
                     to mixtures of solvents including xylene.  
                     Anshelm Olson (1982) investigated 47 workers 
                     employed in paint manufacturing plants where 
                     xylene was the predominant solvent involved.  
                     The subjects had impaired performance in tests 
                     of simple reaction time, perceptual speed and 
                     short-term memory. It was noteworthy that while 
                     in some work tasks xylene levels were above the 
                     TLV of 100 ppm, the estimated overall TWA 
                     concentration of the combined solvents averaged 

                     just 40% of the mixture TLV.  While the 
                     duration of exposure was over 10 years in all 
                     cases, there was no evidence of EEG or clinical 
                     neurological abnormalities.
                     
                     On the other hand, some studies of car painters 
                     exposed to mixtures of solvents including xylene 
                     do suggest that neurophysiological changes and 
                     clinical abnormality may occur (Elofsson et al.,
                      1980; Husman, 1980; Husman and Karli 1980).
                     
                     Irreversible CNS effects have been attributed to 
                     toluene and similar solvents, particularly in 
                     the context of solvent abuse (Knox and Nelson, 
                     1966; King et la., 1981;   Boor and Hurtig, 
                     1977; Sasa et al., 1978; Rosenberg et al., 
                     1988) but also from long-term occupational 
                     exposures (Arlien-Soborg et al., 1979; Juntunen 
                     et al., 1980).  It is possible that comparable 
                     exposure to xylene could have the same outcome.
             9.4.3.2 Peripheral nervous system
                     There is little published evidence to show that 
                     xylene causes peripheral neuropathy but the 
                     possibility cannot be excluded.
             9.4.3.3 Autonomic nervous system
                     No human data.
             9.4.3.4 Skeletal and smooth muscle
                     No human data.
       9.4.4 Gastrointestinal
             Ingestion is likely to cause moderate to severe 
             gastrointestinal irritation and symptoms such as nausea, 
             vomiting, and possibly diarrhoea.
       9.4.5 Hepatic
             There has been little evidence of significant 
             hepatotoxicity at usual exposure levels; in one study, 
             there was no significant difference in serum liver 
             enzymes between exposed and control groups (Kurppa and 
             Husman, 1982). On the other hand, occasional high 
             exposures have resulted in a variety of complications, 
             including hepatic impairment (Morley et al., 1970) as 
             manifested by serum transaminases rising to over 100 IU 
             in one worker and 52 IU in another.  There was a fatal 
             outcome for the third worker in this episode: 
             pathological findings included hepatic cell vacuolation 
             and swelling, mainly centrilobular.
             
             Hepatotoxicity has also occurred after ingestion of 
             relatively small quantities of xylene, as evidenced by 
             toxic hepatitis and enhanced urobilinogen excretion, 
             resolving within 20 days (Ghislandi and Fabiani,1957).  
             Divincenzo and Krasavage (1974) have predicted a 
             relatively low hepatotoxicity for xylene on the basis 
             of effects on serum ornithine carbamyl transferase 
             levels in animal studies.
       9.4.6 Urinary
             9.4.6.1 Renal

                     Reversible kidney damage was observed in one of 
                     the two survivors of the high acute exposure 
                     described by Morley et al.,(1970).  They 
                     estimated air levels to be about 10,000 ppm.  
                     The patient's blood urea rose from 59 mg% to a 
                     maximum of 204 mg% three days after admission, 
                     at which time creatinine clearance was severely 
                     reduced (20 ml/min).  At fifteen days post-
                     admission his blood urea had fallen to 75 mg% 
                     and the creatinine clearance had improved to 
                     just 41 ml/min.
                     
                     Xylene has recently been implicated as possibly 
                     contributing to tubular acidosis (Martinez et 
                     al., 1989) and there may be an increased risk 
                     of proliferative glomerulonephritis (Phillips, 
                     1984); while xylene has been involved in some 
                     cases, it is impossible to assess its specific 
                     role.
                     
                     The authors suggested that a range of solvents 
                     including toluene and xylene, even at typically 
                     low level occupational exposures, may have a 
                     very weak adverse effects on the kidney, 
                     predominantly on tubular function.   With high 
                     xylene exposures, as with glue-sniffing, severe 
                     tubular dysfunction has been implicated in 
                     severe metabolic acidosis and other electrolyte 
                     abnormalities that are sometimes observed 
                     (Martinez et al., 1989).  The patient described 
                     by these authors had elevated serum urea and 
                     creatinine levels for 2 days post-admission, a 
                     situation occurring in only a minority of 
                     patients with a similar syndrome due to toluene 
                     (Streicher et al., 1981).
                     
