Registration Dossier

Administrative data

Description of key information

There is no data available for skin irritation for SDIBP.  A read-across from Sodium cumene sulphonate (CAS No. 28348-53-0) for skin irritation was performed, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5. The study for skin irritation followed the OECD 404 guideline and was conducted according to GLP guidelines. In this study, three females with shaved and intact skin were exposed to 0.5 g of sodium cumene sulfonate with 40% active ingredient for 4 hours (semi-occluded) followed by a 72 hours observation period. The maximum skin irritation score was 1.0 at the 30 minutes observation point and this effect was fully reversible after 24 hours. The read-across study indicated SDIBP  is  "non irritating"  GHS or EU criteria. 
The in vitro eye irritation GLP study with SDIBP was designed using 3 rabbits and a volume of 0.1mL of the test item was applied. The maximal ocular irritation recorded for the test eyes were as follows: corneal swelling (%) for test and control eyes was > 42.4, > 59.1, > 98.0 and 9.6, 19.1, 4.9, for 60, 120, 240 mins respectively.The condition of corneal epithelium was sloughing.
In vivo eye irritation study with SDIBP was performed according to OECD 405 guideline under GLP. 0.1 mL of Eltesol SDIBP 35/B was initially administered onto the right eye of one rabbit. After one hour scores of the first animal, two additional animals were dosed. Scoring was done according to method of Draize. Corneal irritation, moderate iritis and chemosis were fully resolved by study termination, except conjunctival redness persisted until day 6 (observation period).
The in vitro and in vivo eye studies showed that SDIBP is mildly irritating (Cat 2B) to the eyes according to GHS criteria and irritating to the eyes (Xi, R36) according to EU criteria.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
August 7 - 10, 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2007 GLP Guideline Study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 2.40 - 2.77 Kg
- Housing: individually housed in steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Conditioned for at least 5 days prior to study initiation. Maintained according to the recommendations contained in the "Guide for the Care and Use of Laboratory Animals", National Academy Press, 1996.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): "light controlled"


IN-LIFE DATES: From: August 7, 2007 To: August 10, 2007
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 gram
- Concentration (if solution): undiluted; test substance is 40% active ingredient


VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
4 hours; after which excess test material was removed from the site
Observation period:
30 minutes and 24, 48 and 72 hours after patches were removed
Number of animals:
3 (females)
Details on study design:
TEST SITE
- Area of exposure: 6 sq cm
- % coverage:
- Type of wrap if used: 2 layer gauze patch covered with semiocclusive plastic overwrop held in place with Kendall Curity Standard Porous Tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess removed
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hours
Score:
>= 0.25
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
The maximum skin irritation score was 1.0 at the 4.5 hour observation.
Other effects:
Final body weights were within expected values.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Not irritating
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:
01/12/2012-15/01/2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conducted at a GLP accredited laboratory to GLP
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Millbrook
- Age at study initiation: 28 weeks
- Weight at study initiation: 3.8-4.2kg
- Housing:Animals were individually housed in compliance with USDA Guidelines. The room in which the animals were kept was documented in the study records. No other species were kept in the same room.
- Diet (e.g. ad libitum): All animals had access to PMI Certified Hi-Fiber Rabbit Diet #5325.
- Water (e.g. ad libitum): the tap water was available as libitim to each ainmal via an automatic watering device.
- Acclimation period: A min 7 days prior to dosing their housing were acclimated.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 21 °C
- Humidity (%): 38-64
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Controls:
other: other eyes were used as control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Once
Observation period (in vivo):
6 days
Number of animals or in vitro replicates:
3
Details on study design:
Prior to dosing, the eyes were anesthetized using 2 drops of Tetracaine. Eltesol SDIBP 35/B was initially installed into the right eye of one male rabbit. The left eye was untreated. Following to one hour scores of the first animal, two additional animals were dosed. Scoring was done according to method of Draize.
Irritation parameter:
cornea opacity score
Basis:
animal: 2 and 3
Time point:
other: 1 and 24h
Score:
0 - <= 1
Max. score:
3
Reversibility:
fully reversible within: 48h
Remarks on result:
other: mild opacity
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: one hour post dose
Score:
0 - < 1
Max. score:
1
Reversibility:
fully reversible within: 24h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1 hour post dose
Score:
> 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 6 days
Remarks on result:
other: conjunctival redness
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h dose dose
Score:
> 1 - < 4
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
No corneal, iris or conjunctival irritation was observed in the untreated eyes of the rabbits at any time point. Corneal irritation (mild opacity, scores of 1, involving app one quarter to less than three quaters of the corneas, scores of 1-3) was observed in the treated eyes of animals 1952 and 1953 at 1 h and 24hs post dose but resolved by 48hs post dose.
Moderate iritis (score of 1) was observed in animal 1952 at 1 h post dose with resolution by 24hs post dose.
Conjunctival redness (scores of 1) were observed beginning at 1h post dose, with a score of 2 for conjunctival redness for animal 1953 being observed at 24hs post dose. Scores of 1-2 for conjunctival redness persisted until day6.
Chemosis (scores of 1-4) were observed begining at 1h post dose with full resolution by 72hs. Scores of 2-3 for discharge were observed at 1h. Discharge resolved by 48h in 2 of 3 animals with irritation resolving in the remaining animal by 72h post dose. All 3 animals were observed to be normal on day 6 and the study was terminated.
Other effects:
No mortality was observed in the animals during to study. From one h post dose until completion of in-life, animals 1952 and 1953 appeared normal thoughout the study.
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Eltesol SDIBP 35/B was found to be non-irritating to the eyes according to EEC criteria. Eltesol SDIBP 35/B was found to be mildly irritating (cat 2B) to the eyes according to GHS criteria.
Executive summary:

