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EC number: 202-436-9
CAS number: 95-63-6
1,2,4- Trimethylbenzene is irritating to the skin and eyes of rabbits. Respiratory irritation (decreased respiratory rate) was observed in mice with 2842 mg/m3 producing a 50% decrease. No respiratory irritation was noted in human studies but these were conducted at much lower doses than the animal studies.
is no data on 1,2,4-trimethylbenzene itself but the trimethylbenzene
isomers have similar toxicological profiles (Firth 2008). The key study
is provided by Jacobs and Martens (1987) where the skin
irritation potential of the isomer, 1,3,5-trimethylbenzene (mesitylene),
was investigated on shaved rabbit skin. A sample (0.5 mL) was applied
under occlusion for 4 hr with an area of untreated skin serving as
control. The overall mean score for erythema (for all animals over a 72
hour period) was 2.33; no oedema was reported. The results indicate that
1,3,5-trimethylbenzene is irritating to rabbit skin. This study is
supported by other data on 1,3,5-trimethylbenzene demonstrating that
concentrations in excess of 25%
were irritating to rabbit skin (Jacobs
et al, 1987). A
study on undiluted
Shellsol A (a mixture of
trimethylbenzenes CAS# 64742-95-6) also showed that this
a moderate skin irritant following a single 24 hour application to
abraded and non-abraded occluded rabbit skin.
conclusion, the data indicate that 1,2,4-trimethylbenzene has the
potential to be irritating to skin.
1,2,4 -Trimethylbenzene is irritating to the
eye. This was concluded by SCOEL (1994) in relation to all the
trimethylbenzene isomers, but the only reference available is an IUCLID
4 entry (ESBI, 1990) where the results of a rabbit occular irritation
test showed that 1,2,4- trimethylbenzene was irritating to the eyes, but
details are lacking and the study cannot be sourced. An earlier study on
Shellsol A (a mixture of trimethylbenzenes# 64742-95-6) showed that one
drop instilled into the rabbit eye caused an immediate pain reaction but
thereafter was practically non-irritating.
spite of these apparently conflicting results, and in the absence of
reliable information to the contrary, the harmonized EU position
(indicating the 1,2,4- trimethylbenzene is irritating to the eye) is
sensory irritation effects of 1,2,4-trimethylbenzenes in male Balb/C
mice were investigated under conditions of acute exposure (Korsak et al,
Balb/C mice were exposed to trimethylbenzenes for 6 min. Respiratory
sensory irritation was quantified by determination of the decrease in
respiratory rate. 1,2,4-trimethylbenzene depressed respiration rate and
the concentration at which the respiratory rate was decreased to 50%
(RD50) was 578 ppm (2842 mg/m3). A 90 day study is also described
in the same publication (see Section on Repeat dose Toxicity). Rats were
exposed to 1,2,4-trimethylbenzene for 90 days, at concentrations of 25,
100 and 250 ppm. There was no evidence of systemic toxicity at
concentrations up to and including 250 ppm (1230 mg/m3). The
total number of cell macrophages, polymorphonuclear leukocytes and
lymphocytes in the brochiolar lavage (BAL) fluid at all three test
concentrations was increased compared with the controls. Total protein
lactate dehydrogenase and acid phosphatase activity in BAL were also
increased in all exposed groups. These changes are indicative of mild
respiratory irritation, however, a concentration-dependency was not
seen, and therefore some adaptation may have taken place.
conclusion, these data indicate that 1,2,4-trimethylbenzene has the
potential to be irritating to the respiratory tract.
information is available on the potential for trimethylbenzenes to cause
irritation in humans. In human volunteer toxicokinetics studies on
inhaled trimethylbenzenes, subjects were asked to assess (i) Discomfort
in eyes: burning, irritation, or running eyes; (ii) discomfort in nose:
burning, irritation, or running nose; (iii) discomfort in throat or
airways; (iv) headache; (v) fatigue; (vi) nausea; (vii) dizziness;
(viii) intoxication; (ix) difficulty in breathing and (x) smell of
solvent. No effects were reported at concentrations up to 120 mg/m3
(Jarnberg et al, 1996).
-Trimethylbenzene is classified as irritating to skin, eyes and
respiratory tract: Xi, R36, R37 and R38 under DSD; this is equivalent to
a classification of Category 2, H319 Causes serious eye irritation, H335
May cause respiratory irritation and H315 Causes skin irritation, under
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