Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Based on the results from the in vivo irritation studies, the test substance is considered to be corrosive to skin as well as eyes.

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 September 15, 1987 to September 29, 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to section 13 of IUCLID for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K.
- Age at study initiation: 12-16 wk
- Weight at study initiation: 2.19 - 2.42 kg


Type of coverage:
occlusive
Preparation of test site:
other: closely clipping the fur from the dorsal/flank areas using veterinary clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Undiluted
Duration of treatment / exposure:
Upto 60 min
Observation period:
The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Clipped dorsal flanks
- Type of wrap if used: Occlusive patches
- 0.5 mL of test material was applied under occlusive patches on the clipped dorsal flanks of three rabbits and left for 3 min application on one flank and 60 min application on the other flank.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gentle swabbing with cotton wool soaked in 3 % (v/v) aqueous acetic acid followed by cotton wool soaked in distilled water.

EVALUATION:
Approximately 1 h following removal of the patches and 24, 48 and 72 h and 7 and 14 d later, the test sites (a total of six) were examined for evidence of primary irritation and scored according to Draize (1959).
Irritation parameter:
erythema score
Remarks:
(for 1 h exposure)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Eschar, moderate erythema extending beyond site, blanching of skin, scattered punctate formation
Irritation parameter:
edema score
Remarks:
(for 1 h exposure)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 3.56
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Oedema extending beyond site
Irritant / corrosive response data:
No data
Other effects:
No data

After three minutes exposure:

No adverse skin reaction were noted at any treated skin site 1 h after the removal of the patches. Very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at  all  the  treated  sites  at the  48  and 72 h  observations. Very slight oedema was noted at one treated site at the 24 and 48 h observations and at two treated sites at the 72 h observation. 


After one hour exposure:
A light brown discoloration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated  skin  sites 1 h  after  the  removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observation. Blanching and moderate  erythema  extending  up to  approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctate eschar
surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7. On Day 14  sunken  eschar  was  noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7.  The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14.

For result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:
other: Category 1 (corrosive) based on EU CLP criteria
Conclusions:
Based on the results of the read across study, the test substance is considered to be corrosive to skin in rabbits.
Executive summary:

A study was conducted to determine the skin irritation potential of the read across substance, DDAC (80% active in hydroalcoholic solution), according to the OECD Guideline 404, in compliance with GLP. In the study, 0.5 mL read across substance samples were applied under occlusive patches for both 3 and 60 min on the clipped skin of 3 rabbits. Residual read across substance was removed using cotton wool soaked in 3% (v/v) aqueous acetic acid followed by distilled water. The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d. After 3 min exposure, very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at all the treated sites at the 48 and 72 h observations. Very slight oedema was noted at one treated site at the 24 ad 48 h observations and at two treated sites at the 72 h observation. On Day 7 and 14, some hyperkeratinisation (2/3) and desquamation (1/3) was still present.After 1 h exposure, a light brown discolouration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated skin sites 1 h after the removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observations. Blanching and moderate erythema extending up to approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctuate eschar surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7. On Day 14 sunken eschar was noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1 h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7. The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14 (Guest, 1987). Based on the results of the read across study, the test substance is considered to be corrosive to skin in rabbits.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From September 15, 1987 to September 29, 1987
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:
not specified
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K.
- Age at study initiation: 12-16 wk
- Weight at study initiation: 2.19 - 2.42 kg


Type of coverage:
occlusive
Preparation of test site:
other: closely clipping the fur from the dorsal/flank areas using veterinary clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Undiluted
Duration of treatment / exposure:
Upto 60 min
Observation period:
The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Clipped dorsal flanks
- Type of wrap if used: Occlusive patches
- 0.5 mL of test material was applied under occlusive patches on the clipped dorsal flanks of three rabbits and left for 3 min application on one flank and 60 min application on the other flank.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gentle swabbing with cotton wool soaked in 3 % (v/v) aqueous acetic acid followed by cotton wool soaked in distilled water.

