Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 201-074-9
CAS number: 77-99-6
Toxicokinetic assumptions based on the available experimental data with animals and physico-chemical data
The following remarks on the toxicokinetics of trimethylolpropane are
based on the available studies which were recorded within the process of
registration according to the Regulation (EC) No. 1907/2006 (REACH).
Experimental toxicokinetic studies were not available.
Trimethylolpropane (TMP, Molecular weight 134.18): is a white,
crystalline, hygroscopic solid with a melting point ) of 58 °C at 25 °C,
a vapour pressure of 0.0062 Pa at 25°C and log Pow of - 0.47 at room
temperature. TMP dissolves readily in water (>100 g/L at room
temperature), glycerol, ethanol and other low-molecular alcohols, but is
somewhat less soluble in acetone, ethyl acetate and benzene and
virtually insoluble in aliphatic, aromatic and chlorinated hydrocarbons
(Criteria Group for Occup Standards 1995).
The physico-chemical characteristics of TMP (readily soluble in water,
log Pow - 0.47) and the molecular mass are in a range suggestive of
absorption from the gastro-intestinal tract subsequent to oral
ingestion. This assumption of an oral absorption is confirmed by the
data on acute and subchronic oral toxicity. 1-2 hours following single
oral administration of 1000, 2150, 4640, 10000 or21500 mg/kg bw, rats
appeared depressed, exhibited lacrimation, slow and labored respiration
from 2150 mg/kg bw onwards and mortality occurred at 21500 mg/kg bw.
Gross autopsy of the dead animals showed pathological changes in lungs,
stomach, intestine. Changes in the kidneys were seen in surviving rats
dosed with 4640 and 10000 mg/kg bw (Celanese Corp. 1956). Repeated
application of up to and including 1 % TMP in the diet (corresponding to
max 667 mg/kg bw/d) for 90 days led to changes in red blood parameters
and effects on liver, spleen and kidneys.(de Knecht van Eekelen 1969).
All these findings indicate absorption from gastrointestinal tract and
systemic availability after oral application.
Water solubility, n-octanol/water partition coefficient and molecular
weight of TMP are in ranges which favor dermal absorption. However,
applied to the shaved back of rabbits in doses up to 10000 mg TMP/kg bw
as paste for 24 hours followed by a 7 days post exposure observation,
only mild irritational effects and no deaths were reported and at
autopsy effects only on the kidneys were reported (Celanese Corp 1956).
In acute skin and eye irritating studies in rabbits no systemic
intolerance reactions have been reported (Bayer 1979) and no sensitizing
effect has been identified in the Local Lymph Node Assay (Bayer AG 2010)
Water solubility and low molecular weight are
suggestive for inhalation absorption but due to the vapour pressure of
0.02 Pa it is unlikely to occur at workplace. In animal experiments,
acute exposure did not lead to signs of intoxication and/or mortality.
In an early study, at autopsy following repeated exposure up to 1800
mg/m³ daily for 4 hours over a period of 3.5 months, there is some
evidence of absorption shown in only slight disturbance of blood
circulation, slight disturbance of the permeability of the vessel walls,
, interstitial pneumonia, focal emphysema in lungs and parenchymatous
degeneration of the liver but
individual animal data were not shown (Stankevich 1967)
DISTRIBUTION and METABOLISM
As a small molecule with the given water solubility a wide distribution
is expected. This assumption is confirmed by the changes shown in the
repeated dose toxicity studies following oral application or inhalation
exposure (see section Absorption). However, histopathological changes in
spleen, and liver only at the highest test doses in the 90-day feeding
study (de Knecht-van Eekelen 1969) reveal limited distribution into
Based on the results of the in vitro genotoxicity tests (Ames test, with
and without metabolic activation, MHLW 1994) and HPRT test with and
without S9-mix (HarlannCCR 2010) and Chromosome Aberration tests with
and without metabolic activation (MHLW 1994) it is concluded that
DNA-reactive metabolites of TMP will most probably not be generated in
mammals in the course of hepatic biotransformation.
The polar structure of TMP suggests that it will preferably be either
directly conjugated in a phase-II reaction or undergoes further
oxidation in the alcohol moieties of the molecule.
The n-octanol/water partition coefficient (log Pow of - 0.47) is not
suggestive of accumulation of unchanged TMP in fatty tissues subsequent
to absorption from GI tract or from lungs. On the basis of the molecular
structure, the molecular size and the water solubility excretion into
urine in the unchanged form and/or as glucuronide/sulfate is assumed to
be a preferred route of elimination
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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again