Registration Dossier

Administrative data

Description of key information

The test substance is considered to be corrosive to skin and 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:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
other: Transport of dangerous goods, special recommendations relating to Class 8, United Nations handbook, 1977.
Deviations:
no
GLP compliance:
no
Remarks:
Study performed before GLP
Specific details on test material used for the study:
- ca. 50% Cocobenzyldimethylammonium chloride (CAS no.: 61789-71-7) in water.
- Arquad B-50 is based on full coco.
- Chainlength distribution of full coco: C8: 5%; C10: 6%; C12: 50%; C14: 19%; C16: 10%; C18:10%.
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
Concentration: 50 % active substance
Duration of treatment / exposure:
4h
Observation period:
24, 48 and 72h
Number of animals:
1 in pre-test; 3 in main test
Details on study design:
- An amount of 0.5 mL of undiluted test substance (50% a.i.) was applied under occluded dressing onto the skin of 1 rabbit for 3’, 30’, 60’, and 4h. The skin was washed with water upon removal. 
- Observations: 24, 48 and 72h.
- A confirmatory study was performed at 3 min and 60 min applications in 3 rabbits each.
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Details:
After 3’: Well-defined erythema with moderate oedema at 72h; 
After 30’: Severe erythema (necrotic reaction) with slight oedema;
After 60’: Moderate to severe erythema with moderate oedema at 72h;
After 4h: Severe erythema (necrotic reaction) with severe oedema. 
Primary Irritation Index: 7.0
- Main study in 3 rabbits, 2 sites each with exposure for 3’, and another 3 rabbits for 60’. 
Effects at 3’: no dermal reactions at any of the six sites.
Effects at 60’: Moderate erythema with slight oedema at 4 sites and areas of skin necrosis at the other two sites.
Primary irritation index PII: 3 min: 0; 60 min: 4.5
50% active substance was corrosive to the skin
Conclusions:
Under the study conditions, there was evidence of skin necrosis when the test substance was applied under occlusion to intact rabbit skin for a period of 60 minutes. No visible evidence of necrosis was seen after a 3 minute application. As all products from the individual chain lengths between C8 and C18 are corrosive, the results from this test substance with a full coco distribution are representative for the spectrum of commonly used test substance products. Under the conditions of the study, the test substance was corrosive to rabbit skin and requires a classification of Category 1B: Corrosive, according to the EU CLP.
Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the test substance according to the method 'Transport of dangerous goods, special recommendations relating to Class 8, United Nations handbook, 1977'. In this experiment, 0.5 mL of a 50% solution of test substance was applied under occlusive dressing to the skin of 1 rabbit for 3, 30, 60 min and 4 h. The skin was washed with water upon removal of the dressing. Observations were recorded at 24, 48 and 72 h. A confirmatory study was performed with 3 min or 1 h applications in 3 rabbits each. In the main study, no dermal reactions were observed at any of the 6 sites after 3 min application. Moderate erythema with slight oedema at 4 sites and areas of skin necrosis at the other 2 sites were observed following 1 h application (Primary irritation index PII: 3 min: 0; 60 min: 4.5). Under the conditions of the study, the test substance solution was considered to be corrosive to rabbit skin (Liggit, 1982).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
other: U. S. Federal Register, Vol. 41, No. 188, P.42572, September 27, 1976 (U.S. Code of Federal Regulations, Title 49, Part 173, Appendix A, January 3, 1977).
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Test animals:
- Source: From recognized breeder
- Housing: Grid bottomed galvanised metal cages
- Diet: 90-95 g of commercially available pelleted rabbit diet
- Water: automatic watering system
Environmental conditions:
- Photoperiod (hrs dark / hrs light): 14 hrs light/10 hrs dark

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4h, 60 and 3 min
Observation period:
Immediately after the exposure and after 48 h
Number of animals:
6/group
Details on study design:
At least 1h before dosing the rabbits were placed in restraining stocks and the dorsal surfaces of the rabbits closely clipped over an area consisting of approximately 10% of the total surface area, using an Oster model A2 clipper with Angra blade. One test site was selected lateral to the midline of the back.

0.5mL of the test substance was applied to-the test site on a 2.5 cm lint pad and covered with 'Sleek' plastic adhesive wrapping, used as an impervious material to prevent the evaporation of volatile material. The entire trunk of the animal was then wrapped with a length of elastic adhesive bandage 7.5cm wide to secure the lint pad in place on the animal's skin.

