Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

According to REACH Annex X a two-generation reproductive toxicity study does not need to be conducted if the substance is of low toxicological activity and there is no significant human exposure. For ethyl 3-ethoxypropionate (EEP) several repeated dose studies via all routes of exposure (oral, dermal and inhalation) are available and no adverse systemic effects have been observed in any of these studies up to the limit dose (1000 mg/kg bw/d via oral and 1000 ppm via inhalation). Further, definitive conclusions can be drawn regarding damage to reproductive organs through extensive histopathological evaluation of these tissues within the repeated dose studies. Results from these studies indicate that EEP did not cause toxicity to the testes. Specifically, no reduction in testicular weight, no damage to the sperm or sperm-producing cells, and no damage to the epididymis or seminiferous tubules were reported. Likewise, no damage to female reproductive organs was found. Further conclusions may be drawn from developmental toxicity studies (in rats and rabbits) where no effects were seen on the reproductive indices and no treatment-related anomalies were seen at concentrations as high as 1000 ppm EEP (the highest practicably generated vapor concentration). The only adverse effect observed with EEP was local irritation which was considered to be the critical effect for the DNEL derivation and also used by the German MAK Commission for establishing the OEL (work place exposure limit) of 100 ppm. An exposure and risk assessment has been conducted for all identified uses of EEP and the exposure estimates for all uses are clearly below the derived no effect levels via all routes of exposure. Toxicokinetics data shows that EEP is rapidly absorbed, metabolized and excreted following oral administration. A substantial proportion was eliminated as CO2, indicating that the molecule was completely oxidized. The majority of the remaining portion was eliminated in the urine within 24 hours of dosing indicating low potential for bioaccumulation. The major urinary metabolites were ethoxypropionic acid, the monoethyl ester of malonic acid and the glycine conjugate of 3-ethoxypropionic acid. No evidence was found for the production of alkoxyacetic acid metabolites, such as those produced by the metabolism of some low molecular weight ethylene glycol ethers (EGME and EGEE, which are classified for reproductive effects). In conclusion, the evaluation of all existing toxicological data for EEP further testing for reproductive toxicity is not considered to be justified.


Short description of key information:
No fertility study is available for ethyl 3-ethoxypropionate.

Effects on developmental toxicity

Description of key information
Two inhalation teratology studies - in rabbits and rats - of acceptable quality (Klimisch 1 and 2) are available for ethyl 3-ethoxypropionate.
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
5 979 mg/m³
Additional information

In an inhalation developmental toxicity study - conducted under GLP - to evaluate the maternal toxic, embryotoxic, fetotoxic and teratogenic potentia1 of ethyl 3-ethoxypropionate in the New Zealand White rabbit. Animals were exposed to test material for 6 hours/day during the Day 6 -18 gestation period in stainless steel and glass 10 cubic meter chambers. Target exposure levels were 125, 250, 500 and 1000 ppm. Slight maternal toxicity was seen in the form of slightly reduced feed consumption at the 250, 500, and 1000 ppm concentrations of EEP and slighly reduced body weight gain at the 1000 ppm level. Excessive lacrimation was seen in the 500 and 1000 ppm animals on the first day of exposure. No effects were seen on the reproductive indices and no treatment- related external, internal soft tissue, or skeletal anomalies were seen at concentrations as high as 1000 ppm EEP (the highest practicably generated vapor concentration). Thus, 1000 ppm EEP was a no-observed-effect-level (NOEL) for developmental toxicity in this study. In a non-GLP inhalation teratology study in rats with vapor concentrations as high as 1000 ppm of EEP no teratogenicity was observed in the rat. Slight fetotoxicity was seen at 1000 ppm, a concentration which also produced significant maternal toxicity. Slight maternal toxicity was also evident at concentrations of 250 and 500 ppm of EEP. The NOEC for teratogenicity was 1000 ppm.

Justification for classification or non-classification

Fertility studies are not available for ethyl 3-ethoxypropionate (EEP). Since EEP has undergone repeated dose toxicity testing at substantial doses with extensive histopathology, definitive conclusions can be drawn regarding damage to reproductive organs. Results from these repeated dose tests indicate that EEP did not cause toxicity to the testes. Specifically, no reduction in testicular weight, no damage to the sperm or sperm-producing cells, and no damage to the epididymis or seminiferous tubules were reported. Likewise, no damage to female reproductive organs was found. Further inferences may be drawn from developmental toxicity studies. Therefore, ethyl 3-ethoxypropionate should not be classified for reproductive toxicity. Ethyl 3-ethoxypropionate did not cause any developmental effects in rats or rabbits. Therefore no classification for developmental effects is required.