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EC number: 204-528-4
CAS number: 122-20-3
TIPA did not cause gene mutations in
Salmonella typhimurium (Ames test) or in Chinese hamster ovary cells
(CHO/HGPRT; OECD TG 476), nor were chromosomal aberrations induced in
rat lymphocytes (OECD TG 473). All in vitro studies were performed in
the absence and presence of metabolic activation.
RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9
Mutation Assay - Exp. 1
Conc. (ug/ml) Mutants/10-6
Sol. A 4 3
Sol. B 14 25
50 A 21* 5
50 B 27* 8
167 A 12 28*
167 B 13 19*
500 A 20* 6
500 B 51* 4
1667 A 14 10
1667 B 6 17
5000 A 13 3
5000 B 0
Statistically Significant Dose (p<0.01)
CHO/HGPRT Mutation Assay - Exp. 2
Conc. (ug/ml) Mutants/10-6
Sol. A 2 4
Sol. B 2 1
50 A 9 3
50 B 3 1
167 A 6 4
167 B 1 7
500 A 4 0
500 B 5 0
1667 A 8 8
1667 B 3 2
5000 A 3 3
5000 B 0 1
Based upon the frequency of the TG-resistant mutants recovered in
cultures treated with the test material, it was concluded that TIPA 99
did not induce a mutagenic response in the assay system employed.
significant increase in the incidence of abnormal cells was noticed at
any of the treatment levels with or without S-9 activation when compared
to the negative controls. The
positive controls had significantly higher incidences of abnormal cells. Hence,
TIPA 99 was considered to be negative in the in vitro chromosomal
aberration assay utilizing rat lymphocytes.
In an in vivo micronucleus test in mice
(OECD TG 474) no clastogenic effects were observed afer single oral
administration of TIPA at doses up to 2000 mg/kg bw.
Polychromatic and normochromatic
The oral administration of the test
substance led to irregular respiration and piloerection at all three
dose levels after about 30 minutes. In the dose groups of 1,000 mg/kg
and 2,000 mg/kg squatting posture was additionally observed. After 2-4
hours these signs were not observed any longer.
The single administration of the vehicle in
a volume of 10 mL/kg body weight led to 2.4‰ polychromatic erythrocytes
containing micronuclei after the 24-hour sacrifice interval or to 2.7‰
after the 48-hour sacrifice interval.
After the single administration of the
highest dose of 2,000 mg/kg body weight, 3.4‰ polychromatic erythrocytes
containing micronuclei were found after 24 hours and 2.3‰ after 48
hours. In the two lower dose groups rates of micronuclei of about 2 ‰
(1,000 mg/kg group) and 3.2‰ (500 mg/kg group) were detected after a
sacrifice interval of 24 hours in each case.
With 21.4‰ the positive control substance
cyclophosphamide for clastogenicity, as expected, led to a clear
increase in the number of polychromatic erythrocytes containing mainly
small micronuclei at a dose level of 20 mg/kg body
weight. With 112.6‰ the positive control vincristine for spindle poison
effects also led to a clearly enhanced number of micronuclei cntaining
polychromatic erythrocytes with the expected amount of large
micronuclei, i.e. 15.6‰. The number of normochromatic erythrocytes
containing micronuclei did not differ to any appreciable extent in the
negative control or in the various dose groups at any of the sacrifice
Thus, the test substance Triisopropanolamin
did not lead to any increase in the rate of micronuclei. The number of
normochromatic or polychromatic erythrocytes containing small
micronuclei (d < D/4) or large micronuclei (d ≥ D/4) did not deviate
from the solvent control value at any of the sacrifice intervals. No
inhibition of erythropoiesis induced by the treatment of mice with
Triisopropanolamin was detected. The ratio of polychromatic to
normochromatic erythrocytes was always in the same range as that of the
control values in all dose groups .
TIPA was tested in the Ames reverse mutation
assay using S. typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 at
100 to 10,0000 µg/plate with and without metabolic activation. Treatment
with TIPA was not associated with reverse mutations in any of the
strains tested (Zeiger et al., 1987). TIPA was also evaluated at
concentrations of 50 to 5000 µg/mL in a HGPRT assay according to OECD TG
476 using Chinese hamster ovary cells with and without metabolic
activation. No cytotoxicity was observed and negative, vehicle and
positive control responses were valid. TIPA was not associated with
increased gene mutations (Sitek, 1993). Induction of chromosomal
aberrations was tested in an OECD TG 473 study in which rat lymphocytes
were exposed to 50 to 5000 µg/mL with and without metabolic activation.
No cytotoxicity was observed and negative, vehicle and positive controls
exhibited appropriate responses. No significant increases in chromosomal
aberrations upon treatment with TIPA were observed (Dow, 1993).
In an in vivo micronucleus test according to
OECD TG 474, NMRI mice (5/sex/dose) received a single oral dose of 500,
1000 or 2000 mg/kg bw TIPA (BASF, 1995). 24 and 48 hours after
treatment, polychromatic erythrocytes were prepared from bone barrow and
investigated for micronuclei. 30 minutes after treatment, irregular
respiration and piloerection was observed at all dose levels, and
squatting posture was observed in the 1000 and 2000 mg/kg bw dose
groups. After 2-4 hours these signs were no longer observed. Moreover,
treatment with TIPA did not induce any increase in the rate of
micronuclei and no inhibition of erythropoiesis was observed. Vehicle
and positive controls were valid.
In summary, these data indicate that TIPA is
Based on the results of the in vitro and in
vivo genetic toxicity studies, TIPA does not need to be classified
according to the EU Classification, Labelling and Packaging of
Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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.
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