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Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Toxicokinetic assumptions based on the available experimental data with animals and physico-chemical data

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

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)


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 cells.

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