After 4 h the dressings were removed and the test substance removed by wiping with a tissue soaked in sterile distilled water. The sites were assessed for evidence of necrosis or ulceration; immediately and after 48 hours. The sites were also assessed for erythema and oedema, using
the Draize scoring system.
Remarks on result:
other: Corrosive to the skin after 4h application
Irritant / corrosive response data:
Results on Irritation:
 - 4h exposure: Slight irritation of the skin was apparent after a 4h exposure period. The observable reactions increased and eschar formation was apparent at all treated sites at the 48h observation.
- 1h exposure: Slight irritation of the skin was apparent in 3 rabbits following a 1h exposure to the test substance. Reactions in all 6 rabbits were well defined at the 48h observation.
 - 3 minutes exposure: Slight irritation was observed in 1 rabbit immediately following a 3 min exposure to the test substance. Reactions increased and at the 48h observation well defined irritation was observed in 5 rabbits and slight irritation observed in the remaining rabbit of the group.
 
Results on Corrosion:
- 4h exposure: Necrosis of the treated skin was observed in all 6 rabbits at the 48h observation following a 4 h exposure to the test substance.
- 1h exposure: A 1h exposure to the test substance. produced definite necrosis of the treated skin in 4 rabbits, the remaining 2 rabbits of the group exhibiting changes in the skin indicative of the early stages of necrosis.
- 3 minutes exposure: The 48h observation following a 3 min exposure of the skin to the test substance showed 2 rabbits of the group exhibiting necrosis at the treated site. One rabbit exhibited changes in the skin which may have been necrotic.
Conclusions:
Under the test conditions, the test substance was corrosive (Category 1B) to rabbit skin according to the EU CLP.
Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the test substance according to the method 'U. S. Federal Register, Vol. 41, No. 188, P. 42572’. The experiment was performed in rabbits. Six animals were treated with 0.5 mL of the test substance for 4 h under occlusive conditions. As the test proved positive for corrosion after 4 h, it was repeated in a different group of animals for an exposure period of 60 min and then for an exposure period of 3 min. Under the test conditions, the substance was corrosive to rabbit skin (Sugar, 1981).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given, followed methods comparable to guideline EPA OPPTS 870.2500
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
1. In the study, abraded and non abraded skin sites were used; however, the guideline recommends unabraded skin. 2. Exposure period was 24 h; however, guideline recommends 4 h exposure period
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
other: The test substance was applied to both abraded and intact skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Test material
- Amount(s) applied (volume or weight with unit): 0.5 mL


Duration of treatment / exposure:
24h
Observation period:
24 and 72h
Number of animals:
6
Details on study design:
Test site:
- Area of exposure: Back of animal
- Type of wrap if used: The patches consisted of two layers of light gauze cut in squares (2.5 cm on the side). The patches were secured to the test area by thin bands of adhesive tape and the trunk of each animal was wrapped in clear plastic trunk bands after application of the test substance.
- Type of test site: Two areas (intact and abraded) on the back of each animal placed approximately 10 cm apart

Scoring system:
- Skin reactions were scored for erythema and edema, according to Draize Woodland and Calvery scoring system.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24h and 72h
Score:
6.29
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Intact and abraded skin site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h and 72h
Score:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Intact skin site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h and 72h
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Abraded skin site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h and 72h
Score:
2.66
Max. score:
3
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Intact skin site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h and 72h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: Abraded skin site
Irritant / corrosive response data:
- Severe erythema and edema were observed in animals with abraded and intact skin.

Table 1. Individual animal data on the skin irritation response

Rabbit no.

Reaction

24 h

72 h

Intact

Abraded

Intact

Abraded

1

Erythema

4

4

3

4

Edema

2

3

3

3

2

Erythema

3

4

3

3

Edema

2

3

3

3

3

Erythema

4

4

3

3

Edema

3

3

3

3

4

Erythema

4

4

3

3

Edema

2

3

3

3

5

Erythema

3

3

3

3

Edema

3

3

3

3

6

Erythema

4

4

4

3

Edema

2

3

3

3

 

Conclusions:
Under the test conditions, mean values of erythema and edema of the test substance for the intact and abraded sites considering all the test animals were 3.33 (intact skin site), 3.5 (abraded skin site), 2.66 (intact skin site) and 3 (abraded skin site). The primary dermal irritation index was calculated to be 6.29. The test substance was irritating to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the test substance according to US EPA OPPTS 870.2500. The experiment was performed in rabbits. The undiluted test substance was applied on intact and abraded skin sites using occlusive patches for an exposure period of 24 h. The skin was then observed for erythema and edema formation and the scoring was done according to the Draize, Woodland and Calvery scoring system at 24 and 72 h from the onset of exposure. Severe erythema and edema were observed in all the test animals at both the abraded and intact sites. The mean Primary Irritation Index (PII) of the test substance was calculated to be 6.29. The mean values of erythema and edema were 3.33 (intact skin site), 3.5 (abraded skin site), 2.66 (intact skin site) and 3 (abraded skin site). The test substance was irritating to rabbit skin (Wallace, 1975).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
6 rabbits instead of 3, occlusive rather than semi-occlusive application, 24-h exposure rather than 4-h, 2-d instead of 14-d observation, intact and abraded skin
GLP compliance:
no
Specific details on test material used for the study:
- Name of test compound: Arquad DMC-B-80
- Lot no.: 1188-27-3 L26113
- Date of receipt: 10 March, 1976
- Appearance: clear yellow viscous liquid with a slight odour
Species:
rabbit
Strain:
other: albino (not further specified)
Type of coverage:
occlusive
Preparation of test site:
other: clipped and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
24h
Observation period:
2d
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: within 2d
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: within 2d

Table 1. Summary of dermal lesions (following 24-h application)

Animal no.

