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Description of key information

Skin irritation: In a rabbit skin irritation/corrosion test according to OECD TG 404 and EC B.4, the test substance was mildly irritating according to the Draize classification scheme (Allen, 1996), but is not to be classified as irritant to the skin according to the CLP Regulation.
Eye irritation: Based on the data of the key study (performed according to EPA OPPTS 870.2400 and EC Method B.5) and according to the criteria of the CLP Regulation, the test substance is classified as serious eye damage (category 1).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-11-01 - 1994-11-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
- Name of test material (as cited in study report): AMINE C-8
- Substance type: dark brown slightly viscous liquid with crystalline sediment
- Physical state: liquid
- Analytical purity: no data
- Composition of test material, percentage of components: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: responsibility of the sponsor
- Storage condition of test material: at room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.23-2.29 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-20 °C
- Humidity (%): 58-65%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1 November 1994 To: 4 November 1994
Type of coverage:
semiocclusive
Preparation of test site:
shaved
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): not applicable
Duration of treatment / exposure:
patches were removed after exposure periods of 3 min, 1 h and 4 h.
Observation period:
One hour after removal of the patches, and 24, 48 and 72 h.
Number of animals:
3 animals, with 3 test sites each
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: no data
- Type of wrap if used: gauze patches secured with strips of surgical adhesive tape and wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with cotton wool soaked in distilled water
- Time after start of exposure: 3 min, 1 hour and 4 hour

SCORING SYSTEM: Draize (1977) Primary Irritation Index.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0.2
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Classification: mild irritant
Remarks:
4 hours exposure
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: after 1 hour exposure
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: after 3 minutes exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: after 3 minutes, 1 hour and 4 hours of exposure
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: after 4 hours of exposure
Irritant / corrosive response data:
After 3 min and 1 hour exposure: no erythema/eschar formation and no oedema formation.
After 4 hours exposure: very slight erythema in all three animals and very slight oedema in two animals, but fully reversible within 24-48 hours.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material does not need to be classified as a skin irritant according to the CLP Regulation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The in vivo eye irritation study was performed in 2010, according to EU method B.5 and OPPTS 870.2400. This type of data is intended to fulfill the testing requirements for the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.) and the Toxic Substances Control Act (TSCA) (15 U.S.C. 2601).
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Amine C8
- Substance type: no data
- Physical state: viscous amber liquid
- Storage condition of test material: 15-30 °C, room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan or any other USDA approved vendor
- Age at study initiation: young adult (12-18 weeks) at start of dosing; records of dates of birth for animals used in this study will be retained in the Calvert archives.
- Weight at study initiation: 2.0-3.0 kilograms at the outset (Day 1) of the study.
- Housing: Animals are housed individually in compliance with USDA Guidelines. The room in which the animals will be kept will be documented in the study records. no other species will be kept in the same room.
- Diet (e.g. ad libitum): All animals will have access to PMI certified Hi-Fiber Rabbit Diet or equivalent as per Calvert SOP, unless otherwise specified. The lot number and specifications of each lot used are archived in the facility records at Calvert. No contaminants are known to be present in the certified diet at levels that would be expected to interfere with the results of this study. analysis of the diet was limited to that performed by the manufacturer, records of which will be maintained in the Calvert archives.
- Water (e.g. ad libitum): Tap water is available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert SOP's. No contaminants are known to be present in the water at levels that would be expected to interfere with the results of this study. Results of the water analysis will be maintained in the Calvert archives.
- Acclimation period: study animals were acclimated to their housing for a minimum of seven days prior to their first day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 21°C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL


Duration of treatment / exposure:
Only once instilled
Observation period (in vivo):
mortality/morbidity: once daily
clinical observations: prior to dose administration and then daily
ocular observations: at 1 (± 15 minutes), 24, 48 and 72 hours (± 1 hour); if there is no evidence of irritation at 72 hours, the study will be complete. Extended observations may be necessary if there is persistent corneal involvement or other ocular irritation is observed to determine the progress of the lesions and their reversibility or irreversibility. If the cornea, iris or conjunctivae have not healed completely by Day 8, the unhealed animals will be retained and reexamined on Days 15 and 22, if injury persists. In addition to the observations of the cornea, iris and conjunctivae, any other lesions, which are noted, will be recorded and reported. The grades of ocular reaction according to Draize will be manually recorded at each examination.
Body weight: prior to dose administration
Number of animals or in vitro replicates:
Three
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes of the animals will remain un-rinsed for at least 24 hours after instillation of the test article. The treated eyes may be gently washed out (if necessary) using room temperature physiological saline.
- Time after start of exposure: see above

SCORING SYSTEM: An animal has exhibited a positive reaction if the test article has produced at any observation one or more of the following signs: 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 light hyperemia of the circum corneal blood vessels) or an obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids or a diffuse crimson color with individual vessels not easily discernible.
EEC classification of ocular irritants: The total ocular irritation score for the 24, 48 and 72 hour invertvals are individually added for corneal opacity, iris lesion, conjunctival redness and conjunctival edema. For a group of the three animals, the calculated mean scores will remain expressed individually and compared to the EEC ocular evaluation criteria. Scores for two or more animals above the appropriate mean will classify the test article in that particular category. A test substance will be classified as a nonirritant, irritating to the eyes (R36) or risk of serious damage to eye (R41 Risk Phrase) based on the EEC Ocular Evaluation Criteria.

