Registration Dossier

Administrative data

Description of key information

Skin irritation:

Mallory VT (1990) determined in a K2 primary dermal irritation study the skin irritation potential of the test substance in New Zealand White rabbits according to a method equivalent to OECD Guideline 404. The test substance was observed to be corrosive to the skin. This study was selected as key study.

Eye irritation:

Based on the data of a K1 study performed similar to OECD Guideline 405 study, the test substance was shown to cause irreversible effects on the eye of New Zealand White rabbits (Mallory VT, 1982). This study was selected as key study.

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:
1990-08-14 - 1990-08-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The test substance is applied to intact skin, but also to abraded skin. An occlusive dressing is used, instead of a semi-occlusive dressing.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The test substance is applied to intact skin, but also to abraded skin. An occlusive dressing is used, instead of a semi-occlusive dressing.
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): 6398-17-20
- Lot/batch No. 90-006
- Physical state: clear, pale yellow liquid
- Analytical purity: considered to be the responsibility of the sponsor
- Stability under test conditions: no apparent change in the physical state ot the test article during administration
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hare-Marland, Hewitt, NJ
- Age at study initiation: adult
- Weight at study initiation: 2.480 - 2.662 - 2.154 - 2.167 - 2.902 - 2.960 kg
- Housing: Rabbits were housed individually in cages sized in accordance with the ''Guide for the Care and Use of Laboratory Animals'' of
the Institute of Laboratory Animal Resources, National Research Council.
- Diet (e.g. ad libitum): Purina Lab Rabbit Ration HF, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum. Water is monitored for contaminants at periodic intervals according to Standard Operating Procedure PH-018.
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C±3°C (63-73°F)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h light, 12h dark


Type of coverage:
occlusive
Preparation of test site:
other: clipped; one site abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site, 3 sites per animal

Duration of treatment / exposure:
4h (upper dorsal site) and 24h (lower dorsal sites)
Observation period:
Upper dorsal site: at 30min, 60min, 24h ,48h, 72h, daily from Day 4 to Day 14 after patch removal
Lower dorsal sites: at 24h, 48h and 72h, and daily from Day 4 to Day 14 after application of the test material
Number of animals:
6 (3F and 3M)
Details on study design:
TEST SITE
- Area of exposure: upper dorsal trunk (intact), lower dorsal trunk (1 intact and 1 abraded site), clipped free of fur
- Type of wrap if used: gauze patch, rubber dam and an elastic bandage to retard evaporation

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with water and gauze
- Time after start of exposure: 4h (upper sites) and 24h (lower sites)


SCORING SYSTEM: observation
Draize Evaluation of Dermal Irritation, Primary Dermal Irritation Index and Modified Primary Dermal Irritation Index
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
7.92
Max. score:
8
Remarks on result:
other: severe dermal irritation
Irritation parameter:
erythema score
Basis:
animal: 6/6
Time point:
other: 30-60min, 24h, 48h, 72h and daily until Day 14
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
, 4h and 24h exposure) (14 days observation)
Remarks on result:
other: at all sites: severe erythema and necrosis
Irritation parameter:
edema score
Basis:
animal: 6/6
Time point:
other: 24h, 48h, 72h and daily until Day 14
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
, 4h and 24h exposure) (14 days observation)
Remarks on result:
other: at all sites: severe edema, necrosis
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
All animals scored 4 (severe erythema and severe edema) which remained present in all animals during whole observation period (up to 14days).

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
The test article was considered to be a severe dermal irritant at both 4 and 24 hour exposures. Necrosis of the skin at each application site was observed at the 24, 48 and 72 hour observation periods and on Days 4 through 14. The study was terminated following the Day 14 observation period. (Primary Irritation Index, according to Draize = 7.92, modified Primary Irritation Index = 8.00). Based on these results and according to the criteria laid down in the CLP Regulation, the substance is considered classified as corrosive to the skin category 1C.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(occlusive conditions, exposure period up to 20 hours)
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): N,N´-Dimethylpiperazin
- Analytical purity: 99 %
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.97 and 3.38 kg
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
no data
Duration of treatment / exposure:
1, 5, 15 min or 20 h.
Observation period:
8 days
Number of animals:
2
Details on study design:
TEST SITE
A cotton pad (2.5x2.5 cm) was covered with the undiluted liquid test substance and was applied under occlusive conditions onto the skin of the back.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 1x Lutrol and 1x 50% Lutrol
- Time after start of exposure: Immediately after 1, 5 and 15 min exposure.