Effect

h

Days after application

Mean score erythema

(48 h)

Mean score oedema

(48 h)

0

1

2

3

7

14

1

Erythema/ eschar

Oedema

4A

4

-

-

4B

2

-

-

-

-

-

-

4

2

2

Erythema/ eschar

Oedema

4A

4

-

-

4B

2

-

-

-

-

-

-

4

2

3

Erythema/ eschar

Oedema

4A

4

-

-

4B

2

-

-

-

-

-

-

4

2

4

Erythema/ eschar

Oedema

4A

4

-

-

4B

2

-

-

-

-

-

-

4

2

5

Erythema/ eschar

Oedema

4A

4

-

-

4B

2

-

-

-

-

-

-

4

2

6

Erythema/ eschar

Oedema

4A

4

-

-

4B

2

-

-

-

-

-

-

4

2

Mean all animals

4

2

A = entire site necrotic with blanching extending well beyond site; B = entire site and beyond coriaceous

Conclusions:
Under the study conditions, the test substance was corrosive to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the test substance according to OECD Guideline 404. Skin of albino rabbit was used in this experiment. A single 24 h, occluded application of the test substance (undiluted) to the intact and abraded skin of six rabbits produced necrosis with blanching extending beyond the entire site and severe oedema. Forty-eight hours after patch removal, each site and beyond was coriaceous and slight oedema was noted. No further observations were made. Corrosive effects were noted in all 6 rabbits. Under the study conditions, the test substance was corrosive to rabbit skin (Anspach, 1976).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
6 rabbits instead of 3, occlusive rather than semi-occlusive application, 24-h exposure rather than 4-h, 2-d instead of 14-d observation, intact and abraded skin
Principles of method if other than guideline:
A 0.1% solution was tested rather than the undiluted test material.
GLP compliance:
no
Remarks:
pre-GLP
Specific details on test material used for the study:
- Lot no.: 3119
- Tested as a 0.1% aqueous solution
Species:
rabbit
Strain:
other: albino (not further specified)
Type of coverage:
occlusive
Preparation of test site:
other: clipped and abraded skin
Vehicle:
water
Controls:
no
Duration of treatment / exposure:
24h
Observation period:
2d
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48h
Score:
0
Max. score:
4
Irritant / corrosive response data:
None of the rabbits showed erythema or oedema immediately and 48h after patch removal.
Conclusions:
Under the study conditions, a 0.1% aqueous solution of the test substance was not irritating to rabbit skin (following 24-h exposure under occluded conditions).
Executive summary:

A study was conducted to determine the skin irritation / corrosion of the test substance according to OECD Guideline 404. The experiment was performed to assess in albino rabbits (strain not specified). Under the study conditions, a 0.1% aqueous solution of the test substance was not irritating to rabbit skin (following 24 h exposure under occluded conditions) (Hixson, 1968).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From August 08, 1990 to September 06, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Observation period was of 8 days instead of 14 days
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzalkonium chloride (25.5% active)
- Description: Clear colourless liquid
- Lot No.: ST0099
- UN No.: 1760
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
Test animals:
- Source: Charles River (U.K.) Limited, Margate, Kent, England
- Age at study initiation: The males were 49-51 days old and the females 58-70 d old
- Weight at study initiation: The males were in the body weight range 169 - 187 g and the females 173 - 194 g
- Housing: Individually housed in stainless steel grid
- Diet: Pelleted rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: 7-9 d

Environmental conditions:
- Temperature: 21°C
- Humidity: 55%
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12 h dark/ 12 h light

