Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 222-492-8 | CAS number: 3495-36-1
Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From January 14, 1997 to January 21, 1997
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.4470 (Acute Dermal Irritation)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Myrtle's Rabbitry Incorporated (U.S.D.A. licensed supplier) 4678 Bethesda Road Thompson Station, TN 37179
- Age at study initiation: Adult
- Weight at study initiation: 2.516 to 2.728 kg
- Housing: Housed singly in wire mesh suspension cage
- Diet (e.g. ad libitum): Teklad Hi-Fiber Rabbit Diet
- Water (e.g. ad libitum): Tap water
- Acclimation period: 5 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 61- 72 °F
- Humidity (%): 30- 70 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark cycle - Type of coverage:
- semiocclusive
- Preparation of test site:
- other: One day prior to test substance administration, hair from dorsal surface of the trunk was clipped using an electric clipper. The test site was inspected for any signs of irritation, interfering lesions or defects before the application.
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted - Duration of treatment / exposure:
- 4 h
- Observation period:
- The application sites were observed approximately ½ -1, 24, 48 and 72 h after removal of test substance. For animals exhibiting irritation at the 72 h reading, an additional skin reading was conducted on Day 7 to check for the reversibility of the irritation.
- Number of animals:
- Six (three males and three females)
- Details on study design:
- TEST SITE
- Area of exposure: 1 x 1 inch
- % coverage: Not reported
- Type of wrap if used: Two-layered 1 inch2 gauze patch
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Using a paper towel moistened with tap water
- Time after start of exposure: 4 h
SCORING SYSTEM: According to Draize (1995). Appraisal of the safety of chemicals in food, drugs and cosmetics. Association of the food and drug officials of the United States. Austin, Texas - Irritation parameter:
- erythema score
- Basis:
- animal: mean
- Time point:
- other: 0.5 -1 h
- Score:
- ca. 1.67
- Reversibility:
- fully reversible within: 7 d
- Remarks on result:
- other: 0.5 -1 h
- Irritation parameter:
- erythema score
- Basis:
- animal: mean
- Time point:
- 24 h
- Score:
- ca. 1.17
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- erythema score
- Basis:
- animal: mean
- Time point:
- 48 h
- Score:
- ca. 0.83
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- erythema score
- Basis:
- animal: mean
- Time point:
- 72 h
- Score:
- ca. 0.5
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- edema score
- Basis:
- animal: mean
- Time point:
- other: 0.5 -1 h
- Score:
- ca. 1.67
- Reversibility:
- fully reversible within: 7 d
- Remarks on result:
- other: 0.5-1 h
- Irritation parameter:
- edema score
- Basis:
- animal: mean
- Time point:
- 24 h
- Score:
- ca. 0.67
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- edema score
- Basis:
- animal: mean
- Time point:
- 48 h
- Score:
- ca. 0.5
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- edema score
- Basis:
- animal: mean
- Time point:
- 72 h
- Score:
- ca. 0.33
- Reversibility:
- fully reversible within: 7 d
- Irritant / corrosive response data:
- No evidence of corrosion or necrosis was observed in the treated animals.
All animals exhibited slight to well defined erythema and slight edema at ½ to 1 h reading. 3/6 animals were recovered by 72 h and the remaining by Day 7. The primary irritation index was calculated as 1.8. - Other effects:
- Desquamation in texture of the skin was also observed.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the study conditions no evidence of corrosion or necrosis was observed in the treated animals. All animals exhibited only slight to well defined erythema and slight edema, which recovered in three animals by 72 h and in the remaining three animals by Day 7.
- Executive summary:
A study was conducted to determine the skin irritation potential of the test substance in New Zealand White rabbits according to OECD Guideline 404 and EPA Pesticide Assessment Guideline, Subdivision F (81-5) EPA Health Effects Testing Guideline (TSCA Guideline No 798.4470), in compliance with GLP. Following the test site preparation by clipping hair one day prior to application, 0.5 mL of undiluted test substance was applied to the dorsal skin surface under a gauze patch which was then covered by a semiocclusive dressing around the trunk. After 4 h of exposure period, the test substance was removed and the animals were observed during 72 h for skin reactions and additionally until Day 7 for unresolved skin reactions. Scoring was conducted according to the Draize method. Under the study conditions, no evidence of corrosion or necrosis was observed in the treated animals. All animals exhibited only slight to well defined erythema and slight edema, which recovered in three animals by 72 h and in the remaining three animals by Day 7. The primary irritation index was calculated as 1.8(Harrod, 1997).
