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EC number: 202-436-9
CAS number: 95-63-6
Short description of key information on absorption rate: Dermal absorption of 1,2,4-TMB is low at 0.057%
male rats were exposed by inhalation to 25, 100 or 250 ppm
6 hours, concentrations of 1,2,4-trimethylbenzene
blood increased rapidly reaching a plateau before the end of the
exposure period. Absorption
half lives increased with dose from 38 minutes at 25ppm to 101 minutes
at 250ppm (Swiercz et al., 2002).
repeated exposures (6 hour/day, 5 day/week for 4 weeks), concentrations
liver, lung and brain were similar and increased with atmospheric
concentration of 1,2,4-trimethylbenzene. Concentrations
liver were significantly lower following repeated exposures than after a
single exposure; this may indicate induction of metabolising enzymes
(Swiercz et al., 2003).
exposure by inhalation to 1,2,4-trimethylbenzene,
3,4-, 2,4-, and 2,5-dimethylbenzoic acids (3,4-DMBA, 2,4-DMBA and
2,5-DMBA) were all present in blood; concentrations of 3,4-DMBA were
was an approximately linear relationship between the concentration of
each metabolite in blood and the atmospheric concentration of
relative amounts of each DMBA isomer present in blood is dependent on
the metabolic rate constants; those for 3,4-DMBA (Vmax 96mg/h/kg;
Km 28mg/L) being greater than for the other isomers (Vmax
25mg/h/kg; Km 7mg/L) (Swiercz et al., 2003). Repeated
inhalation exposure to high vapour concentrations of 1,2,4-trimethylbenzene
mg/m3, 8 hr/d for 3 days) appeared to result in increased metabolism
(and clearance) of 1,2,4-trimethylbenzene from
blood and brain (McKee et al., 2010).
concentrations of 1,2,4-trimethylbenzene
a biphasic decline following exposure by inhalation to
6 hours. Terminal
half lives increased with dose from 217 minutes at 25ppm to 1140 minutes
at 250ppm (Swiercz et al., 2002). After
repeated exposures (6 hour/day, 5 day/week for 4 weeks), terminal
elimination half lives again increased with atmospheric concentration of
173 minutes at 25 ppm to 594 minutes at 250ppm but were shorter than
after a single exposure indicating possible induction of metabolising
enzymes (Swiercz et al., 2003).
human volunteers were exposed to 2 or 25 ppm 1,2,4-trimethylbenzene
inhalation for 2 hours, the respiratory uptake was approximately 64% and
was independent of atmospheric concentration of 1,2,4-trimethylbenzene. Concentration
arterial blood increased rapidly without reaching any plateau within the
exposure period. Approximately
20% of the respiratory uptake of 1,2,4-TMB
exhaled unchanged during and after exposure while less than 0.002% was
excreted unchanged in urine within 4 hours post-exposure. The
kinetics of 1,2,4-trimethylbenzene
characterised by a large volume of distribution and long terminal
elimination half life (Jarnberg et al., 1996).
a 4 hour exposure by inhalation (5-150 mg/m3), the retention
the lungs was 68%. Elimination
capillary blood following exposure at 150 mg/m3showed a
triphasic decline with a terminal life of approximately
44 hours. The
elimination of DMBA isomers from urine following exposure at 150 mg/m3
was biphasic with a terminal half life of approximately 63 hours
for all isomers (Kostrzewski et al., 1997).
relationships were found between the air concentrations of the
read-across substance 1,3,5-trimethylbenzene and the concentration of
unchanged 1,3,5-trimethylbenzene and its metabolite 3,5-dimethylbenzoic
acid as well as the unchanged substance in blood (Janasik et al., 2008).
metabolism and uptake of trimethylbenzene isomers
Jarnberg et al. (1996) and Kostrzewski et al. (1997)
studied the toxicokinetics of the three isomers of trimethylbenzene
human volunteers. Respiratory
uptake was similar; 64±3, 56±4 and 62±3% for 1.2,4, 1,2,3 and
percentage of the respiratory uptake exhaled unchanged was similar for
1,2,4 and 1,3,5-trimethylbenzene
and 25±6% respectively) but was higher for 1,2,3-trimethylbenzene
in all cases the amount excreted unchanged in urine was negligible. The
three isomers were all metabolised to isomers of dimethylbenzoic acid;
the number of isomers formed depending on the number of unique
substitution patterns available.
Discussion on absorption rate:
The in-vitro percutaneous
absorption of 1,2,4 -trimethylbenzene has been determined after applying
a dose of 128 µL 1,2,4 -trimethylbenzene to occluded skin from a
human donor (exposed area = 0.64 cm2). Steady state
conditions were not attained within 8 hours; the amount absorbed was 64
µg, equivalent to 0.057% of the applied dose (Korinth et al., 2003).
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