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Description of key information

Very slight dermal irritation was noted in the dermal irritation study.

Dowfax 8390 powder is much more irritating to the eye than to the skin. In the key eye irriation study, all effects but conjunctival redness were reversible within 21 days. This finding is supporte by two studies also showing persisting eye effects after 21 days.

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:
supporting study
Study period:
1991
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 404 (Acute Dermal Irritation / Corrosion)
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 test system and environmental conditions:
Three New Zealand White rabbits were supplied by David Percival Ltd., Moston, Sandbach, Cheshire, U.K. At the start of the study the animals weighed 2.50 - 2.84 kg and were approximately twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bistol ) was allowed throughout the study. The animal room was maintained at a temperature of 17 - 19°C and relative humidity of 51 - 60%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
other: solid moistened with distilled water
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 h
Observation period:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours
Number of animals:
3
Details on study design:
On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/ flank area using veterinary clippers. Only
animals with a healthy intact epidermis by gross observation were selected for the study.

On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.59 of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with
cotton wool soaked in distilled water. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal o f the Safety of Chemicals in Foods, Drugs and Cosmetics".
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 h
Score:
0.3
Max. score:
8
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Very slight erythema was noted at all treated skin sites one hour after patch removal and continued to be noted at two treated skin sites at the
24-hour observation and at one treated skin site at the 48-hour observation. Very slight oedema was also noted at one treated skin site one hour
after patch removal. All treated skin sites appeared normal at the 72-hour observation.
Other effects:
None

The test material, DOWFAX 8390, produced a primary irritation index of 0.3 and was classified as a SLIGHT IRRITANT to rabbit skin according to the

Draize classification scheme. No corrosive effects were noted.

The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as NONIRRITANT to rabbit skin. No symbol and risk phrase are therefore required.

Interpretation of results:
other: not classifiable
Remarks:
Criteria used for interpretation of results: other: EU GHS
Conclusions:
The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as NONIRRITANT
to rabbit skin. No symbol and risk phrase are therefore required.
Executive summary:

DOWFAX 8390 Surfactant is a 35% solution in water of mono- and dihexadecyl diphenyloxide mono- and disulfonate, sodium salts. The dermal irritation

potential of a powdered sample was evaluated in rabbits; the purity of the test material was 91.6%. The study conformed to OECD Guideline Number 404 and Method B4 in commission Directive 84/449/EEC.

A quantity of 0.5 g of the test material was moistened with 0.5 ml of distilled water and applied under a gauze patch to the intact skin on the back of three New

Zealand white rabbits. The patch was held in contact with the skin by a bandage for 4 hours; subsequently the patch, bandage and any residual test material were

removed from the animals. The skin was examined for evidence of primary irritation at 1, 24, 48 and 72 hours after removal of the patches. very slight erythema was noted at the treatment site of all animals one hour after patch removal; the erythema persisted in two animals at the 24-hour observation and in one animal at the 48-hour observation. very slight edema was noted at the treatment site of one animal only at the 1-hour observation. The treatment site of all animals appeared normal at the 72-hour observation. No corrosive effects were noted. The primary irritation index was 0.3 on a 1 to 8 scale and was classified as a slight irritant to rabbit skin according to the Draize classification scheme.

The results of this study indicate that DOWFAX 8390 Surfactant does not require a label as a skin irritant according to the criteria of the commission of the

European communities (Annex VI of council Directive 67/548/EEC).

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:
supporting study
Study period:
1987
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 eye irritation test included instillation of an aliquot of 0.1 g of the test material into each conjunctival sac of a male New Zealand White rabbit.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Male New Zealand White rabbit
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
The right eye was washed after a 30 second exposure and the right eye was washed after 1 hour.
Observation period (in vivo):
Eyes were examined up to 21 days after instillation.
Number of animals or in vitro replicates:
1
Details on study design:
The eyes of the rabbit were established as being without defects or irritation 24 hours prior to study initiation. The test material (0.1 g or 0.1 ml) was instilled into the conjunctival sac of the eyes. The right eye was washed for two minutes with tap water after a 30 second exposure. The left eye was washed after a 1 hour exposure. At various time intervals both eyes were examined for conjunctival irritation, corneal injury and irritation of th iris. The eyes were anesthetized if moderate pain was observed or anticipated. A drop of 5% aqueous fluorescein stain was used to aid in assessing corneal injury.
Irritation parameter:
other: conjunctiva 30 s
Basis:
animal #1
Time point:
other: 1, 24 and 48 h
Score:
4
Max. score:
6
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: conjunctiva 30 s
Basis:
animal #1
Time point:
other: 72 h
Score:
3
Max. score:
6
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: conjunctiva 30 s
Basis:
animal #1
Time point:
other: 7, 14 and 21 days
Score:
1
Max. score:
6
Reversibility:
other: not applicable
Irritation parameter:
other: cornea 30 s
Basis:
animal #1
Time point:
other: 1, 24 and 48 h
Score:
4
Max. score:
6
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: After staining
Irritation parameter:
other: cornea 30 s
Basis:
animal #1
Time point:
other: 72 h
Score:
3
Max. score:
6
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: After staining
Irritation parameter:
other: cornea 30 s
Basis:
animal #1
Time point:
other: 7 days
Score:
2
Max. score:
6
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: After staining
Irritation parameter:
other: cornea 30 s
Basis:
animal #1
Time point:
other: 14 and 21 days
Score:
1
Max. score:
6
Reversibility:
other: not applicable
Remarks on result:
other: After staining
Irritation parameter:
other: iris 30 s
Basis:
animal #1
Time point:
other: 1, 24 and 48 h
Score:
2
Max. score:
6
Reversibility:
fully reversible within: 72 h
Irritation parameter:
other: iris 30 s
Basis:
animal #1
Time point:
other: 72 h, 7, 14 and 21 days
Score:
1
Max. score:
6
Reversibility:
other: not applicable
Irritation parameter:
other: conjunctiva 1 h
Basis:
animal #1
Time point:
other: 1, 24, 48, and 72 h and 7 days
Score:
4
Max. score:
6
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
other: conjunctiva 1 h
Basis:
animal #1
Time point:
other: 14 and 21 days
Score:
3
Max. score:
6
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
other: cornea 1 h
Basis:
animal #1
Time point:
other: 1, 24, 48 and 72 h and 7 days
Score:
4
Max. score:
6
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: After staining
Irritation parameter:
other: cornea 1 h
Basis:
animal #1
Time point:
other: 14 and 21 days
Score:
3
Max. score:
6
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: After staining
Irritation parameter:
other: iris 1 h
Basis:
animal #1
Time point:
other: 1, 24, 48 and 72 h
Score:
3
Max. score:
6
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
other: iris 1 h
Basis:
animal #1
Time point:
other: 7 and 21 days
Score:
2
Max. score:
6
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
other: iris 1 h
Basis:
animal #1
Time point:
other: 14 days
Score:
1
Max. score:
6
Reversibility:
other: not applicable
Irritant / corrosive response data:
The single exposure resulted in moderate discomfort, moderate conjunctival redness and swelling, moderate reddening of the iris, and
moderate corneal injury. Ocular effects, which included corneal injury, were absent at day 14 in the eye washed immediately after exposure. Ocular effects were still present at 21 days in the eye where washing was delayed for one hour and included slight conjunctival irritation, slight corneal injury, and very slight reddening of the iris. Ophthalmic anesthetic was administered to alleviate discomfort experienced by the rabbit.
Other effects:
None

