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Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From October 03, 1989 to October 10, 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
RA study
Justification for type of information:
Refer to the section 13 of IUCLID dataset for details on the read across justification. The skin irritation / corrosion study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Test animals
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.32 - 2.68 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

Environmental conditions
- Temperature (°C): 15-20
- Humidity (%): 47-60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free of fur
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1 h, 24 h, 48 h, 72 h
Number of animals:
3
Details on study design:
Test site
- Area of exposure: dorsal/flank area
- Type of wrap if used: elasticated corset (TUBIGRIP)

Removal of the test substance
- Washing (if done): removing by gentle swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: 4h

Scoring system: Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics":

Erythema and Eschar Formation
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema Formation
0 No oedema
1 Very slight oedema (barely perceptible)
2 Slight oedema (edges of area well-defined by definite raising)
3 Moderate oedema (raised approximately 1 millimetre)
4 Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)
Primary Irritation Index
0 Non-irritant
> 0 - 2 Mild irritant
> 2 - 5 Moderate irritant
> 5 - 8 Severe irritant
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0.5
Max. score:
8
Reversibility:
fully reversible
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the substance was not irritating to rabbit skin.
Executive summary:

A study was conducted to determine the in vivo skin irritation / corrosion potential of the substance according to OECD Guideline 404, in compliance with GLP. New-Zealand White rabbits were exposed to 0.5 mL of undiluted test substance for 4 h.The experiment consisted of a semiocclusive coverage on a clipped skin free of fur. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for erythema and oedema were between 0.7 and 1.0 and all effects were reversible within 7 d. Under the study conditions, the substance was not irritating to rabbit skin (Safepharm Laboratories Limited, 1989).

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
From November 10, 2000 to November 17, 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
RA study
Justification for type of information:
The skin irritation / corrosion study with the read across substance is considered to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: Method T11C: "Skin irritation through patch test"
Deviations:
not specified
Principles of method if other than guideline:
Method T11C: "Skin irritation through patch test"
The method consists in an occlusive application of the test substance by means of Finn Chambers (alluminium cells of 20 microlitres volume) on 20 selected subjects’ back or forearm. The irritating activity is clinically evaluated:
- 30 minutes (T1) after application (immediate irritative power);
- 48 hours later (T2) (irritative power);
by observing the erythema induced by the test substance.
Test substances are then ranked on a statement scale ranging from “non irritating” to “strongly irritating” on the basis of the severity of the irritating reactions observed as well as their frequency in the different subjects.
GLP compliance:
yes
Remarks:
and GCP
Specific details on test material used for the study:
Appearance: liquid and transparent
Species:
other: Human
Type of coverage:
occlusive
Preparation of test site:
other: Cleaned from sebum
Vehicle:
other: Vaseline oil or distilled water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
Tested at 7% in S.A.L.
20 µL
Duration of treatment / exposure:
30 min and 48 hours
Observation period:
- 30 min and 48 hours after application. The evident redness after 30 minutes is considered as a sign of irritation caused by the test substance.
- A second check is made 24 hours after the removal of the plaster strip. A persistent redness is considered as subjective allergic reaction to some of the components of the test substance or as a prolonged irritation.
Number of animals:
20 (M/F)
Details on study design:
The test substance was put in Finn Chambers, aluminium cells with a diameter of 8 mm, 50 mm2 area, volume of 20 microlitres. It was put directly into the cells, filled slightly more than half their volume. The two cells containing each productwere then applied on the back or on the forearm of the subject, on healthy skin previously cleaned from sebum.
Irritation parameter:
erythema score
Remarks:
irritative power (%)
Basis:
mean
Time point:
other: 30 min, 48 hours, and 24 hours after removal
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- Immediate irritative power (IIP) (30 minutes after product application) = 0%.
- Irritating power (IP) (48 hours after product application) = 0%
- 24 hours after the test substance removal, no cases of delayed irritation/allergic reactions to the test substance were either observed or reported.
Other effects:
None of the subjects reported itching phenomena.

Interpretation of data:

The immediate irritative power (IIP) and the irritative power (IP) are separately evaluated. The irritative power of the product was evaluated considering:

- the number of reactions that the product caused to the total number of subjects;

- the severity of the irritative reactions.

The reaction of type 2 (light faint homogeneous erythema or “silk paper” skin reactions) disappearing within 24 hours after the test substance has been removed, are not considered. The reactions of type 5 and 6 (erythema and bulla, follicular bulla and pustules or necrosis reactions) are counted twice. The erythema cases appeared within 24 hours after the removal are not included in the final calculation. However they will be reported since they can be regarded as allergic reactions to one or more components of the test substance. On the basis of the data reported in literature, the tested product can be considered: from No reaction to Maximum (%).