Type of coverage:
other: Elizabethan collar was fitted to prevent ingestion of the test substance, and to allow undisturbed absorption of the test substance
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
240 mm3 aliquot of 2.55%, 1.28%, 0.77% and 0.26% w/v
Duration of treatment / exposure:
72h
Observation period:
The dermal test sites were examined immediately before, and at 6, 24, 48 and 72h after application of the dose formulations
Number of animals:
5/sex/group
Details on study design:
The formulated test substance (240 mm3 ) was applied to the closely-clipped dorsum of each animal at the concentrations in the range 2.55-0.26% w/v in distilled water. The test site was protected by an Elizabethan collar for a period of 72h following administration.
Remarks on result:
other: See 'Irritant / corrosive response data'
Irritant / corrosive response data:
- At 2.55% w/v: Very slight or, less frequently, well-defined erythema was observed amongst all animals during most of the observation period. Slight exfoliation and/or eschar formation were apparent in the majority of animals from Day 5 onwards.
- At 1.28% w/v: Very slight to moderate erythema was observed amongst the majority of male and all female animals during the observation period. Two male rats showed very slight oedema 24h after dosing as did one female from Day 6 onwards. Isolated cases of eschar formation, slight exfoliation, sensitivity to touch, hotness to touch and blanching were also recorded.
- At 0.77% w/v: Low incidences of blanching (males only), slight exfoliation and eschar formation (females only) and very slight erythema (male and females) were apparent during the observation period.
- At 0.26% w/v: There were no irritation reactions observed at the test site of any of the animals.
- Brown or yellow discolouration was observed at most of the test sites, but was not considered to be an irritant effect.
Other effects:
There was no death and no systemic sign of reaction to treatment. The animals generally achieved anticipated bodyweight gains.
Conclusions:
Under the study conditions, the 'threshold of irritancy' of the test substance in distilled water was between 0.26% and 0.77% w/v, and the 'maximum tolerated' concentration slightly in excess of 2.55% w/v. The lowest tested concentration of 0.26% w/v was 'non-irritant' to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 404, in compliance with GLP. The experiment was performed with a 25.5% active test substance. The objective of this study was to define a clear "non-irritant" level of administration and the maximum tolerated test concentration (irritancy, but not severe irritancy, corrosivity, toxicity or mortality) following a single topical administration to Wistar rats, and thereby select dosages for an absorption, distribution and excretion study in the same strain of rat. Four groups of five male and five female Wistar rats were treated with 240 mm3 aliquot of 2.55, 1.28, 0.77 and 0.26% w/v test substance. The test site was protected by an Elizabethan collar for a period of 72 h following administration. Under the conditions of this study, the 'threshold of irritancy' of the test substance in distilled water was between 0.26 and 0.77% w/v, and the 'maximum tolerated' concentration slightly in excess of 2.55% w/v. The lowest tested concentration of 0.26% w/v was 'non-irritant' to rabbit skin (Cummins, 1991).

Endpoint:
skin irritation / corrosion
Remarks:
no data
Type of information:
other: Literature data
Adequacy of study:
weight of evidence
Study period:
1989
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
Guideline not mentioned. Collated data from published literature is summarised.
GLP compliance:
not specified
Species:
rabbit
Amount / concentration applied:
Concentration: 1 % active test substance
Remarks on result:
other: Data from published literature suggest that test substance is corrosive to skin.
Irritant / corrosive response data:
- When applying 0.5 mL of test substance on rabbit skin, concentrations of 1% or greater induced skin reactions, while 0.1% was not irritating. Exposure for 24 h to 0.1% aqueous test solution was not irritating to guinea-pig skin, while the same exposure regime of 0.3% concentration caused irritation in rabbits.
- Also, 0.5 mL of a 0.5% aqueous test solution on the skin of nine rabbits for 24h under occlusive patch, resulted to barely perceptible erythema in one animal and no reactions in the others. Another study 0.3% test solution was tested according to the same protocol. Skin irritation was not observed in any of the nine rabbits. A 0.1% aqueous solution of test substance was applied to the skins of rabbits under plastic wrap for 5d. At the end of the period, necrosis and varying degrees of erythema with diffuse areas of eschar and bleeding were noted.
Conclusions:
Data from published literature suggested that test substance was corrosive to rabbit skin.
Executive summary:

A study were conducted to determine the skin irritation / corrosion potential of the test substance. When applying 0.5 mL of test substance on rabbit skin, concentrations of 1% or greater induced skin reactions, while 0.1% was not irritating. Exposure for 24 h to 0.1% aqueous test solution was not irritating to guinea pig skin, while the same exposure regime of 0.3% concentration caused irritation in rabbits. Also, 0.5 mL of a 0.5% aqueous test solution on the skin of nine rabbits for 24 h under occlusive patch, resulted to barely perceptible erythema in one animal and no reactions in the others. In another study, 0.3% test solution was tested according to the same protocol. Skin irritation was not observed in any of the nine rabbits. A 0.1% aqueous solution of test substance was applied to the skins of rabbits under plastic wrap for 5 d. At the end of the period, necrosis and varying degrees of erythema with diffuse areas of eschar and bleeding were noted. Data from published literature suggested that test substance was corrosive to rabbit skin (BIBRA, 1989; CIR, 1989).