                     There have been some conflicting results but a 
                     number of studies also indicate an increased 
                     risk of proliferative glomerulonephritis with 
                     exposure to hydrocarbon solvents (Phillips, 
                     1984) although it is considered virtually 
                     impossible to assess the role of xylene 
                     specifically.  Other studies (in painters) where 
                     exposure was predominantly to xylene and 
                     toluene also report renal effects with increased 
                     urinary excretion of both albumin and red/white 
                     cells (Askergren et al., 1981).
             9.4.6.2 Others
                     No data available.
       9.4.7 Endocrine and reproductive systems
             No data available.
       9.4.8 Dermatological
             Prolonged exposure to vapour may cause dryness of the 
             skin.   Repeated skin contact with the liquid causes 
             irritation and defatting of the skin; dryness, cracking,
              blistering and dermatitis may develop (Von Oettingen, 

             1940).  Total immersion of the hands causes erythema 
             and a burning, prickling sensation of fluctuating 
             severity within a few minutes, persisting for 30 - 60 
             minutes after exposure, and followed the next day by 
             scaling (Riihimaki, 1979).
       9.4.9 Eye, ears, nose, throat: local effects
             Conjunctivitis and corneal burns have been reported 
             following direct eye contact with liquid xylene (Gerarde,
              1960).   Irritation was noted at a concentration of 460 
             ppm of vapour by a panel of observers (Carpenter et al.,
              1975).  This group estimated the odour threshold to be 
             as low as about 4 mg/m3 or 1 ppm.
       9.4.10 Haematological
              There are no reports of bone marrow toxicity in humans 
              attributable specifically to xylene.  Pedersen and 
              Rasmussen (1982) did not note any significant or 
              characteristic haematological abnormality in a group 
              of 122 male patients with suspected organic solvent 
              poisoning; the solvents involved including xylene, 
              toluene and turpentine.
       9.4.11 Immunological
              No data available.
       9.4.12 Metabolic
              9.4.12.1 Acid-base disturbances
                       Martinez et al (1989) described various serum 
                       electrolyte abnormalities in a 28 year old who 
                       developed anorexia, vomiting and progressive 
                       coma about one week after sniffing xylene-
                       containing paints.  There was marked 
                       hypokalaemia, hyponatraemia and hypochloraemia 
                       with a high anion gap metabolic acidosis.  
                       Renal function indices were also markedly 
                       abnormal, with a serum creatinine of 368   
                       mol/l and urea of 18.2 mmol/l on admission. 
                       The acidosis was corrected by treatment with 
                       IV bicarbonate and fluid replacement for 4 
                       days.  The biochemical pattern was suggestive 
                       of renal tubular dysfunction, similar to that 
                       observed in a subgroup of 22 of 25 patients 
                       who had been sniffing toluene-containing 
                       paint (Streicher et al., 1981). However, 
                       Martinez et al (1989) did not mention any 
                       muscle weakness accompanying the hypokalaemia, 
                       as was described with the toluene patients. 
                       Hypocalcaemia was also seen.
              9.4.12.2 Fluid and electrolyte disturbances
                       No data available.
              9.4.12.3 Others
                       No data available.
       9.4.13 Allergic reactions
              No data available.
       9.4.14 Other clinical effects
              No data available.
       9.4.15 Special risks
              No controlled studies of reproductive outcome following 
               xylene exposures have been conducted in humans.  

              McDonald et al., (1987) claimed an association between 
              maternal exposure to xylene and/or toluene and urinary 
              system defects.  However a single case study must be 
              interpreted cautiously.  In one isolated case (Kucera, 
              1968), a solvent abuser was exposed to xylene in the 
              first trimester and delivered a stillborn child with 
              multiple deformities, including sacral agenesis.  Some 
              animal studies have suggested delayed skeletal 
              ossification and increased spontaneous abortion.
              