SDIBP needs to be classified with Xi, R36 and Eye Damage 2, H319 according to classification criteria of Directive 67/548/EEC and Regulation (EC) No 1272/2008, respectively.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, a read-across from sodium cumene sulphonate (CAS No. 28348-53-0) for skin irritation was performed, since no data on skin irritation with SDIBP is available.The skin irritation study was performed according to OECD 404 guideline study under GLP (Stepan, 2007). Three females with shaved and intact skin were exposed to 0.5 g of test substance with 40% active ingredient for 4 hours (semi-occluded) followed by a 72 hours observation period. The primary dermal irritation index (PDII) was >= 0.25 in 72 hours and the maximum score was 1.0 at the 30 minutes observation point and this effect was fully reversible after 24 hours. The test substance was judged to be not irritating according to OECD GHS criteria. Based on the read across study, it can be concluded that SDIBP is considered "non irritating" to the skin based on GHS or EU criteria.

One in vitro and one in vivo eye irritation tests were performed to the SDIBP.

The ocular irritancy potential of the test item was assessed with a GLP in vitro study by applying it onto the cornea of the enucleated eye (Huntsman, 2012). The results of the study are believed to be of value in predicting the ocular irritation potential of the test item in man. Following the equilibration period, corneal thickness values were measured and were recorded. A volume of 0.1ml of the test item was applied as evenly as possible to the surface of the cornea, which had been maintained at temperature of 32 °C within the superfusion chamber. The maximal ocular irritation recorded for the test eyes were as follows: corneal swelling (%) for test and control eyes was > 42.4, > 59.1, > 98.0 and 9.6, 19.1, 4.9, after 60, 120, 240 mins respectively. The condition of corneal epithelium was sloughing. Based on the assessment of the data for all endpoints, the test item was considered to have the potential to cause severe ocular irritancy in vivo.

An in vivo eye irritation study was also performed with SDIBP according to OECD 405 under GLP (Huntsman, 2013). No corneal, iris or conjunctival irritation was observed in the untreated eyes of the rabbits at any time point. Corneal irritation (mild opacity, scores of 1, involving approximately one quarter to less than three quarters of the corneas, scores of 1-3) was observed in the treated eyes of animals 1952 and 1953 at 1 and 24hs post dose but resolved by 48hs post dose. Moderate iritis (score of 1) was observed in animal 1952 at 1-h post dose with resolution by 24hs post dose. Conjunctival redness (scores of 1) was observed beginning at 1h post dose, with a score of 2 for conjunctival redness for animal 1953 being observed at 24hs post dose. Scores of 1-2 for conjunctival redness persisted until day 6. Chemosis (scores of 1-4) were observed beginning at 1h post dose with full resolution by 72hs. Scores of 2-3 for discharge were observed at 1h. Discharge resolved by 48h in 2 of 3 animals with irritation resolving in the remaining animal by 72hs post dose. All 3 animals were observed to be normal on day 6 and the study was terminated. The conclusion of this test was to be irritating to the eyes with Xi, R36 according to EU criteria and mildly irritating (Category 2B) to the eyes according to GHS criteria.

Based on one in vitro and one in vivo study, it can be concluded that SDIBP needs to be classified with Xi, R36 according to EU criteria and is slightly to moderately irritant to the eyes following OECD GHS criteria.

Category Justification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances.

Applying the category approach read-across concept to SDIBP, data will be used from a representative member of the hydrotropes category to avoid unnecessary (animal) testing. The endpoints for which the read-across approach to SDIBP is applied, are: toxicokinetics, short-term toxicity to fish, toxicity to microorganism, acute toxicity (inhalation and dermal), skin irritation/corrosivity, skin sensitisation, genetic toxicity (in vitro, in vivo), repeated-dose toxicity (oral and dermal), screening for carcinogenicity, and screening for reproductive / developmental toxicity.

Hazard assessment related key information for SDIBP:

SDIPB and the hydrotrope members exhibit similar levels of low toxicity. Acute toxicity values are above the classification limits, they are not sensitizing and show no genotoxic effects. Both exhibit neglible irritation to the skin, but are moderately irritating to the eyes (Cat 2B). Together with the chemical structure similarity and their similar chemical properties, it is deemed correct to fill the existing data gaps on mammalian toxicity of SDIPB with the data of the hydrotrope category.


Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Based on available read-across skin irritation study, no classification for skin effects of SDIBP is warranted.

The effects of the eye irritation studies vary from slightly to moderately irritating. A classification as "eye irritant" therefore is justified.

The substance needs to be classified with Xi, R36 and Eye Damage 2, H319 according to classification criteria of Directive 67/548/EEC and Regulation (EC) No 1272/2008, respectively.