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EC number: 200-521-5
CAS number: 61-82-5
Based on available data, the substance is expected to be bioavailable
via the oral and the inhalation routes and barely bioavailable via the
dermal route. The substance may cross cellular barriers or may be
distributed into tissues with a rapid cell turnover. The substance is
rapidly and mainly excreted in urine.
In accordance with the section 8.1.1 of Annex VIII of Regulation
(EC) No 1907/2006 (REACH), the toxicokinetic profile of the
registered substance (i.e. absorption, distribution, metabolism
and elimination) was derived from the relevant available
information collated in the dossier. The physical chemical
characteristics of aminotriazole, the results obtained from acute,
repeated-dose, and reproductive toxicity studies, as well as
information gained from genotoxicity assays were used to predict
its toxicokinetic behaviour.
Physico chemical characteristics
Aminotriazole has a low molecular weight of 84.082 g/mol. The
substance is considered as moderate soluble in phosphate buffer
0.5M (264 g/L) and low volatile according to its vapour pressure
(3.3 x10-5Pa at 20°C). Furthermore, aminotriazole has
no potential for bioaccumulation since it is low hydrophobic based
on the partition coefficient (log Kow = -0.77).
The physical chemical characteristics described above suggest that
aminotriazole is of adequate molecular size to participate in
endogenous absorption mechanisms within the mammalian
gastrointestinal tract. In vivo experiments using14C by
oral route showed a rapid and almost complete absorption from the
gastrointestinal tract followed by rapid excretion in the urine
within 48 hours. Moreover, an acute oral gavage toxicity study
identified neither systemic toxicity (including mortality), nor
clinical or macroscopic effects (LD50 > 10000 mg/kg bw).
The sub-chronic repeated dose toxicity, the pre-natal
developmental toxicity studies and the two-generation reproductive
toxicity study using the oral route gave a NOAEL below 1.5 mg/kg
bw/day (gavage), 4 mg/kg bw/day and 0.12 mg/kg bw/day (diet),
respectively, based on effects on thyroid.
In a ten-week toxicity
study, the absorption and elimination of the substance were also
evaluated by HPLC in serum from satellite animals. Absorption of
the test substance was observed at all time points in both sexes
and comparable Cmaxwere noted 2 hours after the
administration of the test substance (394 and 341 µg/mL in males
females respectively). Extent
as measured by
in the males than in the females (725 and 668 µ.g/h respectively).
The observation of those systemic effects indicates the oral
bioavailability of aminotriazole and/or its metabolites.
However, exposure by oral route is not anticipated in human since
only worker uses are identified for the substance.
Regarding the dermal absorption, being low hydrophobic, the rate
of uptake of aminotriazole into the stratum corneum is expected to
be low (<10%). Data on dermal absorption are available in animals
and in human cells where a low dermal absorption is determined.
Dermal absorption is determined in in vitro using human cells
(3.54%). These results are consistent with the absence of systemic
effects following a single dermal application of aminotriazole up
to 2000 mg/kg bw. Moreover, enhanced skin penetration is not
expected since aminotriazole is not a skin irritant or corrosive.
Both the partition coefficient and the moderate water solubility
of aminotriazole, are favourable for absorption by inhalation.
A study in rats exposed by inhalation is available. Following a
« whole body » or a « head-only » exposure, it is demonstrated
that the substance was bioavailable. However, exposure by
inhalation o vapour is negligeable based on the low volatility of
aminotriazole (3.3 x10-5Pa at 20°C). Moreover,
considering that aminotriazole is not skin and eye irritant, no
respiratory irritation is anticipated that could increase
Distribution of aminotriazole was studied in several in vivo
experiments. After an oral administration in mice and rats, there
is a rapid distribution of the substance throughout the body, with
a slight accumulation in tissues with a rapid cell turnover, and
moderatly in the thyroid gland. After 3 days, a significant amount
was found only in the liver. Moreover, aminotriazole was found
mostly in the cytoplasm of the cells.
Regarding the dermal route of exposure in rabbits, the majority of
the substance was still at the site 24 hours following
application. For the amount of substance that penetrated, it was
mesured in blood after 24 hours extremely rapidly, and then
excreted. The remaining substance after 24 hours was found in
urine, faeces, gall bladder, liver, bladder, gastrointestinal
tract and other organs.
Based on available data, aminotriazole administered in rats by
inhalation exposure was rapidly and mostly found in the urine.
The metabolism of aminotriazole has been studied in rats by a
daily analysis of the urine. Aminotriazole and metabolites were
detected which demonstrated that a few part of the substance is
metabolised by the liver and conjugated with glutathion. The 2
identified metabolites were 3-amino-1,2,4-triazolyl-5-mercapturic
acid and 3-amino-5-mercapto-1,2,4-triazole.
Aminotriazole is bioavailable via oral route and inhalation route
as aerosol. Limited systemic absorption via dermal route is
The bioavailability of aminotriazole should be limited following
exposure by dermal route.
Aminotriazole having a molecular weight lower than 300 g/mol, it
is expected – and demonstrated in several studies – to be mainly
excreted in urine. It is shown in experiments that aminotriazole
is excreted unchanged or as metabolites (i.e.
3-amino-1,2,4-triazolyl-5-mercapturic acid and
3-amino-5-mercapto-1,2,4-triazole) following the metabolisation by
the liver. Following oral ingestion, the low substance amount that
may not be absorbed from the gastro-intestinal tract will be
excreted in the faeces.
Moreover, following an oral exposure, traces of14C were
detected in the expired air within 72 hours.
In the ten-week
toxicity study, elimination, estimated by apparent tmaxwas
not influenced by gender (2 hours for both sexes).
Following dermal exposure, the low amount of substance which has
been absorbed will be excreted mostly in urine, faeces and gall
As for the oral and dermal route, following an inhalation
exposure, the substance is rapidly and mostly absorbed and
excreted via the urine.
* Monograph, Aminotriazole – Volume 3 : B.5 Toxicology and
- Fang, S.C., Khanna, S., Rao, A.V. 1966. Further study on the
metabolism of labelled 3-amino-1,2,4-triazole (ATA) and its plant
metabolites in rats. J. Agric. Food Chem. 14, (3), 262-265
- Fang, S.C., George, M., Yu, T.C. 1964. Metabolism of
3-amino-1,2,4-triazole-5-14C by rats. J. Agric. Food Chem.
12 : 219-223
- Franco L., Municio, A.M. 1975. Comparative metabolism
of 3-amino-1,2,4-triazole. Gen Pharmacol. 6 (2-3) : 163-9
- Grunow, W., Altmann, H.J., Boehme, C. 1975. On the
metabolism of 3-amino-1,2,4-triazole. Arch. Toxicol. 34 (4)
- Mc Donald, C.M., Pullinger, D.H. 1976. A
pharmacokinetic study to compare "head only" and "whole
body" inhalation methods of 14C-amitrole exposure. Hazleton
Labs Europe, UK. Report No.: 291/1. Unpublished report.
- Shah, P.V., Guthrie, F.E. 1977. Dermal Absorption,
Distribution and the Fate of Six Pesticides in the Rabbit.
Pesticide Management and Insecticide Resistance, Academic
- Tjälve, H. 1974. The distribution of labelled
aminotriazole in mice. Toxicology 3 (1) 49-67
* Addendum to Amitrole Monograph, Vol. 3 ANNEX B, Summary,
Scientific Evaluation and Assessment. France : Ministère de
l'Agriculture, DGAL ; March 2000
- Marty, J.M. 1999. In vitro release and diffusion evaluation
through human skin of Amitrole. Faculté de Pharmacie, France.
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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