Globally harmonized system of classification evaluation criteria: for this classification system, the 24-, 48- and 72- hours scores will be added separately for each animal and each total divided by 3 (three time points) to yield the individual mean scores for each animal.

Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 22 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 15 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 15 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 22 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 22 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24 hours post dose
Score:
26
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 48 hours
Score:
31
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 72 hours
Score:
32.67
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: day 5
Score:
30.67
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 8 days
Score:
28.67
Max. score:
110
Reversibility:
fully reversible
Irritant / corrosive response data:
No corneal, iris or conjunctival irritation was observed in the untreated eyes of the rabbit at any time point. In the first animal, scattered to diffuse corneal opacity covering 1/4 or less of the eye was observed at 24 hours post dose. Iritis (grade 1) was observed at 1 hour after dosing, at 24, 48 and 72 hours post dose, on Days 5 through 8. Conjunctival redness (grade 1) was noted at 1 hour after dosing up until study termination on Day 22. Chemosis (grades 3 to 4) was also seen starting at 1 hour post dose and throughout the study until it diminished to grade 1 on Day 22. Discharge (grade 3) was observed in the rabbit throughout the entire duration of the study.
In the second animal, scattered to diffuse corneal opacity covering 1/4 to 1/2 of the total surface area of the eye was observed from 24 hours post dose out to Day 8. Iritis (grade 1) was observed at 1 hour after dosing through to day 8. Conjunctival redness (grade 1) was noted at 1 hour after dosing up until Day 15. Chemosis (grades 3 to 4) was also seen from 1 hour post dose until Day 5. From Days 6-8, chemosis declined to grade 2 and was not apparent by Day 15. Discharge (grade 3) was observed from 1 hour post dose until Day 5. On Days 6-8, discharge decreased to grade 2 and by Day 15 further lowered to grade 1. At Day 22, no discharge was noted.
For the third animal, scattered or diffuse areas of corneal opacity with details of the iris clearly visible covering greater than 1/2 to 3/4 of the whole area of the eye was observed from 48 hrs post dose until Day 15. On Day 22, no ulceration or opacity was observed. Iritis (grade 1) was observed at 1 hour after dosing through to Day 22. Conjunctival redness (grade 1) was noted at 1 hour after dosing through to study termination on Day 22. Chemosis (grades 3 to 4) was also seen from 1 hour post dose through to Day 5. From Days 6 to 22, chemosis declined to grade 2. Discharge (grade 3) was observed from 1 hour post dose until study termination on Day 22.
Other effects:
No mortality or adverse clinical signs were observed in the animals during the study
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the data of this EPA OPPTS 870.2400 and EC Method B.5 study and according to the criteria of the CLP Regulation, the test substance is classified as serious eye damage (category 1).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:


The skin irritation potential of the test substance is investigated in a key, reliable study performed according to OECD guideline 404 (Allen, 1994; Klimisch 1) in 3 rabbits. Semiocclusive patches were removed from shaved test sites after exposure periods of 3 min, 1h, and 4h to 0.5mL of the test substance. The Draize scoring system was used to evaluate the results. No erythema/eschar formation and no oedema formation is observed after 3 min and 1 hour exposure. After 4 hours of exposure, very slight erythema in all 3 animals and very slight oedema in 2 animals was observed, but this was fully reversible within 24 -48 hrs.


No in vitro skin irritation studies were performed as adequate data from an in vivo study was available.


 


Eye irritation:


Calvert Laboratories, Inc. (2010) investigated the eye irritation potential of the test substance in a key, reliable study performed according to EU method B.5 (Klimisch 1) in 3 rabbits. The treated eyes (with 0.1mL test substance) will remain unrinsed for at least 24 hours after instillation. The 24 -, 48- and 72 -hours scores will be added seperately for each animal and each total divided by 3 to yield the individual mean scores for each animal. Based on the data and according to the criterial of the CLP regulation, the test substance is classified as serious eye damage (category 1).


No in vitro eye irritation studies were performed as adequate data from an in vivo study was available.

Justification for classification or non-classification

Based on the available data and according to the criteria laid down in the CLP Regulation (EC) 1272/2008, the test substance is not to be classified as irritant to skin. The test substance does not need to be classified for skin irritation or skin corrosion, as the substance proved to be only mildly irritating in a rabbit skin irritation/corrosion study.


Based on the data and according to the criteria of the CLP Regulation, the test substance is classified as serious eye damage (category 1).