2-dibutylaminoethanol

Endpoint summary

Description of key information

No studies available investigating toxicokinetic, metabolism and distribution. An assessment of the toxicokinetic behaviour was made taken together the physico-chemical parameters of 2-dibutylaminoethanol and all available substance-related toxicological informations.

Additional information

There was no data available for the determination of toxicokinetics, metabolism and distribution.

Assessment of Toxicokinetic Behaviour 

2-dibutylaminoethanol (CAS-No. 102-81-8) is a clear, slightly yellow liquid with a molecular weight of 173.3 g/mol and a vapour pressure of 0.05 hPa (20°C). It is very soluble in water (11.57 g/L) at 25°C and bioaccumulation can therefore be excluded.

Absorption:

Data for absorption can be taken from acute and repeated toxicity studies.

In a BASF study (No. XVII/143, 1967) the oral LD50 was determined to be > 550 - < 688 mg/kg body weight for male and female rats. In the two higher dose groups (1376, 688 mg/kg bw) all animals died within 1 hour post application, 1 animal died in the 344 mg/kg bw dose group and no animals died in the 430, 550 and 172 mg/kg bw dose groups. Tremor, convulsion, sounds of pain, dyspnoea, secretion out of the oral cavity, reddened eyes, ruffled fur and accelerated respiration were observed. The surviving animals recovered within 2 to 5 days. At necropsy, extended blood content in the liver and blood in the intestinal loops was observed in the animals that died. In the animals, that were sacrificed at the end of the observation period, bronchitis and bronchiectasis (430, 550 mg/kg bw) were observed as the only abnormalities. Similar results were obtained in two other acute oral toxicity studies (BASF, No. XV/127, 1965; Smyth, 1954).

Additional information can be taken from repeated dose toxicity studies. In a 28-day repeated dose oral (gavage) toxicity study with subsequent 14-day recovery 2-dibutylaminoethanol was administered to male and female Sprague-Dawley rats (Ministry of Health, Labour and Welfare, Japan, 2004). Both males and females were divided into 4 groups in total, to which the test substance at doses of 25, 100 and 400 mg/kg bw/day and vehicle (corn oil) was given respectively. For both, males and females, 5 each belonged to the respective groups; and another 5 animals each were added to the control and 400 mg/kg bw groups in view of the recovery test. The NOAEL under the conditions of this study was 100 mg/kg bw/day for both males and females and the LOAEL was set to 400 mg/kg bw due to mortality and severe findings in nervous system, liver and kidney. Additional data was provided by Cornish et al. (1969). A five week oral toxicity study of 2-dibutylaminoethanol (purity unknown) was undertaken by adding neutralized 2-dibutylaminoethanol to rats’ (Sprague-Dawley) drinking water at concentrations of 4, 2 and 1 g/L (corresponding to 0.43, 0.2, 0.13 g/kg bw/day for the males and 0.33, 0.24, 0.14 g/kg bw/day for the females). A control group was maintained on distilled water. Five male and five female rats were maintained on each dose level. The NOAEL was set to 430 mg/kg bw/day for male animals and to 330 mg/kg bw/day for female animals (highest dose tested) as no adverse effects were observed.

Based on the results of these studies as well as on the structure, the molecular weight and the physico-chemical properties, 2-dibutylaminoethanol can be considered to be bioavailable via the gastrointestinal tract.

Three inhalation hazard tests investigating inhalation toxicity of the test substance are available (BASF No. XVII/143, 1967; BASF No. XV/127, 1965; Smyth et al., 1954). No mortality, clinical signs and no abnormalities at necropsy were observed.

