Palm oil, epoxidized

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Toxicity to Reproduction (Screening study):

In accordance with Column 2 of ANNEX VIII of the REACH Regulation, screening for reproductive/developmental toxicity study does not need to be conducted as a read-across pre-natal developmental toxicity study from ESBO (EC No. 232-391-0) is available.

Toxicity to Reproduction (Two generation study):

In accordance with Column 2 of ANNEX IX of the REACH Regulation, a two generation reproductive toxicity study does not need not to be conducted as the existing read across combined chronic toxicity/carcinogenicity study from ESBO (EC No. 232-391-0) is available and does not indicate clear adverse effects on reproductive organs or tissues.

Short description of key information:
Toxicity to Reproduction (Screening study):
In accordance with Column 2 of ANNEX VIII of the REACH Regulation, screening for reproductive/developmental toxicity study does not need to be conducted as a read-across pre-natal developmental toxicity study from ESBO (EC No. 232-391-0) is available.

Toxicity to Reproduction (Two generation study):
In accordance with Column 2 of ANNEX IX of the REACH Regulation, a two generation reproductive toxicity study does not need not to be conducted as the existing read across combined chronic toxicity/carcinogenicity study from ESBO (EC No. 232-391-0) is available and does not indicate clear adverse effects on reproductive organs or tissues.

Justification for selection of Effect on fertility via oral route:
In accordance with Column 2 of ANNEX VIII of the REACH Regulation, screening for reproductive/developmental toxicity study does not need to be conducted as a read-across pre-natal developmental toxicity study from ESBO (EC No. 232-391-0) is available.

In accordance with Column 2 of ANNEX IX of the REACH Regulation, a two generation reproductive toxicity study does not need not to be conducted as the existing read across combined chronic toxicity/carcinogenicity study from ESBO (EC No. 232-391-0) is available and does not indicate clear adverse effects on reproductive organs or tissues.

Effects on developmental toxicity

Description of key information

Read-across to ESBO (EC No. 232-391-0) - Pre-natal developmental toxicity study: NOAEL (maternotoxic, embryofetal): 1000 mg/kg bw/day (OECD 414/GLP)

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The key study was a read-across study from ESBO and is the only study available. It was assigned a Klimisch score of 2.
The predicted NOAEL value for EPO for pre-natal developmental toxicity is derived from this read-across study of ESBO (RL2). The default assessment factor of 1 is increased to 2 to account for uncertainty in the quality of the whole database, based on the available developmental study. This modification should be sufficient to account for any uncertainty. The overall quality of the database is medium.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

There is no pre-natal developmental toxicity data available for EPO. A read across approach was conducted with a pre-natal developmental toxicity study from ESBO (EC No. 232-391-0).

The read-across pre-natal developmental toxicity study (RL2) was conducted according to OECD 414 and GLP. In this study, ESBO was administered to 4 groups of Sprague Dawley rats (25 females/group) by gavage at dose levels of 0, 100, 300 or 1000 mg/kg bw/day from days 6 through 15 of gestation.

No treatment-related macroscopic changes were observed at necropsy of the females. No deaths occurred in the females of any group. No abortions were noted. The mean food consumption for the females with completed pregnancy was similar in the control and treated groups. The mean body weight gain of the females with completed pregnancy was similar in the control and treated groups. The maternotoxic NOAEL is 1000 mg/kg bw/day. A maternotoxic NOAEL of 1000 mg/kg bw/day is also predicted for EPO.

No dead foetuses were noted in the control, 100 and 300 mg/kg bw/day groups. In the 1000 mg/kg bw/day group, 1 out of 269 foetuses died. This very low incidence of dead foetuses (0.4 %) was considered to be of no toxicological significance. The mean number of live foetuses was similar in the control and treated groups. The mean fetal body weight was similar in the control and treated groups. No treatment-related effects were noted on the sex-ratio.

The mean number of corpora lutea and implantation sites was similar in the control and treated groups. The pre-implantation loss was higher in each treated group when compared to the control group. (23 %; p < 0.05 in the 100 mg/kg bw/day group - 20.4 % N.S. in the 300 mg/kg bw/day - 24.4 %; p < 0.01 in the 1000 mg/kg bw/day group vs. 16.6 % in the control group). As the treatment of the females began after the implantation of the ova, the increase of the pre-implantation loss is considered not to have a toxicological significance. The rate of resorptions was similar in the control (2.6 %) and the 100 (2.7 %), 300 (1.6 %) and 1000 (1.1%) mg/kg bw/day groups. The post-implantation loss was similar in the control and treated groups.

No external malformations were observed in the fetuses of the control and treated groups. No soft tissue anomalies were noted in the fetuses of the control and 100 mg/kg bw/day groups. In the 300 mg/kg bw/day group, 3 out of 122 fetuses (2.5 % ) had dilated renal pelvis associated for two of them (1.6 % ) with ureteral dilatation. In the 1000 mg/kg bw/day group, 3 out of 130 fetuses (2.3 % ) had dilated renal pelvis associated for one of them (0.8 % ) with ureteral dilatation. These two findings which are within the range of the laboratory (C.I.T.) Historical control data are considered to be incidental. No soft tissue malformations were noted in the fetuses of the control, 100 and 1000 mg/kg bw/day groups. In the 300 mg/kg bw/day group, 1 out of 122 fetuses had a cerebral venticular dilatation. This malformation which was noted only in one fetus and which was not observed at a higher dose level is considered as incidental.

The fetal and litter incidences of reduced ossification of the 6th sternebra were significantly different in the 1000 mg/kg bw/day group from those of the control group. As these incidences are lower than those of the control group and within the range of the laboratory (C.I.T.) control historical data, they are considered to have no toxicological significance. In the same way, the fetal incidence and the litter incidence of unossification of the 5th sternebra were significantly different from those of the control group in the 1000 mg/kg/day group but lower and within the range of the laboratory (C.I.T.) historical data. Therefore they are considered not to have a toxicological significance. In the 300 mg/kg/day group, the fetal incidence was not significantly different from that of the control group, but the litter incidence was lower and within the range of the laboratory (C.I.T.) historical data. The fetal incidence of unossification of the 4th metacarpal was significantly higher in the 1000 mg/kg bw/day group, when compared to the control group. These incidences are very low and below the range of the laboratory (C.I.T.) control historical data and therefore are not considered related to treatment. No other dose-related effects were noted on the incidence of the skeletal variations. The fetal incidence of reduced ossification of thoracic vertebrae was higher in the 300 and 1000 mg/kg/day groups. As the differences from the control groups are very slight and within the range of the laboratory (C.I.T.) control historical data, a treatment-related effect is ruled out. The incidence of the few other skeletal anomalies was similar in the control and treated groups. No skeletal malformations were observed in fetuses of any group. The embryofetal NOAEL is 1000 mg/kg bw/day. An embryofetal NOAEL of 1000 mg/kg bw/day is also predicted for EPO.

The full read-across report justification is attached.

Justification for selection of Effect on developmental toxicity: via oral route:
Only one read-across study was available.

Justification for selection of Effect on developmental toxicity: via inhalation route:
An oral read-across pre-natal developmental toxicity study from ESBO (EC No. 232-391-0) is available.

Justification for selection of Effect on developmental toxicity: via dermal route:
An oral read-across pre-natal developmental toxicity study from ESBO (EC No. 232-391-0) is available.

Justification for classification or non-classification

Based on the available information in the dossier, the substance EPO (CAS No. 1006899‐79‐1) does not need to be classified for reproductive toxicity when the criteria outlined in Annex I of 1272/2008/EC are applied, based on the results of the read-across study from ESBO.