Registration Dossier

Administrative data

Description of key information

The substance showed moderate acute oral toxicity in female rats (LD50 = 500 mg/kg bw). Regarding dermal exposure, the LD50 is above 2000 mg/kg bw for male and female rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
500 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute oral toxicity

In a GLP compliant study according to OECD guideline 423 and EU method B.1tris the acute oral toxicity of EEA-NH4 following a single oral administration in the Sprague-Dawley CD strain rat was investigated (SafePharm Laboratories, 2005).

A group of three fasted females was treated with EEA-NH4 at a dose level of 2000 mg/kg bw. Based on the results from this dose level further groups of fasted females were treated at a dose level of 300 mg/kg bw. The test material was administered orally as a solution in distilled water.

All animals treated at a dose level of 2000 mg/kg bw were found dead or killed in extremis.There were no deaths noted in animals treated at a dose level of 300 mg/kg bw.

Signs of systemic toxicity noted in two animals treated at a dose level of 2000 mg/kg bw were hunched posture, ataxia, lethargy, decreased respiratory rate, noisy respiration, dehydration and diuresis. There were no signs of systemic toxicity noted in animals treated at a dose level of 300 mg/kg bw.

The surviving animals showed expected gains in bodyweight over the study period.

Abnormalities noted at necropsy of the animals that died during the study (2000 mg/kg bw) were abnormally red lungs, dark liver, dark kidneys and clear liquid present in the stomach. No abnormalities were noted at necropsy of the animal that was killedin extremisor at necropsy of animals that were killed at the end of the study.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was approximately 500 mg/kg bw.

Acute dermal toxicity

In a GLP compliant study according to OECD guideline 402 the acute dermal toxicity of EEA-NH4 following a single administration in Sprague-Dawley SPF strain rats (5 males and 5 females per group) was investigated (Gotemba Laboratory, 2008). Three dose levels, 500, 1000 and 2000 mg/kg bw, were examined. A vehicle control was also included.

No deaths occurred. Regarding clinical observations, there were no abnormalities in any animal of either sex. No changes were observed at the application site and effects of administration were not observed.

All male and female animals in the test substance groups showed similar body weight development compared to the vehicle control group. At necropsy, no abnormalities were observed in either sex of both the test substance groups and the vehicle control group.

The acute dermal lethal dose (LD50) of the test material in male and female Sprague-Dawley SPF strain rats was estimated to be higher than 2000 mg/kg bw.

A second acute dermal toxicity study which is considered as a supporting study was also available (TNO Quality of Life, 2008). A sample of EEA-NH4 was examined for acute dermal toxicity in an experiment with 5 male and 5 female rats (limit testing), according to OECD guideline 402. A dose level of 400 mg/kg bw was examined and the dermal contact period was 24 hours. A 2000 mg/kg bw dose level was not examined because the test substance appeared to be corrosive to skin in an in vitro test. No mortality or clinical signs were observed after treatment. Macroscopic examination of the animals at the end of the observation period did not reveal any treatment-related gross changes.

Acute inhalation toxicity

In accordance with column 2 of REACH Annex VIII-X, in addition to the oral route, for substances other than gases, an acute toxicity study for at least one other route is required. The choice of the second route will depend on the nature of the substance and the likely route of human exposure. As the dermal route is the most likely route of exposure and as an acute dermal toxicity study is available, an acute inhalation toxicity study is not needed.

Justification for classification or non-classification

Based on the oral LD50 value of 500 mg/kg bw, the substance has to be classified according to Directive 67/48/EEC as Xn – R22 (Harmful if swallowed). In accordance to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance has to be classified for Acute toxicity, Cat. 4 - H302 (Harmful if swallowed). No classification for acute dermal toxicity is warranted.