Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
450 mg/kg bw/day
Additional information

In the two-generation reproduction study (BASF SE, 2007, Schneider et al., 2005, according to OECD 416), a NOAEL of 450 mg/kg bw/day was established based on secondary number of implantation sites and secondary delayed sexual maturation.

Short description of key information:
Reproduction toxicity (oral) in rat (OECD 416). NOAEL: 450 mg/kg bw/day

Effects on developmental toxicity

Description of key information
- Developmental toxicity (oral) in rat (equivalent of OECD 414). NOAEL: 1000 mg/kg bw/day
- Developmental toxicity (oral) in rabbit (equivalent of OECD 414). NOAEL: 1000 mg/kg bw/day
Effect on developmental toxicity: via oral route
Dose descriptor:
1 000 mg/kg bw/day
Additional information

The two key studies were chosen because of the dosing ranges that were tested in different species (Burgin, 1983, Kistler, 1983). Both supporting studies were limit tests with a similar design. In one supporting study (Burgin, 1986, equivalent of OECD 414) for oral developmental toxicity (limit test) in rabbits, no effects were found at 500 mg/kg bw/day. In another supporting study in rats (Eckhardt, 1985, equivalent of OECD 414) for the same endpoint, no effects at 1000 mg/kg bw/day were observed. This justifies the NOAEL of 1000 mg/kg bw/day as was established in the key studies.

Toxicity to reproduction: other studies

Additional information

A Rodent Hershberger assay (BASF SE, 2003) and a Uterotrophic Assay (BASF SE, 2001) were available as other supporting studies for the endpoint of toxicity to reproduction. The first study exposed rats for 10 days to doses up to 1000 mg/kg bw/day and found that ethylhexyl methoxycinnamate had no anti-androgen efficacy. The second study found no uterotrophic (estrogenic) effect of the submission substance up to an oral dose of 1000 mg/kg bw/day for 3 days in rats.

A further supporting study undertaken was a Hormone study in female Wistar rats (BASF SE, 2004; Robust Study Summary see section 7.5.1) 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.

These studies support the findings in the two generation study which indicate that in vivo ethylhexyl methoxycinnamate does not have an adverse effect on reproductive function or endocrine function up to high dosages.

Justification for classification or non-classification

Based on the results, the substance Ethylhexyl Methoxycinnamate does not need to be classified as reprotoxic based on the criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.