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Administrative data

Description of key information

Skin irritation: Skin irritation studies of sufficient quality and conducted in a method comparable to OECD guideline 404 showed that the test substance was corrosive to rabbit skin.  

Eye irritation: An eye irritation study of sufficient quality and conducted in methods comparable to OECD guideline 405 showed that the test substance was corrosive to rabbit eyes. pH value of 11.7 indicated that the test substance was corrosive.

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:
1982-08-30 to 1982-09-02
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Limited details were provided on the test substance (e.g., purity was lacking) and environmental conditions of animals. Details on measurement of the area of test application site was missing, but it can be assumed that it was smaller than the recommended 6cm^2 based on the patch that covered it was only 1 in^2. Observations were only made at 4 and 44 hours after test substance administration.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Limited details were provided on the test substance (e.g., purity was lacking) and environmental conditions of animals. Details on area of test application site was missing. Observations were only made at 4 and 44 hours.
GLP compliance:
no
Specific details on test material used for the study:
- Name as cited in study report: poly[oxy(methyl-1,2-ethanediyl)], alpha-(2-aminomethylethyl)-omega-(2-aminomethylethoxy)
- Substance type: Active
- Color: clear
- Storage: no change in physical state of test substance during administration
-Lot: 5601-9-1, order#J-154
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Douglassville, Pennsylvania
- Weight at study initiation: 2-3 kg
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1982-08-30To: 1982-09-01
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 was applied once directly on the intact skin site (one non-abraded skin site per animal).


Duration of treatment / exposure:
4 hours
Observation period:
Animals were observed at 4 and 44 hours after treatment.
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: All application sites were clipped free of fur and non-abraded. No further information was provided on the area of exposure.
- Type of wrap if used: Following the application of the test substance, one-inch square gauze patches were applied to the test site. The trunk of the animal was then wrapped with a rubber dam and an Ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the four hour exposure period, the wrappings were removed and the skin was wiped to remove any remaining test substance.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Corrosion was considered to have resulted if the test substance in contact with the rabbit skin had caused destruction or irreversible alteration of the tissue on at least two out of each six rabbits tested. Tissue destruction was considered to have occurred if at any of the readings there was ulceration or necrosis.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 4h
Remarks on result:
other: visible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 44h
Remarks on result:
other: visible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4h
Remarks on result:
other: visible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 44h
Remarks on result:
other: visible
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 4h
Remarks on result:
other: visible in 2 out of 6 rabbits
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 44h
Remarks on result:
other: visible in 5 out of 6 rabbits
Irritant / corrosive response data:
Erythema and edema were visible at 4 and 44 hours after treatment. Signs of necrosis were visible in two of six rabbits at the 4 hour reading and in five of six rabbits at the 44 hour observation period. Based upon the results, the test substance was considered to be corrosive.
Interpretation of results:
corrosive
Conclusions:
The test substance was evaluated for primary dermal corrosivity in rabbits. Based on the results of the study, the test substance was determined to be corrosive and considered to be classified as category 1C according to CLP Regulation.
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:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1978-12-12 to 1979-01-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Limited details were provided on the test substance (e.g., purity was lacking), animals and environmental conditions. Details on measurement of the area of test application site was missing, but it can be assumed that it was smaller than the recommended 6cm^2 based on the patch that covered it was only 2.5 cm^2. Observations were only made at 24 and 72 hours after treatment.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Limited details were provided on the test substance (e.g., purity was lacking), animals and environmental conditions. Details on size of testing site were lacking. Observations were only made at 24 and 72 hours after treatment.
GLP compliance:
no
Specific details on test material used for the study:
- Name as cited in study report: Poly[oxy(methyl-1,2-ethanediyl)], alpha-(2-aminomethylethyl)-omega-(2-aminomethylethoxy)
- substance type: Active
- Date of receipt: 1978-11-03
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: at least 8 weeks
- Housing: The animals were housed in elevated wire cages in a temperature controlled room reserved exclusively for rabbits on acute tests.
- Diet (e.g. ad libitum): ad libitum (fresh Purina Rabbit Chow)
- Water (e.g. ad libitum): ad libitum (tap water)
- Other: The animals selected were in good health when received from the local supplier and remained in good health during the equilibration period in the laboratory. The cages and room were kept clean in accordance with the standards of AAALAC of which the laboratory was an approved member.
Type of coverage:
occlusive
Preparation of test site:
other: clipped (abraded and non-abraded areas were included)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml


