Benzene, 1,1'-oxybis-, tetrapropylene derivs., sulfonated, sodium salts

Endpoint summary

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 for cross-reference:

reference to same study

Reason / purpose for cross-reference:

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 or test system 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 for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Remarks:

Not specified in report

Qualifier:

according to guideline

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	f
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).