Additional information can be taken from repeated dose toxicity studies. A GLP-compliant investigation of the toxicological effects resulting from repeated inhalation exposure to Wistar rats was performed following OECD guideline 422 (BASF SE, 2013). Groups of ten male and ten female rats (F0 animals) per test group were exposed nose-only to a dynamic atmosphere of 2-dibutylaminoethanol aerosol for 6 hours per day on each day. The duration of treatment covered a 2-week pre-mating and 2-week mating period in both sexes, 1 day post-mating in males, and the entire gestation period of the females. Additionally, all parental females were exposed to the test substance on 4 consecutive days after the lactation period and necropsy of the pups. The target concentrations were 25, 75 and 225 mg/m³ (measured concentrations: 20.6, 72.1, 236.3 mg/m³). A concurrent control group was exposed to conditioned air. The main effects after inhalative administration of 2-dibutylaminoethanol were local irritating effects. Therefore, considering histopathological changes the NOAEC for local effects was 20.6 mg/m³. The test did not cause any adverse effects with regard to reproductive and developmental parameters, but only transiently reduced food consumption, body weight and body weight gain. Thus, concerning systemic toxicity, reproductive and developmental parameters the NOAEC for 2-dibutylaminoethanol was determined to be 236.3 mg/m³ for male and female animals (highest dose tested). Additional data was provided by Cornish et al. (1969). 50 male Sprague-Dawley rats were whole-body exposed 6 hours daily for a 6 months period to 2-dibutylaminoethanol vapours (analytical concentration: 22 ppm, corresponding to 156 mg/m³). Animals were sacrificed periodically after 1, 4, 15, 27 and 29 weeks (5 test and 5 control animals each exposure period). No animal died. Serum bilirubin levels were higher than controls in 3 of 5 rats in the animals that were sacrificed after 4 weeks of exposure. Kidney to body weight ratios were somewhat elevated at the end of the first week on this schedule. No other toxicological signs were observed. Histological sections of the organs from animals exposed for 6 months were not different from the controls. As only one concentration was tested and only limited details were given, no NOAEC was identified. In addition, 5 male Sprague-Dawley rats were exposed to 2-dibutylaminoethanol vapours (analytical concentrations: 33 and 70 ppm, corresponding to 234 and 495 mg/m3) 6 hours daily for 5 days. Exposure to high levels (70 ppm, 495 mg/m³) of 2 -dibutylaminoethanol produced tremors and convulsive seizures in rats. In addition, visual signs of eye and nasal irritation were evident in those animals exposed to approximately 70 ppm. One animal died and great weight losses occurred in these animals. A one week exposure to 33 ppm (234 mg/m³) resulted in a lack of growth, but no other significant findings. Slightly elevated bilirubin levels in some, but not all rats, were noted at the end of 5 days of exposure to 70 ppm. A similar elevation was not evident in the 33 ppm group. Organ to body weight ratios of livers and kidneys of the 70 ppm animals showed marked elevations due to the great weight loss during this period. Concerning the 33 ppm animals, liver to body weight ratios were normal, while kidney to body weight ratios were slightly elevated. There was no histological evidence of tissue damage in these groups of animals. As only two concentrations were tested and only limited details were given, no NOAEC was identified.

Due to the test results and the vapour pressure of 0.05 hPa (20°C) bioavailability and systemic toxicity of 2-dibutylaminoethanol after inhalative administration is of less importance. The main effects were local effects due to the corrosive potential of the test substance.

In the study by Smyth et al. (1954) the acute dermal median lethal dose (LD50) was determined to be 1680 (1200 - 2360) mg/kg bw in rats. No further information was given on mortality, clinical signs, body weights or necropsy. Since mortality was observed, dermal absorption is expected. Nevertheless, local effects caused by the corrosive properties of the test substance which might led to destruction of membrane barriers during the acute dermal toxicity study were more important than toxicity via systemic availability.

 

Taken together, 2-dibutylaminoethanol resulted in mortality after oral, and dermal exposure. Via inhalation, one animal died in a study conducted from Cornish et al (1969). However, this study is described in a publication with limited information. Thus, the substance is expected to be systemically available following oral or dermal upake, whereas bioavailability following inhalation appears to be of less importance. However, as 2-dibutylaminoethanol is also caustic the existing data indicate that corrosion and also irritation of the respiratory tract (local effects) are the primary effects.

Studies on genotoxicity resulted in both negative (Ames-Test, in vitro MN-test, HPRT-Test) and positive results (chromosome aberration test in-vitro), i.e. indication of a reactivity of 2-dibutylaminoethanol or its metabolites under the test conditions cannot be excluded. A testing proposal for an in vivo micronucleus test is provided to clarify the present situation.

Excretion:

Due to its molecular weight, as well as its vapour pressure, 2-dibutylaminoethanol is expected to be excreted predominantly via the urine (ECHA guidance document 7c, 2008).