IJT - CIR - February 2024 - 98S

98S
International Journal of Toxicology 43(Supplement 1)
Table 2. Data on Trimellitic Acid, Trimellitic Anhydride, and Constituent Alcohols.
Test Substance
Summary Data
Trimellitic Acid
single dose (acute) toxicity-inhalation: LC50 >3750 mg/m3 (4-h exposure), with necropsy findings considered within
normal limits
repeated dose toxicity-oral: in rats dosed by gavage with 0-1000 mg/kg/day for 5 days/wk for 4 wks, GI effects were
observed with 1000 mg/kg/day, but not with doses ≤300 mg/kg/day
repeated dose inhalation toxicity: rats were exposed to 50 µg/m3 for 6 h/day for 5 days, and then challenged after a 3 wk
non-treatment period with a single exposure of trimellitic acid, trimellitic anhydride, or unfiltered air - there were no
signs of respiratory sensitization or cross-reactivity with the anhydride; in a 13-wk study in rats, no lung lesions or
increased antibody levels were observed with exposure to .05, .1, or .3 mg/m3 for 6 h/day, 5days/wk for 13 wks
genotoxicity: because trimellitic anhydride is rapidly hydrolyzed to the acid in aqueous solutions, the acid is expected to
have similar genotoxic effects (negative, see below)
dermal irritation and sensitization: mild irritation in rabbits (score=1.7/8.0) following a 500 mg dermal dose applied to a
240 cm2 patch of pre-moistened skin for 4 hours
ocular irritation: severe eye irritation potential trimellitic anhydride is rapidly converted to trimellitic acid in the body, so
the toxicity of trimellitic acid is expected to be similar to that of trimellitic anhydride (below), with the exceptions that
the allergic symptoms with the anhydride are attributable to its reaction with amino acids to form haptens, and the acid
does not react this way, and there may be differences in the magnitude of the response at the reaction sites
Trimellitic Anhydride single dose (acute) toxicity-dermal: LD50 = 5600 mg/kg
single dose (acute) toxicity-oral: oral LD50 in rats of 2030 mg/kg (females) to 3340 mg/kg (males); stomach lesions
appearing as the most consistent lesion upon necropsy
single dose (acute) toxicity-inhalation: the inhalation LC50 value in rats was >2330 mg/m3 (4-h exposure), with lung lesions
appearing as the most consistent lesion upon necropsy
repeated dose toxicity-oral: in rats fed 50-500 mg/kg/day for 90-days, a dose-dependent increase in leukocyte count was
observed in one study but not another, and may have been due to respiratory infection in control and treated animals;
in 2 dogs/sex/group fed 25-500 mg/kg/day for 13 wks, no microscopic lesions were observed
repeated dose toxicity-inhalation: - in mice, exposure to .010, .070, or .150 mg/m3 for 30 min/day for 5 days produced
altered breathing patterns (decreased time of inspiration and expiration, increased length of apneic periods), but no
microscopic changes; no adverse effects were observed in rats exposed to .3 mg/m3 for 6 h/day, 5 days/wk for 2 wk; in
rats exposed to .1 mg/m3 for 6 h/day, minimal and marked lung injury was observed after 6 and 10 days of exposure,
respectively; a dose-dependent increase in antibody levels and lung foci was observed in rats exposed to .010, .030, .10
or .30 mg/m3 for 6 h/day, 5 days/wk for 1-2 wk, and the lung foci completely resolved within 12 days after the last
exposure, but reappeared following exposure to a single challenge concentration; exposure to .5 mg/m3 produced
hemorrhagic foci of the lung and increased antibody levels in rats treated for 6 hours/day, 5 days/week for 2 wk -
estrogen treatment reduced the number of lung foci in both male and female rats, while testosterone treatment had no
effect; a dose-dependent increase in lung lesions (hemorrhagic foci, inflammatory cell infiltration, bronchoalveolar
pneumonia) and antibody levels was observed; in rats exposed to .002, .015, or .054 mg/m3 for 6 h/day, 5 days/wk for up
to 13 wk, and these effects were more pronounced in rats following 6.5 wk of exposure than observed in animals
following 13 wk of exposure, suggesting some degree of adaptation; mechanistic studies demonstrate that when the
immune system of rats is suppressed, exposure to trimellitic anhydride does not produce lung lesions
reproductive and developmental toxicity: in gravid rats exposed to .5 mg/m3 on days 6-15 of gestation, lung foci and
increased antibody levels were observed, and while there were no fetotoxic or teratogenic effects, increased antibody
levels were reported in neonates; no reproductive, fetotoxic, or teratogenic effects were observed in an inhalation
study in which guinea pigs were exposed to .5 mg/m3 on days 6-15 of gestation
genotoxicity: negative in Ames test in S. typhimurium and in chromosomal aberration assay and assay for HGPRT
mutations (≤2000 mg/L in CHO cells), with and without metabolic activation
dermal irritation and sensitization: irritation score of .7/8.0 following a 500 mg dermal application to rabbits, and irritation
was greatest during the first 60 min and generally reversible by 48-72 h; dermal sensitization in guinea pigs with 30% in
DMSO induction and 5% in acetone challenge (but not with 300 mg powder); in mice with 10-50% (in acetone/olive oil);
in rats with 25-50% in acetone/corn oil
ocular irritation: severe eye irritation potential
effects on the respiratory tract: may be a respiratory sensory irritant; in repeated dose inhalation studies, the principal
effects were on the immune system and the lung; elevated antibody levels, asthma, allergic rhinitis, and a late respiratory
systemic syndrome were associated with occupational exposures in some workers
Caprylic Alcohol
dermal irritation - non-human: produced a mild irritation when applied undiluted to intact or abraded rabbit skin
irritation - human: produced no irritation in a 48 h closed-patch test in 25 human subjects when tested at 2% in
petrolatum
(continued)
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Reference
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