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
Referenceopen allclose all
Individual scores
Score for each rabbit for erythema and eschar formation |
||||||||
No. 1 |
No. 2 |
No. 3 |
No. 4 |
No. 5 |
No. 6 |
Total Score |
Average Score |
|
½ -1 h |
2 |
2 |
2 |
1 |
2 |
1 |
10 |
1.67 |
24 h |
1 |
1 |
1 |
1 |
2 |
1 |
7 |
1.17 |
48 h |
1 |
1 |
0 |
1 |
1 |
1 |
5 |
0.83 |
72 h |
1 |
0 |
0 |
1 |
1 |
0 |
3 |
0.50 |
Day 7 |
0 |
ND |
ND |
OW |
OW |
ND |
0 |
0.00 |
Score for each rabbit for edema formation |
||||||||
No. 1 |
No. 2 |
No. 3 |
No. 4 |
No. 5 |
No. 6 |
Total Score |
Average Score |
|
½ -1 h |
2 |
2 |
1 |
1 |
2 |
2 |
10 |
1.67 |
24 h |
1 |
1 |
0 |
0 |
1 |
1 |
4 |
0.67 |
48 h |
1 |
1 |
0 |
0 |
1 |
0 |
3 |
0.50 |
72 h |
1 |
0 |
0 |
0 |
1 |
0 |
2 |
0.33 |
Day 7 |
0 |
ND |
ND |
0 |
0 |
ND |
0 |
0.00 |
Maximum score for erythema and eschar formation: 2, and Maximum score for edema formation: 2
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Endpoint:
- eye irritation: in vivo
- Type of information:
- other: NA
- Adequacy of study:
- key study
- Study period:
- From January 13, 1997 to January 21, 1997
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.4500 (Acute Eye Irritation)
- Deviations:
- no
- Principles of method if other than guideline:
- None
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Myrtle's Rabbitry Incorporated (U.S.D.A. licensed supplier) 4678 Bethesda Road Thompson Station, TN 37179
- Age at study initiation: Adult
- Weight at study initiation: 2.470 to 2.708 kg
- Housing: Housed singly in wire mesh suspension cages
- Diet (e.g. ad libitum): Teklad Hi-Fiber Rabbit Diet
- Water (e.g. ad libitum): Tap water
- Acclimation period: At least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 61- 72 °F
- Humidity (%): 30- 70 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark cycle - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): Undiluted - Duration of treatment / exposure:
- Duration of treatment similar as observation period
- Observation period (in vivo):
- The eyes were examined for any ocular reaction approximately 1, 24, 48, and 72 h after the treatment. For animals exhibiting irritation at the 72 h reading, an additional ocular examination was conducted on Day 14 d or until all apparent ocular effects subsided.
- Number of animals or in vitro replicates:
- 6 animals
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): None
- Time after start of exposure: Not applicable
SCORING SYSTEM: According to Draize (1995). Appraisal of the safety of chemicals in food, drugs and cosmetics. Association of the food and drug officials of the United States. Austin, Texas.
TOOL USED TO ASSESS SCORE: Visualization of cornea was done under ultraviolet illumination after the application of Fluorescein Sodium Ophthalmic Solution U.S.P - Irritation parameter:
- cornea opacity score
- Remarks:
- iris score, conjunctiva score
- Basis:
- animal #1
- Time point:
- other: 1 h to Day 14
- Score:
- ca. 17
- Reversibility:
- fully reversible within: 14 d
- Irritation parameter:
- overall irritation score
- Remarks:
- iris score, conjunctiva score
- Basis:
- animal #2
- Time point:
- other: 1 h to Day 14
- Score:
- ca. 21
- Reversibility:
- fully reversible within: 14 d
- Irritation parameter:
- cornea opacity score
- Remarks:
- iris score, conjunctiva score
- Basis:
- animal #3
- Time point:
- other: 1 h to Day 7
- Score:
- ca. 15
- Reversibility:
- fully reversible within: 14 d
- Irritation parameter:
- cornea opacity score
- Remarks:
- iris score, conjunctiva score
- Basis:
- animal #4
- Time point:
- other: 1 h to Day 14
- Score:
- ca. 17
- Reversibility:
- fully reversible within: 14 d
- Irritation parameter:
- cornea opacity score
- Remarks:
- iris score, conjunctiva score
- Basis:
- animal #5
- Time point:
- other: 1 h to Day 14
- Score:
- ca. 17
- Reversibility:
- fully reversible within: 14 d
- Irritation parameter:
- cornea opacity score
- Remarks:
- iris score, conjunctiva score
- Basis:
- animal #6
- Time point:
- other: 1 h to Day 14
- Score:
- ca. 19
- Reversibility:
- fully reversible within: 14 d
- Irritant / corrosive response data:
- Irritation parameters examined in this study included cornea score, iris score and conjunctivae score. No evidence of corrosion was observed.
