Itaconic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Itaconic Acid caused mortality and clinical signs of toxicity during the study in three animals at high dose; besides one female of this group was sacrificed by animal welfare and confirmed aborting. No effects on body weight, body weight gain and food consumption were observed. No effects were observed in functional observational battery, hematology and clotting parameters, clinical chemistry parameters and organ weight. The most common macroscopic and microscopic lesions were congestion and hemorrhagic in some organs in either males or females. In all cases these findings were considered Test Item related with toxicological significance. All treated females showed lower implantation sites, corpora lutea and pups, however, these findings were no dose related and then was considered as no clear Test Item related at low and mid dose.

Accordingly, in the experimental conditions of this study, the No Observed Adverse Effect Level (NOAEL) of the test item Itaconic Acid in Wistar rats was 300 mg/kg/day for males and females and 300 mg/kg/day for maternal-embryo-fetal toxicity.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

According to guideline OECD 415, Itaconic acid was administered by gavage at dosages of 250, 500 or 1000 mg/kg/day to groups of 22 pregnant rats (CD strain) from day 6 to day 15 of gestation inclusive. Control animals received the vehicle (water) throughout the same treatment period. All females were killed on day 20 of gestation for examination of their uterine content.

Post-dosing salivation was observed at high doses. There was an increase of brown staining of one or more regions of the body at 500 and 1000 mg/kg/day. All the females were pregnant and no deaths occurred.

The rate of bodyweight gain during gestation was unaffected by treatment. Food intake during gestation was similar for all groups. Water intake was increased during treatment and up to termination at 1000 mg/kg/day when compared to controls.

Macroscopic examination of females on day 20 did not reveal any treatment-related abnormalities. Litter responses as indicated by the survival, growth and development of foetuses in utero revealed no treatment-related effects.

Foetal examination at necropsy, and following free-hand serial sectioning or skeletal examination, did not revealed any treatment-related findings.

With the exception of increased salivation after dosing, increased number of females with brown body staining and an increase of maternal water consumption at dosage of 1000 mg/kg/d, there was no effects related to the treatment at a dosage of 1000 mg/kg/day and below.

The NOAEL level for maternal responses and the NOEL level for foetuses was therefore considered to be 1000 mg/kg/day.

Justification for classification or non-classification

Itaconic acid is not classified as toxic for the development according to the criteria of Regulation (EC) No 1272/2008.