Arginine

Endpoint summary

Description of key information

L-arginine did not cause any mortality in an acute oral toxicity study. The LD50 derived from this limit test was > 5110 mg/kg bw.

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

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-03-10 to 1983-04-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Qualifier:

no guideline available

Guideline:

other: No guideline available at that time

Deviations:

not applicable

Principles of method if other than guideline:

Intercomparison study on the determination of single administration toxicity in rats, Commission of the European Communities, Health and Safety Directorate, J. Assoc. Off. Anal. Chem. 62, 864-873, 1979

GLP compliance:

no

Remarks:

Study performed prior to implementation of GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: males48 - 51 days, females 59 - 62 days
- Weight at study initiation: males 0.130 - 0.136 kg, females 0.130 - 0.147 kg
- Fasting period before study: 16 hours
- Housing: Makrolon cages type II
- Diet (e.g. ad libitum): standardised test animal diet ALTROMIN
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days acclimatisation period before study begin

ENVIRONMENTAL CONDITIONS
According to method

IN-LIFE DATES: From: To: no data available

Route of administration:

oral: gavage

Vehicle:

other: Tragant

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 238 mg/ml
- Amount of vehicle (if gavage): 21.5 ml/kg
- Justification for choice of vehicle: solubility, inherent vehicle
- Lot/batch no. (if required): not applicable
- Purity: ca. 100 %

MAXIMUM DOSE VOLUME APPLIED: 21.5 ml/kg

Doses:

5110 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data available
- Necropsy of survivors performed: no data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 110 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the observation period of 14 days.

Clinical signs:

other: No signs of toxicity were observed, neither at the male nor the female animals.

Gross pathology:

no data available

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The LD50 value of L-arginine via the oral route represented by male and female rats was > 5110 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 110 mg/kg bw

Quality of whole database:

Klimisch code 2: Comparable to guideline study with acceptable restrictions

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
No acute toxic effects were observed for the oral route up to the maximum dose of 5110 mg/kg body weight. This result shows that the toxicity of L-arginine via the oral route is extremely low.
Inhalation is not a relevant route based upon the vapour pressure and particle size (granulometry) of L-arginine.
There is sufficient weight of evidence for the absence of acute toxicity via the inhalative route. The study is not conducted in accordance with Annex XI no. 1.2. REACH and for reasons of animal welfare:
"Where sufficient weight of evidence for the presence or absence of a particuliar dangerous property is available, further testing on vertebrate animals for this property shall be omitted..."

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:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
No acute toxic effects were observed for the oral route up to the maximum dose of 5110 mg/kg body weight. This result shows that the toxicity of L-arginine 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-arginine.
No data on acute dermal toxicity for L-arginine is available. Due to its very low systemic toxicity and the fact that L-arginine (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.
As there is sufficient weight of evidence for the absence of acute toxicity via the dermal route this study is not conducted in accordance with Annex XI no. 1.2. REACH and for reasons of animal welfare: "Where sufficient weight of evidence for the presence or absence of a particular dangerous property is available, further testing on vertebrate animals for this property shall be omitted..."

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

L-arginine did not cause any mortality in an acute oral toxicity study. No acute toxic effects were observed for the oral route up to the maximum dose of 5110 mg/kg body weight. The LD50 value of L-arginine via the oral route represented by male and female rats was > 5110 mg/kg body weight. This key study is considered most reliable.

In another study L-arginine HCl was administered to rats intraperitoneally. Read-across from L-arginine HCl to L-arginine was applied because of their structural similarity. L-arginine-HCl as such is not a natural constituent of peptides and proteins. L-arginine-HCL is the salt resulting from the reaction of the basic L-arginine with HCl. Due to its higher water solubility L-arginine-HCl is often preferably applied than L-arginine, in particular when bioavailability is a desired property for the intended use. L-arginine-HCl dissociates in aqueous solution to ionic L-arginine as well as H+ and Cl-. The inorganic ions resulting from physiological concentrations are not of concern for toxicokinetics as the “background” concentration in the body is by magnitudes higher. LD50 of L-arginine HCl was calculated to be 3792 mg/kg bw. The LD50 of L-arginine was calculated to be 3136 mg/kg bw, using the ratio of molecular weights of the test substance and L-arginine. This result confirms the very low systemic toxicity of L-arginine. This study was performed prior to the availibility of an OECD guideline or any other international test guideline and read-across was used; thus it is seen less reliable than the key study.

These results show that the toxicity of L-arginine 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-arginine.

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

No data on acute dermal toxicity for L-arginine is available. Due to its very low systemic toxicity and the fact that L-arginine (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

key study

Justification for classification or non-classification

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