Duration of treatment / exposure:
24 hours
Observation period:
The animals were scored at 24 hours and 72 hours after treatment.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Prior to treatment the fur was clipped from the backs and sides of the test animals with an Oster Model 2 clipper with an ANG-RA clipper head designed specifically for clipping rabbits. The left-side of the spinal column of each rabbit was abraded with a 21 gauge bent tip needle. The abrasions scratched the stratum corneum but did not reach the derma or produce bleeding. Three abrasions, approximately 2-3 cm apart, extending the length of the exposure site were made on each back. The right side of each back was not abraded. The test substance was applied to one abraded and one intact site per rabbit.
- Type of wrap if used: the test substance was covered with 2 ply gauze, 2.5 cm square. The patches were secured with adhesive tape and the entire trunk of the rabbit was wrapped with impervious material, 2 ml thick plastic.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM: the scoring system of Draize was used. The primary dermal index was calculated as cited in 16 CFR 1500.41. By definition, a primary irritatant was a substance which was not corrosive and had an empirical score of 5 or more (16 CRF 1500.3). See scoring scale below.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: combination of 48 and 72 hour observations
Score:
ca. 6.54
Max. score:
8
Reversibility:
no data
Irritant / corrosive response data:
The skin reactions observed were, in some instances, greater than the highest value on the Draize scale. These were noted as 4+. The test substance was therefore considered to be corrosive.

Rabbit Number

24 hours

1

2

3

4

5

6

Mean Score

Intact skin

Erythema & Eschar

4bw

4bw

4g

4bwg

4bwg

4bwg

4

Edema

2

2

3

2

2

3

2.33

Abraded skin

Erythema & Eschar

4bw

4bw

4g

4bwg

4bwg

4bwg

4

Edema

2

2

3

2

3

3

2.5

72 hours

1

2

3

4

5

6

Mean Score

Intact skin

Erythema & Eschar

4bs

4bs

4bw+

4bsw+

4bw+

4bwg

4

Edema

2

2

3

3

3

3

2.67

Abraded skin

Erythema & Eschar

4bs

4bs

4bw+

4bsw+

4bw+

4bw+

4

Edema

2

2

3

3

3

3

2.67

Sum of mean scores

26.17

Primary Dermal Index

6.54

Maximum Possible Score

8.0

b=brown

g=greenish areas

s=slight eschar

w=white areas

+=moderate eschar

Interpretation of results:
corrosive
Conclusions:
The test substance was evaluated for dermal irritation in New Zealand White Rabbits. The skin reactions observed were in some instances greater than the highest value on the Draize scale. Therefore, the test substance was considered to be corrosive.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1984-12-05 to 1984-12-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Study conducted with methods similar to OECD Guideline 404. However, details on the test substance (e.g, purity) were lacking. Details on application site were limited (location and size were missing). Results were limited.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Details on the test substance (e.g., purity) were lacking. Details on application site were limited (location and size were missing). Results were limited.
GLP compliance:
no
Specific details on test material used for the study:
- Name as cited in study report: Poly[oxy(methyl-1,2-ethanediyl)], alpha-(2-aminomethylethyl)-omega-(2-aminomethylethoxy)
- Substance type: Active
- Color: clear
- Stability: no change in physical state of test substance during administration
Species:
rabbit
Strain:
other: Albino 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: 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 Resources, National Research Council.
- Diet (e.g. ad libitum): ad libitum (Wayne Rabbit Ration)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: 5 days

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

IN-LIFE DATES: From: 1984-12-05 To: Termination date was listed as 1984-12-05. No data was provided if the animals were sacrificed.
Type of coverage:
not specified
Preparation of test site:
other: clipped free of hair
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml was applied directly on the intact skin sites.
Duration of treatment / exposure:
4 hours
Observation period:
Animals were observed at 3 and 60 minutes and 4 hours after treatment.
Number of animals:
2 males and 1 female
Details on study design:
TEST SITE
- Area of exposure: The test substance was applied directly on the intact skin sites (one site per animal). However, no further information was provided on the sties.


