Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 > 16000 mg/kg bw, in female and male CFY rats, comparable to OECD Test Guideline 401, non-GLP study

Acute inhalation toxicity: No study available, particle size, partition coefficient and water solubility of the test item indicate that although its solubility is high and the partition coefficient is low, the mean median diameter is above the threshold for inhalation, thus, exposure via inhalation is not expected. Due to the low vapour pressure the exposure to aerosols is also not expected.

Acute toxicity: dermal: No study available, partition coefficient, water solubility and molecular weight indicate that the test item although small enough is considered to be highly hydrophilic and dermal penetration is considered to be very low.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
16 000 mg/kg bw
Quality of whole database:
The available study was conducted similar to guideline and is of sufficient quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute oral toxicity study conducted similar to OECD Test Guideline 401, non-GLP, female and male CFY rats were administered 16000 mg/kg bw L-Asparagine and subsequently observed for 14 days, no premature mortality occurred and no adverse effects were observed, thus, the LD50 was considered to be > 16000 mg/kg bw.

Several supporting studies, either with oral administration or i.p applied L-Asparagine, all of minor reliability substantiate the results of the above mentioned study. L-Asparagine was administered with 1000, 3000 and 6000 mg/kg bw (acute) or with 1000, 500 and 250 mg/kg bw to male Sprague Dawley rats to evaluate whether L-Asparagine protects against chemically or physically induced seizures. Although L-Asparagine failed to protect against seizures, there was no sign of L-Asparagine-related toxicity in this study (Swinyard et al.). Similarily, the effect of L-Asparagine on ethanol and hexobarbital induced immobility and sleeping time was investigated. There was no sign of L-Asparagine related toxicity up to 2000 mg/kg bw, but the substance seems to aggravate the ethanol induced adverse effects (Forney et al.).

In another study L-asparagine was administered as protective agent (anticonvulsant) against pharmacologically induced seizures. The doses applied were 225 mg/kg bw and 300 mg/kg bw. In mice receiving 225 mg/kg bw and 300 mg/kg bw L-asparagine, respectively, the mortality and the occurrence of seizures were reduced by 70%. Therefore, L-asparagine is not considered to mediate adverse effects in the concentration administered (Hawkins JE).

Furthermore, the effect of infusion of several amino acids on uric acid synthesis in chicken was determined. Infusion of in total 792.7 mg/kg bw asparagine resulted in an increase of plasma uric acid of 5.6 mg/100 mL plasma and in an increase of urinary uric acid of 142.7 mg/ 50 min of infusion. No adverse effects were reported. These results indicate that asparagine is readily metabolised via urea cycle in chicken (Karasawa et al.).

According to the Draft COMMISSION REGULATION (EU) amending Annexes VII and VIII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity, recent “scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. The oral LD50 was determined to be > 2000 mg/kg bw based on a study conducted similar to OECD guideline 401. Thus, no toxicity via the dermal route is to be expected. Based on the available information, the acute toxicity of L-Asparagine is low. There are no data gaps in acute toxicity.

Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

References:

Hawkins JE. ON THE EFFICACY OF ASPARAGINE, GLUTAMINE, y-AMINOBUTYRIC ACID AND 2-PYRROLIDINONE IN PREVENTING CHEMICALLY INDUCED SEIZURES IN MICE. Clinica Chimica Acta, Vol.2 pp. 481-484.1957

Forney RB, Hughes FW, Richards AB and Gates PW. Toxicity  and  Depressant  Action  of  Ethanol  and  Hexobarbital  after  Pretreatment  with  Asparagine. Toxiciology and applied Pharmacology 5, 790-793.1963

Karasawa Y, Tasaki I, Yokota HO, Shibata F. Comparative Effect of Intravenously Administered Anitrogenous Compounds on Uric Acid Synthesis in Chicken Fed a 20% Protein Diet. J.Nutr. 103:1208-1211. 1973

Swinyard EA, Chin L, Cole FR and Goodman LS. Anticonvulsant Properties oi I-Glutamine and I-Asparagine in Nlice and Rats. P.S.E.B.M., 1957, v94.

Justification for classification or non-classification

Based on the available, reliable 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 acute toxicity.