Endpoint:
skin corrosion: 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:
supporting study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
observation period was 3d only; 6 animals rather than 2-3 were used.
GLP compliance:
no
Remarks:
pre-GLP
Specific details on test material used for the study:
- Name of test compound: Arquad DMC-B-80 (no composition detail)
- Lot no.: 1188-27-3 L26113
- Date of receipt: 10 March 1976
- Apperance: clear yellow viscous liquid with a slight odour
- Used as received (undiluted)
Species:
rabbit
Strain:
other: albino (not further specified)
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
one single application into the right eye, the left eye remained untreated
Observation period (in vivo):
72h
Number of animals or in vitro replicates:
6
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24/48/72h
Score:
4
Max. score:
4
Remarks on result:
other: observation until 72h only
Irritation parameter:
iris score
Time point:
other: 24/48/72h
Max. score:
2
Remarks on result:
other: unable to score due to severe corneal opacity
Irritation parameter:
conjunctivae score
Time point:
other: 24/48/72h
Max. score:
3
Remarks on result:
other: entire conjunctivae blanched
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24/48/72h
Score:
3
Max. score:
4
Remarks on result:
other: observation until 72h only

Table 1. Ocular lesions

Anim.

No.

Effect

Hours

Days after application

Mean

score cornea

Days

1/2/3

Mean

score iritis

Days 1/2/3

Mean score redness Days 1/2/3

Mean score chemosis Days 1/2/3

1

1

2

3

7

21

7

Cornea*

Iris

Redness

Chemosis

-

-

-

-

4

A

B

3

4

A

B

3

4C

A

B

3

-

-

-

-

-

-

-

-

4

-

-

3

8

Cornea*

Iris

Redness

Chemosis

-

-

-

-

4

A

B

3

4

A

B

3

4

A

B

3

-

-

-

-

-

-

-

-

4

-

-

3

9

Cornea*

Iris

Redness

Chemosis

-

-

-

-

4

A

B

3

4

A

B

3

4

A

B

3

-

-

-

-

-

-

-

-

4

-

-

3

10

Cornea*

Iris

Redness

Chemosis

-

-

-

-

4

A

B

3

4

A

B

3

4D

A

B

3

-

-

-

-

-

-

-

-

4

-

-

3

11

Cornea*

Iris

Redness

Chemosis

-

-

-

-

4

A

B

3

4

A

B

3

4D

A

B

3

-

-

-

-

-

-

-

-

4

-

-

3

12

Cornea*

Iris

Redness

Chemosis

-

-

-

-

4

A

B

3

4

A

B

3

4

A

B

3

-

-

-

-

-

-

-

-

4

-

-

3

Mean all anim.

4

-

-

3

* In all animals, at 1, 2, and 3d after application, three quarters to the whole area of the cornea was involved; A = unable to score for iritis due to severe corneal opacity; B = entire conjunctivae blanched; C = fissuring of the upper conjunctivae; D = crystallization of the eyeball

Conclusions:
Under the study conditions, the undiluted (purity not mentioned) test substance produced serious eye damage in rabbits and needs classification as an eye irritant.
Executive summary:

A study was conducted to determine the eye irritation / corrosion potential of the test substance (purity not mentioned) according to a method similar to OECD Guideline 405. The experiment was performed in albino rabbits. A single application of the undiluted (purity not mentioned) test substance to the non-irrigated eye of 6 rabbits produced severe corneal opacity, conjunctivitis and blanching of the conjunctival membranes. Iritis could not be scored due to the severe corneal opacity. Crystallization and fissuring were noted in one or two animals. The animals were observed for 3 days after application. Under the study conditions, the undiluted test substance produced serious eye damage to rabbits and needs classification as an eye irritant (Anspach, 1976).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
observation period was 7d only; 9 animals rather than 2-3 animals were used.
GLP compliance:
no
Remarks:
pre-GLP
Specific details on test material used for the study:
- Name of test compound: Arquad B-100
- Lot no.: 3119
- Used as a 0.1% aqueous solution
Species:
rabbit
Strain:
other: albino (not further specified)
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
One single application into the right eye, the left eye remained untreated
- 3 animals: eyes unwashed
- 3 animals: eyes washed 2 sec after treatment with 20 mL of water
- 3 animals: eyes washed 4 sec after treatment with 20 mL of water
Observation period (in vivo):
7d
Number of animals or in vitro replicates:
9
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
4
Remarks on result:
other: no changes
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
2
Remarks on result:
other: no changes
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24/48/7 h
Score:
0
Max. score:
3
Remarks on result:
other: after 1h score 2 obtained in 5/9 animals; no separate results for chemosis reported

The test substance (0.1% aqueous solution) was essentially non-irritating to the rabbit eye. The only changes observed were 1h after application:

- without washing: 1/3 animals showed grade 2 for conjunctivae (no separation made between redness and chemosis)

- with washing after 2 sec: 1/3 animals showed grade 2 for conjunctivae (no separation made between redness and chemosis)