Interpretation of results:
study cannot be used for classification
Conclusions:
Under the study conditions, the substance was not considered to be irritant to human skin.
Executive summary:

A supporting study was conducted to determine the in vivo skin irritation / corrosion potential of the read-across substance L-Glutamic acid, N-(1-oxooctyl)-, sodium salt (1:2) in humans according to the Method: T11C: "Skin irriation through patch test", in compliance with GLP and GCP. The method consists in an occlusive application of the test substance by means of Finn Chambers (aluminium cells of 20 microlitres volume) on 20 selected subjects’ back or forearm. The irritating activity/power (%) was clinically evaluated after 30 minutes (T1) following application (immediate irritative power) and 48 hours later (T2) (irritative power); by observing the erythema induced by the test substance. Test substances were then ranked on a statement scale ranging from “non irritating” to “strongly irritating” on the basis of the severity of the irritating reactions observed as well as their frequency in the different subjects. A second check was made 24 hours after the removal of the plaster strip. The irritating power of the test substance was 0% and 24 hours after the test substance removal; no cases of delayed irritation/allergic were either observed or reported. None of the subjects reported itching phenomena. Under the study conditions, the substance was not considered to be irritant to human skin (Sirigu, 2000).

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
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From October 09, 1989 to October 26, 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
RA study
Justification for type of information:
Refer to the section 13 of IUCLID dataset for details on the read across justification. The eye irritation study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Test system
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.32-2.74 kg
- Housing: individually house in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

Environmental conditions
- Temperature (°C): 14-20
- Humidity (%): 52-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 mL
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Scoring system:
The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of opacity). For each tissue the total score was calculated as follows:

Total score for conjunctivae = (A + B + C) x 2
Total score for iris = D x 5
Total score for cornea = (E x F) x 5

Tool used to assess score: standard ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Under the study conditions, the substance was considered to be irritating to rabbit eye.
Executive summary:

A study was conducted to determine the in vivo eye irritation potential of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 405, in compliance with GLP. Eyes of New-Zealand White rabbits were exposed to 0.1 mL of the undiluted test substance. The other eye served as control. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for cornea, conjunctiva, iris effects and chemosis were determined to be 1.8, 2.9, 1.0 and 2.4. All effects were reversible within 14 d. Under the study conditions, the substance was considered to be irritating to rabbit eye (Safepharm Laboratories Limited, 1989).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion - in vivo:

A study was conducted to determine the in vivo skin irritation / corrosion potential of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 404, in compliance with GLP. New-Zealand White rabbits were exposed to 0.5 mL of undiluted test substance for 4 h.The experiment consisted of a semiocclusive coverage on a clipped skin free of fur. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for erythema and oedema were between 0.7 and 1.0 and all effects were reversible within 7 d. Under the study conditions, the substance was not irritating to rabbit skin (Safepharm Laboratories Limited, 1989).

A supporting study was conducted to determine the in vivo skin irritation / corrosion potential of the read-across substance L-glutamic acid, N-(1-oxooctyl)-, sodium salt (1:2) in humans according to Method: T11C: "Skin irriation through patch test", in compliance with GLP and GCP. The method consists in an occlusive application of the test substance by means of Finn Chambers (aluminium cells of 20 microlitres volume) on 20 selected subjects’ back or forearm. The irritating activity/power (%) was clinically evaluated after 30 minutes (T1) following application (immediate irritative power) and 48 hours later (T2) (irritative power); by observing the erythema induced by the test substance. Test substances were then ranked on a statement scale ranging from “non irritating” to “strongly irritating” on the basis of the severity of the irritating reactions observed as well as their frequency in the different subjects. A second check was made 24 hours after the removal of the plaster strip. The irritating power of the test substance was 0% and 24 hours after the test substance removal; no cases of delayed irritation/allergic were either observed or reported. None of the subjects reported itching phenomena. Under the study conditions, the substance was not considered to be irritating to human skin (Sirigu, 2000).

Eye irritation - in vivo:

A study was conducted to determine the in vivo eye irritation potential of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 405, in compliance with GLP. Eyes of New-Zealand White rabbits were exposed to 0.1 mL of the undiluted test substance. The other eye served as control. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for cornea, conjunctiva, iris effects and chemosis were determined to be 1.8, 2.9, 1.0 and 2.4. All effects were reversible within 14 d. Under the study conditions, the substance was considered to be irritating to rabbit eye (Safepharm Laboratories Limited, 1989).

Justification for classification or non-classification

Based on in vivo skin and eye irritation studies with the read-across substances L-glutamic acid, N-coco acyl derivs., monosodium salts and L-glutamic acid, N-(1 -oxooctyl)-, sodium salt (1:2),

the substance warrants classification as Eye Irrit. 2: H319 (Causes serious eye irritation) according to EU CLP (1272/2008) criteria.