Registration Dossier

Administrative data

Description of key information

- subchronic (90 d study) repeated dose toxicity study oral (diet), rat Fischer 344/DuCrj m/f (OECD TG 408), dose levels: 1.25%, 2.5%, and 5% , corresponding to 857, 1708 and 3466 mg/kg bw/day (females) and 753, 1537 and 3242 mg/kg bw/day(males); NOAEL = 1730 mg/kg bw/day (females) and 1650 mg/kg bw/day (males).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
1 650 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The available study was conducted according to guideline and is of high quality. Additionally, supporting data with methodological limitations are available.
System:
other: Clinical biochemistry, body and organ weights
Organ:
kidney
brain
testes

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

Mode of Action Analysis / Human Relevance Framework

Additional information

Fischer/344DuCrj rats were administered L-asparagine (1.25, 2.5 and 5%, corresponding to 857, 1708 and 3466 mg/kg bw/day act. ing. (females) and 753, 1537 and 3242 mg/kg bw/day act. ing. (males) in the diet for 90 days according to OECD guideline 408. At the highest dose, the treatment-related findings were changes in clinical biochemistry, body and organ weight changes and microscopic changes in the lungs, ovaries and Zymbal´s glands. At 2.5% ALP was decreased in male rats but there was no dose-response relationship. In 5% treated females, GLU, PL, TG, K and ALT were significantly increased and at 2.5% TG was increased. In 1.25% treated females, GLU and TG were also increased and CRN was decreased. Significant increases of relative organ weights of the brain, kidney and testes were observed in 5% treated males. Hence, the NOAEL was considered to be 2.5% (i.e., equivalent to 1650/1730 mg a.i./kg bw/d).

In the supporting study male Wistar rats were administered 210 mg/kg bw/d L-asparagine and observed for 14 days. Since this study was conducted in order to determine the body weight gain of a diet supplemented with amino acids the results reported are considered not relevant in terms of information requirement for registration according to Regulation (EC) No 1907/2006 but provided further indications for a low oral toxicity of L-asparagine.

Justification for classification or non-classification

Based on the available, relevant and adequate data the substance does not need to be classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labeling of Chemicals (GHS) with respect to specific target organ toxicity-repeated exposure.