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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: Kouseisho-21 Yakuhatsu-424
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Sprague-Dawley strain SPF rats [Crl:CD(SD)]
- Test period: 2007.10.17 - 2008.01.31
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
L-Serine was administrated once each to groups of 5 males and 5 female Sprague-Dawley strain SPF rats [Crl:CD(SD)] at one dose level of
2,000 mg/kg.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred in males and females in any test article group. Therefore, the lethal dose level was estimated to be higher than 2,000 mg/kg for
L-serine.
Clinical signs:
There were no abnormalities in clinical signs in any male or female animal during the observation period.
Body weight:
All male and female animals showed nearly normal body weight development during the observation period.
Gross pathology:
There were no abnormalities in the external appearance, or in organs/tissues in the cranial, thoracic or abdominal regions in any male or female
animals.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Based on the results of the study report, it was estimated that the toxicity of L-serine was extremely low.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

In an acute oral toxicity GLP study according to OECD 420, groups of Sprague-Dawley rats (5/sex) were given a single oral dose of test item at doses of 2000 mg/kg bw. All animals survived and no toxicity (differences in body weight, feed consumption, clinical observations, gross organ necroscopy) could be observed. The resulting oral LD50 is >2000 mg/kg bw.

This result was confirmed in another published acute oral toxicity study according to OCED420 (van de Mortel 2010).

However, the true LD50 is much higher. This is clearly demonstrated by the results of a 13 -week subchronic oral toxicity study published by Kaneko et al. (2009) in which 3000 mg/kg bw was the NOEL for L-serine. In an older study which was performed prior to GLP the LD50 was determined to be 14 (12.8 -15.3) g/kg bw. The study was well documented and acceptable for assessment.

These results clearly indicate the very low acute toxicity of this amino acid.

 

Acute inhalative toxicity

No data on acute inhalation toxicity for L-serine is available. Significant exposure of humans via inhalation is unlikely taking into account the vapour pressure and the particle size of the substance, while exposure of humans via skin contact is likely.

However, there is an in vivo OECD 403 GLP-guideline study available for L-threonine. L-Serine and L-threonine belong to the group of polar amino acids as their side chains are polar but not charged. Their chemical structure is very similar with both having the same set of functional groups. The only difference between the two molecules is that L-threonine contains one additional methyl group in the amino acid side chain. Both substances have a low molecular weight, nearly identical logKow values (~-3) and also very similar pKa values. In addition to the similar physico-chemical properties also the toxicological and ecotoxicological/fate data indicate a very low toxicity (if any) of both substances for the environment (toxicity for aquatic organisms) as well as a very low toxicity for human health (toxicity to experimental animals). The absence of significant toxicity is not surprising as both substances are ubiquitous occurring substances (also in body fluids of animals and humans) which serve as building blocks for protein synthesis in all animals (including humans). Due to the very similar chemical structure resulting in very similar physico-chemical properties and a very low (eco)toxicity profile of both substances it is justified to fulfil the data requirement with regard to inhalative toxicity for L-serine by a read-across approach from available data for L-threonine.

The aim of the available limit test with L-threonine was to obtain information on the acute inhalative toxicity following a single 4 hour exposure of rats. No signs of toxicity were observed at 5.15 +/-0.1 mg test substance/l.

 

Acute dermal toxicity

No data on acute dermal toxicity for L-serine is available. The substance is of very low systemic toxicity as no systemic effects were observed in limit acute oral toxicity studies (2000 mg/kg bw) as well as in repeated dose toxicity studies (3000 mg/kg bw). The LD50 for the acute oral toxicity was 14000 mg/kg bw. Due to this very low toxicity and the fact that L-serine 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. Therefore and for animal welfare reasons no further acute dermal toxicity study is justified and the dermal LD50 is assumed to be > 2000 mg/kg bw.

Justification for classification or non-classification