Sodium 1,4-diisodecyl sulphonatosuccinate

Endpoint summary

Description of key information

Irritation studies for skin and eye were conducted according to Draize method in rabbits with a test item containing 63-67% active ingredient. Scoring according to Draize demonstrated  mean 24-72h scores of 2/4 and 1.1/4 for skin erythema and edema, respectively. For the eye, mean 24-72h scores were 1.4/4 for cornea, 1/2 for iris, 3/3 for conjuctiva and 2.6/4 for chemosis. Changes were still observed after the 72h period, but were reversible within 14 days. Based on the scores, the substance was considered irritating for skin (CLP category 2) and, in combination with various eye findings which were not reversible, causing severe eye damage (CLP category 1).

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:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to GLP and valid testing guidelines, therefore it is considered relevant, adequate and reliable for classification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, conventional breeding
- Age at study initiation: Ca. 3-5 months
- Weight at study initiation: 2.1-2.5 kg
- Fasting period before study: Not provided
- Housing: Individual cages
- Diet (e.g. ad libitum): Altromin 2123 Haltungsdiät- Kaninchen, Altromin GmbH, Lage/Lippe, ad libitum as well as hay (ca. 15 g täglich)
- Water (e.g. ad libitum): Deionized, chlorinated water from automatic drinkers, ad libitum
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

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:

Not provided

Observation period:

72 hours and after this period additional observations till 21 days for the positive findings

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: In the dorsal region of the trunk
- % coverage: Not provided
- Type of wrap if used: An adhesive patch (2.5 x 2.5 cm) with cellulose coating (Custom-made by Fa. Beiersdorf AG, Hamburg) was fixed to the prepared skin site. Under these patches 0.5 mL of the undiluted test substance was applied. Subsequently, the area was covered with a semi-occlusive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Erythema and eschar formation as well as edema formation were evaluated numerically. All other skin changes were recorded.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Irritant / corrosive response data:

One to 48 hours after removal of the patch, the animals showed barely perceptible to clearly defined erythema and partially very slight to slight edema .
72 hours after application partially clearly defined to moderate erythema and very slight edema were observed. In one animal the reddening was not assessable due to discoloration.
7 days after application no irritation was observed. 14 to 21 days after application, one animal showed barely perceptible to moderate erythema. The irritations 24 hours to 14 days after patch removal partially were dry, brittle, fine or large flaking and parchment-like skin surface, fissured skin, induration, eschar formation and large-area yellow or light-brown skin discoloration.

Table 2. Individual findings

Time after patch removal	1h			24h			48h			72h			7d			14d			21d
Animal No.	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3
Erythema and eschar formation	2	1	1	2	2	1	2	2	2	3	*	2	0	0+	0+	0	3	0	0	1	0
Edema	2	1	1	0	2	2	0	2	2	0	1	1	0	0	0	0	0	0	0	0	0
Skin surface: -dry, brittle - scaly -large scaly -indurated -parchment-like
							x			x			x
													x
													x
							x			x	x	x		x	x
														x	x		x	x
Deeply fissured skin										x
Eschar formation										x
Skin discoloration -large area yellow -large area light-brown
					x			x	x		x	x		x	x

* due to discoloration not assessable + judged for the discoloration

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on this study and taking into account any other skin changes, the test item is classified as irritant according to the classification criteria of Directive 83/467/EEC and the Hazardous Substances Regulation and is labeled R 38- irritating to the skin.

Executive summary:

Three New Zealand White rabbits were shaved in an area of ca. 25 cm²_,dorsal of the trunk , approximately 24 hours before the start of the study. An adhesive patch (2.5 x 2.5 cm) with cellulose coating (Custom-made by Fa. Beiersdorf AG, Hamburg) was fixed to the prepared skin site. Under these patches 0.5 mL of the undiluted test item was applied. Subsequently, the area was covered with a semi-occlusive bandage.

Observations were performed 30-60 minutes and 24, 48 and 72 hours after removal of the patch. At 72 hours there were still findings , thus additional observations were done at 7, 14 and 21 days after patch removal.
Erythema , eschar formation and edema were numerically scored. Mean 24-72h scores were 2/4 for erythema and 1.1/4 for edema. All other skin changes were recorded.

