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Description of key information

Degree of irritation / corrosivity was variable and depended on the test substance lot and chemical impurities. In essence, the substance class is irritating to the skin and the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001-06-07 to 2001-06-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Guideline 11 Nousan No. 6283 (October 1, 1999); First Revision: 12 Nousan 8628 (December 6, 2000)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 3329 to 3867 grams
- Housing: individual housing in suspended wire mesh cages
- Diet: 150 g/day, standard laboratory rabbit diet PMI Nutrition International, Inc. Certified Rabbit LabDiet® 5322
- Water: ad libitum, municipal water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66-71
- Humidity (%): 50-75
- Air changes (per hr): no data
- Photoperiod: 12 hour light/dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its one control with adjacent area of untreated skin.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
3
Details on study design:
PRE-EXPERIMENTAL PROCEDURE
On the day prior to dosing, the hair was removed from the backs and flanks of the rabbits using an electric clipper.

ADMINISTRATION OF THE TEST ARTICLE
Prior to use, the original container of the test article was agitated to insure a homogeneous mixture. A sufficient amount of test article was dispensed into a labeled storage vessel and a stir bar was added. The test article was stirred continuously throughout the dosing procedure. Each 0.5-ml was applied to an area of skin approximately 2.5 x 2.5 cm under a two-ply gauze patch secured in place with Micropore™ tape. The patches were overwrapped with a gauze binder and secured with Dermiform® tape. Plastic restraint collars were applied to the animals to prevent ingestion of the test article and/or bandages. The application sites were observed for erythema, edema and other dermal findings approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and on study days 4, 7, 10 and 14.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours
At the end of four hours, the collars and bandages were removed and the sites wiped with disposable paper towels moistened with deionized water.

SCORING SYSTEM: Dermal irritation was graded in accordance with the method of Draize
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Very slight erythema (score 1) in all animals at day 14
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
CLINICAL SKIN OBSERVATIONS
- All animals were noted with moderate to severe erythema and very slight to slight edema. Focal eschar was noted for two animals on study day 7, and desquamation was noted for all animals on study days 7 through 14.

REVERSIBILITY
- Very slight erythema was still present for all animals at study termination (study day 14).
Other effects:
TOXIC EFFECTS OTHER THAN SKIN IRRITATION
- There were no deaths during the study.
- Body weights: No remarkable body weight changes were noted during the study.










Irritant/corrosive response data for each animal at each observation time

Score at time point

Erythema

Edema

Max. score: 4

Max. score: 4

0.5-1 hour

3/2/2

1/1/1

24 hours

3/3/3

1/2/2

48 hours

3/3/3

1/1/2

72 hours

3/3/3

1/1/1

4 days

3/3/3

1/1/1

7 days

2d/2dg/3dg

1/1/1

10 days

2d/2d/2d

0/0/1

14 days

1d/1d/1d

0/0/0

d=desquamation; g = focal eschar

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
Interpretation is based on erythema/eschar and edema calculated as mean scores for each animal following grading at 24, 48 and 72 hours after removal of the test material, in consideration of reversibility. The following mean scores were calculated for oleic-acid based IQAC, DMS quaternised: erythema 3/3/3 and edema 1/1.33/1.67. Edema were fully reversible within 14 days in all animals, whereas very slight erythema (score 1) was still present in all animals at study termination (day 14).
Executive summary:

In a primary skin irritation study according to US Guideline EPA OPPTS 870.2500 (1998), OECD Guideline 404 (1992), EU Guideline B.4 (1992) and Japanese Guideline Nousan No. 6283 (1999), revised Nousan 8628 (2000), three White New Zealand rabbits were semi-occlusive dermally exposed to 0.5 ml of oleic-acid based IQAC, DMS quaternised (according to sponsor information: 80 % of CAS No. 72749-55-4, 15 % of CAS No. 9004-96-0 (Oleic acid, ethoxylated) and 5 % of CAS No. 25322-68-3 (Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated)) for 4 hours. Animals then were observed for 14 days. Irritation was scored by the method of Draize.