SCORING SYSTEM: The original BASF grading was converted into the numerical grading according the OECD Draize system.
Irritation parameter:
other: necrosis, 15 min and 20 h exposure
Basis:
mean
Remarks on result:
other: lethery necrosis was observed in both animals 24 hours after the 15 min exposure; lethery and hard necrosis was observed in one animal 24 hours after the 20 h exposure and in the other one after 72 hours
Irritation parameter:
erythema score
Remarks:
1 min exposure
Basis:
mean
Time point:
other: 24,48,72 hours post exposure
Score:
2.15
Max. score:
4
Reversibility:
not fully reversible within: after 8 days (in one animal)
Irritation parameter:
erythema score
Remarks:
5 min exposure
Basis:
mean
Time point:
other: 24,48,72 hours post exposure
Score:
1.8
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
1 min exposure
Basis:
mean
Time point:
other: 24,48,72 hours post exposure
Score:
0.3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
5 min exposure
Basis:
mean
Time point:
other: 24,48,72 hours post exposure
Score:
0.65
Max. score:
4
Reversibility:
not fully reversible within: 8 days

Mean erythema score after 24, 48 and 72 h (animal1/2)

 Exposure time  24 h  48 h  72 h  mean
 1 min  3/2  3/1  3/1  3/1.3
 5 min  2/3  2/2  X/2  1.3/2.3
 15 min  X/X  X/X  X/X  X/X
 20 h  X/X  X/X  X/X  X/X

Mean edema score after 24, 48 and 72 h (animal1/2)

 Exposure time  24 h  48 h  72 h  mean
 1 min  0/0  2/0 0/0  0.6/0
 5 min  2/0 2/0 X/0 1.3/0 
 15 min  X/X  X/0  X/0  X/X
 20 h  X/X  X/X X/X X/X

X: The application of the test substance caused necrosis to the exposed skin. Around the necrosis erythema (grade 2) and edema (grade 2) was observed.

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Lethery necrosis was observed in both animals 24 hours after the 15 min exposure; lethery and hard necrosis was observed in one animal 24 hours after the 20 h exposure and in the other one after 72 hours. Based on these results and according to the criteria laid down in the CLP Regulation, the substance is to be considered classified as corrosive to the skin category 1B.
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:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-13-20
- Physical state: clear liquid
- Analytical purity: responsibility of the Sponsor
- Lot/batch No.: J-160
- Stability under test conditions: no apparent change in the physical state of the test article during administration
- Storage condition of test material: no data
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Inc., Douglassville, Pennsylvania
- Age at study initiation: no data
- Weight at study initiation: 2.207-2.579 kg
- Housing:individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council
- Diet (e.g. ad libitum): Wayne Rabbit Ration, ad libitum
- Water (e.g. ad libitum):fresh tap water, fit for human consumption, ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3°C
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12h light/12h dark


IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml



Duration of treatment / exposure:
1 second
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
6 (3♂ and 3♀)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: observation
-method of Draize, J. H. (1965): scale for scoring ocular lesions
An animal exhibited a positive reaction when the test substance produced one or more of the following signs: ulceration of the cornea (other than a fine stippling), opacity of the cornea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae or a light hyperemia of the circumcorneal blood vessels), or an obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids and a diffuse crimson color with individual vessels not easily discernible.


TOOL USED TO ASSESS SCORE: 2% sodium fluorescein stain
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1h
Score:
51.7
Max. score:
110
Remarks on result:
other: severely irritating
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
24 h
Score:
87
Max. score:
110
Remarks on result:
other: extermely irritating
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 and 72 hours
Score:
95
Max. score:
110
Remarks on result:
other: extremely irritating
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 7 days
Score:
91.7
Max. score:
110
Remarks on result:
other: extremely irritating
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 10 day
Score:
92
Max. score:
110
Remarks on result:
other: extremely irritating
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 13 day
Score:
79.5
Max. score:
110
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: severely irritating
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
80
Max. score:
80
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
80
Max. score:
80
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
53.33
Max. score:
80
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
66.67
Max. score:
80
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
80
Max. score:
80
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
80
Max. score:
80
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Max. score:
10
Reversibility:
not reversible
Remarks on result:
not determinable
Remarks:
due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Max. score:
10
Reversibility:
not reversible
Remarks on result:
not determinable
Remarks:
due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
6.67
Max. score:
10
Reversibility:
not reversible
Remarks on result:
not determinable
Remarks:
at 24h due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.67
Max. score:
10
Reversibility:
not reversible
Remarks on result:
not determinable
Remarks:
at 48 and 72h due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Max. score:
10
Reversibility:
not reversible
Remarks on result:
not determinable
Remarks:
due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Max. score:
10
Reversibility:
not reversible
Remarks on result:
not determinable
Remarks:
due to high degree of opacity
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
9.33
Max. score:
20
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
13.33
Max. score:
20
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
9.33
Max. score:
20
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
12.67
Max. score:
20
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
9.33
Max. score:
20
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
10
Max. score:
20
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
High degrees of opacity and excessive discharge were observed during the course of the study. Necrosis of the globe, rupture of the globe and keratoconus were also observed. Positive ocular responses were observed in every rabbit through all study.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Forty-two positive responses were recorded during the course of the study. (Draize Score = 95.0, extremely irritating). Based on the results and according to the criteria laid down in the CLP Regulation, the test substance is considered classified as causing serious eye damage category 1.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(only 50 µl of the test substance were used and the observation period was 8 days)
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): N,N´-Dimethylpiperazine
- Analytical purity: 99%
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.48 and 2.9 kg.
Vehicle:
unchanged (no vehicle)
Controls:
other: The adjacent eye served as saline control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µl
- Concentration (if solution): undiluted

Duration of treatment / exposure:
single application
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Details on study design:
50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 24 h on the day of treatment and on day 3 and 8 afterwards.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.5
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.65
Max. score:
2
Reversibility:
not fully reversible within: 8 days

Findings: animal1/animal2

 Time  opacity  iritis  erythema chemosis        
 1 h 1/1  0/0 2/2   1/2        
 24 h 2/1  0/0 2/2  1/1          
 48 h 2/1  2/0 2/2   1/1          
 72 h 2/1  2/0 2/2  1/1          
 8 d 2/3  2/0 2/1 0/0          

The original BASF grading was converted into the numerical grading according the OECD Draize system.