- with washing after 4 sec: 3/3 animals showed grade 2 for conjunctivae (no separation made between redness and chemosis)

Interpretation of results:
not irritating
Conclusions:
Under the study conditions, the test substance as a 0.1% aqueous solution was not irritating to the rabbit eye.
Executive summary:

A study was conducted to determine the eye irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 405. The experiment was performed in albino rabbits. A single application of the test substance as a 0.1% aqueous solution to the non-irrigated eye of nine rabbits produced moderate effects on the conjunctivae 1 h after application, but these had disappeared within 1 day. The animals were observed for 7 days after application. Under the study conditions, the test substance as a 0.1% aqueous solution was not irritating to the rabbit eye (Hixson, 1968).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
observation period was 7d only; 6 rabbits rather than 2-3 were used.
GLP compliance:
no
Specific details on test material used for the study:
- Name of test compound: Arquad DMMCB-50 (no data on composition)
- Lot no.: CH.11501
- Appearance: light yellow clear slight viscous liquid
- Used as received (undiluted)
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
one single application into the left eye, the right eye remained untreated
Observation period (in vivo):
up to 7d
Number of animals or in vitro replicates:
6
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 5/6/7 d
Score:
3.83
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 5/6/7 d
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 5/6/7 d
Score:
1
Max. score:
3
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 5/6/7 d
Score:
2.28
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 d

Table 1. Summary of ocular lesions

Animal no.

Effect

Hours

Days after application

Mean

Cornea

Day 5/6/7

Mean

Iritis

Day 5/6/7

Mean

Erythema

Day

5/6/7

Mean

Chemosis

Day

5/6/7

1

1

2

3

4

5

6

7

1

Cornea*

Iris

Redness

Chemosis

0

0

1

0

1

1

1

3

1

1

1

3

2

2

1

3

3

2

1

3

4

2

1

3

4

2

1

3

4

2

1

3

4

2

1

3

2

Cornea*

Iris

Redness

Chemosis

0

0

1

0

1

1

1

3

1

1

1

3

2

2

1

3

3

2

1

3

4

2

1

3

4

2

1

3

4

2

1

2

4

2

1

2.67

3

Cornea*

Iris

Redness

Chemosis

0

0

1

0

1

1

1

2

1

1

1

2

2

2

1

2

3

2

1

2

4

2

1

2

4

2

1

2

4

2

1

2

4

2

1

2

4

Cornea*

Iris

Redness

Chemosis

0

0

1

0

1

1

1

3

1

1

1

2

2

2

1

2

3

2

1

2

4

2

1

2

4

2

1

2

4

2

1

2

4

2

1

2

5

Cornea*

Iris

Redness

Chemosis

0

0

1

0

1

1

1

2

1

1

1

2

2

2

1

2

3

2

1

2

4

2

1

2

4

2

1

2

4

2

1

2

4

2

1

2

6

Cornea*

Iris

Redness

Chemosis

0

0

1

0

1

1

1

3

1

1

1

3

2

2

1

2

3

2

1

2

4

2

1

3

4

2

1

2

1

2

1

2

3

2

1

2

Mean all animals

3.83

2

1

2.28

* In all animals, at all days after application, the whole area of the cornea was involved

Conclusions:
Under the study conditions, the undiluted test substance (purity not mentioned) was considered irritant to rabbit eye (irreversible effects on the eye), because it produced severe corneal opacity and iritis, moderate erythema and moderate swelling of the eye lids. It was noted that there was a delayed occurrence of the effects, therefore, the mean values on Days 5-7 were chosen for the evaluation.
Executive summary:

A study was conducted to determine the eye irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 405. The experiment was performed in New Zealand rabbits. A single application of the undiluted test substance (purity not mentioned) to the eye of 6 rabbits produced severe corneal opacity, iritis, and moderate erythema and chemosis. There was a delayed occurrence of the effects, therefore, the mean values on Days 5 -7 were chosen for the evaluation. Under the study conditions, the test substance produced serious eye damage to rabbits (Sterner, 1981).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given, test method comparable to guideline OPPTS 870.2400
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
no
Remarks:
(Pre-GLP)
Specific details on test material used for the study:
- Name of test material (as cited in study report): Barquat MB-80
- Analytical purity: >93%
- Stability under test conditions: Test substance is hydrolytically and photolytically stable under the conditions of this study and has been shown to be stable in aqueous, alcohol and alcohol/aqueous solutions for extended periods, e.g. at least five years under standard laboratory conditions.
Species:
rabbit
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as control
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
72h (no eye wash done)
Observation period (in vivo):
24, 48 and 72h
Number of animals or in vitro replicates:
6
Details on study design:
Removal of test substance:
- Washing (if done): Eyes were not washed throughout the study.
- Time after start of exposure: 72h
Scoring system: Ocular reactions were evaluated according to Draize scale for scoring ocular lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
other: 24-72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
mean
Time point:
other: 24-72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritant / corrosive response data:
The test substance produced severe and irreversible damage in rabbit eyes.
Conclusions:
Under the test conditions, the test substance produced severe and irreversible damage in rabbit eyes.
Executive summary:

A study was conducted to determine the eye irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 405. The experiment was performed in rabbits. All six test rabbits received 0.1 mL of the undiluted test substance in one eye. The other eye remained untreated. Eyes were not washed throughout the study. After 24, 48 and 72 h, eyes were evaluated for ocular lesions according to the Draize scale. Under the conditions of the study, the test substance produced severe and irreversible damage in rabbit eyes (Wallace, 1975).

