Registration Dossier

Administrative data

Description of key information

Oral toxicity:
- 90-day rat (OECD 408). NOAEL: 450 mg/kg bw/day
Dermal toxicity:
- 28-day rat (OECD 410). NOAEL: 5000 mg/kg bw/day
- 21-day rabbit (EPA OPPTS 870.3200). NOAEL: 1500 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
450 mg/kg bw/day

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
1 500 mg/kg bw/day

Additional information

Repeated dose toxicity: oral

The 90-day oral toxicity study in rat (Camponovo, 1984, OECD 408) indicated that a dose of 1000 mg/kg/day induced liver changes (histopathology), resulting in a NOAEL of 450 mg/kg bw/day. This study was considered as key study.

A further supporting study undertaken was a Hormone study in female Wistar rats (BASF SE, 2004) with administration at 1000 mg/kg bw/day in the diet over 4 weeks. Multiple hormone assays were undertaken. The rat is considered a very sensitive species for indirect thyroid hormone effects in comparison to man. Serum thyroid stimulating hormone (TSH) and total triiodothyronine (T3) were not affected. Slightly increased serum thyroxine (T4) concentrations were observed but, in the absence of effects on TSH or T3, ethylhexyl methoxycinnamate was not considered to be a true thyroid modulator or thyroid toxicant. In the other hormone investigations, in particular for estradiol and progesterone, no treatment-related effects were observed. (further studies on the endocrine system were performed: see section 7.8.3)

Repeated dose toxicity: dermal

A 28-day dermal toxicity study in rat (Keller, 1980, equivalent of OECD 410) indicated only dermal irritation, but no systemic toxicity. Therefore, a NOAEL of 5000 mg/kg/day was established. A 21-day dermal toxicity study in rabbit (Keller, 1980, non-OECD, but EPA OPPTS 870.3200) indicated multiple effects, which were attributed to ill-health (skin irritation) rather than direct organotoxicity. This resulted in a NOAEL of 1500 mg/kg/day. As the effects were not seen in other treatment groups or the control group, the effects could be caused by the high dose of ethylhexyl methoxycinnamate. The NOAEL of 1500 mg/kg bw/day is therefore chosen as the key parameter for repeated dermal exposure.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; glandular: thyroids

Repeated dose toxicity: dermal - systemic effects (target organ) cardiovascular / hematological: bone marrow; cardiovascular / hematological: hematopoiesis; digestive: liver; other: skin; other: all gross lesions and masses

Justification for classification or non-classification

Based on the key parameters (NOAELs) given above, ethylhexyl methoxycinnamate does not need to be classified for repeated dose toxicity, as the NOAEL values are significantly higher than the guidance values for "Specific Target Organ Toxicity (STOT) - Repeated Exposure (RE) Category 2" as outlined in regulation 1272/2008/EC.

Guidance values used:

- Oral, rat, 90-days: 100 mg/kg bw/day

- Dermal, rat/rabbit, 28-days: 600 mg/kg bw/day (corrected by a factor of 3 for 90-days exposure, as indicated in regulation 1272/2008/EC)