              Kucera (1968) presented a preliminary report reviewing 
              the 9 cases of sacrococcygeal agenesis (caudal 
              regression syndrome) recorded in Czechoslovakia from 
              1959-1966.  Six of the nine mothers of these infants 
              had been exposed to chemicals during pregnancy, five of 
               them being solvents and one xylene specifically.  
              Follow-up investigations using chick embryos revealed 
              a higher incidence of malformations in those exposed 
              at a critical stage to xylene, and nearly half of 
              these cases involved "rumplessness" which may reflect 
              a similar developmental abnormality to that resulting 
              in the caudal regression syndrome in humans.
     9.5 Others
       No data available.
     9.6 Summary
    10. MANAGEMENT
      10.1 General principles
         There is no specific antidote and management will be largely 
         supportive.
      10.2 Relevant laboratory analyses and other investigations
         10.2.1 Sample collection
         10.2.2 Biomedical analysis
         10.2.3 Toxicological analysis
         10.2.4 Other investigations
      10.3 Life supportive procedures and symptomatic treatment
         With ingestions, observe pulmonary function for 4 to 6 hours 
         because of the possibility of aspiration, particularly if 
         coughing is a prominent early symptom.  Baseline chest 
         radiograph and arterial blood gases are indicated with 
         severe cough or pulmonary symptoms or signs.  Significant 
         abnormality warrants hospital admission.
      10.4 Decontamination
         Following ingestion, emesis or preferably lavage is 
         indicated with amounts over 1 ml/kg if seen within 1 hour.  
         Airway protection is required in comatose patients and/or 
         with inadequate gag reflex.
      10.5 Elimination
         No methods have been established as effective in hastening 
         xylene metabolism or excretion.  Assisted ventilation will 
         be of little help in this regard due to the minor 
         contribution of the lung as a route of elimination.
      10.6 Antidote treatment
         10.6.1 Adults
                There are no specific antidotes.
         10.6.2 Children
                There are no specific antidotes.

      10.7 Management discussion
         The usefulness of charcoal in the decontamination of xylene 
         requires investigation.
    11. ILLUSTRATIVE CASES
      11.1 Case reports from literature
         Case 1
         
         Morley et al., (1970) described the situation of a severe 
         exposure of three man to paint vapour, the solvent of which 
         was over 90% xylene. These workers were painting a double-
         bottomed storage tank.  The retrospective estimation of 
         probable xylene airborne levels was 10,000 ppm, assuming 
         still air conditions.  Ventilation of the space, by a 
         length of 8.9cm diameter ducting connected to an extractor 
         fan, was minimal and respirators were not worn.  There was 
         no evidence in spite of the confined nature of the space 
         that oxygen levels would have been significantly reduced.
         
         Two men were comatose and one had died when found the 
         following morning 18 hours later.  It is not clear when 
         they first became unconscious.  It is probable that this 
         occurred during the first 6 hours as they were unaccounted 
         for after this, their scheduled finishing time, until they 
         were found next morning.  The two survivors recovered 
         consciousness within 15 and 18 hours respectively with 
         supportive management, including in one case tracheal 
         aspiration, oxygen and prophylactic antibiotics.  This 
         subject showed evidence of impaired renal function, with 
         blood urea rising from 59 mg/100 ml on admission to 204 
         mg/100 ml after 3 days, at which time creatinine clearance 
         was severely reduced at 19.7 ml/min. Partial but by no 
         means complete reversal had occurred after 15 days, with a 
         blood urea of 75 mg/100 ml and creatinine clearance 41 
         ml/min.  Both subjects had confusion and amnesia and 
         displayed evidence of mil hepatotoxicity with serum 
         transaminase rising to a maximum after 48 hours of over 100 
         IU and 52 IU respectively.  Autopsy in the other worker 
         revealed severe pulmonary congestion and oedema with focal 
         intra-alveolar haemorrhage, swelling and vacuolation of 
         large centrilobular hepatocytes and anoxic neuronal damage.
         
         Case 2
         
         Martinez et al., (1989) described a 28 year-old man with a 
         long history of heavy ethanol consumption (approximately 60 
         g daily) and solvent (paint) abuse, who presented with a 
         one week history of anorexia, vomiting and progressive coma 
         in association with the sniffing of paints containing 
         xylene. Findings included hyponatraemia (120 mmol/l), 
         hypochloraemia (80 mmol/l), hypokalaemia (1.8 mmol/l), 
         metabolic acidosis (pH 7.08, bicarbonate 9.4 mmol/l) with a 
         high anion gap (31 mmol/l) and evidence of impaired renal 
         glomerular function (creatinine 368 mol/l, urea 18.2 
         mmol/l). Cardiopulmonary examination was normal (other than 
         ECG signs of hypokalaemia) and there was no mention of 
         muscle weakness. The biochemical abnormalities were 