EVALUATION:
Approximately 1 h following removal of the patches and 24, 48 and 72 h and 7 and 14 d later, the test sites (a total of six) were examined for evidence of primary irritation and scored according to Draize (1959).
Irritation parameter:
erythema score
Remarks:
(for 1 h exposure)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Eschar, moderate erythema extending beyond site, blanching of skin, scattered punctate formation
Irritation parameter:
edema score
Remarks:
(for 1 h exposure)
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 3.56
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Oedema extending beyond site
Irritant / corrosive response data:
No data
Other effects:
No data

After three minutes exposure:

No adverse skin reaction were noted at any treated skin site 1 h after the removal of the patches. Very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at  all  the  treated  sites  at the  48  and 72 h  observations. Very slight oedema was noted at one treated site at the 24 and 48 h observations and at two treated sites at the 72 h observation. 


After one hour exposure:
A light brown discoloration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated  skin  sites 1 h  after  the  removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observation. Blanching and moderate  erythema  extending  up to  approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctate eschar
surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7. On Day 14  sunken  eschar  was  noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7.  The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14.

For result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:
other: Category 1 (corrosive) based on EU CLP criteria
Conclusions:
Under the study conditions, the test substance was found to be corrosive to skin in rabbits.
Executive summary:

A study was conducted to determine the skin irritation potential of the test substance, DDAC (80% active in hydroalcoholic solution), according to the OECD Guideline 404, in compliance with GLP. In the study, 0.5 mL test substance samples were applied under occlusive patches for both 3 and 60 min on the clipped skin of 3 rabbits. Residual test substance was removed using cotton wool soaked in 3% (v/v) aqueous acetic acid followed by distilled water. The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d. After 3 min exposure, very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at all the treated sites at the 48 and 72 h observations. Very slight oedema was noted at one treated site at the 24 ad 48 h observations and at two treated sites at the 72 h observation. On Day 7 and 14, some hyperkeratinisation (2/3) and desquamation (1/3) was still present.After 1 h exposure, a light brown discolouration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated skin sites 1 h after the removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observations. Blanching and moderate erythema extending up to approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctuate eschar surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7. On Day 14 sunken eschar was noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1 h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7. The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14. Under the study conditions, the test substance was found to be corrosive to skin in rabbits (Guest, 1987).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From May 28, 1980 to June 4, 1980
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study conducted according to guideline Association of Food and Drug Officials of the US, based on Draize, 1965 and pre-GLP. Not suitable for classification purposes due to aberrant exposure duration.
Qualifier:
according to guideline
Guideline:
other: Association of Food and Drug Officials of the US, based on Draize, 1965
Deviations:
not specified
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
Pre GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratories, Inc., Denver, Penn. USA
- Age at study initiation: ca. 14 wk
- Weight at study initiation: 2509 - 2813 g
- Housing: Individually in screen bottom cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: 14 d

IN-LIFE DATES: From: 28 May 1980 To: 4 June 1980
Type of coverage:
occlusive
Preparation of test site:
other: clipped and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Neat material
Duration of treatment / exposure:
24 h
Observation period:
After treatment, at 72 h (48 h after patch removal), and if signs of irritation had increased at 96 h (72 h after patch removal) and 7 d (6 d after patch removal).
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: Not indicated
- Area of coverage: 5.0 x 5.0 cm gauze patch
- Type of wrap if used: Saran wrap and elstoplast tape, plus collars

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test material was wiped (not washed)
- Time after start of exposure: After 24 h

SCORING SYSTEM:
EVALUATION OF SKIN REACTIONS
A. Erythema and eschar formation
No erythema 0
Doubtful or barely perceptible 0.5
Very slight erythema 1
Slight not well defined 1.5
Well-defined erythema 2
Moderate 2.5
Moderate to severe erythema 3
Severe not beet red 3.5
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

