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Description of key information

Skin Irritation

There are 2 studies available, one on the test substance (target) and one on a structurally similar substance (source 1). Both studies conclude that the test substance is a skin irritant.

 

Eye Irritation

Available study is on the target substance, studies conclude that the test substance is an occular irritant.

 

As a result, the test substance is classified as a skin and eye irritant under GHS classification criteria.

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:
experimental study
Adequacy of study:
supporting study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Study protocol followed OECD guideline 404
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Study was terminated after 72 hours even though effects had not fully reversed.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Young adult male and female New Zealand White rabbits weighing between 1500-2500 grams were used in this study. All animals were housed individually in stainless steel cages and offered food and water ad libitum
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
0.5 mL of undiluted sample
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
Hair is clipped from the abdomen of six albino rabbits, and four areas of the abdomen approximatley ten centimeters appart. Two one-square inch sites on the right side are abraded while similar sites on the left side remain unbraded. 0.5mL of undiluted test material is placed on the under a one-inch square piece of cotton gauze which is held in place with adhesive tape. the entire trunk of the animal is then wrapped with a rubberised cloth and remains for a 24 hours exposure period. After 24 hours the patches are removes, and the skin is examined for signs of irritation (erythema/oedema). The skin is examined ahain at the end of the 72 hour observation period.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
72 hours
Remarks on result:
positive indication of irritation
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based on the results of this study the test material is considered to be a skin irritant under GHS classification criteria
Executive summary:

Young adult male and female New Zealand White rabbits weighing between 1500 -2500 grams were exposed to 0.5ml of undiluted test material for 24 hours. The hair was clipped from the abdomen and two one-square inch sites on the right side are abraded bilse similar sites on the left side remain unabraded. The test substance is placed on the skin under a one-inch square piece of corron gauze which is held in place with adhesive tape. The entire trunk of the animal is then wrapped with a rubberised cloth and remains for a 24 hour exposure period. After 24 hours the patches are removed, and the skin is examined for signs of irritation. The skin is examined again at the end of 72 hours.

All animals showed signs of erythema and oedema at the end of the 24 and 72 hour observation period.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2 October 2002 to 7 November 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without deviations
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: >= 8 weeks
- Weight at study initiation: 2.84 - 3.07 kg
- Housing: individually in stainless steel cages with perforated floors
- Diet (e.g. ad libitum): 125 g/day standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellets ), dietary supplement of hay
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >= 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-20°C. The study protocol indicated that the target temperature range was 15-23°C, however, the range was changed to 16-20°C on 4th November 2002. The change was to accord with the UK Home Office Animals (Scientific Procedures) Act 1986 Code of Practice for the Housing and Care of Animals used in Scientific Procedures (1989).
- Humidity (%): 40-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours continuous artificial light in each 24 hour period
Type of coverage:
semiocclusive
Preparation of test site:
other: Intact skin, clipped hair
Vehicle:
unchanged (no vehicle)
Remarks:
The treatement site was wetted with 0.5 mL of reverse osmosis water.
Controls:
other: An additional site of the test animals was similarly treated with the exception of test substance and acted as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g on wetted skin
Duration of treatment / exposure:
4 hours (a single animal received three exposures (of three minutes, one or four hours duration) in a step-wise manner and acted as a preliminary screen)
Observation period:
15 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: On the day before application of the test substance, hair was removed with clippers from the dorso-lumbar region of each rabbit exposing an appropriate sized area of skin.
- % Coverage: approximately 25 mm x 25 mm was covered with substance
- Type of wrap if used: Test substance was applied under a 2-ply porous gauze pad. For exposures of one hour or more each treatment site was covered with cotton wool and "Tubigrip" elasticated bandage dressing for the duration of the exposure period.
- Preparation of test site: The skin treatment site was wetted with 0.5 mL of water before application of the powder.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

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

Oedema formation:
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
Very-slight to moderate to severe erythema with or without very-slight or, in one case, slight oedema was apparent during the first week after bandage removal, persisting in two cases until termination on Day 15. Loss of flexibility was evident in two animals 72 hours after bandage removal and in one case on Day 8; eschar formation or exfoliation was apparent in two animals on Day 8 or 15.
Other effects:
There was no sign of toxicity or ill health in any rabbit during the observation period.