         attributed to distal tubular dysfunction and it was noted 
         that blood ethanol was absent.  Treatment consisted of 
         rehydration with electrolyte and bicarbonate repletion (the 
         latter at more than 240 mg daily) which was necessary for 
         about 4 days to correct the metabolic acidosis.   
         Hypocalcaemia and hypophosphataemia were also observed.  The 
         authors suggested that the conjugated metabolite of xylene, 
         methylhippuric acid, perhaps accumulating due to a reduced 
         glomerular filtration rate, could have titrated 
         extracellular bicarbonate and contributed to the high anion 
         gap metabolic acidoses.
         
         Case 3
         
         Arthur and Curnock (1982) discussed the case of a 15 year-
         old boy with a past history of petit mal absence seizures 
         for 2 years which had been treated successfully with 
         ethosuximide.  These attacks were precipitated on several 
         occasions following use of an aeromodelling glue containing 
         xylene as solvent but not by glue containing methyl ethyl 
         ketone and tetrahydrofuran.  He later presented with 
         generalized grand mal seizure about 24 hours after 
         aeromodelling after again using xylene-based glue.  Further 
         bouts of petit mal occurred at a later date, again about 24 
         hours after use of xylene glue.  It should be added that 
         these later returned in the absence of such exposure, and 
         that an electroencephalogram done after sniffing glue 
         showed no acute changes, but the history suggests a causal 
         relationship.
         
         Case 4
         
         Goldie (1960) had previously reported acute symptoms 
         resembling an epileptic seizure in an 18-year-old boy who 
         developed weakness, dizziness and aphasia followed by loss 
         of consciousness for twenty minutes with clonic contraction 
         of the limbs.  A briefer episode occurred later in the 
         hospital, followed by a full recovery.  He had been one of 
         eight workers painting gun towers with a paint containing 
         80% xylene and 20% methyl glycol acetate.  Xylene levels 
         had been sufficient inside the tower to result in an 
         identifiable odour and the ventilation system had not been 
         utilized.  Most workers had developed headache, vertigo, 
         gastric discomfort, throat dryness and slight 
         "drunkenness". The first symptoms of the epileptiform attack 
         commenced when the 18-year-old was cycling home from work.  
         It was suggested on the basis of previous but ill-defined 
         "auras" occurring in this subject that he may have had a 
         latent susceptibility for epilepsy and that xylene provoked 
         or precipitated the grand mal episode.
      11.2 Internally extracted data on cases
         No data available.
      11.3 Internal cases
    12. ADDITIONAL INFORMATION
      12.1 Availability of antidotes
         Not relevant

      12.2 Specific preventive measures
         No data available.
      12.3 Other
         No data available.
    13. REFERENCES
    Anshelm Olson B (1982) Effects of organic solvents on behavioral 
    performance of workers in the paint industry.  Neurobehav 
    Toxicol Teratol  4:703-708.
    
    Anshelm Olson B, Gamberale F & Iregren A (1985) Coexposure to 
    Toluene and p-xylene in man: central nervous functions.  British 
    Journal of Industrial Medicine 42:117-122.
    
    Arlien-Soborg P, Bruhn P, Gyldensted C & Melgaard B (1979) 
    Chronic painters' syndrome.  Acta Neurol Scandinav  60:149-156.
    
    Arthur LJH & Curnock DA (1982)  Xylene-induced epilepsy following 
    innocent glue sniffing (Letter) Brit Med  J  284:1787
    
    Askergren A (1981)  Studies on kidney function in subjects 
    exposed to organic solvents.  III  Excretion of cells in the 
    urine.  Acta Med Scan 210:103-106.
    
    Askergren A, Allgren L-C, Karlsson C, Lundberg I & Nyberg E 
    (1981)  Studies on kidney function in subjects exposed to organic 
    solvents. I Excretion of albumin and beta-2-microglobulin in the 
    urine.  Acta  Med  Scan  209:479-483.
    
    Astrand I,  Engstrom J & Ovrum P (1978)  Exposure to xylene and 
    ethylbenzene.  I Uptake, distribution and elimination in ma. 
    Scand J Work  Environ & Hlth  4:185-194.
    
