Sodium 5-oxo-1-palmitoyl-L-prolinate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27.May.2008-17.June.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Sponsor's identification: LCA08009
Date received: 14 May 2008
Container : plastic flask (n-1)
Form: liquid
Quantity : 142.44 g (container + contents)
Colour : brown
Batch no : LCA08009
Storage : room temperature
Purity: 30%
It was identified under the code number: PH-08/0227.
The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. A safety data sheet and an information data sheet concerning the test item were provided by the study monitor.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals
Three female albino New Zealand rabbits were supplied by the Elevage de Gérome (Quartier Labaste - F40260 Linxe). They were kept during a minimal 5-day acclimatisation period. During the test, the animals weighed between 2,50 kg and 3.22 kg. At the beginning of the test, the animals were l l to 12 weeks old.

Housing
Each animal was kept in an individual box installed in conventional air conditioned animal husbanding; the environmental conditions were:
- temperature: between 19°C and 23°C - relative humidity: between 39% and 53% - lighting time: 12 hours daily - rate of air exchange: at least ten changes per hour

Food and drink
Drinking water (tap-water from public distribution system) and foodstuff (SDS-C15) were supplied freely, Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux (I.E.E.B).

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 g of the test item, as supplied

Duration of treatment / exposure:

4 hours

Observation period:

The skin reactions were appreciated 1 hour and then 24, 48 and 72 hours after removal of the patch.

Number of animals:

3
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first animal, two additional animals were treated.

Details on study design:

Approximately 24 hours before the test, the rabbits backs and flanks were shorn using electric clippers equipped with a fine comb, so as to expose an area of skin about 6 cm.
As no tissue destruction was noted after a treatment during 3 minutes and 1 hour, the test item was applied, as supplied, at a dose of 0.5g, on an undamaged skin area of one flank of each animal, during 4 hours. The patch was secured in position with a strip of surgical adhesive tape. After the removal of the patch, the treated area was rinsed with distilled water, On the opposite flank an untreated area was served as the control. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1.7

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

fully reversible

Irritant / corrosive response data:

A well defined erythema associated with a slight oedema was noted, on the treated area, 24 hours after the test item application. The oedematous reactions were totally reversible between D5 and D6 and the erythematous reactions were totally reversible at D6. On the cutaneous structure, a dryness was noted on the treated area, from D3 in two animals and from D4 in the last one. A slight dryness was still noted at the end of the observation time (D14) in the three animais.

Interpretation of results:

GHS criteria not met

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item LCA08009, according to the scales of interpretation retained:
- is irritant to skin (PSi = 3.8) according to the classification established in the Journal Officiel de la
République Francaise dated February 21, 1982,
- and, must be classified R38 “irritating to skin', according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 99/45. The item must be characterised by the symbol “Xi' and the warning label “irritant”. In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category2 “irritant'. No signal word and hazard statement are required.

Executive summary:

The test item LCA08009 was applied, as supplied, at the dose of 0.5g, under semi-occlusive dressing during 4 hours on an undamaged skin area of three rabbits. The experimental protocol was established from the O.E.C. D. guideline n° 404 dated April 24", 2002 and the test method B.4 of the directive n° 2004/73/EC.

 

A well defined erythema associated with a slight oedema was noted, on the treated area, 24 hours after the test item application. The oedematous reactions were totally reversible between D5 and D6 and the erythematous reactions were totally reversible at D6, On the cutaneous structure, a dryness was noted on the treated area, from D3 in two animals and from D4 in the last one. A slight dryness was still noted at the end of the observation time (D14) in the three animals.

 

The results obtained, in these experimental conditions, enable to conclude that the test item LCA08009 must be classified R38 “irritating to skin', according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 99/45. The item must be characterised by the symbol “Xi' and the warming label “irritant”, In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category 2 “irritant'. No signal word and hazard statement are required.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.June.2008-23.June.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Sponsor's identification: LCA08009
Date received: 14 May 2008
Container : plastic flask (n=1)
Form: liquid
Quantity : 142.44 g (containers+ contents)
Colour: brown
Batch n : LCAO8009
Storage : room temperature
Purity: 30%
It was identified under the code number: PH-08/0227.
The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. An information data sheet and a safety data sheet concerning the test item were provided by the study monitor.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animal
One female albino New Zealand rabbits was supplied by the Elevage de Gérome (Quartier Labaste - F40260 Linxe). It was kept during a minimal 5-day acclimatisation period. During the test, the animal weighed between 2.60 kg and 3.05 kg. At the beginning of the test, the animal was 12 weeks old.

Housing
The animal was kept in an individual box installed in conventional air conditioned animal husbanding; the environmental conditions were:
- temperature: between 19°C and 23°C - relative humidity: between 38% and 62% - lighting time: 12 hours daily - rate of air exchange: at least ten changes per hour

Food and drink
Drinking water (tap-water from public distribution system) and foodstuff (SDS- C15) were supplied freely. Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux (I.E.E.B.).

