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Description of key information

Repeated dose oral (non-guideline study): 90-days feeding study in Harlan Albino rats,  70-3770 mg/kg bw test substance; NOEL = 720 mg/kg bw (Hilltop Research Institute E-151, 1956)

Repeated dose oral (non-guideline study): 90-days feeding study in Sprague-Dawley rats,  500 mg/kg bw test substance; NOAEL = 500 mg/kg bw (MJ Dunphy, 1991)

Repeated dose oral (GLP & OECD 422): gavage study in Wistar rats, 0-1000 mg/kg bw test substance; NOAEL = 300 mg/kg bw (BASF SE 95R0628/04108; 2009)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

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

Additional information

To assess toxicity of ethylenediamine, +4PO upon subacute oral exposure, Wistar rats of both sexes were administered with 0, 100, 300, 1000 mg/kg bw test substance (vehicle: water) by gavage for 30 (males) or 49 (females) days in a GLP and OECD 422 guideline study (BASF, 95R0628/04108, 2009). Adverse effects were exclusively seen in the high dose group. All animals treated with 1000 mg/kg bw ethylenediamine, +4PO displayed vacuolisation of the epithelial cells of the choroid plexus of the lateral ventricles in the brain. Detailed behavioural and neurological examinations of these animals did not reveal any physiological consequences of this vacuolisation. Although the further impact of the observed phenomenon in the choroid plexus is unclear, it is considered to be an adverse effect. However, similar effects were not recorded for the other dose groups. No mortalities occured and parameters of clinical chemistry and haematology did not show treatment related changes. No gross lesions were reported during necropsy. Thus, under the study conditions chosen, a NOAEL of 300 mg/kg bw was derived for general sytemic toxicity.

In a 90-days repeated dose feeding study, Harlan strain Albino rats were administered with 70, 210, 720, 2170 and 3770 mg/kg bw ethylenediamine, +4PO (Hill Top Research Institute E-151; 1955). At higher dose levels (≥ 2170 mg/kg bw) rats displayed cellular degeneration and necrosis in the liver. The NOEL is 720 mg/kg bw. In an additional 90-days feeding study, Sprague-Dawley rats were dosed with 500 mg/kg bw ethylenediamine, +4PO (MJ Dunphy, 1991). No adverse observations were reported. Thus, a NOAEL of 500 mg/kg bw was determined. However, in none of the 90 -days studies, the brain was examined during necropsy or histopathology. Taking into account this limitation, the results of the Hill Top study and the report of MJ Dunphy are in line with the BASF repeated dose study 95R0628/04108.

Justification for classification or non-classification

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC and 1272/2008/EEC. In conclusion, ethylenediamine, +4PO does not require classification.