    Aviado DM & Belej MA (1974)  Toxicity of aerosol propellants o 
    the respiratory and circulatory system.  I Cardiac arrhythmias in 
    the mouse. Toxicology   2:31-42.
    
    Baker EL & Fine LJ (1986)  Solvent neurotoxicity: the current 
    evidence.  J Occ Med 28(2):126-129.
    
    Bass M (1970)  Sudden sniffing death.  JAMA 212:2075-2079.
    
    Bergman K (1979)  Whole-body autoradiography and allied tracer 
    techniques in distribution and elimination studies of some 
    organic solvents: benzene, toluene, xylene, styrene, methylene 
    chloride, chloroform, carbon tetrachloride and  
    trichloroethylene.  Scand J  Work Environ Health 5(Supp 1):1-
    263.
    
    Bonnichsen R, Maehly AC & Moeller M (1966) Poisoning by volatile 
    compounds. I  Aromatic hydrocarbons.  J  For Sci  11:186-204.
    
    Bonzel KE, Muller-Wiefel DE & Ruder H  et al., (1987) 
    Antiglomerular basement membrane antibody-mediated 
    glomerulonephritis due to glue sniffing.  Eur  J  Pediatr  
    146:296-300.
    

    Boor JW & Hartig HI (1977)  Persistent cerebellar ataxia after 
    exposure to toluene.   Annals  Neurol  442.
    
    Bos RP, Brouns RME, Van Doorn R, Theuns JLG & Hendersson P Th 
    (1981) Non-mutagenicity of toluene, o-, m-, p- xylene, o-
    methylbenzylalcohol and o-methylbenzylsulfate in the Ames assay. 
    Mutat  Res  88:273-279.
    
    Browning E (1965)  Xylene In: Toxicity and Metabolism of 
    industrial solvents.  Elsevier, New York.
    
    Campbell L, Wilson HK, Samuel AM & Gompertz D (1988)  
    Interactions of m-xylene and aspirin metabolism in man.  British 
    Journal of Industrial Medicine  45:127-132.
    
    Caperos JR & Fernandez JG (1977) Simultaneous determination of 
    toluene and xylene  metabolites in urine by gas chromatography.  
    Brit J Ind Med 34:229-233.
    
    Carpenter CP, Kinkead ER, Geary Jr DL, Sullivan LJ & King LM 
    (1975) Petroleum hydrocarbon toxicity studies.  V Animal and 
    human response to vapors of  mixed xylenes.  Toxicol  Appl  
    Pharmacol 33:543-558.
    
    CCINFO (1989) Canadian Centre for Occupational Health and Safety.
    
    Clark DG & Tinston DJ (1973)  Correlation of the cardiac 
    sensitizing potential of halogenated hydrocarbons with their 
    physiochemical properties. Br J  Pharmacol 49:355-357.
    
    Divincenzo GD, Krasavage WJ (1974)  Serum ornithine carbamyl 
    transferase as a liver response test for exposure to organic 
    solvents. Am  Ind  Hyg Assoc  J  35:21-29.
    
    Donner M, Maki-Paakkanen J, Norppa H, Sorsa M & Vainio H (1980)  
    Genetic toxicology  of xylenes.  Mutat  Res  74:171-172.
    
    Dutkiewicz T, & Tyras H (1968)  Skin absorption of toluene, 
    styrene and xylene by  man.  Brit  J  Industr  Med 25:243.
    
    Elofsson S, Gamberale F, Hindmarsh T, Iregren A, Isaksson A, 
    Johnsson I, Knave B,  Lydahl E, Mindus P, Persson HE, Philipson B,
     Steby M, Struwe G, Soderman E, Wennberg  A & Widen L (1980) 
    Exposure to organic solvents:  a cross-sectional epidemiologic  
    investigation on occupationally exposed car and industrial spray 
    painters with  special reference to the nervous system. Scan J 
    Work Environ Health 6:239-273.
    
    Engstrom K, Husman K & Rantanen J (1976) Measurement of toluene 
    and xylene  metabolites by gas chromatography.  Int  Arch Occup  
    Environ Health 36:156-160.
    
    Engstrom K, Husman K & Riihimaki V (1977)  Percutaneous 
    absorption of m-xylene in  man.  Int  Arch  Occup  Environ  Hlth  
    39:181-189.
    

