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Description of key information

Butyldiethanolamine is expected to be well absorbed orally, based on the systemic effects in the acute oral toxicity study in rats, its low molecular weight (161.24 g/mol), high water solubility (> 10,000 mg/L) and LogPow of 0.58. Concerning the absorption after exposure via inhalation, as the chemical has vapour pressure of 1.2 Pa (a value not indicative for absorption by inhalation), it is clear, that the substance is marginally available for inhalation. Given its lipophilicity (LogPow 0.58) - if absorbed - it is expected to be absorbed directly across the respiratory tract epithelium or through aqueous pores and/or be metabolized by the alveolar and bronchial tissue. Butyldiethanolamine is not expected to be absorbed following dermal exposure into the stratum corneum and into the epidermis, due to its high hydrophilicity. Moreover, the absence of irritating properties of Butyldiethanolamine cannot enhance absorption through the skin. Butyldiethanolamine is expected to distribute into the inner of cells and into the intravascular compartment. The substance does not indicate a significant potential for accumulation. Butyldiethanolamine is expected to be metabolised via Phase I reactions leading to hydroxylated derivatives and/or derivatives of oxidative deamination. Further, they can either be involved into intermediary metabolism for further oxidative reactions or be excreted. Butyldiethanolamine and its metabolites are expected to be eliminated mainly via the urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information


The toxicokinetic profile of Butyldiethanolamine (BDEA) was not determined by actual absorption, distribution, metabolism or excretion measurements. Rather, the physico-chemical properties of this substance were integrated with its available toxicological data as well as the data on the read-across substances butylethanolamine (CAS 111-75-1) and dibutylethanolamine (CAS 102-81-8) to create a prediction of the toxicokinetic behavior. The read-across substances shows very similar physico-chemical properties (high water solubility (miscible in all proportions in water, similar LogPow, no hydrolysis in water) and are thus believed to behave very similar in aqueous solutions.


Toxicological profile of Butyldiethanolamine


BDEA is not acutely toxic via oral route of exposure. An oral LD50 of 4800 mg/kg bw was established in an oral study in rats (BASF, 1967; Report No. XVII/49). No acute inhalation studies are available for BDEA since it has low vapour pressure (1.2 Pa at 25°C; ECS, 2013). In an acute dermal toxicity study, BDEA did not produce systemic effects in animals (LD50 >2000 mg/kg bw; Harlan, 2014; Report No. 41402071). There were also mild dermal reactions in several animals. Similarly, BDEA was not irritating to rabbits’ skin after 4-hour exposure (Lab Research, 2009). The substance produced, however, severe damage to eyes (BASF, 1967; Report No. XVII/49). In a skin sensitization study according to Buehler method, the substance was not sensitizing (Elf Atochem North America Inc., 1995, Report No.95-8735-21). BDEA was not mutagenic in three mutagenicity studies: Ames Test (BASF, 1999, Report No. 40M0580/964324), the OECD 476 study with mouse lymphoma L5178Y cells (Harlan Laboratories, 2014; Report No. 41402073) and in the OECD 473 chromosome aberration study (Harlan Laboratories, 2014, Report No. 41402072).

There is no repeated dose toxicity study for BDEA. A source substance Dibutylethanolamine was not toxic to reproduction the Combined Repeated Dose and Reproduction/Developmental Toxicity Screening Test in Wistar Rats (OECD 422; BASF, 2013, Project No. 87R0286/05I017).

Toxicokinetic analysis of Butyldiethanolamine

BDEA is a colourless liquid without specific odour (MW of 161.24 g/mol) at 20°C. The substance is completely soluble in water (> 10, 000 mg/L, MSDS, Taminco, 2010; 7.2E5 mg/L at 25°C, EPIWIN) and has a LogPow of 0.58. It has a low vapour pressure of 1.2 Pa at 25 °C (ECS, 2013; Chemservice, 2015) and melts at -70°C under atmospheric conditions (MSDS, Taminco, 2010). BDEA is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyse under environmental conditions.



Oral absorption

Oral absorption is favoured for small water-soluble molecules with MW up to 200 which can pass through aqueous pores or can be carried with the bulk passage of water (TGD, Part I, Appendix IV, 2003). Based on the molecular weight of 161.24, the high water solubility and the logPow of 0.58, BDEA is expected to be readily absorbed via the gastrointestinal (GI) tract by passive diffusion. This thesis is supported by the fact that the substance, even though it has low intrinsic toxicity by oral route of exposure (LD50 ca. 4800 mg/kg bw; BASF, 1967, Report No. XVII/49), produced mortalities in rats at 3100, 3900 and 6200 mg/kg bw. The clinical signs reported were irregular breathing, slight dyspnoea, agitation, slight salivation, high legged walking, and slight tremor when touched. 100% oral absorption is considered appropriate for the hazard assessment (DNEL derivation) based on this acute toxicity data and on the physico-chemical properties which are in the range suggestive of absorption from the gastro-intestinal tract.

