Levoglutamide

Endpoint summary

Description of key information

A 13 week study on oral toxicity is available (see section 7.5). For the oral route a NOAEL of 1.25% diet (833 mg/kg/d) was estimated in a sub-chronic toxicity study. A supporting acute oral toxicity study supports the low systemic toxicity. A study on a higher tier exists, thus a study on a lower tier is not required.

The acute inhalation study and the acute dermal study were waived based on the physico-chemical and toxikokinetic properties.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute oral toxicity study was waived, because a 13-week oral toxicity GLP guideline study of L-glutamine with rats is available (see section 7.5). The feeding of L-glutamine was not associated with overt signs of toxicity. Infrequent changes were witnessed in the urinalysis and blood chemistry in the 2.5% and 5.0% (w/w) groups. All of those changes were determined toxicologically insignificant. No effects of the administration were observed in the 1.25% (w/w) group. Therefore, the definitive toxic Ievel for L-glutamine was determined to be above 5.0% (w/w), and the no-observed-adverse-effect Ievel (NOAEL) was estirnated at 1.25% (w/w) for both genders (males 0.83 ± 0.01 g/kg/day; females, 0.96 ± 0.06 g/kg/day). This GLP guideline study was selected as key study for repeated dose toxicity (see section 7.5).

An acute oral toxicity study was performed with groups of 5 male and 5 female rats. The results of this supporting indicate that the median lethal oral dose (LD 50) of L-glutamine is ca. 16g/kg bw.

These results show that the toxicity of L-glutamine via the oral route is extremely low. The absence of acute toxic effects even at application of increased value doses indicates a low systemic toxicity of L-glutamine.

Inhalation is not a relevant route based upon the vapour pressure and particle size (granulometry) of L-glutamine.

No data on acute dermal toxicity for L-glutamine is available. Due to its very low systemic toxicity and the fact that L-glutamine (with high water solubility and a log P value well below 0) may be too hydrophilic to cross the lipid rich environment of the stratum corneum it is highly improbable that an acute dermal toxicity study would result in any toxicity.

Justification for selection of acute toxicity – oral endpoint

A 13 week study on oral toxicity is available (see section 7.5). For the oral route a NOAEL of 1.25% diet (833 mg/kg/d) was estimated in a sub-chronic toxicity study. A supporting acute oral toxicity study supports the low systemic toxicity. A study on a higher tier exists, thus a study on a lower tier is not required.

Justification for classification or non-classification

Based on the data available no classification for acute toxicity (oral toxicity, dermal toxicity, inhalation toxicity) is required.