None

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
A single exposure of New Zealand White rabbit eyes to the test material resulted in moderate discomfort, moderate conjunctival redness and swelling , moderate reddening of the iris, and moderate corneal injury. Ocular effects , which included corneal injury , were absent at day 14 of the test in the eye washed immediately after exposure. Ocular effects were still present at day 21 in the eye washed one hour after exposure and included slight conjunctival irritation, slight corneal injury, and very slight reddening of the iris.
Executive summary:

A single exposure of New Zealand White rabbit eyes to the test material, XU-40341.00 DOWFAX 8390, powder form, resulted in moderate discomfort, moderate conjunctival redness and swelling , moderate reddening of the iris, and moderate corneal injury. Ocular effects, which included corneal injury, were absent at day 14 of the test in the eye washed immediately after exposure. Ocular effects were still present at day 21 in the eye washed one hour after exposure and included slight conjunctival irritation, slight corneal injury, and very slight reddening of the iris. Ophthalmic anesthetic was administered to alleviate discomfort experienced by the rabbit.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Dowfax 8390 powder is much more irritating to the eye than to the skin. In the key eye irritation study, all effects but conjunctival redness were reversible within 21 days. This finding is supported by two studies also showing persisting eye effects after 21 days. In the studies, 1/1 rabbit eyes tested with 91.6% a.i. and 1/3 rabbit eyes tested with 37% a.i. Dowfax 8390 test material showed persistent damage at Day 21. Therefore, Category 1 eye classification is appropriate. The remaining two studies with Dowfax 8390 liquids and dilutions show CLP category 2 eye damage.


Justification for selection of skin irritation / corrosion endpoint:
A quantity of 0.5 g of the test material was moistened with 0.5 ml of distilled water and applied under a gauze patch to the intact skin on the back of three New Zealand white rabbits. The patch was held in contact with the skin by a bandage for 4 hours; subsequently the patch, bandage and any residual test material were removed from the animals. The skin was examined for evidence of primary irritation at 1, 24, 48 and 72 hours after removal of the patches. very slight erythema was noted at the treatment site of all animals one hour after patch removal; the erythema persisted in two animals at the 24-hour observation and in one animal at the 48-hour observation. very slight edema was noted at the treatment site of one animal only at the 1-hour observation. The treatment site of all animals appeared normal at the 72-hour observation. No corrosive effects were noted. The primary irritation index was 0.3 on a 1 to 8 scale and was classified as a slight irritant to rabbit skin according to the Draize classification scheme.

Similarly in a study of an aqueous formulation (percent active not stated but believed to be 37%), slight, immediate oedema and erythema resulted from contact with the test substance; the erythema persisted for two days in two of the animals. In a study of a 10% formulation there was no evidence of skin irritation observed.

Justification for selection of eye irritation endpoint:
In the key study of the powder, a single exposure resulted in moderate discomfort, moderate conjunctival redness and swelling , moderate reddening of the iris, and moderate corneal injury. Ocular effects, which included corneal injury, were absent at day 14 of the test in the eye washed immediately after exposure. Ocular effects were still present at day 21 in the eye washed one hour after exposure and included slight conjunctival irritation, slight corneal injury, and very slight reddening of the iris. Ophthalmic anesthetic was administered to alleviate discomfort experienced by the rabbit. The findings of irriversible eye effects are supported by two more studies showing persisting eye effects after 21 days.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

The results of the skin irritation study indicate that DOWFAX 8390 Surfactant does not require a label as a skin irritant according to the criteria of the EU CLP.

The results of the eye irritation studies indicate that DOWFAX 8390 Surfactant should be labeled as Category 1 eye irritant according to the criteria of the EU CLP Regulation (EC) No. 1272/2008.

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