B. Oedema formation
No oedema 0
Doubtful or barely perceptible 0.5
Very slight oedema 1
Slight not well defined 1.5
Slight oedema (edges of area well-defined by
definite raising) 2
Edges well defined but less than 1 mm 2.5
Moderate oedema (raised approximately 1 mm) 3
Greater than 1 mm, exposure area only or 1 mm
extending beyond exposure area 3.5
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
ca. 3.75
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
ca. 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
ca. 3.42
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
ca. 3.92
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
ca. 3.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
ca. 3.92
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Abraded skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
ca. 3.5
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Abraded skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
ca. 4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Abraded skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/72 h
Score:
ca. 7.5
Max. score:
8
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
- Blanching of the test sites was observed in all the animals at 24, 72 and 96 h readings (0, 48 and 72 h after patch removal).
- Five animals exhibited blanching of the test sites at 7 d.
- Subcutaneous hemorrhage was observed within the test sites of all animals at the 72 and 96 h and 7 d readings.
- Eschar formation was observed within the test sites of all animals at the 7 d observation
Other effects:
None

For result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:
other: Category 1 (corrosive) based on EU CLP criteria
Conclusions:
Under the study conditions, the test substance was considered to be skin corrosive in rabbits.
Executive summary:

A study was conducted to determine the skin irritation potential of the test substance, C12 -18 DAQ (75% active in hydroalcoholic solution) according to guideline of Association of Food and Drug Officials of the US, based on Draize, 1965. The test substance was applied to four test sites per rabbit (2 abraded and 2 intact) under an occlusive dressing for 24 h. Skin irritation was scored according to Draize, at patch removal, 72 and 96 h and 7 d later. Blanching of the test sites was observed in all of the animals at 24, 72 and 96 h. Five rabbits exhibited blanching of the test sites at 7 d. Subcutaneous haemorrhage was observed within the test sites of all animals at the 72 and 96 h and 7 d observations. Eschar formation was observed within the test sites of all animals at the 7 d observation. The primary dermal irritation index (the average of the 24 and 72 hour primary dermal irritation scores) was 7.5. Oedema scores on intact skins were 3.75, 4 at 24, 72 h and on abraded skins were 3.67, 3.92 at 24, 72 h, respectively. Erythema scores on intact skins were 3.42, 3.92 at 24, 72 h and on abraded skins were 3.5, 4 at 24, 72 h, respectively. Under the study conditions, the test substance was considered to be skin corrosive in rabbits (Thompson, 1980).

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
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From May 27, 1980 to June 17, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
Pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoppers Unlimited, Verona, WI, USA
- Age at study initiation: ca. 14 wk
- Housing: Individually in screen bottom cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 7 d

IN-LIFE DATES: From: 28 May To: 17 June 1980
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated left eye of each animal served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): neat material
Duration of treatment / exposure:
Two groups of animals were used, in one group (II) the eyes were washed after 30 sec exposure and in the other group the eyes were not washed (I). The study continued to 21 d
Observation period (in vivo):
Readings were done after 24, 48, 72 and 96 h and after 7, 14 and 21 d. At the 72 h, 7, 14 and 21 d reading sodium fluorescein and UV light were used.
Number of animals or in vitro replicates:
Group I: 6 animals
Group II: 3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): in 3 out of 9 rabbits, the eyes of the other 6 remained unflushed.
- Time after start of exposure: ca. 30 sec


SCORING SYSTEM:
DRAIZE SCALE FOR SCORING OCULAR IRRITATION (1959)

1. CORNEA
(A) Degree of Opacity (most dense area used)
No opacity 0
Scattered or diffuse areas, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Opaque, iris invisible 4
(B) Area of Cornea involved
One quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three quarters 3
Greater than three quarters, up to whole area 4
THE TOTAL SCORE = (A x B) x 5, MAXIMUM TOTAL = 80

2. IRIS
(A) Values
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection
(any or all of these or combination of any thereof), iris still reacting to light
(sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2
THE TOTAL SCORE = A x 5, MAXIMUM TOTAL = 10

3. CONJUNCTIVAE
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson rad, indiviual vessels not easily discernible 2
Diffuse beefy red 3
(B) Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids half closed to completely closed 4
(C) Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs and considerable area around the eye 3
THE TOTAL SCORE (A + B + C) x 2, MAXIMUM TOTAL = 20

