Xylene

1330-20-7

Solvent in resins, lacquers, enamels and rubber cements, in
aviation fuel, and in the manufacture of polyester,
pharmaceuticals, dyes, insecticides, asphalt and naphtha.

Threshold odour concentration in water: 1 - 2 mg/l (Zoeteman et
al. 1974).

Quality: sweet
Hedonic tone: neutral to pleasant
Threshold odour concentration
absolute: 0.08 ppm
50 % recognition: 0.27 ppm
100 % recognition: 0.27 ppm
Odour index 100 % recognition: 29 222
(Hellman & Small 1974)

106.17

Relative volatility (nBuAc=1) = 0.6

Confirmed to be biodegradable (Anon. 1987).

Xylene is thought to be well absorbed by the gastrointestinal
tract, and distributed to the lipid-rich tissues. 
Metabolism in
the liver is rapid, but the pathways differ slightly, depending
on the isomer (Fawell & Hunt 1988).

In man, about 60 % of inhaled xylene is retained by the lungs
(Sedivec & Flek 1976, Astrand et al. 1978). 

Percutaneous absorption also occurs readily. 
Although there are 
no data on gastrointestinal absorption, xylene would be 
expected to be readily absorbed in view of its lipophilic 
nature (Engström et al. 1977).

The distribution of xylene in the body is dependent on the fat
content of individual tissues. 
The highest levels of xylene are
found in lipid-rich tissues such as the adipose tissue,
subcutaneous fat, adrenal glands, brain and liver (Fawell &
Hunt 1988).

The metabolic pathways differ for each xylene isomer. 
The meta-
and para-isomers are 80 - 90 % metabolized to the corresponding
toluic acids and glycine conjugates (Williams 1959). 
Only 60 % 
of ortho-xylene is transformed to ortho-toluic acid, and of 
this roughly half remains free, about half is conjugated with
glucoronide, and only 0.3 % is conjugated with glycine (Bray et
al. 1949, Ogata et al. 1970). 
Aromatic ring oxidation to
hydroxyxylenes (xylenols) has also been reported for each
isomer, but this appears to be only a very minor route (Bakke &
Scheline 1970). 
Methylbenzylmercapturic acids have also been
identified as metabolites of xylenes, though only
transformation of ortho-xylene in this manner appears to be of
any quantitative significance (Van Doorn et al. 1980).

Xylene is excreted in the urine as methylhippuric acids, free
toluic acids, toluogluronic acids, dimethylphenols and
methylbenzylmercapturic acids. 
A small amount of unchanged
xylene can be exhaled from the lungs (Sedivec & Flek 1976).

The xylenes are of low acute toxicity in experimental animals.

At high doses their principal effects are CNS depression and
membrane irritation. 
The xylenes also appear to be of low
chronic toxicity, though they have not been tested by the oral
route (Fawell & Hunt 1988).

Fabacher & Hodgson (1977) were unable to demonstrate enhanced
hepatic microsomal O- or N-demethylase activity, or changes in
the liver weight/body weight ratio of mice given daily
intraperitoneal injections of 100 mg/kg of xylene for 3 days.

In another study, increased serum ornithine-carbamyl
transferase activity and higher levels of hepato-lipids were
found in guinea-pigs following intraperitoneal injection of 1
g/kg xylene in corn oil (Divincenzo & Krasavage 1974).

Combined administration of ethanol and xylene appears to result
in additive effects on both the CNS and hepatic enzyme
activities (Elovaara et al. 1980, Savolainen 1980, Riihimäki et
al. 1982).

No significant changes in blood parameters were found in rats
and rabbits exposed by inhalation to 690 ppm of mixed xylenes, 8
hours/day, 6 days/week for 130 days. 
Exposure of rabbits to
1150 ppm for 55 days in the same study was found to result in
lowered numbers of erythrocytes and leukocytes, and an increase
in platelet numbers (Fabre & Truhaut 1954). 
No myelotoxic
effects were observed in rabbits given 300 mg/kg/day of xylene
by subcutaneous injection for 6 weeks or 700 mg/kg/day of
xylene for 9 weeks (Speck and Moeschlin 1968).

Acute exposure to very high doses of xylene can cause erythema,
dehydration, defatting and blistering of the skin, irritation
of mucous membranes, peripheral vasodilation, giddiness,
fatigue, 'drunkenness', narcosis and unconsciousness (Fawell &
Hunt 1988).

