Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 905-588-0
CAS number: -
A number of studies addressing neurobehavioural effects of xylenes in rodents and humans have been reported, however these often use a limited range of exposure concentrations with some conflicting results and are therefore considered to be generally unreliable. However when reviewing this information, the EU Scientific Expert Group (SEG; 1992) concluded that indications of mild CNS effects noted in some individuals exposed to 100 ppm (442 mg/m3) provided the best available basis for setting an exposure limit for xylene isomers. As the effects seen were minimal, 50 ppm (221 mg/m3) was considered a NOAEC by the SEG.
The critical health effects underpinning the
IOELV for xylene isomers were mild irritation of the eye and upper
respiratory tract and mild CNS effects noted in some individuals exposed
to 100 ppm (442 mg/m3). The findings were considered by the SEG to
provide the best available basis for setting an exposure limit for
xylene isomers. As the effects seen were minimal, 100 ppm (442 mg/3) was
taken as a LOAEL. Application of an uncertainty factor of 2 gave an 8-hr
TWA for xylene isomers of 50 ppm (221 mg/m3). A STEL of 100 ppm (442
mg/m3) was recommended to limit peak exposures which could result in eye
and respiratory tract irritation.
The multi-constituent substances covered by
this registration comprise individual xylene isomers (m-xylene,
o-xylene, p-xylene) and ethyl benzene (>10% - <20%). The following
information is available to characterise their potential neurotoxicity.
Exposure levels of the xylene isomers
associated with neurological effects in animals are well defined. Acute
exposures to concentrations inducing behavioural changes included a 6
hour inhalation exposure to the individual xylene isomers at a
concentration of 3000 ppm (Korsak, 1990). Rotarod performance was tested
in male rats before and immediately after exposure. The results
indicated that the toxic effects of exposure to o- and m-xylene were
more pronounced than those of p-xylene at the single exposure level
evaluated (Korsak et al, 1994). Sensory deficits resulting from exposure
to p-xylene were observed in a key study of the acute neurotoxic effects
(Dyer, 1988). A significant depression in amplitude of flash-evoked
potential peak N3 was observed following an oral dose of 250 mg/kg or
more of p-xylene and following inhalation exposure to 1600 ppm for 4
hours. These effects were indicative of altered processing of visual
information but were described as possibly being secondary to changes in
arousal or excitability. 125 mg/kg was an acute NOAEL for the oral route
and 800ppm was an acute NOAEC for exposure by inhalation. A variety of
neurological effects have been seen in rats following repeated exposures
to 100 ppm m-xylene these include impaired passive avoidance learning
(when tested 5 weeks after exposure) and impaired acquisition, but not
retention, of the two-way active avoidance response tested 9 weeks after
exposure) (Gralewicz and Wiaderma, 2001), reduced rotarod performance
(Korsak et al, 1992, 1994) and changes in sensitivity to pain (Korsak et
al, 1994, Gralewicz and Wiaderma, 2001). In the Korsak 1994 study
statistically significant increased sensitivity to pain was observed at
50 and 100 ppm m-xylene (8.6 and 8.7 seconds, respectively, vs. 12.2
seconds for controls; measurements were made 24 hours post exposure)
whereas Gralewicz and Wiaderna (2001) reported a statistically
significant decrease in pain sensitivity (35 seconds vs. 10 seconds in
control) at 100 ppm m-xylene, the lowest dose tested. The variation in
the response to m-xylene in these two studies decreases the confidence
in using the pain sensitivity endpoint as the critical effect.
Ethyl benzene induces transient, depression
and neuromuscular impairment in experimental animals exposed to high
concentrations of inhaled ethylbenzene (RAR, 2008). In a 90 day oral
guideline study (Mellert et al, 2006) specifically designed for the
detection of neurotoxic effects of ethyl benzene at dose levels up to
500 mg/kg bw/d, did not lead to findings indicative of neurotoxicity in
is supported by results from an
870.6200 (Neurotoxicity Screening Battery) compliant study where no
treatment-related changes in FOB and motor activity, or occurrence of
microscopic findings in nervous system, were
found in male and female rats
given ethyl benzene at doses up to 500 mg/kg bw/d by oral gavage for 90
et al., 2010).
No indications for such morphological alterations of the central
nervous system have been reported in other animal experiments including
the 2-year bioassay with exposures up to 750 ppm (NTP, 1999).
According to the ATSDR (2007), the
neurological effects of xylene in humans following inhalation exposure
have been evaluated in a number of experimental studies, case reports,
and occupational studies. Results of experimental studies with humans
indicate that acute inhalation exposure to mixed xylene or m-xylene
causes impaired short term memory, impaired reaction time, performance
decrements in numerical ability, and alterations in equilibrium and body
balance. Available case reports and occupational studies together
provide suggestive evidence that acute and chronic inhalation exposure
to xylene or solvent mixtures containing xylene may be associated with
neurological effects; however, most studies are difficult to evaluate
because the exposure conditions either have not been well characterized
or the subjects may have been exposed to other chemicals in addition to
When reviewing this information, the EU
Scientific Expert Group (SEG; 1992) concluded that indications of mild
CNS effects noted in some individuals exposed to 100 ppm (442 mg/m3)
provided the best available basis for setting an exposure limit for
xylene isomers. As the effects seen were minimal, 50 ppm (221 mg/m3) was
considered a NOAEC.
For ethyl benzene there are no specific data
on neurotoxicity resulting from (monoexposure) in humans (RAR, 2008).
Similar to other aromatic solvents, such as xylene, depressive and
narcotic effects in humans and especially in animals are anticipated for
No classification of mixed xylenes is
warranted when ethylbenzene content is <10%.
Where ethylbenzene is >=10%, mixed xylenes warrants
classification under DSD or CLP as Xn, R48/20 with the equivalent
classification as STOT-RE Cat 2 H373 under CLP (see Specific
Investigations: other studies - ototoxicity).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again