MAXIMUM TOTAL SCORE POSSIBLE = 110
NB In this scoring system also half grades were used (0.5, 1.5, 2.5, or 3.5)

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 3.89
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: Unwashed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
2
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: Unwashed eyes
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
3
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: Unwashed eyes
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 4
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: Unwashed eyes
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: washed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
2
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: washed eyes
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
3
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: washed eyes
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 4
Max. score:
4
Reversibility:
not reversible
Remarks:
(within 21 d)
Remarks on result:
other: washed eyes
Irritation parameter:
overall irritation score
Remarks:
unwashed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 99.1
Max. score:
110
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Remarks:
washed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 55.78
Max. score:
110
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
- Blanching and areas of necrosis were observed in the conjunctivae of all rabbits at the 24, 48, 72, 96 h and 7 and 14 d readings and in 3 rabbits at 21 d.
- Hypopyon was observed in 4 rabbits at 7 d.
- Red ocular discharge was exhibited in 3 animals at 7 d and in 2 animals at 14 d.
- Panophthalmitis was exhibited by 1 animal at 14 days and by all animals at 21 days.
Other effects:
None

Table 1. Eye irritation scores (Draize) in rabbits exposed to 0.1 mL test substance and the eyes was not washed

Time

Corneal Opacity

Iris

 

2997

2999

2947

3057

3051

3050

2997

2999

2947

3057

3051

3050

24 h

4

3

4

3

4

4

2m

2m

2m

2m

2m

2m

48h

4

4

4

4

4

4

2m

2m

2m

2m

2m

2m

72h

4

4

4

4

4

4

2m

2m

2m

2m

2m

2m

96 h

4

4

4

4

4

4

2m

2m

2m

2m

2m

2m

7 d

3.5k

3.5k

m

3.5k

m

3.5k

2m

2m

2m

2m

2m

2m

14 d

4

4

4

q

4

4

2m

2m

2m

2m

2m

2m

21 d

q

q

q

q

q

q

q

q

q

q

q

q

Mean 24-72 h

4

3.67

4

3.67

4

4

2

2

2

2

2

2

 

 

Time

Conjunctivae - Redness

Conjunctivae - Chemosis

Conjunctivae - Discharge

 

2997

2999

2947

3057

3051

3050

2997

2999

2947

3057

3051

3050

2997

2999

2947

3057

3051

3050

24 h

1

1

1

1

1

1

4

4

4

4

4

4

3a

3a

3a

3a

3a

3a

48 h

0jd

0jd

0jd

0jd

0jd

0jd

4

4

4

4

4

4

3a

3a

3a

3a

3a

3a

72 h

0jd

0jd

0jd

0jd

0jd

0jd

4

4

4

4

4

4

3a

3a

3a

3a

3a

3a

96 h

0jd

0jd

0jd

0jd

0jd

0jd

4

4

4

4

4

4

3a

3a

3a

3a

3a

3a

7 d

0

0

m

0

m

0

4

3.5

4

4

4

3.5

2a

2.5a

3pa

3pa

3a

2.5pa

14 d

2jd

2jd

2jdl

ljdm

2jdl

2jdl

4

4

4

4

4

4

3ap

2a

2a

2a

2a

2ap

21 d

2jd

2jd

m

m

m

2.5

3

3.5

4

3

3.5

4

2.5a

2a

1a

1a

2a

2a

Mean 24-72 h

0.33

0.33

0.33

0.33

0.33

0.33

4

4

4

4

4

4

3

3

3

3

3

3

 

a Purulent discharge

d Blanching

k hypopyon

l Hair loss around the eye

J Conjunctivae appear necrotic

m Unable to visualise

p red discharge

q Panopthalmitis

Table 2. Eye irritation scores (Draize) in rabbits exposed to 0.1 mL test substance and the eyes was flushed for one minute