One to 48 hours after removal of the patch, the animals showed barely perceptible to clearly defined erythema and partially very slight to slight edema . 72 hours after application partially clearly defined to moderate erythema and very slight edema were observed. In one animal the reddening was not assessable due to discoloration. 7 days after application no irritation was observed. 14 to 21 days after application, one animal showed barely perceptible to moderate erythema. The irritations 24 hours to 14 days after patch removal partially were dry, brittle, fine or large flaking and parchment-like skin surface, fissured skin, induration, eschar formation and large-area yellow or light-brown skin discoloration.
Based on this study and taking into account any other skin changes the test item is classified as irritant according to the classification criteria of Directive 83/467/EEC and the Hazardous Substances Regulation and is labeled R 38- irritating to the skin.

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:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to GLP and valid testing guidelines, therefore it is considered relevant, adequate and reliable for classification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, conventional breeding
- Age at study initiation: Ca. 3-5 months
- Weight at study initiation: 2.3-3.0 kg
- Fasting period before study: Not provided
- Housing: Individual cages
- Diet (e.g. ad libitum): Altromin 2123 Haltungsdiät- Kaninchen, Altromin GmbH, Lage/Lippe, ad libitum as well as hay (ca. 15 g täglich)
- Water (e.g. ad libitum): Deionized, chlorinated water from automatic drinkers, ad libitum
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours (1, 24, 48 and 72h after application) and 14 days (7 and 14 days after application) in addition for the positive findings

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with physiological saline solution
- Time after start of exposure: 24 h after application and at all observation points


SCORING SYSTEM: See under “Any other information on material and methods incl. tables”

TOOL USED TO ASSESS SCORE: fluorescein (at 24 and 72 hours and for positive findings at 7 and 14 days))

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2.6

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

One to 72 hours after application, the conjunctivae showed a diffuse bright red color and a very clear swelling to a swelling with more than half-closed lids. The iris was red, the cornea showed diffuse opacity areas to easily discernible translucent areas. 7 Days after application significant hyperemia of some blood vessels to diffuse crimson-red colored conjunctivae and very slightly to significantly swollen conjunctivae were observed. One animal showed scattered areas of opacity of the cornea. 14 Days after application all signs of irritation were reversible. One hour to 7 days after application, the irritation was accompanied with a clear, colorless or white mucous discharge. One animal showed 24 hours to 7 days after application partially white discolorations, bleeding and detachments of parts of the conjunctivae and nictitating membrane.

Table 2. Individual findings

Time after application	1h			24h			48h			72h			7d			14d
Animal No.	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3
Conjunctivae chemosis	3	3	2	3	2	2	4	2	3	4	2	1	2	1	1	0	0	0
Conjunctivae redness	3	3	3	3	3	3	3	3	3	3	3	3	2	1	1	0	0	0
Iris	1	1	1	1	1	1	1	1	1	1	1	1	0	0	0	0	0	0
Cornea opacity	1	0	1	1	1	2	2	1	2	2	1	1	1	0	0	0	0	0
Fluorescein Test*				4	4	3				3	1	1	1	0	0	0	0	0
Eye discharge
- clear, colorless	x	x	x
-white, mucous				x	x	x	x	x	x	x	x	x
Conjunctivae
- white discoloration				x			x			x			x
- detachment of part							x			x			x
- with bleeding													x
Iris
-reddened	x	x	x	x	x	x	x	x	x	x	x	x

  *Indicated is the area of whitening of the corneal surface under UV light after instillation of a drop of fluorescein sodium (0.01%)

0= no whitening

1= punctiform to 1/4

2= more than 1/4 to 1/2

3= more than 1/2 to 3/4

4= more than 3/4 to 4/4

 

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on this study and taking into account any other eye changes the test item is classified as irritant according to the classification criteria of Directive 83/467/EEC and the Hazardous Substances Regulation and is labeled R 36- irritating to the eyes.

Executive summary:

