2-ethylhexyl 14-ethyl-6,6-dioctyl-4,8,11-trioxo-5,7,12-trioxa-6-stannaoctadeca-2,9-dienoate

Endpoint summary

Description of key information

NOAEL (oral)= 5 mg/kg diet (based on the effects noted in the thymus) in the rat, equivalent to 0.3-0.4 mg/kg bw/day for male animals and 0.3-0.5 mg/kg bw/day for female animals.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

0.525 mg/kg bw/day

Study duration:

subacute

Species:

rat

System:

endocrine system

Organ:

thymus

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

For the evaluation of the toxicity of the substance after repeated dose, data on Similar Substance 01 is used. Justification for Read Across is given in Section 13 of IUCLID.

The repeated dose toxicity of the analogue substance was assessed in a repeated dose toxicity and reproductive and developmental screening study in rats. The study was performed in accordance with GLP and to the standardised guideline OECD 422. Four groups of 12 male and 12 female rats were exposed to 0 (control), 5, 25 and 250 mg/kg diet daily for 28 days. All animals were observed for mortality, clinical signs, body weight and were subjected to clinical chemistry haematology analysis and neurobehavioural examination. Microscopic examination was performed on the collected organs of all rats in the control and high-dose group. The reproductive organs of males that failed to sire (mated female which was not pregnant) and females that were non-mated or non-pregnant of the mid and low dose groups were microscopically examined. The liver and ovaries of females and the thymus of the male and female rats in the low and mid-dose groups were also evaluated.

Only one death was noted during the study, and this was not attributed to toxicity of the test material. The absolute thymus weight in the males of the 250 and 25 mg/kg groups and the relative thymus weight in the high dose male rats were found to be significantly decreased. In the mid-dose group the relative thymus weight was also statistically significantly decreased. Microscopic evaluation of the thymus revealed moderate to very severe lymphoid depletion in all animals (both sexes) of the 250 mg/kg group and in all females of the 25 mg/kg group. The macroscopically observed thymi in 5 control and 7 low dose females exhibited no microscopic abnormalities.

Based on the effects noted in the thymus in both male and female rats in the 25 mg/kg diet groups, the NOAEL (oral) was concluded to be the lowest group tested, 5 mg/kg diet which was equivalent to 0.3-0.4 mg/kg bw/day for male animals and 0.3-0.5 mg/kg bw/day for female animals.

For the chemical safety assessement, the NOAEL of 0.3 mg/kg bw/day is used which corresponds to Similar Substance 01 doses. Readjusting to Target substance doses, considering the molecular weights of both substances, a 0.525 mg/kg bw/day is calculated.

Justification for classification or non-classification

The classification or non-classification of the substance as specific target organ toxicant following repeated exposure was assessed by taking into consideration the results of the Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test. During the short-term oral repeated toxicity study, decreased thymus weight and microscopic and macroscopic changes in the thymus were observed at the 25/mg kg/diet group. Based on these effects a NOAEL (oral) equal to 5 mg/kg diet equivalent to 0.3-0.4 mg/kg bw/day for male rats and 0.3-0.5 mg/kg bw/day for female rats was determined.

Significant toxic effects observed in the 28-day repeated-dose study conducted in rats are seen to occur below the guidance values (C) proposed in the CLP Regulation. In accordance with the CLP Regulation (EC) No. 1272/2008, the substance is classified as STOT Rep. Exp. 1: H372: Causes damage to organs (thymus) through prolonged or repeated exposure.