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye.

Duration of treatment / exposure:

Until natural elimination

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following
treatment

Number of animals or in vitro replicates:

One animal
Initially, a single animal was treated. After consideration of the ocular responses produced in the first
treated animal, two additional animals were not treated.

Details on study design:

0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye. The other eye
remained untreated serving as control.
Initially, a single animal was treated. After consideration of the ocular responses produced in the first
treated animal, two additional animals were not treated.
Grading of reactions
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following
treatment.
NOTE :
If no reaction is observed 72 hours after instillation, the study is terminated. In case of persistent reactions, additional
observations can be carried out from D4 to D21 in order to determine the reversible character of the lesions observed.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2.3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Reversibility:

not fully reversible within: still noted at D21 (moderate intensity)

Irritant / corrosive response data:

The ocular reactions observed during the study have been moderate and partially reversible:
- at the conjunctivae level: a moderate redness associated with a moderate chemosis, registered 1 hour after the test item instillation and totally reversible at D21,
- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation, and still noted at the end of the observation time (moderate intensity).
Moreover, a corneal neo-vascularisation was noted between D7 and D17.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item LCA08009:
- is highly irritant for the eye (Max, O.I = 54) according to the classification established in the
Journal Officiel de la République Française dated July 10", 1992.
- and, must be classified R41 "Risk of serious damage to eyes" taking into account the irreversibility of the reactions, according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive n° 67/548, 2001/59 and 9945. It must be characterised by the symbol “Xi' and the danger label “irritant”. In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must be classified in category “irreversible effects on the eye'. The signal word “Danger' and hazard statement H318 “Causes serious eye damage' are required.

Executive summary:

The test item LCA08009 was instilled as supplied, into the eye of one New Zealand rabbit at the dose of 0.1 mL. The experimental protocol was established on the basis of the official method as defined in the OECD, guideline n° 405 dated April 24", 2002 and the test method B.5 of the directive 2004/73/EC.

The ocular reactions observed during the study have been moderate and partially reversible: - at the conjunctivae level: a moderate redness associated with a moderate chemosis, registered 1 hour after the test item instillation and totally reversible at D21, - at the corneal level: a moderate opacity, registered 24 hours after the test item instillation, and still noted at the end of the observation time (moderate intensity), Moreover, a corneal neo-vascularisation was noted between D7 and D7.

In conclusion, the result obtained, under these experimental conditions, enable to conclude that the test item LCA08009 must be classified R41 "Risk of serious damage to eyes" taking into account the irreversibility of the reactions, according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive in 67/548, 2001/59 and 99/45. It must be characterised by the symbol “Xi” and the danger label "irritant, In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must be classified in category 1 "irreversible effects on the eye'. The signal word “Danger' and hazard statement H318 “Causes serious eye damage” are required.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation

The test item LCA08009 was applied, as supplied, at the dose of 0.5g, under semi-occlusive dressing during 4 hours on an undamaged skin area of three rabbits. The experimental protocol was established from the O.E.C. D. guideline n° 404 dated April 24", 2002 and the test method B.4 of the directive n° 2004/73/EC.

 

A well defined erythema associated with a slight oedema was noted, on the treated area, 24 hours after the test item application. The oedematous reactions were totally reversible between D5 and D6 and the erythematous reactions were totally reversible at D6, On the cutaneous structure, a dryness was noted on the treated area, from D3 in two animals and from D4 in the last one. A slight dryness was still noted at the end of the observation time (D14) in the three animals.

 

The results obtained, in these experimental conditions, enable to conclude that the test item LCA08009 must be classified R38 “irritating to skin', according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 99/45. The item must be characterised by the symbol “Xi' and the warming label “irritant”, In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category 2 “irritant'. No signal word and hazard statement are required.

 

Eye irritation

The test item LCA08009 was instilled as supplied, into the eye of one New Zealand rabbit at the dose of 0.1 mL. The experimental protocol was established on the basis of the official method as defined in the OECD, guideline n° 405 dated April 24", 2002 and the test method B.5 of the directive 2004/73/EC.

The ocular reactions observed during the study have been moderate and partially reversible: - at the conjunctivae level: a moderate redness associated with a moderate chemosis, registered 1 hour after the test item instillation and totally reversible at D21, - at the corneal level: a moderate opacity, registered 24 hours after the test item instillation, and still noted at the end of the observation time (moderate intensity), Moreover, a corneal neo-vascularisation was noted between D7 and D7.

In conclusion, the result obtained, under these experimental conditions, enable to conclude that the test item LCA08009 must be classified R41 "Risk of serious damage to eyes" taking into account the irreversibility of the reactions, according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive in 67/548, 2001/59 and 99/45. It must be characterised by the symbol “Xi” and the danger label "irritant, In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must be classified in category 1 "irreversible effects on the eye'. The signal word “Danger' and hazard statement H318 “Causes serious eye damage” are required.