The oleic-acid based IQAC, DMS quaternised induced in all animals moderate to severe erythema and very slight to slight edema. Focal eschar was noted for two animals on study day 7, and desquamation was noted for all animals on study days 7 through 14. Very slight to slight erythema was still present for all animals at study termination (study day 14). Mean scores from gradings at 24, 48 and 72 hours after removal of the test material for erythema were for all animals >/=2.3 but < 4. Edema were less severe. Inflammation persisted to the end of the observation period (14 days) in all three animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001-06-14 to 2001-07-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Guideline 11 Nousan No. 6283 (October 1, 1999); First Revision: 12 Nousan 8628 (December 6, 2000)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products Inc. Denver, PA, USA
- Age at study initiation: Young adult
- Weight at study initiation: 2577 to 2758 grams
- Housing: individual housing in suspended wire mesh cages
- Diet: 150 g/day, standard laboratory rabbit diet PMI Nutrition International, Inc. Certified Rabbit LabDiet® 5322
- Water: ad libitum, municipal water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66-77
- Humidity (%): 48-80
- Air changes (per hr): no data
- Photoperiod: 12 hour light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its one control. The test article was introduced into the conjunctival sac of one eye, the untreated eye serving as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml
- Concentration: The test article was applied unchanged as received
Duration of treatment / exposure:
Eyes were not rinsed after treatment.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no washing was done

SCORING SYSTEM: in accordance with Draize, as published in the guidelines in Subsection F. Hazard Evaluation: Human and Domestic Animals distributed in 1984 and the EPA-OPPTS Health Effects Test Guidelines (1998).

TOOL USED TO ASSESS SCORE: A direct ophthalmoscope was used during these observations to examine the corneal tissue. In addition, both eyes were further examined at 24 hours and at all subsequent observations with sodium fluorescein.

PREPARATION and SELECTION of ANIMALS: Both eyes of all rabbits were examined for ocular abnormalities prior to initiation of dosing. The pre-initiation examination included the use of sodium fluorescein and a direct ophthalmoscope for detection of corneal abnormalities. Only rabbits with no
pre-existing ocular abnormalities were assigned to study.
Both eyes of all rabbits were examined macroscopically for ocular irritation in accordance with the method of Draize at approx. 1, 24, 48, 72 h, 4, 7, 14 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
other: #1, #2
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: day 14
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: day 21
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal: #1, #2
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
fully reversible within: 17 days
Irritant / corrosive response data:
Positive corneal, iridal and conjunctival findings were noted for all animals. Corneal neovascularization was noted for two animals on study days 7 through 14 or 17. Iridal irritation subsided by study day 7, and corneal and conjunctival irritation completely subsided by study termination (study day 21).
The Maximum Average Score for the test substance was 50.3 at 48 hours post-instillation.
Other effects:
There were no deaths or remarkable body weight changes during the study period.

Irritant/corrosive response data for each animal at each observation time

Score at time point / Reversibility

Cornea opacity

Cornea - Area  involved

Iris

Conjunctivae

Redness

Conjunctivae

Chemosis

Conjunctivae

Discharge

Fluorescein test (% of cornea retaining stain)