Three New Zealand White rabbits underwent a single application in the conjunctival sac of the left eye of 0.1 mL of the test item. The untreated eye served as a control. 24 Hours after administration of the test item as well as to all other assessment time points at which, the treated eyes still showed discharges or in which a corneal examination with fluorescein sodium solution was done, the treated eyes were thoroughly washed with physiological saline solution (ca. 37°C).
The assessments of the eyes were made 1, 24, 48 and 72 hours after instillation. In addition the cornea was also examined under UV light, after instillation of a drop of fluorescein sodium solution, at the assessment time points 24 and 72 hours. Damage to the cornea, iris and conjunctivae were scored numerically. Mean 24 -72h scores were 1.4/4 for cornea, 1/2 for iris, 3/3 for conjuctiva and 2.6/4 for chemosis. All other changes were recorded. Because eye effects were still present at 72 hours, an additional assessment was carried out after 7 and 14 days.
One to 72 hours after application, the conjunctivae showed a diffuse bright red color and a very clear swelling to a swelling with more than half-closed lids. The iris was red, the cornea showed diffuse opacity areas to easily discernible translucent areas. 7 Days after application significant hyperemia of some blood vessels to diffuse crimson-red colored conjunctivae and very slightly to significantly swollen conjunctivae were observed. One animal showed scattered areas of opacity of the cornea. 14 Days after application all signs of irritation were reversible. One hour to 7 days after application, the irritation was accompanied with a clear, colorless or white mucous discharge. One animal showed 24 hours to 7 days after application partially white discolorations, bleeding and detachments of parts of the conjunctivae and nictitating membrane.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a key study for skin irritation, three New Zealand White rabbits were treated with registered substance under occlusion with 0.5 mL containing 63 -67% active ingredient of the test item on the skin for 24 hours (Kreiling and Jung, 1988a). Observations were performed 30-60 minutes and 24, 48 and 72 hours after removal of the patch. Mean 24 -72h scores were 2/4 for erythema and 1.1/4 for edema. At 72 hours there were still findings, thus additional observations were done at 7, 14 and 21 days after patch removal. One to 48 hours after removal of the patch, the animals showed barely perceptible to clearly defined erythema and partially very slight to slight edema . 72 hours after application partially clearly defined to moderate erythema and very slight edema were observed. In one animal the reddening was not assessable due to discoloration. 7 days after application no irritation was observed. 14 to 21 days after application, one animal showed barely perceptible to moderate erythema. The irritations 24 hours to 14 days after patch removal partially included dry, brittle, fine or large flaking and parchment-like skin surface, fissured skin, induration, eschar formation and large-area yellow or light-brown skin discoloration.

In conclusion, irritation was observed with the 63-67% formulation and no data were available for higher concentrations, nevertheless there were no hints for corrsosion and the findings were generally reversible, therefore skin irritation Categgory 2 is also assumed for the neat substance.

 

Eye irritation

In a key study for eye irritation, three New Zealand rabbits underwent a single application of the registered substance in the conjunctival sac of the left eye of 0.1 mL containing 63 -67% active ingredient of the test item (Kreiling and Jung, 1988b). The untreated eye served as a control. 24 Hours after administration of the test item as well as to all other assessment time points at which, the treated eyes still showed discharges or in which a corneal examination with fluorescein sodium solution was done, the treated eyes were thoroughly washed with physiological saline solution (ca. 37°C). Mean 24 -72h scores were 1.4/4 for cornea, 1/2 for iris, 3/3 for conjuctiva and 2.6/4 for chemosis. One to 72 hours after application, the conjunctivae showed a diffuse bright red color and a very clear swelling to a swelling with more than half-closed lids. The iris was red, the cornea showed diffuse opacity areas to easily discernible translucent areas. 7 Days after application significant hyperemia of some blood vessels to diffuse crimson-red colored conjunctivae and very slightly to significantly swollen conjunctivae were observed. One animal showed scattered areas of opacity of the cornea. 14 Days after application all signs of irritation were reversible. One hour to 7 days after application, the irritation was accompanied with a clear, colorless or white mucous discharge. One animal showed 24 hours to 7 days after application partially white discolorations, bleeding and detachments of parts of the conjunctivae and nictitating membrane.

In conclusion, moderate eye scores were observed during the 72h period, followed by additional observations during the recovery period, including opacity in one animal. Allthough all signs of irritation were reversible, a worst case Category 1 is assumed for the registered substance, which complies with the Categroy 1 group classification for eye damage for the di-ester sulfosuccinates.

 

Conclusion

The substance tested for skin irritation containing 63 -67 % active ingredient was concluded to be irritating for skin (CLP Category 2) and causing severe eye damage (CLP Category 1). As the skin findings were generally reversible and there were no hints for corrsosion, skin irritation Categgory 2 can also be assumed for the neat substance.

-Further information supporting the classification is provided in the read across justification for the Di-ester category, showing that all substances in the group were group classified to cause skin irritation (CLP category 2) and severe eye damage (CLP category 1).

Justification for classification or non-classification

According to CLP regulation (No. 1272/2008 of 16 December 2008), the substance is classified as Category 2, with signal word 'Warning' and hazard statement: H315 - Causes skin irritation. For the eye, Category 1, with signal word 'Danger' and hazard statement: H319 -Causes serious eye damage is proposed.