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Description of key information

Under the study conditions, the test article was found to be irritating to the eyes. As the test substance is classified as corrosive to the skin, it is classified as category 1 serious eye damage , according to CLP regulation.

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:
weight of evidence
Study period:
February 28, 1985 - March 14,1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor; 5601-49-1

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: There was no apparent changes in the physical state of the test article during administration

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None; used as received
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2-3 kg
- Housing: Standard individual 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): ad libitum, Wayne Rabbit Ration
- Water (e.g. ad libitum): ad libitum, fresh tap water, fit for human consumption
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site; applied directly on the intact and abraded skin sites
- Concentration (if solution): As received

Duration of treatment / exposure:
24 hrs
Observation period:
14 days
Number of animals:
3 males, 3 females
Details on study design:
TEST SITE
- Area of exposure: 1 abraded and 1 intact site per animal, clipped free of hair. The skin was abraded using a 21 gauge burred needle; the abrasion penetrated the stratum corneum but not the derma. following the application of the test material, one inch square gauze patches were applied to each of the two sites.
- Type of wrap if used: Gauze patch, wrapped with a rubber dam, followed by an Ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure, the wrappings were removed and the test item removed in a suitable manner
- Time after start of exposure: 24 hrs

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) At 24 and 72 hrs, then on days 4-14.

SCORING SYSTEM:
- Method of calculation: Draize scoring
1) Draize Evaluation of Dermal Irritation

I. Dermal observations.
Erythema and Eschar Formation (most severely affected area graded):
- No erythema: 0
- Veyr slight erythema (barely peceptible): 1
- Well-defined erythema: 2
- Moderate to severe erythema: 3
- Severa erythema (beet redness) to slight eschar formation (injuries in depth): 4

Edema Formation (most severly affected area graded):
- No edema: 0
- Very slight edema (edges of area well perceptible): 1
- Slight edema (edges of area well-defined by definite raising): 2
- Moderate edema (raised approximately 1 mm):
- Severe edema (raised more than 1 mm and extending beyond area of exposure): 4

II: Primary Irritation Index.
Mean values (6 animals are calculated and summed as follows):
* Erythema and Eschar formation
Intact skin - 24 and 72 hours - 2 values
Abraded skin - 24 and 72 hours - 2 values

* Edema formation
Intact skin - 24 and 72 hours - 2 values
Abraded skin - 24 and 72 hours - 2 values

Total: 8 values
Sum of mean values divided by 4 = Primary Irritation Index

1) Draize, J. H. 1959. The Appraisal of Chemicals n Foods, Drigs and Cosmetics, pp. 36-45. Association of food and drug officials of the united states, Austin, Texay
Federal Hazardous Substances Act Regulations. 16 CFR 1500.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: Average of 6 animals
Time point:
14 d
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
probability of severe irritation
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
abraded and intact skin
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: value for 48h post treatment is not available
Remarks:
value is 0 for abraded and intact skin at day 14.
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean for intact skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
not fully reversible within: 14 days
Remarks:
value of 1 at day 14.
Remarks on result:
other: value for 48h post treatment is not available
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean for abraded skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks:
value of 4 at day 14
Remarks on result:
other: value for 48h post treatment is not available
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean for intact skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks:
value of 4 at day 14.
Remarks on result:
other:
Remarks:
value for 48h post treatment is not available
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean for intact skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: value for 48h post treatment is not available
Remarks:
value of 4 at days 14.
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
mean for abraded skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: value is 0 for abraded and intact skin at day 14.
Remarks:
value for 48h post treatment is not available
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
mean for abraded skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: value is 0 for abraded and intact skin at day 14.
Remarks:
value for 48h post treatment is not available
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
mean for abraded skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: value is 0 for abraded and intact skin at day 14.
Remarks:
value for 48h post treatment is not available
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean for abraded and intact skin (24 + 72 hours)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: value for 48h post treatment is not available
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean for abraded and intact skin
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
other: abraded skin provide a score of one at day 14 and a score of 0 for the intact skin.
Remarks on result:
other: value for 48h post treatment is not available.
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean for abraded and intact skin
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks:
score value is 1 at days 14
Remarks on result:
other: value for 48h post treatment is not available.
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
intact skin
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: value for 48h post treatment is not available.
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
abraded skin
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: value for 48h post treatment is not available
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
mean for abraded and intact skin.
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 dyas
Remarks on result:
other: value for 48h post treatment is not available
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
mean for abraded and intact skin
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: value for 48h post treatment is not available
Irritant / corrosive response data:
- Primary Irritation Index is calculated using the sums of the mean edema and erythema values from both sites at 24 and 72 hrs, and dividing by 4. The Primary Irritation Index for this study was calculated to be 3.5.
- very slight to severe erythema and edema were observed at every observation period
- necrosis was also observed during the course of the study

pH of the test article was 13.8

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the conditions of this study, the test article was found to be an irritant, with a Primary Irritation Index of 3.5. According to these data, the test substance should be considered classified as category 2 according to the CLP regulation. However, in a weight of evidence approach with an in vivo skin corrosion test, the substance is classified as category 1 corrosive to the skin.
Executive summary:

The purpose of the study was to evaluate the dermal irritation produced in rabbits by the administration of the test article on intact and abraded skin.