    Engstrom J & Riihimaki V (1979)  Distribution of m-xylene to 
    subcutaneous adipose  tissue in short-term experimental human 
    exposure. Scand J Work Environ & Health   5:126-134.
    
    Franchini I, Cavatorta A, Falzoi M, Lucertini S & Mutti A (1983)  
    Early indicators of  renal damage in workers exposed to organic 
    solvents.  Int Arch  Occup  Environ   Health 52:1-9.
    
    Gamberale F, Annwall G, Hultengren M (1978) Exposure to xylene 
    and ethylbenzene.  III Effects on central nervous functions.  
    Scand J Work Environ   Health 4:204-211.
    
    Gerarde HW (1959)  Toxicological studies on hydrocarbons.  III  
    The biochemomorphology of the phenylalkanes and phenylalkenes.  
    Am  Med  Assoc Arch  Ind   Hlth  19:403-418.
    
    Gerarde HW (1960)  Toxicology & Biochemistry of Aromatic 
    Hydrocarbons. Elsevier  Publishing Co., London p171-180.
    
    Gerner-Smidt P & Friedrich U (1978)  The mutagenic effect of 
    benzene, toluene, and xylene studied by the SCE technique.  Mutat 
    Res 58:313-316.
    
    Ghislandi E & Fabiani A (1957)  Hepatic lesions due to accidental 
    ingestion of  solvent for nitrocellulose varnishes.  Med Lav  
    48:577-579 (translated).
    
    Goldie I (1960) Can xylene (xylol) provoke convulsive seizures? 
    Ind Med Surg 29:33-35.
    
    Haglund U, Lundberg I & Zech L (1980)  Chromosome aberrations and 
    sister chromatid  exchanges in Swedish paint industry workers. 
    Scand J Work Environ & Hlth 6:291-298.
    
    Hanninen H, Eskelinen L, Husman K & Nurminen M (1976)  Behavioral 
    effects of  long-term exposure to a mixture of organic solvents.  
    Scand J  Work Environ  Health   4:240-255.
    
    Hayden JW & Comstock EG (1976)  The clinical toxicology of 
    solvent abuse. Clinical  Toxicology 9:169-183.
    
    Herd PA, Lipsky M & Martin HF (1974)  Cardiovascular effects of 1,
    1,1 trichloroethane.  Archives of Environmental Health 28:227-
    233.
    
    Hine CH & Zuidema HH (1970) The toxicological properties of 
    hydrocarbon solvents.   Ind Med Surg  39:215-220.
    
    Hood RD & Ottley MS (1985) Development effects associated with 
    exposure to xylene: a  review.  Drug and Chemical Toxicology 
    8(4):281-297.
    
    Hudak A & Ungvary G (1978)  Embryonic effects of benzene and its 
    methyl derivatives:   toluene, xylene.  Toxicology 11:55-63.
    
    Husman K (1980) Symptoms of car painters with long term exposure 

    to amixture of organic solvents.  Scand  J  Work Environ  Health  
    6:19-32.
    
    Husman K & Karli P (1980)  Clinical neurological findings among 
    car painters exposed to a mixture of organic  solvents.  Scand J 
    Work Environ Health   6:33-39.
    
    Joyner RE & Pegues WL (1961)  A health hazard associated with 
    epoxy resin-concrete  dust.  J Occup  Med 3:221.
    
    Juntunen J, Hernberg S, Eistola P & Hupli V (1980)  Exposure to 
    industrial solvents  and brain atrophy.  Eur Neurol 19:366-375.
    
    Juntunen J, Hupli V, Hernberg S & Luisto M (1980)  Neurological 
    picture of organic poisoning in industry.  Int Arch Occup Environ 
    Health  46:219-231.
    
    King MD, Day RE, Oliver JS, Lush M & Watson JM (1981)  Solvent 
    encephalopathy.  Br  Med  J  283:663-665.
    
    Knox J & Nelson IR (1966)  Permanent encephalopathy from toluene 
    inhalation.  N Engl J Med  275:1494-1496.
    
    Kucera J (1968) Exposure to fat solvents: A possible cause of 
    sacral agenesis in man.  The Journal of Pediatrics  72:857-859.
    
    Kurppa K, Husman K (1982)  Car painter's exposure to mixture of 
    organic solvents.   Serum activities of liver enzymes.  Scand J 
    Work Environ Health 8:137-140.
    
