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Description of key information

The results from an oral 28-day subacute repeated dose toxicity study showed that EEA-NH4 exerted effects on the kidney, liver and stomach. The NOAEL of EEA-NH4 in rats under the present study conditions was estimated to be 5 mg/kg bw/day since absolute and relative kidney weights were increased in males of the 25 mg/kg bw/day group and more.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
5 mg/kg bw/day
Study duration:
subacute
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

In a 28-day repeated oral dose toxicity GLP study according to OECD guideline 407 and EU method B.7, groups of five male and five female Crl: CD(SD) rats were dosed with EEA-NH4 (Hita Laboratory, 2006). The high dose was set at 100 mg/kg bw/day, and altogether 3 doses including 25 and 5 mg/kg bw/day were employed. Recovery groups were also set for the 100 mg/kg bw/day and vehicle control groups.

In the present study, no death occurred throughout the study. No abnormalities were noted in the clinical signs, detailed clinical observations, sensorimotor function, body weights and food intakes during the dosing period, and urinalyses at the end of the dosing period.

Concerning the hematological examinations, decreased RBC, Hb and Ht in males and females and increased Reticulo in female were observed in the 100 mg/kg bw/day group. PT was prolonged in males of the 100 mg/kg bw/day group.

Concerning the blood chemical examinations, increased ALT and A/G ratio and decreased T-Cho were observed in males of the 100 mg/kg bw/day group.

Concerning the organ weights, absolute and relative kidney weights were increased in males of the 25 mg/kg bw/day group and more, and absolute and relative liver weights were increased in males of the 100 mg/kg bw/day group.

Concerning the necropsy, elevation of limiting ridge in the forestomach in males and females and enlargement of the liver in males were observed in the 100 mg/kg bw/day group.

Concerning the histopathological examinations, hyperplasia of squamous epithelium in limiting ridge of the forestomach in males and females, diffuse hypertrophy of hepatocytes with granular degeneration in males and focal necrosis of hepatocytes in females were observed in the 100 mg/kg bw/day group.

In the recovery test, all changes observed at the end of the dosing period were recovered.

The above-mentioned results showed that EEA-NH4 exerted effects on the kidney, liver and stomach. The NOAEL of EEA-NH4 in rats under the present study conditions was estimated to be 5 mg/kg bw/day since absolute and relative kidney weights were increased in males of the 25 mg/kg bw/day group and more.

Justification for classification or non-classification

Based on the results of the subacute oral repeated dose toxicity study, classification according to EU Directive 67/584/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 is not needed.