L-4-hydroxyproline

Endpoint summary

Description of key information

The substance L-4 -hydroxyproline does not require classification.

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:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study dates from 1971, although not meeting the current acute toxicity guidelines and GLP requirements and lacking described details, the study reveals usefull data considering the LD50 in rats.

Qualifier:

no guideline available

Principles of method if other than guideline:

- Principle of test: Oral gavage of very high dose
- Parameters analysed / observed: Mortality, behaviour, signs of toxicity; macroscopic examination

GLP compliance:

no

Test type:

other: Divided doses at 2 h intervals.

Limit test:

no

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Carworth Europe, Huntingdon
- Weight at study initiation: 62 - 123 g
- Fasting period before study: 20 hours before dosing and 4 hours after dosing
- Housing: caged in groups according to sex and age

Route of administration:

oral: gavage

Vehicle:

other: water or methyl cellulose

Details on oral exposure:

Vehicle:
- Concentration in vehicle: 30% solution in water or suspension

Doses:

Test 1: 0, 4, 8, 16 g/kg bw
Test 2: 0, 8.0, 10.0, 12.5, 16.0 g/kg bw

No. of animals per sex per dose:

Test 1: 2 males and 2 females
Test 2: 5 males and 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once a week
- Necropsy of survivors performed: yes
- Other examinations performed: body weight/behaviour

Statistics:

Method of Litchfield J.T., Wilcoxon F (1949), J. Pharmac. exp. Ther. 96, 99

Preliminary study:

The results of the preliminary range finding indicated that the median lethal dose LD50 was in the range of 16000 mg/kg bw.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality occured 22 hours after dosing

Clinical signs:

other: Lethargic behaviour wa sthe only observed sign of reaction to the treatment.

Gross pathology:

Autopsy did not reveal any specific cause of death.

Other findings:

Recovery of survivors, as jugged by external appearance and behaviour, was apparently complete within 3 days.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 16000 mg/kg

Executive summary:

LD50 > 16000 mg/kg

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

16 000 mg/kg bw

Quality of whole database:

K2

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
[Specific explanation in addition to field 'Justification for data waiving']

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Dermal absorption is unlikely because of the poor lipophilicity of L-4-hydroxyproline. It suggests that the substance is not likely to cross the stratum corneum. Moreover, the low volatility in combination with the high water solubility and the negative Log P value indicate that the substance may be too hydrophilic to cross the lipid rich stratum corneum and thus dermal uptake will be unlikely.

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

LD50 (oral) > 16000 mg/kg.

Exposure of humans via inhalation is unlikely to occur.

Dermal resorption is not expected.