The test article was applied to one intact and one abraded skin site on each of six rabbits (three males and three females).

Observations were recorded at 24 and 72 hours and on days 4 through 14.

Very slight to severe erythema were observed ar every observation period.

Necropsis was also observed during the course of the study.

The study was terminated on day 14.

Primary Irritation Index = 3.5

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
April 9, 1985-April 19, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline followed
Principles of method if other than guideline:
DOT corrosivity test, with procedure in accordance with generally accepted scientific standards and described in sufficient detail
GLP compliance:
not specified
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:- 5601-49-1
- Standard handling and storage, normal precautions
- Test item applied as received

- Stability under test conditions: There was no apparent change in the physical state of the test article during administration
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sqarlet's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2-3 kg
- Housing: Standard size individual cages
- Diet (e.g. ad libitum): ad libitum, Wayne Rabbit Ration
- Water (e.g. ad libitum):ad libitum, fresh tap water
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C, +/- 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):12 h dark/12 h light
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site
- Concentration (if solution): Applied as recieved

Duration of treatment / exposure:
4 hours
Observation period:
Observations recorded at 4 and 48 hours
Number of animals:
4
Details on study design:
TEST SITE
- Area of exposure: 1 inch square patch on trunk
- Type of wrap if used: Rubber dam wrapped with ace bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wiped only
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 4 and 48 hours

SCORING SYSTEM:
- Method of calculation: Corrosion was considered to have resulted if destruction or irreversible alteration of the tissue ocurred.
Irritation parameter:
other: necrosis
Basis:
animal #1
Time point:
other: 4 hours
Reversibility:
not specified
Remarks:
necrosis at 100% at site of application.
Remarks on result:
other: necrosis observed
Remarks:
necrosis observed
Irritation parameter:
other: necrosis
Basis:
animal #1
Time point:
48 h
Reversibility:
not specified
Remarks:
necrosis
Remarks on result:
other: necrosis (100%) of application site + moderate erythema of skin surrounding application site
Remarks:
necrosis (100%) of application site + moderate erythema of skin surrounding application site
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Reversibility:
not specified
Remarks:
erythema and herdening
Remarks on result:
other: slight erythema and hardening of the skin (10%) at application site
Remarks:
slight erythema and hardening of the skin (10%) at application site
Irritation parameter:
other: necrosis
Basis:
animal #3
Time point:
other: 4 hours
Reversibility:
not reversible
Remarks:
necrosis
Remarks on result:
other: animals unwrapped and necrosis (100%) at site of application.
Remarks:
animals unwrapped and necrosis (100%) at site of application.
Irritation parameter:
other: necrosis
Basis:
animal #4
Time point:
other: 4 hours
Reversibility:
not reversible
Remarks:
necrosis
Remarks on result:
other: animals unwrapped and necrosis (100%) at site of application.
Remarks:
animals unwrapped and necrosis (100%) at site of application.
Irritation parameter:
erythema score
Basis:
animal: animal 1 to 4
Time point:
24/48/72 h
Reversibility:
other: not appliacble
Remarks:
observation made at 4 and 48 hours after exposure
Remarks on result:
not measured/tested
Remarks:
no observation made at 24/48 and 72 hours.
Irritation parameter:
edema score
Basis:
animal: animal 1 to 4
Time point:
24/48/72 h
Reversibility:
other: not applicable
Remarks:
observation made at 4 and 48 hours after exposure
Remarks on result:
not measured/tested
Remarks:
no observation made at 24/48 and 72 hours.
Irritant / corrosive response data:
3 of 4 rabbits exhibited skin necrosis at 4 and 48 hrs after application of test article.
Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
Based upon the results of this study, the test article was considered to be corrosive. Therefore the test substance is considered classified as category 1C corrosive to the skin, according to CLP regulation.
Executive summary:

The test article was applied to an intact skin site on each of four rabbits (two males and two females). The test substance remained in contact with the skin for four hours.

Animals were observed at 4 and 48 hours after treatement. Skin necrosis was visible in three of the four rabbits at the 4 hour and 48 hour observation period.

Based upaon the results of the DOT Corrosivity study in, the test item was considered to be corrosive.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
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
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Additional information

Justification for classification or non-classification

Based on the above mentioned results the substance does need to be classified as corrosive sub-categories 1C ( H314: Causes severe skin burns and eye damage) according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).