Registration Dossier

Administrative data

Description of key information

2 studies on skin irritation, supported by data from two other category members are available on DOWFAX 2A1.
4 in vivo studies and 1 in vitro BCOP assay on eye irritation are available on the registered substance.

Additional eye irritation studies are available on other category members (see the Justification Document) that show similar, highly irritating behaviour of this class of materials.

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guideline/s and GLP, but the report contains sufficient data for interpretation of study results.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The skin irritation test included topical application of 0.1 ml of neat Dowfax 2A1 to the ear, and 0.5 ml to intact and abraded skin on the abdomen of a male New Zealand White (NZW) rabbit. The animal was bandaged for 24 hours after application of the test material to provide occlusion and prevent grooming of the application site. Twenty four hours after application the bandage was removed and the application sites were
graded. Five consecutive daily doses of Dowfax 2A1 were applied to the intact abdominal skin, and the apex of the left pinna, and three consecutive daily applications to the abraded abdominal site. Observations were recorded up to 72 hours after the final dose.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Male New Zealand White rabbit.
Type of coverage:
other: ear- open; intact and abraded abdomen- occluded
Preparation of test site:
other: shaved intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml- ear
0.5 ml- intact and abraded abdomen
Duration of treatment / exposure:
Five consecutive daily doses of Dowfax 2A1 were applied to the intact abdominal skin, and the apex of the left pinna, and three consecutive daily
applications to the abraded abdominal site.
Observation period:
Twenty four hours after application the bandage was removed and the application sites were graded. Observations were recorded out to 72 hours after the last dose.
Number of animals:
1
Details on study design:
The skin irritation test included topical application of 0.1 ml of neat Dowfax 2A1 to the ear, and 0.5 ml to intact and abraded skin on the abdomen of a male New Zealand White (NZW) rabbit. The abdomen of the rabbit was shaved with a straight razor at least three days prior to test initiation. The animal was bandaged for 24 hours after application of the test material to provide occlusion and prevent grooming of the application site. Twenty four hours after application the bandage was removed and the application sites were graded. Five consecutive daily doses of Dowfax 2A1 were applied to the intact abdominal skin, and the apex of the left pinna, and three consecutive daily applications to the abraded abdominal site. The study was terminated 72 hours after the final dose.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1d, 2d, 3d, 4d, 5d
Score:
1
Max. score:
6
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
ear/all timepoints/ Non-Draize test
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1d, 2d, 3d, 4d, 5d
Score:
1
Max. score:
6
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
ear/all timepoints/Non-Draize test
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1d, 2d, 3d, 4d
Score:
1
Max. score:
6
Reversibility:
not specified
Remarks on result:
not determinable
Remarks:
Intact abdomen/ Non-Draize test
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: day 5
Score:
2
Max. score:
6
Reversibility:
not specified
Remarks on result:
not determinable
Remarks:
Intact abdomen/Non-Draize test
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1d, 2d, 3d, 4d, 5d
Score:
1
Max. score:
6
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
abraded abdomen/ all timepoints/Non-Draize test
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: day 1
Score:
1
Max. score:
6
Reversibility:
not specified
Remarks on result:
not determinable
Remarks:
abraded abdomen/Non-Draize test
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 2d, 3d, 4d, 5d
Score:
2
Max. score:
6
Reversibility:
not specified
Remarks on result:
not determinable
Remarks:
abraded abdomen/Non-Draize test
Irritant / corrosive response data:
No irritation was observed on the ear. Very slight erythema was observed at the intact site after the last application. Very slight erythema was observed at the abraded site on test day two through test day five. The study was terminated 72 hours after the final dose.
Other effects:
The animal survived the test period. No clinical signs indicative of systemic toxicity were observed.

None

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
No irritation was observed on the ear. Very slight erythema was observed at the intact site after the last application. Very slight erythema was observed at the abraded site on test day two through test day five. The study was terminated 72 hours after the final dose.
Executive summary:

A sample of Dowfax 2A1 was submitted by Specialty Chemicals, The Dow Chemical Company, Midland, MI for evaluation of acute oral and dermal toxicity and skin and eye irritation. This compound is a potential surfactant in cleaning solutions.

The skin irritation test included topical application of 0.1 ml of neat Dowfax 2A1 to the ear, and 0.5 ml to intact and abraded skin on the abdomen of a male New Zealand White (NZW) rabbit. Five consecutive daily doses of Dowfax 2A1 were applied to the intact abdominal skin, and the apex of the left pinna, and three consecutive daily applications to the abraded abdominal site. No irritation was observed on the ear. Very slight erythema was observed at the intact site after the last application. Very slight erythema was observed at the abraded site on test day two through test day five. The study was terminated 72 hours after the final dose. Based on the outcomes on the intact ear and abdomen rabbit skin, it was concluded that Dowfax 2A1 has only minimal skin irritation potential.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Remarks:
Not specified in report
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Remarks:
Not specified in report
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source: Charles River Deutschland, Kisslegg, Germany
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.

Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 15.5 – 21.5°C), a relative humidity of 30-70% (actual range: 51 - 84%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.

Accommodation
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
Water
Free access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7, 14 and/or 21 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.
Number of animals or in vitro replicates:
3
Details on study design:
All available data relevant to the potential eye irritation/corrosivity of the substance was taken into account prior to start of the test.

No severe effects were to be expected since the in-vitro bovine eye (BE) assay (Notox project 380609) indicated that moderate irritation may be expected after acute eye exposure to the substance.

This eye irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner two weeks later, after considering the degree of eye irritation observed in the first animal.

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.

Each animal was treated by instillation of 0.1 ml the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.

Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. When considered necessary, this procedure was repeated to assess recovery. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Observations
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation) and at termination.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7, 14 and/or 21 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

The results were evaluated according to the EC criteria for classification and labeling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Communities).
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
7 d
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
7 d
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
7 d
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
other: Conjunctivae (Discharge)
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks:
1/3 animals
Remarks on result:
probability of severe irritation
Irritation parameter:
other: Conjunctivae (Discharge)
Basis:
mean
Time point:
48 h
Score:
1.66
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: not fully reversible within 21 days
Irritation parameter:
other: Conjunctivae (Discharge)
Basis:
mean
Time point:
72 h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: not fully reversible within 21 days
Irritation parameter:
other: Conjunctive (Discharge)
Basis:
mean
Time point:
21 d
Score:
0.5
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: n=2, one of the animals was completely cleared by 14 days therefore iritation scores were not conducted on day 21
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
7 d
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
7 d
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
14 d
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
7 d
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 7d, 14d, 24d
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 7d, 14d
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
21 d
Score:
1
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 7d, 14d
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Instillation of 0.1 ml of the test substance resulted in effects on the cornea, iris and conjunctivae. Corneal injury was seen as opacity (maximum grade 1 or 2) and epithelial damage (maximum 90% of the corneal area). As a result of the corneal injury, pannus (neovascularisation of the cornea) was apparent 7 or 14 days after instillation in two animals. The corneal injury had resolved within 14 or 21 days and persisted in one animal until termination. Iridial irritation (grade 1) was observed which had completely resolved within 24 hours or 7 days.

Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 14 or 21 days in two animals and persisted in one animal until termination. Reduced flexibility of the eyelids was observed in one animal after 48 and 72 hours.
Other effects:
Colouration / Remnants
No staining of (peri) ocular tissues by the test substance was observed.

Toxicity / Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

 Individual scores

 

Cornea

Iris

Conjunctivae

 

Time after dosing

Opacity

Area

Fluor area (%)

 

Redness

Chemosis

Discharge

Comments

1 hour

1

2

1

2

4

3

24 hours

1

3

90

1

3

3

2

-

48 hours

2

1

0

3

2

1

72 hours

2

1

50

1

3

1

1

f

7 days

1

1

25

0

2

1

0

p

14 days

0

0

0

0

0

0

0

-

 

 

 

 

 

 

 

 

 

1 hour

1

1

1

2

3

3

 -

24 hours

1

3

90

1

3

3

2

-

48 hours

1

3

1

3

3

2

72 hours

1

2

50

1

2

2

1

-

7 days

1

1

25

0

1

1

0

-

14 days

0

0

0

0

1

0

0

p

21 days

0

0

0

0

0

0

0

 

 

 

 

 

 

 

 

 

1 hour

1

2

1

2

4

3

24 hours

1

3

90

0

2

3

2

-

48 hours

1

3

0

2

3

2

72 hours

1

2

80

0

2

2

2

-

7 days

1

1

70

0

2

1

1

-

14 days

1

1

10

0

2

1

1

-

21 days

1

1

5

0

1

0

1

-

Fluor area (%): green staining (percentage of total corneal area) after fluorescein treatment.

 

Comments:

f. = Reduced elasticity of the eyelids.

p. = Pannus (neovascularisation of the cornea)

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the degree and persistence of the corneal injury as seen in one animal, it was concluded that ocular corrosion had occurred by instillation of DOWFAX* 2A1 SURFACTANT SOLUTION into the rabbit eye.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), DOWFAX* 2A1 SURFACTANT SOLUTION should be labelled as: risk of serious damage to eyes (R 41).
Executive summary:

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B.5, "Acute Toxicity - Eye irritation", OECD No.405, "Acute Eye Irritation/Corrosion" and US EPA, OPPTS 870.2400, Acute Eye Irritation, EPA 712-C-98-195, August 1998.

Single samples of 0.1 ml of DOWFAX* 2A1 SURFACTANT SOLUTION were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7, 14 and/or 21 days after instillation.

Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae. Corneal injury was seen as opacity (maximum grade 1 or 2) and epithelial damage (maximum 90% of the corneal area). As a result of the corneal injury, pannus (neovascularisation of the cornea) was apparent 7 or 14 days after instillation in two animals. The corneal injury had resolved within 14 or 21 days and persisted in one animal until termination.

Iridial irritation (grade 1) was observed which had completely resolved within 24 hours or 7 days. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 14 or 21 days in two animals and persisted in one animal until termination. Reduced flexibility of the eyelids was observed in one animal after 48 and 72 hours.

Based on the degree and persistence of the corneal injury as seen in one animal, it was concluded that ocular corrosion had occurred by instillation of DOWFAX* 2A1 SURFACTANT SOLUTION into the rabbit eye.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), DOWFAX* 2A1 SURFACTANT SOLUTION should be labelled as: risk of serious damage to eyes (R 41).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

This substance has been tested in 2 skin irritation assays. The key study for this endpoint is the repeated application assay conducted in 1993 that demonstrated minimal irritation, but not sufficient to warrant classification. Similar (minimal) irritation potential was seen with the other ADPODS category members tested for skin irritation potential (refer to full ADPODS category justification document).

Eye irritation:

The available data indicate that this substance is capable of causing irreversible damage to the eyes.


Justification for selection of skin irritation / corrosion endpoint:
Acceptable study to assess skin irritating properties of the REACH registered substance

Justification for selection of eye irritation endpoint:
OECD Guideline, GLP study

Effects on skin irritation: Not irritating

Effects on eye irritation: Irreversible damage

Justification for classification or non-classification

No classification is required for skin irritation. For eye irritation, classification as irreversible damage to the eyes is applied (Category 1, according to CLP).