2-ethylhexanoic acid, cerium salt

Endpoint summary

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

Species:

other: rat and mice

Additional information

No repeated dose toxicity study with 2-ethylhexanoic acid, cerium salt is available, thus the repeated dose toxicity will be addressed with existing data on the dissociation products cerium and 2-ethylhexanoic acid.

 

Cerium

Braun (2013) performed a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in RccHan: WIST (SPF) rats with cerium trinitrate. The substance was administered at 0, 110, 330 and 1000 mg Ce(NO₃)₃/kg bw/day to male rats for 47 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum.

The NOEL (No observed effect level) for systemic toxicity of the parent animals was considered to be 110 mg/kg/day, based upon the changes in the stomachs of rats treated with 330 mg/kg bw/day and 1000 mg/kg bw/day as well as differences in the mean daily food consumption/body weight development at 1000 mg/kg bw/day. Although these changes were considered to be related to the treatment with the test item, the morphological changes in the stomachs were considered to be local effects rather than systemic toxicity and the differences in the food consumption/body weight were considered secondary to the changes in the stomach. However, as two animals treated with 1000 mg/kg bw/day died as a result of the stomach findings, the NOAEL (No Observed Adverse Effect Level) for systemic toxicity of the parent animals was considered to be 330 mg test item/kg bw/day, corresponding to 142 mg Ce/kg bw/day. The NOEL (No observed Effect level) and the NOAEL (No Observed Adverse Effect Level) for reproduction/developmental toxicity was considered to be 330 mg test item/kg bw/day, corresponding to 142 mg Ce/kg bw/day.

For further information on the toxicity of cerium, please refer to the relevant sections in the IUCLID and CSR.

 

2-Ethylhexanoic acid

In a 90-day repeated dose toxicity study in rats and mice with 2-ethylhexanoic acid, a diet containing 0.5% 2-ethylhexanoic acid caused no adverse effect in rats in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%, calculated NOAEL ca. 300 mg/kg bw/day). No adverse effect was observed in mice receiving a diet containing 0.5 % 2-ethylhexanoic acid in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%). The NOAEL was calculated to be 200 mg/kg bw/day. Both NOAELs were based on reduced food consumption and a decreased rate of body weight gain in the high dose groups. In both studies, all toxicity observed at higher concentrations (changes in clinical chemistry, absolute and relative organ weights, microscopic changes in kidney liver and fore stomach) was reversible within 28 days after exposure ceased.

For further information on the toxicity of 2-ethylhexanoic acid, please refer to the relevant sections in the IUCLID and CSR.

 

2-ethylhexanoic acid, cerium salt

Since no repeated dose toxicity study is available specifically for 2-ethylhexanoic acid, cerium salt, information on the individual constituents cerium and 2-ethylhexanoic acid will be used for the hazard assessment and when applicable for the risk characterisation of 2-ethylhexanoic acid, cerium salt.

For the purpose of hazard assessment of 2-ethylhexanoic acid, cerium salt, the point of departure for the most sensitive endpoint of each constituent will be used for the DNEL derivation:
animal data for cerium: NOAEL(rat)=142 mg Ce/kg bw/day
animal data for 2-ethylhexanoic acid: NOAEL(rat)=300 mg/kg bw/day, NOAEL(mice)=200 mg/kg bw/day