Endpoint:
eye irritation
Type of information:
other: Publication
Adequacy of study:
supporting study
Study period:
1989
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No guideline followed
GLP compliance:
not specified
Conclusions:
Due to the direct corrosive effect, there is danger of irreversible damage to the eyes upon exposure to the undiluted solution. Testing for acute eye irritation is, due to its corrosive effects, not ethical. It has been established (CIR, 1989) that concentrations above 1% and higher caused severe damage of the rabbit eye upon twice daily instillation for 7d.
Executive summary:

Due to the direct corrosive effect, there is danger of irreversible damage to the eyes upon exposure to the undiluted solution. Testing for acute eye irritation is, due to its corrosive effects, not ethical. It has been established (CIR, 1989) that concentrations above 1% and higher caused severe damage of the rabbit eye upon twice daily instillation for 7 d (CIR, 1989).

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
other justification
Justification for data waiving:
other:
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin

Study 1. A study was conducted to determine the skin irritation / corrosion potential of the test substance according to the method 'Transport of dangerous goods, special recommendations relating to Class 8, United Nations handbook, 1977'. In this experiment, 0.5 mL of a 50% solution of test substance was applied under occlusive dressing to the skin of 1 rabbit for 3, 30, 60 min and 4 h. The skin was washed with water upon removal of the dressing. Observations were recorded at 24, 48 and 72 h. A confirmatory study was performed with 3 min or 1 h applications in 3 rabbits each. In the main study, no dermal reactions were observed at any of the 6 sites after 3 min application. Moderate erythema with slight oedema at 4 sites and areas of skin necrosis at the other 2 sites were observed following 1 h application (Primary irritation index PII: 3 min: 0; 60 min: 4.5). Under the conditions of the study, the test substance solution was considered to be corrosive to rabbit skin (Liggit, 1982).

Study 2. A study was conducted to determine the skin irritation / corrosion potential of the test substance according to the method 'U. S. Federal Register, Vol. 41, No. 188, P. 42572’. The experiment was performed in rabbits. Six animals were treated with 0.5 mL of the test substance for 4 h under occlusive conditions. As the test proved positive for corrosion after 4 h, it was repeated in a different group of animals for an exposure period of 60 min and then for an exposure period of 3 min. Under the test conditions, the substance was corrosive to rabbit skin (Sugar, 1981).

Study 3. A study was conducted to determine the skin irritation / corrosion potential of the test substance according to US EPA OPPTS 870.2500. The experiment was performed in rabbits. The undiluted test substance was applied on intact and abraded skin sites using occlusive patches for an exposure period of 24 h. The skin was then observed for erythema and edema formation and the scoring was done according to the Draize, Woodland and Calvery scoring system at 24 and 72 h from the onset of exposure. Severe erythema and edema were observed in all the test animals at both the abraded and intact sites. The mean Primary Irritation Index (PII) of the test substance was calculated to be 6.29. The mean values of erythema and edema were 3.33 (intact skin site), 3.5 (abraded skin site), 2.66 (intact skin site) and 3 (abraded skin site). The test substance was irritating to rabbit skin (Wallace, 1975).

Study 4. A study was conducted to determine the skin irritation / corrosion potential of the test substance according to OECD Guideline 404. Skin of albino rabbit was used in this experiment. A single 24 h, occluded application of the test substance (undiluted) to the intact and abraded skin of six rabbits produced necrosis with blanching extending beyond the entire site and severe oedema. Forty-eight hours after patch removal, each site and beyond was coriaceous and slight oedema was noted. No further observations were made. Corrosive effects were noted in all 6 rabbits. Under the study conditions, the test substance was corrosive to rabbit skin (Anspach, 1976).

Study 5. A study was conducted to determine the skin irritation / corrosion of the test substance according to OECD Guideline 404. The experiment was performed to assess in albino rabbits (strain not specified). Under the study conditions, a 0.1% aqueous solution of the test substance was not irritating to rabbit skin (following 24 h exposure under occluded conditions) (Hixson, 1968).

