Glutens, hydrolyzates, reaction products with lauroyl chloride, sodium salts

Endpoint summary

Description of key information

Test material: the liquid marketed product "Proteol OAT" which contains ca.27.5% of the solid substance "Glutens, hydrozylates, reaction products with lauroyl chloride, sodium salts".

Two GLP studies following OECD guidelines 404 and 405 were performed.

The registered substance is not irritating to the skin but is irritating to eyes

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:

2008-06-03 to 2008-06-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline, GLP 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)

Remarks:

2008-07-16

Specific details on test material used for the study:

Sponsor's identification: LCE08088
Container: plastic flask
Quantity: 1056,60 g
Batch: 0801000014
Form: liquid
Colour: yellow
Storage: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three male albino New Zealand rabbits were supplied by the Elevage de Gérome (Quartier Labaste — F40260 Liuxe). They were kept during a minimal 5-day aclimatisation period. During the test, the animals weighed between 2.33 kg and 3.08 kg. At the beginning of the test, the animais were 11 to 12 weeks old.

Housing
Bach animal was kept in an individual box installed in conventional air conditioned animal husbanding; the environmentai conditions were:
- temperature : between 19°C and 23°C
- relative huniidity : between 39% and 52%
- lighting time: 12 hours daiiy
- 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.
Microbiologieal and chemical analyses of the water were carried ont once every six months by the
Institut Européen de l’Environnement de Bordeaux (1.E.E.B.).

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Other side

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24, 48 and 72 hours after patch removal

Number of animals:

3

Details on study design:

Treatment
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 cm2.
As no tissue destruction vas noted afler a treatment during 3 minutes and during 1 hour, the test item was applied, as supplied, al a dose of 0.5 mL, on an undamaged skin area of one flank of one animal, during 4 hours. The patch was secured in position with a strip of surgical adhesive tape. Afler the removal of the patch, the treated area ;vas rinsed with distilled water.
On the opposite flank an untreated area vas served as the control.
Initially, a single animal was treated. After consideration of the cutaneous responses produeed in the first treated animal, two additional animais were treated during 4 hours.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

2

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1.5

Max. score:

2

Irritant / corrosive response data:

It was noted, 24 hours after the test item application, on the treated area, a well defined erythema associated with a slight oedema. The oedematous reactions were totally reversible between D2 and D6 and the erythematous reactions were totaly reversible between D3 and D6.
On the cutaneous structure, a slight dryness vas noted on the treated area, between D3 and D8 in two animais. In the last animal, a dryness vas registered between D3 and D14 (end of tire observation time).

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item LCEO8O88, according to the scales of interpretation retained:
- is irritant to skin (PSi 3.2) according to the classification established in the Journal Officiel de la République Française dated February 2], 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, 2 001/59 and 99/45. The item must ho cliaracterised by the symbol “Xi” and the warning label “irritant”.
In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 2 “irritant”. No signal word and hazard statement are required.

Executive summary:

The test item LCEO8O88 was applied, as supplied, at the dose of 0.5 mL, 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 24th, 2002 and the test method B.4 cf the directive n° 2004/73/EC’.

It was noted, 24 hours afler the test item application, on the treated area, a well defined erythema associated with a slight oedema, The oedematous reactions were totally reversible between D2 and D6 and the erythematous reactions were totally reversible between D3 and D6. On the cutaneous structure, a slight dryness vas noted on the treated area, between D3 and D8 in two animals, In the last animal, a dryness was registered between D3 and D14 (end of the observation time).

The results obtained, in these experimental conditions, enable to conclude that the test item LCEO8O88 must be classffied 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, 2 001/59 and 99/45. The item must be characterised by the symbol “Xi” and the warning label “irritant”. In accordance with the Globally Harmonized System (COM(2007)355 fmal), 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

Justification for type of information:

This Draize test (OECD 405) was performed in 2008, at that time no in vitro test evaluating the eye irritation potential was set up (OECD tests n° 437 and 438 adopted in 2009, OECD tests n°491 and 492 adopted in 2015) and no "top-down/bottom-up" approach existed.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-06-09 to 2008-07-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline, GLP study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Test item
Sponsor's identification: LCE08088
Container: plastic flask (n=1)
Quantity: 1056,60 g (container + contents)
Batch: 0801000014
Form: liquid
Colour: yellow
Storage: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

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 animais weighed between 3.04 kg and 3.71 kg. At the beginning ofthe test, the animals were 13 weeks old.