SCORING SYSTEM: The test substance was classified by the length of time of contact necessary to produce visible necrosis of the skin tissue as follows:
1. Group 1 (very dangerous)-caused visible necrosis of the skin tissue in 3 minutes or less
2. Group 2 (medium danger)- caused visible necrosis of the skin tissue in a time period of 3 to 60 minutes
3. Group 3 (minor danger)- caused visible necrosis of the skin tissue in 60 to 240 minutes
Irritation parameter:
erythema score
Basis:
other: 3 animals
Time point:
other: 60 min and 4h
Remarks on result:
other: slight to moderate erythema
Irritant / corrosive response data:
No signs were observed at the 1-3 minute observation period. Slight to moderate erythema was observed at the 60 minute and 4 hour observation periods. Signs of necrosis were visible in one animal at the 4 hour observation period.

Based on the results, the test substance was classified as a Group 3 substance (producing minor danger).

Interpretation of results:
other: minor damage
Remarks:
Criteria used for interpretation of results: other: International Civil Aviaiton Organization (ICAO) for Air Shipments
Conclusions:
The test substance was evaluated for dermal irritation. Based on the results the test substance was determined to produce minor damage.
Endpoint:
skin irritation / corrosion
Remarks:
no data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No information on study design and methodology was presented.
Qualifier:
no guideline available
GLP compliance:
not specified
Specific details on test material used for the study:
No test item information provided
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): test substance as received

Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
No information provided
Details on study design:
TEST SITE
- Type of wrap if used: Impervious patch
- Performed on intact and abraded skin and evaluated as per Draize protocol at 24 and 72 hours post dose.

SCORING SYSTEM: Draize
The maximum possible value for a skin reaction (excluding necrosis) is 4. The primary irritation score is the sum of the mean values divided by 4.
Interpretation of results:
corrosive
Remarks:
Criteria used for interpretation of results: expert judgement
Conclusions:
The test substance is corrosive to the skin of the rabbit. Therefore, precautions should be observed to prevent skin contact with the product.
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:
1978-12-26 to 1979-01-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Study conducted with methods similar to OECD Guideline 405. However, limited details were provided on the animals, environmental conditions and the test substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Limited details were provided on the animals, environmental conditions and the test substance.
GLP compliance:
no
Specific details on test material used for the study:
- Name as cited in study report: Poly[oxy(methyl-1,2-ethanediyl)], alpha-(2-aminomethylethyl)-omega-(2-aminomethylethoxy)
- Substance type: Active
- Color: clear
- Date of receipt: 1978-11-3
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: The animals were housed two per cage in suspended wire mesh cages in a temperature controlled room reserved exclusively for rabbits on acute tests.
- Diet (e.g. ad libitum): ad libitum (fresh Purina Rabbit Chow)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: at least one week
- Other: The animals were in good health when received from the local supplier and remained in good health during the equilibration period in the laboratory. The cages and room were kept clean in accordance with the standards of AAALAC of which the laboratory was an approved member. Prior to testing, the rabbits' eyes were closely examined for signs of irritation or damage. Only rabbit with healthy eyes were used.

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye of each animal served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml of the test substance was instilled into one eye of each rabbit. The lids were held together briefly to insure adequate distribution of the test substance over the surface of the eye.


Duration of treatment / exposure:
No data were provided in the study on washing the eye after treatment. The eyes were scored up for up to 14 days.
Observation period (in vivo):
14 days (The ocular reactions were graded at 1, 24, 48 and 72 hours and again at 7 days. If any corneal score was present on day 7, the eyes were scored again at 14 days.)
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The study did not specify if washing was done.


SCORING SYSTEM: The eye irritation potential was determined as defined in 16 CFR 1500.3 and 1500.42. See below for scale used for scoring of ocular lesions (Draize, J.H. et al. J. Pharm. Exp. Ther. 82:377-390, 1944).
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 h
Score:
ca. 41.3
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 h
Score:
ca. 55.7
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 h
Score:
ca. 66.6
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72 h
Score:
ca. 61.4
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 7 d
Score:
ca. 57.3
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 14 days
Score:
ca. 72
Max. score:
110
Reversibility:
not reversible
Irritant / corrosive response data:
The test substance was corrosive to the rabbit eye.
Other effects:
One animal died during the study.

