Itaconic acid

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 969 mg/kg bw

Additional information

Based on the guideline EEC 84/449 B3, a group of ten rats ‑ 5 males and 5 females ‑ was given a single dermal application of itaconic acid formulated in gum arabic, at a dose level of 2000 mg/kg bodyweight. All surviving animals were sacrificed and examined macroscopically on day 15, the end of the observation period. There were no death and no sign of systemic reaction to treatment. Bodyweight gains were normal and no abnormalities were recorded at the macroscopic examination on day 15. The acute lethal dermal dose to rats of itaconic acid was found to be greater than 2000 mg/kg bodyweight.

Based on guideline EEC 84/449 B1, fasted rats 5 males and 5 females per dose were given a single dose by gavage of itaconic acid, formulated in gum arabic at 0, 2560, 3100, 3750, 4130, 4550 and 5000 mg/kg bodyweight. All surviving animals were sacrificed and examined macroscopically on day 15, the end of the observation period.

Clinical signs were ataxia, pilo erection and ptosis associated to cyanosis. Low bodyweight gains were recorded for males at doses higher than 2560 mg/kg and females at 4130 and 4550 mg/kg. Congested stomach and coloured lungs were observed in dead animals. No abnormalities were recorded at macroscopic examination at termination of the study.

The acute oral LD 50 of itaconic acid was estimated to be 2969 mg/kg bodyweight (2530-3485 mg/kg) according to Lichfield and Wilcoxon.

There is also oral toxicity data from QSAR exist, Nonlinear ANN QSAR model for acute oral toxicity – toxic class method (rat) was performed. The predicted value, log (LD50) = 0.92 corresponds to the value of LD50 = 1090 mg/kg bw.

Compared the data from testing and QSAR, it is considered that the testing data (according to EEC 84/449 B1, GLP) has a higher reliability and adequacy. So LD50=2969 is used for CSA.

Justification for classification or non-classification

The LD50 for dermal acute toxicity or oral acute toxicity is > 2000 mg/kg bw and is above the limit for the classification criteria which is 2000 mg/kg bw for both dermal and oral acute toxicity according to the Regulation (EC) No 1272/2008, and itaconic acid is not easily inhaled. According to this Regulation, Itaconic acid is not classified as an acute toxic substance.