Time

Corneal Opacity

Iris

Conjunctivae - redness

Conjunctivae- chemosis

Conjunctivae- discharge

2958

2935

3018

2958

2935

3018

2958

2935

3018

2958

2935

3018

2958

2935

3018

24 h

1.5

3

1.5

1inj

2m

1inj

2jd

2jd

2jd

4

4

4

3a

3a

3a

48h

1

3

1.5

1inj

2m

1inj

2jd

0jd

1jd

4

4

4

3a

3a

3a

72h

2

3

1.5

1inj

2m

1inj

3jd

3jd

3jd

4

4

4

3pa

3a

3a

96 h

1.5

4

1.5

1inj

2m

1inj

3jd

3jd

3jd

4

4

4

3pa

3a

3pa

7 d

3.5k

4k

3

1inj

2m

1inj

3cjd

0jd

3cjd

4

4

3.5

3a

3a

3a

14 d

4h

4

4h

2m

2m

2m

2jd

2jdl

2cjd

2

4

4

1.5a

2a

2a

21 d

4

q

4

2m

q

2m

2.5cjd

2.5jd

3.0kcjd

3

4

3

3a

2.5p

3a

Mean 24-72 h

1.5

3

1.5

1

2

1

2.3

1.67

2

4

4

4

3

3

3



a Purulent discharge

c Petite hemorrhage

d Blanching

k Conjunctivae appears necrotic

j Conjunctivae appears necrotic

inj Injected

m Unable to visualise

p Red discharge

q Panopthalmitis

Interpretation of results:
other: Category 1 (irreversible effects on the eye) based on EU CLP criteria
Conclusions:
Under the study conditions, the test substance was considered to be corrosive to eyes in rabbits.
Executive summary:

A study was performed to determine the eye irritation potential of test substance, C12 -18 DAQ (75% active in hydroalcoholic solution), according to the method equivalent or similar to OECD 405. Two groups of New Zealand white rabbits were used to in the study. 0.1 mL test substance was instilled into the eye of 9 rabbits (leaving the other eye untreated as a control). In one group (with 3 animals) the eyes were washed after 30 sec exposure and in the other group (with 6 animals) the eyes were not flushed. Readings (according to Draize) were done after 24, 48, 72 and 96 h and after 7, 14 and 21 d. At the 72 h, 7, 14 and 21 d reading sodium fluorescein and UV light were used. Blanching and areas of necrosis were observed in the conjunctivae of all rabbits at the 24, 48, 72 and 96 h and 7 and 14 d readings and in three animals at 21 d. Hypopyon was observed in four animals at 7 d. Red ocular discharge was exhibited in three animals at the 7 d and two animals at 14 d. Panopthalmitis was exhibited by one animal at 14 d and by all animals at 21 d. Under the study conditions, the test substance was considered to be corrosive to eyes in rabbits (Thompson, 1980).

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 conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A study was conducted to determine the skin irritation potential of the test substance, C12-18 DAQ (75% active in hydroalcoholic solution) according to guideline of Association of Food and Drug Officials of the US, based on Draize, 1965.The test substance was applied to four test sites per rabbit (2 abraded and 2 intact) under an occlusive dressing for 24 h. Skin irritation was scored according to Draize, at patch removal, 72 and 96 h and 7 d later. Blanching of the test sites was observed in all of the animals at 24, 72 and 96 h. Five rabbits exhibited blanching of the test sites at 7 d. Subcutaneous haemorrhage was observed within the test sites of all animals at the 72 and 96 h and 7 d observations. Eschar formation was observed within the test sites of all animals at the 7 d observation. The primary dermal irritation index (the average of the 24 and 72 hour primary dermal irritation scores) was 7.5.Oedema scores on intact skins were 3.75, 4 at 24, 72 h and on abraded skins were 3.67, 3.92 at 24, 72 h, respectively. Erythema scores on intact skins were 3.42, 3.92 at 24, 72 h and on abraded skins were 3.5, 4 at 24, 72 h, respectively. Under the study conditions, the test substance was considered to be skin corrosive in rabbits (Thompson, 1980).