    Lindbohn M, Taskinen H, Sallmen M & Hemminki K (1990)  
    Spontaneous abortions among women exposed to organic solvents. 
    Amer J Ind Med 17:449-463.
    
    Lindstrom K (1973)  Psychological performance of workers exposed 
    to various solvents.   Wk  Env  Hlth  10:151-155.
    
    Litton Bionetics (1978)  Teratology study in rats - xylene.  
    Final report.  Unpublished report prepared by Litton Bionetics, 
    Inc., Kensington, MD, for American  Petroleum Institute, 
    Washington, DC, LBI Project No. 20698-5.
    
    Martinez JS, Sala JJG, Vea AM & Casals EC (1989)  (Letter)  Renal 
    tubular acidosis  with an elevated anion gap in a glue sniffer.  
    Human Toxicol 8:139-140.
    
    MC Donald JC, Lavoie J, Cote R et al., (1987)  Chemical exposures 
    at work in early  pregnancy and congenital defect:  a case-
    referent study. Br J Ind Med  44:527-533.
    
    Mirkova E 81983)  Prenatal toxicity of xylene.  J Hyg Epidermiol  
    Microbiol Immunol 27:337-343.
    
    Mirkova E, Hinkova L, Vassileva L & Bogdanova N (1979)  Xylene 
    neurotoxicity in pregnant rats and fetuses. Activ Nerv Sup 
    (Praha) 21:265.

    
    Mirkova E, Zaikov C, Antov G, Mikhailova A, Khinkova L & Benchev 
    I (1983) Prenatal toxicity of xylene.  J Hyg Epidem  Micro 
    Immunol 27:337.
    
    Morley R, Eccleston DW, Douglas CP, Greville WEJ, Scott DJ & 
    Anderson J (1970)   Xylene poisoning - a report on one fatal case 
    and two cases of recovery after  prolonged unconsciousness.  Br 
    Med J 3:442-443.
    
    Nelson KW, Ege J, Ross M, Woodman LE & Silverman L 81943)  
    Sensory response to  certain industrial solvent vapours.  J Ind 
    Hyg Toxicol  25:282.
    
    Ogata M, Tomokuni K & Takatsuka Y (1970)  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. Brit J industr Med  27:43.
    
    Pedersen LM, Mygaard E, Nielsen OS & Saltin B (1980a) Solvent 
    induced occupational myopathy. J Occup Med 22:603-607.
    
    Pedersen LM & Rasmussen JM (1982)  The haematological and 
    biochemical pattern in occupational organic solvent poisoning and 
    exposure.  Int Arch Occup Environ Health  51:113-126.
    
    Phillips SC (1984)  A review of the human kidney effects of 
    hydrocarbon exposure.   In:  Mehlman MA, Hemstreet GP, Thorpe JJ, 
    Weaver NK (Eds), Advances in Modern  Environmental Toxicology Vol 
    7: Renal Effects of Petroleum Hydrocarbons, p 185. Princeton 
    Scientific Publishers,  Princeton NJ.
    
    RTECS (April 1990)  National Institute for Occupational Safety 
    and Health.
    
    Reinhardt CF, Mullin LS & Maxfield ME (1973)  Epinephrine-induced 
    cardiac arrythmia potential of some common industrial solvent.  J 
    Occup Med 15:953-955.
    
    Riihimaki V (1979c)  Percutaneous absorption of m-xylene from a 
    mixture of m-xylene an isobutyl alcohol in man. Scand J Work 
    Environ Health 5:135-142.
    
    Riihimaki V, Pfaffli P & Savolainen K (1979)  Kinetics of m-
    xylene in man. Influence of intermittent physical exercise and 
    changing environmental concentrations on  kinetics.
    Scand J Work Environ & Hlth 5:232-248.
    
    Riihimaki V & Savolainen K (1980)   Human exposure to m-xylene.  
    Kinetics and acute  effects on the central nervous system.  Ann 
    Occup Hyg  23:411-422.
    
    Riihimaki V, Savolainen K, Pfaffli P, Pekari K, Sippel HW & Laine 
    A (1982) Metabolic  interaction between m-xylene and ethanol.  
    Arch Toxicol  49:253-263.
    

    Rosenberg NL, Kleinschmidt-Demasters BK, Davis KA et al (1988)  
    Toluene abuse causes  diffuse central nervous system white matter 
    changes. Ann Neurol  23:611-614.
    