Study 6. A study was conducted to determine the skin irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 404, in compliance with GLP. The experiment was performed with a 25.5% active test substance. The objective of this study was to define a clear "non-irritant" level of administration and the maximum tolerated test concentration (irritancy, but not severe irritancy, corrosivity, toxicity or mortality) following a single topical administration to Wistar rats, and thereby select dosages for an absorption, distribution and excretion study in the same strain of rat. Four groups of five male and five female Wistar rats were treated with 240 mm3 aliquot of 2.55, 1.28, 0.77 and 0.26% w/v test substance. The test site was protected by an Elizabethan collar for a period of 72 h following administration. Under the conditions of this study, the 'threshold of irritancy' of the test substance in distilled water was between 0.26 and 0.77% w/v, and the 'maximum tolerated' concentration slightly in excess of 2.55% w/v. The lowest tested concentration of 0.26% w/v was 'non-irritant' to rabbit skin (Cummins, 1991).

Study 7. A study were conducted to determine the skin irritation / corrosion potential of the test substance. When applying 0.5 mL of test substance on rabbit skin, concentrations of 1% or greater induced skin reactions, while 0.1% was not irritating. Exposure for 24 h to 0.1% aqueous test solution was not irritating to guinea pig skin, while the same exposure regime of 0.3% concentration caused irritation in rabbits. Also, 0.5 mL of a 0.5% aqueous test solution on the skin of nine rabbits for 24 h under occlusive patch, resulted to barely perceptible erythema in one animal and no reactions in the others. In another study, 0.3% test solution was tested according to the same protocol. Skin irritation was not observed in any of the nine rabbits. A 0.1% aqueous solution of test substance was applied to the skins of rabbits under plastic wrap for 5 d. At the end of the period, necrosis and varying degrees of erythema with diffuse areas of eschar and bleeding were noted. Data from published literature suggested that test substance was corrosive to rabbit skin (BIBRA, 1989; CIR, 1989).

Eye

Study 1. A study was conducted to determine the eye irritation / corrosion potential of the test substance (purity not mentioned) according to a method similar to OECD Guideline 405. The experiment was performed in albino rabbits. A single application of the undiluted (purity not mentioned) test substance to the non-irrigated eye of 6 rabbits produced severe corneal opacity, conjunctivitis and blanching of the conjunctival membranes. Iritis could not be scored due to the severe corneal opacity. Crystallization and fissuring were noted in one or two animals. The animals were observed for 3 days after application. Under the study conditions, the undiluted test substance produced serious eye damage to rabbits and needs classification as an eye irritant (Anspach, 1976).

Study 2. A study was conducted to determine the eye irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 405. The experiment was performed in albino rabbits. A single application of the test substance as a 0.1% aqueous solution to the non-irrigated eye of nine rabbits produced moderate effects on the conjunctivae 1 h after application, but these had disappeared within 1 day. The animals were observed for 7 days after application. Under the study conditions, the test substance as a 0.1% aqueous solution was not irritating to the rabbit eye (Hixson, 1968).

Study 3. A study was conducted to determine the eye irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 405. The experiment was performed in New Zealand rabbits. A single application of the undiluted test substance (purity not mentioned) to the eye of 6 rabbits produced severe corneal opacity, iritis, and moderate erythema and chemosis. There was a delayed occurrence of the effects, therefore, the mean values on Days 5 -7 were chosen for the evaluation. Under the study conditions, the test substance produced serious eye damage to rabbits (Sterner, 1981).

Study 4. A study was conducted to determine the eye irritation / corrosion potential of the test substance according to a method similar to OECD Guideline 405. The experiment was performed in rabbits. All six test rabbits received 0.1 mL of the undiluted test substance in one eye. The other eye remained untreated. Eyes were not washed throughout the study. After 24, 48 and 72 h, eyes were evaluated for ocular lesions according to the Draize scale. Under the conditions of the study, the test substance produced severe and irreversible damage in rabbit eyes (Wallace, 1975).

Study 5. Due to the direct corrosive effect, there is danger of irreversible damage to the eyes upon exposure to the undiluted solution. Testing for acute eye irritation is, due to its corrosive effects, not ethical. It has been established (CIR, 1989) that concentrations above 1% and higher caused severe damage of the rabbit eye upon twice daily instillation for 7d (CIR, 1989).

Justification for classification or non-classification

Skin

In an in vivo skin irritation study, there was evidence of skin necrosis when 50% active test substance was applied under occlusion to intact rabbit skin for a period of 60 minutes. Hence, the data justifies classification as Skin Corr. 1B; H314: causes severe skin burns and eye according to CLP (EC 1272/2008) criteria.

Eye

Undiluted test substance (0.1 mL) produced severe and irreversible damage in the eyes. Also, the test substance is skin corrosive. The data justifies classification as Eye Damage 1-H318: Causes serious eye damage according to CLP (EC 1272/2008) criteria.