- Other effects:
- Additional observations included blistering, blanched or hemorrhagic appearance of areas of conjunctiva and nictitating membrane. These effects were also resolved by Day 14.
- Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- Under the study conditions swelling (chemosis) of the conjunctivae with a mean score equal to or above 2, persisting for more than 24 h was observed.
- Executive summary:
A study was conducted to determine the primary eye irritation potential of the test substance in New Zealand White rabbits according to OECD Guideline 405, in compliance with GLP. 0.1 mL of undiluted test substance was applied to the right eye of three male and three female rabbits. The left untreated eye served as control. Animals were examined for ocular reactions approximately 1, 24, 48 and 72 h after treatment. For animals exhibiting irritation at the 72 h reading, an additional ocular examination was conducted on Day 14 or until all apparent ocular effects subsided. Scoring was conducted according to the Draize method. No corneal opacity was produced. Iritis was cleared by 24 h and conjunctival irritation was cleared by Day 14. Blistering, hemorrhage and blanched appearance was observed in the conjunctiva and/or the nictitating membrane and all the signs were resolved by Day 14. No evidence of corrosion was observed.Under the study conditions swelling (chemosis) of the conjunctivae with a mean score equal to or above 2, persisting for more than 24 h was observed (Harrod, 1997).
Referenceopen allclose all
Table showing the scores of irritation parameters in test animals:
Animal No. and sex |
Reading |
Cornea A B |
Iris |
Conjunctiva C D E |
|||
1-22 Male |
1 h |
0 |
0 |
1 |
IL |
2 |
3 |
24 h |
0/0 |
0/0 |
0 |
2L |
2 |
2 |
|
48 h |
0/0 |
0/0 |
0 |
2LS |
1 |
0 |
|
72 h |
0/0 |
0/0 |
0 |
2LS |
1 |
0 |
|
Day 4 |
0/0 |
0/0 |
0 |
2S |
1 |
0 |
|
Day 7 |
0/0 |
0/0 |
0 |
1 |
1 |
0 |
|
Day 14 |
0/0 |
0/0 |
0 |
0 |
0 |
0 |
|
2-23 Male |
1 h |
0 |
0 |
1 |
2LTH |
3 |
3 |
24 h |
0/0 |
0/0 |
0 |
2L |
2 |
3 |
|
48 h |
0/0 |
0/0 |
0 |
2LS |
2 |
1 |
|
72 h |
0/0 |
0/0 |
0 |
2SR |
1 |
0 |
|
Day 4 |
0/0 |
0/0 |
0 |
1SR |
1 |
0 |
|
Day 7 |
0/0 |
0/0 |
0 |
1S |
1 |
0 |
|
Day 14 |
0/0 |
0/0 |
0 |
0 |
0 |
0 |
|
3-24 Male |
1 h |
0 |
0 |
1 |
1L |
2 |
2 |
24 h |
0/0 |
0/0 |
0 |
2L |
2 |
2 |
|
48 h |
0/0 |
0/0 |
0 |
2L |
1 |
0 |
|
72 h |
0/0 |
0/0 |
0 |
1 |
1 |
0 |
|
Day 4 |
0/0 |
0/0 |
0 |
1 |
1 |
0 |
|
Day 7 |
0/0 |
0/0 |
0 |
0 |
0 |
0 |
|
4-49 Female |
1 h |
0 |
0 |
1 |
1LT |
2 |
3 |
24 h |
0/0 |
0/0 |
0 |
2L |
2 |
2 |
|
48 h |
0/0 |
0/0 |
0 |
2LHS |
2 |
0 |
|
72 h |
0/0 |
0/0 |
0 |
2LSR |
1 |
0 |
|
Day 4 |
0/0 |
0/0 |
0 |
1SR |
1 |
0 |
|
Day 7 |
0/0 |
0/0 |
0 |
1S |
1 |
0 |
|
Day 14 |
0/0 |
0/0 |
0 |
0 |
0 |
0 |
|
5-50 P Female |
1 h |
0 |
0 |
1 |
1L |
2 |
3 |
24 h |
0/0 |
0/0 |
0 |
2L |
2 |
1 |
|
48 h |
0/0 |
0/0 |
0 |
2LR |
2 |
1 |
|
72 h |
0/0 |
0/0 |
0 |
2SR |
1 |
0 |
|
Day 4 |
0/0 |
0/0 |
0 |
1SR |
1 |
0 |
|
Day 7 |
0/0 |
0/0 |
0 |
1S |
1 |
0 |
|
Day 14 |
0/0 |
0/0 |
0 |
0 |
0 |
0 |
|
6-51 Female |
1 h |
0 |
0 |
1 |
2LH |
2 |
3 |
24 h |
0/0 |
0/0 |
0 |
2L |
2 |
1 |
|
48 h |
0/0 |
0/0 |
0 |
2LS |
2 |
0 |
|
72 h |
0/0 |
0/0 |
0 |
2S |
1 |
