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: 144°C 139°C 138°C
Melting point: -25°C -47°C 13.4°C
Flash point: 34.4°C 30.6°C 30.0°C
Vapour pressure: 0.91kPa 1.12kPa 1.118kPa
Relative molecular
mass: 0.876 0.860 0.857
Autoignition temperature: about 500°C
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.
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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)