L-4-hydroxyproline

Endpoint summary

Description of key information

The substance L-4-hydroxyproline is neither irritating nor corrosive to the skin.

The substance L-4-hydroxyproline did not exhibit any eye irritating or corrosive properties to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-03-07 to 1997-04-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Principles of method if other than guideline:

Objective: To determine by epidermal contact the primary or cumulative irritation and/or sensitization potential of the test material.
Participants:
Fifty-four (54) subjects, male and female, ranging in age from 18 to 73 years, who qualified were selected for this evaluation. Forty-nine (49) subjects completed this study. The remaining subjects discontinued their participation for various reasons, none of which were related to the use of the test material
The criteria for selection were
1. Willingness to cooperate,
2. Absence of any visible skin disease which might be confused with skin reactions from the test material,
3. Avoidance of use of topical or systemic steroids and/or antihistamines for several days prior to study initiation,
4. Dependability and intelligence in following directions, and
5. Reading, understanding, and signing an Informed Consent Form.

GLP compliance:

not specified

Specific details on test material used for the study:

Lot 96003, manifactured by Kyowa Hakoo Kogyo Co., Ltd.

Species:

other: Humans

Strain:

other: Humans

Type of coverage:

occlusive

Preparation of test site:

other: None

Vehicle:

water

Amount / concentration applied:

0.2 g of the test material was applied to the 3/4" x 3/4" gauze portion of an adhesive dressing* moistened with approximately 0.2 ml of distilled water. The
resultant test concentration was 50% aqueous. This was then applied to the appropriate treatment site to form an occluded patch.

*Manufactured by Keridall Healthcare Products, Inc. , Greenwood, SC

Duration of treatment / exposure:

The procedure described above was followed three times per week: Monday, Wednesday, and Friday for a total often applications. If a participant was unable to report for an assigned test day, one (1) makeup day was permitted. This day was added to the Induction Period. The site was marked to ensure the continuity of patch application. The participants were instructed to remove this patch after twenty-four hours, The evaluation of this site was made just prior to re-application.

Observation period:

24 h following each Tuesday and Thursday removal, and 48 h h following each Saturday removal.

Number of animals:

54 male and femal humans, of which 49 completed the study. Age ranging from 18 - 73 years.

Details on study design:

The upper back between the scapulae served as the treatment area.
If the test site exhibited a moderate (2+) reaction during the Induction Phase, application was moved to an adjacent area. Applications were discontinued
for the remainder of this test phase, ifa moderate (2+) reaction was observed on this new test site. Applications would also be discontinued if a marked
(3+) reaction was noted.
Rest periods consisted of twenty-four hours following each Tuesday and Thursday removal, and forty-eight hours following each Saturday removal
At the conclusion of a rest period of approximately two weeks following the tenth application, a challenge patch was applied to the original site and to a
virgin site. Each site was evaluated at twenty-four and forty-eight hours after application. The volar forearm served as the virgin test site.

Irritation parameter:

erythema score

Basis:

other: All subjects

Time point:

other: 10 d induction phase, followed by 24 h / 48 h observation.

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

other: All subjects

Time point:

other: 10 d induction phase, followed by 24 h / 48 h observation period

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

The subsatnce is not irritant to the skin.

Executive summary:

The substance was applied to 54 male and female humans who had voluntered for the study. 49 subjects completed this study. The remaining subjects discontinued their participation for various reasons, none of which were related to the use of the test material.

The substance was repeatedly applied to the skin of the subjects.

Under the conditions of this study, test material L-4-Hydroxyproline, did not indicate a potential for dermal irritation and/or sensitization.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-03-24 to 1997-03-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: lot 96003:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble and stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: test item suspended at 50 % distilled water

FORM AS APPLIED IN THE TEST (if different from that of starting material): est item suspended at 50 % distilled water

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: ca. 3 months
- Weight at study initiation: ca. 2 kg
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Lab Diet Certified Rabbit Diet #5322
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24 °C
- Humidity (%): monitored
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 1997-02-27 To:1997-03-27

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 50 %

VEHICLE
- Purity: distilled water

Duration of treatment / exposure:

24 h

Observation period (in vivo):

24, 48, 72 h

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with distilled water
- Time after start of exposure: 24 h

SCORING SYSTEM: Severity of ocular lesions

Irritation parameter:

cornea opacity score

Basis:

other: All 6 animals

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

other: Area of cornea involved

Basis:

other: All 6 animals

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness, chemosis, discharge

Basis:

other: All 6 animals

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irrittaing to the eye.

Executive summary:

6 New Zealand white rabbits, free from visible ocular defects, each received a single intraocular application of 0.1 mI of the test article in 1 eye. The contralateral eye, remaining untreated, served as a control. The eyes of all animals remained unwashed for 24 hours' Observations of corneal opacity, intis, and conjunctivitis were recorded 24, 48, and 72 hours after treatment. The test article was used as a 50 percent suspension in distilled water (test article and distilled water were added together in aratio of 1:1 2 grams of each).

The substance did not show any eye irritating properties under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The substance L-4-hydroxyproline did not exhibit any

irritating nor corrosive properties to the skin.

The substance L-4-hydroxyproline did not exhibit any eye irritating or corrosive properties to the eye.