Registration Dossier

Administrative data

Description of key information

The NOAEL of 1000 mg/kg bw/day, based on the read-across with monoethanolamine, will be taken forward as a point of departure for DNEL derivation for monoethanolamine oleate. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
1 000 mg/kg bw/day

Mode of Action Analysis / Human Relevance Framework

Additional information

No substance-specific data on the repeated dose toxicity of monoethanolamine oleate are available. However, according to Article 13 of the REACH legislation, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across.

Monoethanolamine oleate is a salt of monoethanolamine and oleic acid and is expected to dissociated into the respective monoethanolammonium cation and oleate anion upon uptake by the body. Therefore it is considered to be acceptable to derive lacking information on toxicological properties of monoethanolamine oleate by read-across from its starting materials. Oleic acid is exempted from the registration under REACH according to Annex V of REACH legislation as a non-hazardous substances. Therefore toxicological properties of monoethanolamine oleate are expected to be governed solely by monoethanolamine.

Oral route of exposure

No reliable conventional repeated dose toxicity studies with monoethanolamine are available. However, monoethanolamine hydrochloride was tested in an oral two-generation reproduction toxicity study with rats according to OECD Guideline 416 under GLP (BASF AG, 2009). The test substance was administered to groups of 25 male and 25 female rats (F0 parental generation) in diet at dose levels of 0, 100, 300 and 1000 mg/kg bw/day. At least 75 days after the beginning of treatment, F0 animals were mated to produce a litter (F1 generation). After weaning of F1 pups the F0 generation parental animals were terminated.  25 male and 25 female F1 pups from each dose group were chosen to be F1 generation parental animals. They were treated with the test substance at the same dose levels up to about one day before they were terminated. At least 75 days after assignment of the F1 generation parental animals, the males and females were generally mated and the females were allowed to litter and rear their pups (F2 generation pups) until Day 4 (standardization) or 21 post-partum. Shortly after the F2 generation pups had been weaned, the F1 generation parental animals were terminated. All sacrificed F0 and F1 animals were necropsied and assessed by gross pathology and histopathology.

At 1000 mg/kg bw/day, signs of systemic toxicity were observed in parental females, manifested as reduced food consumption and/or body weight gain during gestation and lactation. In the mid and high dose F1 animals statistically significant increases of absolute and relative kidney weights were observed; however, these increases were not accompanied by histopathological changes. In the high-dose F0 and F1 males absolute and relative organ weights of cauda epididymidis and epididymides were statistically significantly decreased. Prostate weight and the number of homogenization resistant caudal epididymal sperm were statistically significantly decreased in the F0 males. These findings were not accompanied by histopathological changes.

Based on the results of the study, the NOAEL for general toxicity was set at 300 mg/kg bw/day. Inhalation route of exposure

In a 28 days inhalation toxicity study performed according to OECD guideline 412 and under GLP (BASF AG, 2010), groups of five male and five female rats were exposed nose-only to target concentrations of 0, 10, 50 and 150 mg/m3 of monoethanolamine for 28 days, 6 h/day, 5 days/week. Animals were observed for clinical signs, body weight changes and food consumption. Ophthalmological examinations were performed prior to exposure and towards the end of the exposure. Hematological and clinical examinations were performed before the end of the study. Gross pathological and histopathological examinations were performed on all animals.

There were no deaths or clinical signs related to treatment. No effects were noted on the body weight and body weight gain, food consumption, organ weights and clinical and hematological parameters at all concentration levels. Concentration-related lesions in larynx, trachea and lung were observed in the mid- and high concentration groups. At 150 mg/m3, submucosal inflammation, degeneration of submucosal glands, focal epithelial necrosis, focal squamous metaplasia and focal epithelial hyperplasia were observed in the larynx of male and female animals. In the trachea, focal squamous metaplasia (carina) accompanied by inflammation in males was observed. At 50 mg/m3, submucosal inflammation and squamous metaplasia of the larynx in males and females was observed. At 10 mg/m3 no adverse effects were noted. No histopathological effects were seen in any other organ outside the respiratory tract. The highest concentration of 150 mg/m3 was considered a NOAEC for systemic toxicity. The lowest tested concentration of 10 mg/m3 was considered a NOAEC for local effects.

The local effects observed in the inhalation toxicity study are expected to be related to the corrosive nature of monoethanolamine and are not relevant for monoethanolamine oleate, which is not an irritating substance. Choosing the NOAEL of 300 mg/kg bw/day from the oral two-generation toxicity study as a point of departure, and applying a correction for molecular weight, a NOAEL of 300× 343.31/61.08 = 1686 mg/kg bw/day can be calculated for monoethanolamine oleate. This value is above the limit dose value of 1000 mg/kg bw/day recommended by OECD Guidelines and far above the cut-off values for the classification according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. As the calculated value for NOAEL is excessively high and may exceed the maximal tolerated physiological dose, the OECD guideline limit value of 1000 mg/kg bw/day will be taken forward for risk assessment and will be used for DNEL derivation.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: epididymides; urogenital: kidneys; urogenital: prostate

Justification for classification or non-classification

As the calculated NOAEL for monoethanolamine oleate, based on the read-across from monoethanolamine, is far above the classification limits of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and EU Directive 67/548/EEC, classification for repeated dose toxicity is not warranted.