Housing
The animals were kept in an individual box installed in conventional air conditioned animal husbanding; the environmental conditions were:
- temperature : between 19°C and 24°C
- relative humidity : between 38% and 64%
- 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 - C 15) were supplied freely, Microbiologicai 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:

other: other eye as control

Amount / concentration applied:

0.1 mL

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.
If no reaction is observed 72 hours after instillation, the study is termined. In case of persistent reactions, additional observations can be carried out from D4 to D21 in order to determine the reversibility character of the lesions observed.

Number of animals or in vitro replicates:

3

Details on study design:

0.1 mL of the test item vas instilled, into the conjunctival sac of one eye. The other eye remained untreated serving as control.
lnitially, a single animal vas treated. Alter consideration of the ocular responses produced in the fïrst treated animal at D14, two additionai animals
were treated.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Irritant / corrosive response data:

The ocular reactions observed during the study have been moderate, and totally reversible in the three animals:
- at the conjuctivae level: a moderate redness, noted 1 hour after the test item instillation and totally reversible between D8 and D9.
- at the corneal level: a moderate opacity, registered 24 hours alter the test hem instillation and totally reversible between D9 and D 17,
- at the iris level: a congestion noted 1 hour and 24 hours alter the test item instillation in two animals and between 1 hour alter the test hem instillation and D6 in the Iast animal.

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The results obtained, under these experimental conditions, enable to conclude that the test item LCE08088:
- is highly irritant for the eye (Max. 0.1 = 54.3) according to the classification established in the Journal Officiel de la République Française dated July 10th, 1992.
- and, must be classified R36 “irritating to eyes” according to the criteria for the classification, packaging and labelling of dangerous substances in
compliance with the E.E.C. Directive n° 67/548, 200 1/59 and 99/45. The test item must be characterised by the symbol “Xi” and the warning label
“irritant “.
In accordance with the Globally Harmonized System (COM(2007)3 55 final), the test item must be classified in category 2 “irritating to eyes”. The
signal word and hazard statement H319 “Causes serious eye irritation” are required.

Executive summary:

The test item LCE08088 was instilled as supplied, at the dose of 0.1 mL into the eye of three New Zealand rabbits, The experimental protocol was established on the basis of the official method as defined in the O.E. C.D. 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 totally reversible in the three animals: - at the conjunctivae level: a moderate redness, noted 1 hour afler the test item instillation and totally reversible between D9 and D11, associated with a moderate chemosis, noted 1 hour afler the test item instillation and totally reversible between D8 aud D9; - at the corneal level: a moderate opacity, registered 24 hours afler the test hem instillation and totally reversible between D9 and Dl7, - at the Iris level: a congestion noted 1 hour and 24 hours afler the test hem instillation in two animals and between 1 hour afler the test item instillation and D6 in the last animal.

In conclusion, the result obtained, under these experimental conditions, enables to conclude that the test item LCE08088 must be classified R36 “irritating to eyes” according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive n° 67/548, 2001/5 9 and 99/45. The item must be characterised by the symbol “Xi” and the warning label “irritant”. In accordance with the Globally Harmonized System (COM(2007)355 fmal), the test item must be classifïed in category 2 “irritating to eyes”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must be classified in category 1 “severely irritating to eyes, H318.

Indeed, eye irritation classification is based on a worst case assumption for the effects of 100% neat substance, based on the study results obtained on 27.5 % substance solutions. The registered substance is an organic marketed or used in aqueous formulation, clear liquid form and yellow tint color at 20°C and 101.3kPa.