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Description of key information

Read-across to ESBO (EC No. 232-391-0) - Repeated dose toxicity (combined chronic/carcinogenicity, NOEL (rat): 1000 mg/kg bw/day (male); 1400 mg/kg bw/day (female)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
The key study was a read-across from ESBO and is the only study available. It was assigned a Klimisch score of 2.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no repeated dose toxicity data available for EPO. A read across approach was conducted with a combined chronic/carcinogenicity toxicity study from ESBO (EC No. 232-391-0).

The read-across combined chronic toxicity/carcinogenicity study (RL2) was conducted according to a guideline that was equivalent or similar to OECD 453. In this study, ESBO was administered daily to groups of 48 male and female Wistar rats in the diet at dose levels of 0, 0.025, 0.25 and 2.5% for 104 weeks. Another control group were given 2.5% SBO under the same conditions. There was no adverse effect on survival. The males given 2.5% ESBO gained more weight than the controls, while the females were slightly lighter. The same rats consumed slightly less food than controls, the difference being greater in females than males. The water intake of the females given 2.5% ESBO was lower than the control, especially in the second year of the study. Haematological examination and investigations of urine at 3, 6, 12, 18 and 24 months did not reveal any adverse effects. A lower volume of more concentrated urine was excreted by the females given 2.5% ESBO compared with the controls, with occasional increases in urinary cell excretion. The organ weights in females were similar to controls, while in males given 2.5% ESBO, several organs were heavier than control. This was related to the growth changes since when expressed relative to body weight the value were normal. The incidence of histological findings, including tumours, was similar in treated and control groups. All the male rats had some degree of glomerulonephrosis and there was a tendency for less severe glomerulonephrosis in the ESBO-treated rats. There was a marginally increased incidence of uterine changes in the females given 2.5% ESBO; since there were similar changes in the females given SBO, these changes could not be clearly related to ESBO or epoxidation. It was concluded that ESBO was not carcinogenic when fed to rats at up to 2.5% of the diet. The NOEL was 2.5% (1000 mg/kg bw/day in males and 1400 mg/kg bw/day in females). A NOEL of 1000 mg/kg bw/day in males and 1400 mg/kg bw/day in females for EPO is also predicted.

The full read-across report justification is attached.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one read-across study was 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 specific target organ toxicity (repeated) when the criteria outlined in Annex I of 1272/2008/EC are applied, based on the results of the read-across study from ESBO.