Astudy was conducted to determinethe skin irritation potential of the read across substance, DDAC (80% active in hydroalcoholic solution), according to OECD Guideline 404, in compliance with GLP.In the study,0.5 mL read across substance samples were applied under occlusive patches for both 3 and 60 min on the clipped skin of 3 rabbits. Residual read across substance was removed using cotton wool soaked in 3% (v/v) aqueous acetic acid followed by distilled water. The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d.After 3 min exposure, very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at all the treated sites at the 48 and 72 h observations. Very slight oedema was noted at one treated site at the 24 ad 48 h observations and at two treated sites at the 72 h observation. On Day 7 and 14, some hyperkeratinisation (2/3) and desquamation (1/3) was still present.After 1 h exposure, a light brown discolouration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated skin sites 1 h after the removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observations. Blanching and moderate erythema extending up to approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctuate eschar surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7.On Day 14 sunken eschar was noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1 h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7. The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14 (Guest, 1987). Based on the results of the read across study, the test substance is considered to be corrosive to skin in rabbits.

Further, read across studies with C18 DAQ, which have been reviewed in the EU RAR (EU, 2002) are described below: 

In a test with rabbits according to OECD guidelines 404, moderate skin irritation was detected for C18 DAQ (purity approx. 97%): Three albino rabbits were tested with 0.5 g of the substance pasted with isotonic saline using semi-occlusive patches. All animals revealed mild to moderate erythema (mean scores for 24, 48 and 72 observation periods: 2/1/0.3) that reversed within 14 days. In addition, the treated skin areas were sporadically dry-rough, discolored light brown and demonstrated fine or coarse scales during the observation period of 14 days. Edema were not seen (Hoechst AG 1986c, 1986d, unpublished reports).

Another study with technical grade C18 DAQ, containing 77% dimethyldioctadecylammonium chloride, 11.3% isopropanol and 11.7% water, however, caused corrosion after a 4-hours contact with the skin of rabbits: A test with 6 rabbits according to OECD 404 (semi-occlusive application of 0.5 ml for 4 hours) resulted in moderate irritation, the effects increased after the day of application till exhibition of severe necrosis after a 14-day observation time (Hoechst AG 1989a, unpublished report).

Overall, based on the available information, the test substance is considered to be corrosive to skin.

Eye irritation

A study was performed to determine the eye irritation potential of the test substance, C12 -18 DAQ(75% active in hydroalcoholic solution),according to the method equivalent or similar to OECD 405.Two groups of New Zealand white rabbits were used to in the study.0.1 mL test substance was instilled into the eye of 9 rabbits (leaving the other eye untreated as a control).In one group (with 3 animals) the eyes were washed after 30 sec exposure and in the other group (with 6 animals) the eyes were not flushed. Readings (according to Draize) were done after 24, 48, 72 and 96 h and after 7, 14 and 21 d. At the 72 h, 7, 14 and 21 d reading sodium fluorescein and UV light were used. Blanching and areas of necrosis were observed in the conjunctivae of all rabbits at the 24, 48, 72 and 96 h and 7 and 14 d readings and in three animals at 21 d. Hypopyon was observed in four animals at 7 d. Red ocular discharge was exhibited in three animals at the 7 d and two animals at 14 d. Panopthalmitis was exhibited by one animal at 14 d and by all animals at 21 d.Under the study conditions, the test substance was considered to be corrosive to eyes in rabbits (Thompson, 1980).

Justification for classification or non-classification

Based on the results of thein vivoskin irritation studies with the test and read across substances, the test substance warrants a corrosive, ‘Skin Corr. 1C; H314: Causes severe skin burns and eye damage’ as well as serious eye damage, ‘Eye dam. 1; H318: Causes serious eye damage’ classification according to EU CLP criteria (Regulation EC 1272/2008). Labelling for this endpoint is covered by the above classifications for skin effects. 

With regard to respiratory tract irritation, although the dialkyl quats are very corrosive substances, the low vapour pressure prohibits occurrence of respiratory irritation by vapour. Further, the classification of corrosive is already considered to implicitly cover the potential of RTI and additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5).