0 |
|
Day 4 |
0/0 |
0/0 |
0 |
1S |
1 |
0 |
|
Day 7 |
0/0 |
0/0 |
0 |
1S |
1 |
0 |
|
Day 14 |
0/0 |
0/0 |
0 |
0 |
0 |
0 |
|
A - Degree of opacity
B - Area affected
C - Erythema
D - Swelling
E - Discharge
L - Blistered appearance to conjunctiva
T - Blistered appearance to nictitating membrane
H - Areas of conjunctiva appears hemorrhagic
S - Areas of nictitating membrane appears blanched
R - Areas of nictitating membrane appears hemorrhagic
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin
A study was conducted to determine the skin irritation potential of the test substance in New Zealand White rabbits according to OECD Guideline 404 and EPA Pesticide Assessment Guideline, Subdivision F (81-5) EPA Health Effects Testing Guideline (TSCA Guideline No 798.4470), in compliance with GLP. Following the test site preparation by clipping hair one day prior to application, 0.5 mL of undiluted test substance was applied to the dorsal skin surface under a gauze patch which was then covered by a semiocclusive dressing around the trunk. After 4 h of exposure period, the test substance was removed and the animals were observed during 72 h for skin reactions and additionally until Day 7 for unresolved skin reactions. Scoring was conducted according to the Draize method. Under the study conditions, no evidence of corrosion or necrosis was observed in the treated animals. All animals exhibited only slight to well defined erythema and slight edema, which recovered in three animals by 72 h and in the remaining three animals by Day 7. The primary irritation index was calculated as 1.8 (Harrod, 1997).
Eye
A study was conducted to determine the primary eye irritation potential of the test substance in New Zealand White rabbits according to OECD Guideline 405, in compliance with GLP. 0.1 mL of undiluted test substance was applied to the right eye of three male and three female rabbits. The left untreated eye served as control. Animals were examined for ocular reactions approximately 1, 24, 48 and 72 h after treatment. For animals exhibiting irritation at the 72 h reading, an additional ocular examination was conducted on Day 14 or until all apparent ocular effects subsided. Scoring was conducted according to the Draize method. No corneal opacity was produced. Iritis was cleared by 24 h and conjunctival irritation was cleared by Day 14. Blistering, hemorrhage and blanched appearance was observed in the conjunctiva and/or the nictitating membrane and all the signs were resolved by Day 14. No evidence of corrosion was observed. Under the study conditions swelling (chemosis) of the conjunctivae with a mean score equal to or above 2, persisting for more than 24 h was observed (Harrod, 1997).
Justification for classification or non-classification
Skin
The available in vivo skin irritation data suggests that the substance does not warrant classification for this endpoint according to CLP (EC 1272/2008) criteria.
Eye
Based on effects observed in an in vivo eye irritation study, the substance warrants classification as Eye Irrit. 2 - H319: Causes serious eye irritation according to CLP (EC 1272/2008) criteria.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