Absorption by inhalation:

Substances with logPow values above 0 have the potential for absorption directly across the respiratory tract epithelium. BDEA has a moderate log Pow value of 0.58 and is according to this criterion favourable for absorption directly across the respiratory tract epithelium by passive diffusion. Further parameter which should be considered is the volatility. Substances with low volatility have a vapour pressure of less than 0.5 kPa. A vapour pressure of 1.2 Pa is indicative for low volatility, assuming low availability for inhalation and consequently low systemic exposure (ECHA guidance R7.c, 2014). Based on low volatility of BDEA, exposure by inhalation is not really relevant for this substance. It is unlikely, that considerable amounts of the substance reach the lung and when this occurs, the substance is expected to be absorbed directly across the respiratory tract epithelium or through aqueous pores due to the logPow of 0.58. The source substance BEA, which physico-chemical properties are very similar to BDEA, was tested in an acute inhalation study in rats (BASF, 1977; Report No. XXVI/45). In this study, rats were exposed to a saturated vapour atmosphere of the test substance for 8 hours. The mean nominal concentration of the test substance was 24.69 mg/L. No animal died. Mucous membrane irritation was observed and no abnormalities at necropsy. Irritating to the mucous membranes can intensify the absorption. Based on these data, 50% absorption is considered for inhalation for BDEA.

Dermal absorption

Similarly, based on the physico-chemical properties of BEA, the substance is likely to penetrate the skin to only a limited extent as it is very soluble in water (completely soluble in all proportions). According to TGD, Part I, Appendix IV (2003) and ECHA guidance R.7C (Chapter R. 7.12), absorption through the skin is anticipated to be limited if water solubility higher than 10,000 mg/L and logPow is under 0. In case of BDEA, the criterion for very high water solubility meets but the criterion for logPow does not meet (it is slightly above 0). The molecular weight of 161.24 g/mol is also suggestive of absorption through the skin. However, the substance BDEA may be too hydrophilic to cross lipid rich environment of the stratum corneum and achieve the epidermis. Low penetration rate is supported by the result of the acute dermal study in rats where no systemic effects of toxicity were observed in treated animals (Harlan, 2014; Report No. 41402071). Further, the charged molecules of BDEA will be hindered to be absorbed through the skin. Additionally, BDEA was not irritating to skin in the skin irritation study in rabbits (Lab Research, 2009) and in the acute dermal study in rats (Harlan, 2014; Report No. 41402071). Therefore, it can be concluded that an enhanced absorption through damaged skin can be ruled out. Based on the absence of the toxicity potential via dermal route of exposure in animal studies and on the non-irritating property of BDEA and taken into account physico-chemical properties of BDEA (especially low water solubility), 10% of dermal absorption is considered appropriate for BDEA for the purposes of derivation of dermal systemic DNEL.

Distribution and accumulative potential

A significant amount of BDEA via oral route is expected to be available for distribution. As the cell membranes require a substance to be soluble in both water and lipids to be taken up, BEA is expected to reach the inner cell compartment due to its optimal molecular weight of 161.24 g/mol, its LogPow of 0.58 and a sufficiently high solubility in water (> 10,000 mg/L). The substance is also expected to be distributed into the intravascular compartment. As it is known that “substances with LogPow values of 3 or less would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace” (TGD, Part 1), no enhanced risk for accumulation will be associated with the substance.


BDEA is not expected to undergo hydrolysis in gastrointestinal tract or in body fluids, due to the absence of hydrolysable functional groups. It is expected to be excreted unchanged due to its high water solubility (> 10, 000 mg/L) and molecular weight of 161.24 g/mol. If case of entering the cell inner, BDEA can undergo Phase I reactions: hydroxylation at a carbon of butyl tail leading to hydroxyl derivatives (i.e 4-[bis(2-hydroxyethyl)amino]butan-2-ol, metabolite No. 2, see Table below) or oxidative deamination with splitting-off ofdiethanolamine (No. 4), the first source substance BEA (No. 6), ethanolamine (No. 8) and butylamine (No. 11). Further possible reaction is N-oxidation to 2-[butyl(2-hydroxyethyl)nitroryl]ethanol (No. 7). Primary and secondary metabolites like butanal (No. 5), hydroxyacetaldehyde (No. 3), butanoic acid (No. 9), hydroxyacetic acid (No.10) or oxoacetic acid (No. 12) can be involved into intermediary metabolism or excreted unchanged or in form of conjugates.

Metabolites of BDEA predicted by “Rat liver metabolism simulator” (the OECD QSAR Toolbox, v.3.3, 2014, for exact structures please see attached file).


BDEA (target substance)





2. Hydroxylated product



3. Hydroxyacetaldehyde


4. Diol amine


Diethanolamine (DEA)

(dealkylated product of BDEA)





6.Secondary alkylalkanolamine



7.N-oxidation products



8. Ethanolamine


9.Butanoic acid


10.Hydroxyacetic acid


11. Primary amine



12.Oxoacetic acid



Since BDEA is a stable compound and sufficiently soluble in water, it can be filtered by the kidneys and undergo primarily urinary excretion. Molecular weight of BDEA (161.24 g/mol) and vapour pressure of < 1.33 Pa are also suggestive of excretion via the urine (ECHA Guidance R.7c, 2014). Excretion via the urine is a major pathway for the oxidised and/or hydroxylated derivatives of BDEA as well. Metabolites which re-enter the system are expected to occur in a lesser extent.