Table 1 - Scoring of irritance responses

Test site: 0.5 g DV6850, semi occluded for four hours, dorso lumbar

Control site: No treatment

Animal

number and sex

Type of response

1 hour

24 hours

48 hours

72 hours

Day 8

Day 15

Test site

Control site

Test site

Control site

Test site

Control site

Test site

Control site

Test site

Control site

Test site

Control site

4617 M *

Erythema

0

0

2

0

3

0

3

0

1 Lf

0

0

0

Oedema

0

0

1

0

1

0

1

0

1

0

0

0

4660 M

Erythema

1

0

1

0

1

0

2 Lf

0

2 E

0

1 D

0

Oedema

0

0

1

0

1

0

2

0

1

0

1

0

4662 M

Erythema

1

0

1

0

1

0

1 Lf

0

1 D

0

1 D

0

Oedema

1

0

1

0

1

0

1

0

0

0

0

0

M: Male

*: Sentinel animal

Lf: Loss of flexibility

D: Exfoliation

E: Eschar

Classification Criteria

The study protocol indicated that the criteria regarding classification, packaging and labelling of dangerous substances of the European Communities as outlined in Directive 93/21/EEC would be employed. However, the updated criteria as documented in 2001/59/EC was employed.

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Although the mean scores were below the labelling threshold of Commission Directive 2001 /59/EC the persistent nature of the treatment related findings in two cases indicates significant irritation. Accordingly, DV6850 required labelling with the risk phrase R38, "Irritating to skin" (DSD) or Skin irrit. 2, H315 (CLP).
Executive summary:

A study was performed to assess the skin irritation potential of DV6850 to the rabbit. The methods followed were that described in EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (Skin Irritation), OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion", adopted 17 July 1992 and EPA Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation EPA 712 -C-98-196, August 1998.

Three rabbits received a single four hour, semi-occlusive, dermal administration of approximately 0.5 g of the test substance as supplied on wetted skin and were observed for fifteen days.

Very-slight to moderate to severe erythema with or without very-slight or, in one case, slight oedema was apparent during the first week after bandage removal, persisting in two cases until termination on Day 15. Loss of flexibility was evident in two animals 72 hours after bandage removal and in one case on Day 8; eschar formation or exfoliation was apparent in two animals on Day 8 or 15. Mean individual scores at 24, 48 and 72 h after application were 2.7, 1.3, 1.0 for erythema and 1.0, 1.3, 1.0 for edema, for rabbits No. 1, 2, 3, respectively. Although the mean scores were below the labelling threshold of Comission Directive 2001 /59/EC the persistent nature of the treatment related findings in two cases indicates significant irritation. Accordingly, DV6850 required labelling with the risk phrase R38, "Irritating to skin" (DSD) or Skin irrit. 2, H315 (CLP).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals were housed individually in stainless steel cages
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.1 mL of undiluted test material
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
6
Details on study design:
The test sample was instilled into the conjunctival sac of the right eye of each rabbit, with the left eye serving as a control. The general technique followed that of the Draize method. At each scoring interval the cornea, iris and conjunctivae were examine dand graded for irritation and injury in accordance with the Draize scoring system.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible within:
Remarks:
14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.416
Max. score:
2
Reversibility:
fully reversible within:
Remarks:
14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.35
Max. score:
4
Reversibility:
fully reversible within:
Remarks:
14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
3
Reversibility:
fully reversible within:
Remarks:
14 days
Remarks on result:
positive indication of irritation
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Substance is classiifed as H319 under GHS classification criteria
Executive summary:

The test sample was instilled into the conjunctival sac of the right eye of each rabbit, with the left eye serving as a control.  The general technique followed that of the Draize method.  At each scoring interval the cornea, iris and conjunctivae were examine dand graded for irritation and injury in accordance with the Draize scoring system.  

Followoijgn gradings over 24, 48 and 72 hours the mean score for cornea opacity, Iritis, conjunctivae redness and swelling was 1.6, 0.41, 1.6 and 1.35, respectively. All effects were fully reversed by the end of the 14 day observation period. Based on the results of this study the test substance is considered to be an eye irritant under GHS classification criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Boundary composition.001 (Composition of C18:1 amidopropyl betaine containing ≥0.1% and < 10% C18:1 aminopropyl amide)

The target substance (TS) is classified as H314:Causes severe skin burns and eye damage and H318: Causes serious eye damage according to Commission Regulation (EU) No 286/2011 of 10 March 2011 (second amendment of CLP regulation) due to the presence of a corrosive impurity. The corrosive classification was considered as part of the chemical safety assessment.

 

Boundary composition.002_(Composition of C18:1 amidopropyl betaine containing < 0.1% C18:1 aminopropyl amide)

The target substance (TS) is classified as H315: Causes skin irritation and H319: Cause serious eye irritation

According to Commission Regulation (EU) No 286/2011 of 10 March 2011 (second amendment of CLP regulation)