Average Scores

1 h

24 h

48 h

72 h

7 d

14 d

Cornea (max 80)

18.3

30.0

40.8

34.2

35.0

54.0

Iris (max 10)

5.0

6.7

7.5

9.2

5.0

0.0

Conjunctivae (max 20)

18.0

19.0

18.3

18.0

17.3

18.0

 

Interpretation of results:
corrosive
Conclusions:
The test substance was evaluated for eye irritation in New Zealand White rabbits. Based on the results, the test substance was determined to be corrosive to the eyes and considered to be classified as category 1 (serious eye damage) according to CLP Regulation.
Endpoint:
eye irritation: 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:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No information on study design and methodology was presented.
Qualifier:
no guideline available
GLP compliance:
not specified
Specific details on test material used for the study:
No test item information provided
Species:
rabbit
Strain:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): used product as received

Duration of treatment / exposure:
No information provided
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
No information provided
Details on study design:
SCORING SYSTEM: Draize

The maximum possible scores for eye irritation reactions (excluding necrosis) are: Cornea, 80; Iris, 10; Conjuctivae, 20.

Irritation parameter:
other: corrosive; no irritation scores provided
Reversibility:
not reversible
Remarks on result:
other: corrosive within 24 hours of exposure
Irritant / corrosive response data:
Destruction or irreversible change of any tissue in 24 hours or less.
Interpretation of results:
corrosive
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance is corrosive to the eye of the rabbit. Therefore, precautions should be observed to prevent its introduction into or near eyes.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In one skin irritation study of sufficient quality and tested with methods similar to OECD guideline 404, 0.5 mL test substance was applied to the intact skin of rabbits (Pharmakon research International Inc, 1982; Klimisch 2). Animals were observed at 4 and 44 hours after treatment. Signs of necrosis were visible in two of six rabbits at the 4 hour reading and in five of six rabbits at the 44 hour observation period.

In another skin irritation study tested with methods similar to OECD guideline 404 (MB Research Laboratories Inc, 1979; Klimisch 2). 0.5 mL test substance was applied to non-abraded and abraded skin of rabbits. Animals were observed at 24 and 72 hours after treatment. The primary dermal index was determined to be 6.54 indicating corrosivity.

In a skin irritation study conducted in methods comparable to OECD guideline 404, 0.5 ml test substance was applied directly on the intact skin sites (Pharmakon Research International Inc, 1984; Klimisch 2). Animals were observed at 3 and 60 minutes and 4 hours after treatment. No signs were observed at the 1-3 minute observation period. Slight to moderate erythema was observed at the 60 minute and 4 hour observation periods. Signs of necrosis were visible in one animal at the 4 hour observation period.

In a similar study, 0.5 mL test substance was applied to non-abraded and abraded skin of rabbits for 1 hour (American Cyanamid company, 1968; Klimisch 4). Animals were observed 72 hours after treatment. The primary dermal index was determined to be 6.4. The degree of second degree chemical burn was moderate and diffuse.

An in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available.

Eye irritation

In one eye irritation study of sufficient quality and tested with methods similar to OECD guideline 405, 0.1 ml of the test substance was instilled into one eye of each rabbit (MB Research Laboratories Inc, 1979; Klimisch 2). The ocular reactions were graded at 1, 24, 48 and 72 hours and again at 7 days. If any corneal score was present on day 7, the eyes were scored again at 14 days. The maximum mean total scores (MMTs) were 41.3, 55.7, 66.6, 61.4, 57.3, and 72 at 1h, 24h, 48h, 72h, 7 day, and 14 day, respectively. Cornea and conjunctivae effects were not reversible within 14 days. The test substance was corrosive to rabbit eyes.

An in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available.

Justification for classification or non-classification

Based on the available data, a classification category 1C is warranted for skin irritation/corrosion.

Based on the available data, a classification category 1 (serious eye damage) is warranted for eye irritation.

No study is available on respiratory irritation. Data for classification is lacking.