Mean values over 24, 48, and 72 h

Animal 1: Erythema: 2 ; Opacity: 2; Chemosis: 1; Iritis: 1.3

Animal 2: Erythema: 2 ; Opacity: 1; Chemosis: 1; Iritis: 0

The substance led to heavy redness, edema and opacity. At the end of the observation period after 8 days bleeding of the mucous membrane was observed and staphyloma formation was induced. Severe corneal opacity and staphyloma formation are considered to be irreversible effects to ophthalmic tissue.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the results of this study, the test substance could be classified as irritating to eyes. But, since a study on skin irritation revealed skin corrosion category 1B, this categorisation already implies corrosive effects on the eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

In a primary dermal irritation study performed by Mallory VT (1990), 6 rabbits were exposed to 0.5 ml of undiluted test substance on both intact and abraded skin. Exposure time was 4 hours (upper dorsal site) and 24 hours (lower dorsal site) under an occlusive dressing. Scoring according to Draize occurred at 30 minutes, 60 minutes, 24 hours , 48 hours, 72 hours, daily from day 4 to day 14 after patch removal (upper dorsal site) and at 24 hours, 48 hours and 72 hours, and daily from day 4 to day 14 after application of the test material (lower dorsal site).

The test article was considered to be a severe dermal irritant at both 4 and 24 hour exposures. Necrosis of the skin at each application site was observed at the 24, 48 and 72 hour observation periods and on Days 4 through 14. The study was terminated following the Day 14 observation period. (Primary Irritation Index, according to Draize = 7.92, modified Primary Irritation Index = 8.00). This study was assigned as key study.

In addition, the substance was considered to be a skin corrosive substance in a supporting study (BASF, 1968). BASF performed a skin irritation test in 2 Vienna White rabbits (BASF, 1968). A cotton pad (2.5x2.5 cm) was covered with the undiluted liquid test substance and was applied under occlusive conditions onto the skin of the back. Expose lasted 1, 5, 15 minutes or 20 hours. The original BASF grading was converted into the numerical grading according the OECD Draize system. Lethery necrosis was observed in both animals 24 hours after the 15 min exposure; lethery and hard necrosis was observed in one animal 24 hours after the 20 h exposure and in the other one after 72 hours.

 

Finally, Environmental Health Laboratory (Central Medical Department) (1964) performed a skin irritation test in 2 rabbits that were exposed to 0.5 mL of undiluted test substance on both intact and abraded skin. Exposure time was 24 hours under an occlusive dressing. Based on the available data, it was concluded in the study report that the substance would probably be classified as a moderate skin irritant. However, no observation of the substance was done at 72 hours and the erythema and edema recorded were not fully reversible after 48 hours. Therefore, no conclusion on classification can be made based on CLP criteria for this study.

Eye irritation

In the key study by Pharmakon Research (1982), 6 rabbits were instilled 0.1 ml of undiluted test substance in one eye. The eyes were examined at 1, 24, 48 and 72 hours and 7, 10 and 13 days after treatment. Positive ocular responses were observed in every rabbit at 1, 24, 48 and 72 hours and on days 7, 10 and 13 after treatment. Rupture of the globe and keratoconus were observed. Forty-two positive responses were recorded during the course of the study (Draize score = 95.0).

In the supporting study of BASF (1968), 2 rabbits were instilled 50 µL of undiluted test substance to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 24 hours on the day of treatment and on day 3 and 8 afterwards. Based on the results of this study, the test substance could be classified as irritating to eyes. But, since a study on skin irritation revealed skin corrosion category 1B, this categorisation already implies corrosive effects on the eye.

 

In the supporting study of the Environmental Health Laboratory (Central Medical Department) (1964), 5 rabbits were instilled 0.1 mL of undiluted test substance in one eye. The eyes were examined at 72 hours. Eye reactions were not graded at 72 hours. After one week, 1 eye had a normal appearance while 4 showed signs of a secondary infection. No individual scores based on Draize scoring were reported. In addition, no scoring has been performed at 72 hours. Therefore substance cannot be classified based on CLP criteria.

Justification for classification or non-classification

Based on the available data and the criteria of the CLP Regulation, the test substance is classified as Skin corrosive category 1C (H314) (corrosive in > 1 animal, 4 hours of exposure and <=14 days of observation), covering both skin and eye corrosive effects.

According to the results of the eye irritation study and the criteria of the CLP Regulation, the test substance is classified as Eye Effects Cat. 1 (H318). These classifications are however covered already with the classification for skin corrosion.