The most common effects of acute exposure to lower levels of
xylene are CNS-related. 
Gamberale et al. 
(1978) exposed 8
healthy men to 1300 mg/m3 of xylene in inspired air for 70
minutes, 30 minutes of which was spent on a bicycle ergometer
(100 W). 
The authors reported clear evidence of performance
decrement in three out of a battery of behavioural test.

Changes in dopamine and noradrenaline levels in selected areas
of the brain have been found in rats exposed by inhalation to
2000 ppm of xylene, 6 hours/day for 3 days (Andersson et al.
1981).

There appears to be no information on the carcinogenicity of
xylenes other than two skin-painting studies of inadequate
length (Fawell & Hunt 1988).

Although no evidence for carcinogenicity was found in two 6
month skin painting experiments in mice (Kennaway 1924,
Berenblum 1941), these studies were of insufficient duration,
and therefore only very limited conclusions can be drawn.

Long-term studies of mixed xylenes (60 % meta, 14 % para and 9 %
ortho- and 17 % ethylbenzene) given by gavage at doses of 250 or
500 mg/kg to rats and 500 or 1000 mg/kg to mice, indicated
no evidence of carcinogenicity (US National Toxicology Program
1986).

The xylenes do not appear to be mutagenic in the Ames test, but
there is only limited information available in higher test
systems (Fawell & Hunt 1988).

All three isomers of xylene have given negative results for
mutagenicity in the Ames test with Salmonella typhimurium, both
in the presence and absence of either rat liver or hamster
liver S-9, and at doses ranging from 1.0 - 500 µg/plate (Bos et
al. 1981, Haworth et al. 1983).

Xylenes have been shown not to be mutagenic in the Salmonella /
microsome assay, bacterial DNA repair, not cause chromosome
aberrations or sister chromatid exchanges in mammalian cells in
vitro. 
Equivocal results were obtained in Drosophila germ
cells but they did not cause chromosome aberrations in rat bone
marrow in vivo (Dean 1978, 1985).

Dose levels of 0.0152 - 1.52 mg/ml of xylene were not found to
increase chromosome aberrations or sister chromatid exchanges
in human lymphocytes in vitro (Gerner-Smidt and Friedrich
1978). 
Although no experimental data were given, Bos et al.

(1981) reported that ortho-, meta- and para-xylene had
given negative results for unscheduled DNA synthesis in primary
cultures of rat hepatocytes.

Mohtashamipur et al. 
(1985) report that ortho-, meta- and
para-xylenes did not induce micronuclei in the bone marrow
polychromatic erythrocytes of mice.

There is some evidence that xylene is teratogenic in mice at
very high dose levels (Fawell & Hunt 1988).

Xylene has been found at higher concentrations in cord blood
than in maternal blood (Dowty et al. 1976).

Two studies in mice have reported teratogenic effects of
xylene. 
Nawrot and Staples (1980) dosed CD-1 mice by gavage
with 0.3, 0.75 or 1.0 ml/kg/day of pure ortho-, meta-, or
para-xylene on days 6 - 15 of gestation. 
Increased incidences
of cleft palate and foetal resorptions were found at the two
higher dose levels with the ortho- and para-isomers. 
In the
other study, Marks et al. 
(1982) dosed CD-1 mice by gavage with
0.52, 1.03, 2.06, 2.58, 3.10 or 4.13 g/kg/day of a commercial
xylene mixture (60.2 % m-xylene, 9.1 % ortho-xylene, 13.6 %
p-xylene and 17 % ethylbenzene) in cottonseed oil, on days 6 -
15 of gestation. 
A significant increase in the incidence of
malformed foetuses was found at the 2.06, 2.58 and 3.10 g/kg
dose levels. 
The major malformation was again cleft palate.

Other studies have noted embryotoxic effects, but failed to
observe teratogenic effects in pregnant CFY rats exposed by
inhalation to xylene isomers at up to 700 ppm on days 7 - 14 of
gestation (Hudak & Ungvary 1978, Ungvary et al. 1980).

The xylenes have been regularly identified in the atmosphere
and in water, but no data appear to be available on levels in
food (Fawell & Hunt 1988).