Max. score: 4

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

Max.: 100 %

1 hour

1/1/1

1/1/1

1/1/1

2/2/1

3/2/3

3b/3b/3b

no

24 hours

1/1/1

4/4/1

1/1/0

3/2/2

4/3/3

3b,p/3b,p/3b,p

yes 75/65/10

48 hours

2/2/1

4/4/1

1/1/0

3/3/2

4/4/3

3b,p/3b/3b,p

yes 65/45/5

72 hours

2/2/1

4/3/1

1/1/0

3/2/2

3/4/2

3b,p/3b/1b,p

yes 50/30/0

4 days

2/2/1

4/3/1

1/1/0

3/2/2

3/3/2

2b,p/2b/1b,p

yes 50/20/0

7 days

2k/1k/0

2/1/0

0/0/0

2/2/1

2/2/1

1b/0/0

yes 15/5/0

10 days

1k/1k/0

1/1/0

0/0/0

1/2/1

1/1/1

0/0/0

yes 0/0/0

14 days

1k/1k/0

1/1/0

0/0/0

1/1/0

0/1/0

0/0/0

yes 0/0/0

17 days*

0/1k/-

0/1/-

0/0/-

0/1/-

0/0/-

0/0/-

yes 0/0/-

21days**

-/0/-

-/0/-

-/0/-

-/0/-

-/0/-

-/0/-

yes -/0/-

* only the two animals with responses at 14 days examined

** only the animal with responses at 17 days examined

b = clear discharge, p = purulent discharge in conjunctival sac, k = corneal neovascularization

Interpretation of results:
Category 2A (irritating to eyes)
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
Interpretation is based on effects on the cornea, iris and conjunctiva calculated as mean scores following grading at 24, 48 and 72 hours after instillation of the test material, in consideration of reversibility. Slight to moderate effects of cornea and iris were observed and moderate to severe conjunctivae and chemosis scores. All symptoms were fully reversible within 21 days.
Executive summary:

In a primary eye irritation study according to US Guideline EPA OPPTS 870.2400 (1998), OECD Guideline 405 (1987), EU Guideline B.5 (1992) and Japanese Guideline Nousan No. 6283 (1999), revised Nousan 8628 (2000), 0.1 ml of oleic-acid based IQAC, DMS quaternised (according to sponsors information: 80 % of CAS No. 72749-55-4, 15 % of CAS No. 9004-96-0 (Oleic acid, ethoxylated) and 5 % of CAS No. 25322-68-3 (Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated)) was instilled into the conjunctival sac of three White New Zealand rabbits. The eyes were not rinsed after substance application. Animals then were observed for 21 days. Irritation was scored by the method of Draize.

Positive corneal, iridal and conjunctival findings were noted for all animals. Corneal neovascularization was noted for two animals on study days 7 through 14 or 17. Iridal irritation subsided by study day 7, and corneal and conjunctival irritation completely subsided by study termination (study day 21).

The test substance induced a maximum mean total score of 50.3 (maximum possible mean total score of 110) at 48 hours post-instillation. Mean scores following grading at 24, 48 and 72 hours after instillation of the test material for corneal opacity were >/= 1but < 3, for iritis >/= 1 but < 1.5 and for conjunctival redness and oedema >/= 2. All effects were completely reversible in all animals within 21 days.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The degree of irritation / corrosivity was variable and most likely depends on undeclared chemical impurities in some of the test substances.

For the eye effects of an oleic-acid based IQAC, DMS quaternised, with by-products of approx. 10 % of nonylphenol ethoxilate, 1 % of free amine and 0.5 % of hydrogen peroxide, the corrosive effects can be attributed to the alkyl phenol, which causes severe damage to eyes. Though this substance contains the highest content of IQACs tested, its eye damaging potential is untypical for the substance class and can be rationalised as being due to its by-products.

Studies performed according to US Federal Hazardous Substances Act (FHSA) pointing to skin corrosion and serious eye damage had significant deficiencies in methodology regarding time of exposure, post-exposure observation time and reporting and are therefore not regarded as reliable data. In essence, the substance class is irritating to skin and eyes.


Justification for selection of skin irritation / corrosion endpoint:
Data from a GLP compliant study with reliability 1, according to acutal guidelines.

Justification for selection of eye irritation endpoint:
Data from a GLP compliant study with reliability 1, according to acutal guidelines.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation: Cat. 2 according to GHS/CLP; R38, Irritating to Skin according to Directive 67/548/EEC

Eye irritation: Cat. 2 according to GHS/CLP; R36, Irritating to Eyes according to Directive 67/548/EEC