    Sandmeyer EE (1981)  Aromatic hydrocarbons.  In: Patty's 
    Industrial Hygiene and Toxicology  (Eds Clayton GD & Clayton FE)  
    John Wiley and Sons, New York.
    
    SASA M, Igarashi S, Miyazaki T et al., (1978)  Equilibrium 
    disorders with diffuse brain atrophy in long-term toluene 
    sniffing. Archives of Otorhinolaryngology 221-163-169.
    
    Savolainen K (1980)  Combined effects of xylene and alcohol on 
    the central nervous system.  Acta  Pharmacol  Toxicol  46:366-
    372.
    
    Savolainen K, Riihimaki V, Linnoila M (1979)  Effects of short-
    term xylene exposure on psychophysiological functions in man.  
    Int  Arch Occup Environ Health  44:201-211.
    
    Savolainen K, Riihimaki V, Luukkonen R & Muona O (1985)  Changes 
    in the sense of balance correlate with concentrations of m-xylene 
    in venous blood. Br  J  Indust  Med 42:765-769.
    
    Savolainen K, Riihimaki V, Seppalainen AM & Linnoila M (1980)  
    Effects of short term m-xylene exposure and physical exercise on 
    central nervous system.  Int  Arch Occup Environ Health  45:105-
    121.
    
    Schmid E (1956)  Diseases of the cornea in furniture polishers. 
    Arch Gewerbepath 15(1):37-44.
    
    Searle CE (ED) (1976)  Chemical Carcinogens.  American Chemical 
    Society, Washington  D.C.
    
    Sedivec V & Flek J (1976)  The absorption, metabolism and 
    excretion of xylenes in man. Int Arch Occup Environ Hlth 37:205-
    217.
    
    Senczuk W & Orlowski J 81978)  Absorption of m-xylene vapours 
    through the respiratory  tract and excretion of m-methylhippuric 
    acid in urine. Br J Ind Med  35:50-55.
    
    Sikora H & Gala J (1967)  Myocardial damage in acute xylene 
    poisoning (in Polish)   Med Pr 18:75-77.
    
    Smyth HF, Carpenters CP, Weil CS, Pozzani UC & Striegel JA (1962) 
     Range-finding  toxicity data: List VI  Am  Ind Hyg  Assoc  J  
    23:95-107.
    
    Spencer PS & Scheumburg H.H. (1985)  Organic solvent 
    neurotoxicity: facts and  research need.  Scand  J  Work Environ  
    Health  Supp  I:53-60.
    
    Streicher HZ, Gabow PA, Moss AH, Kono D & Kaehny WD (1981)  
    Syndromes of Toluene  Sniffing in Adults.  Annals of internal 

    Medicine 94:758-762.
    
    Svirbely JL, Dunn RC & Von Oettingen WF (1943)  The acute 
    toxicity of vapours of certain solvents containing appreciable 
    amounts of benzene and toluene.  J  Ind Hyg Tox 25:366-373.
    
    Tomaszewdki R, Gandurski P & Chmielewski J (1978)  Junctional 
    rhythm in xylene  poisoning.  Wiad  Led  31:193-194.
    
    Van Roosmalen PV & Drummond I (1978)  Simultaneous determination 
    by gas  chromatography of the major metabolites in urine of 
    toluene, xylene and styrene.  Br  J Ind Med  35:56-60.
    
    Von Oettingen WF (1940)  Publ  Health  Bull  No.255, US Public 
    Health Service, Washington DC.
    
    Will AM & Mclaren EH (1981)  Reversible renal damage due to glue 
    sniffing (British Medical Journal  283:525-526.
    
    Wolf MA, Rowe VK, McCollister DD, Hollingsworth RC &  Oyen F 
    (1956) Toxicological studies of certain alkylated benzenes and 
    benzene.  Am Med Assoc Arch Ind Hlth  14:387-398.
    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
    ADDRESSES
    Author:   Dr M. Beasley
              National Toxicology Group
              University of Otago Medical School
              P.O. Box 913
              Dunedin
              New Zealand
    
              Tel: 64-3-4797248
              Fax: 64-3-4770509
    
    Date:     January 1992
    
    Peer Review:   Newcastle-upon-Tyne, United Kingdom, February 1992 
    
                   (Reviewers: E. Wickstrom, J.C. Berger, N. Bateman, 
    
                   R. Fernando, W. Temple)




    See Also:
       Toxicological Abbreviations