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Description of key information

The acute oral median lethal dose (LD50) of SDIPB in the female Wistar strain rat was estimated to be > 2000 mg/kg bw.  In accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, read across data from hydrotropes were used for inhalation (LC50> 6.41 mg/L, aerosol) and dermal  toxicity (LD50 > 2000 mg/kg bw). The conclusion from these studies is that  SDIBP is "practically non-toxic" by EU criteria in acute oral, dermal and inhalation exposure. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12/03/2012-03/05/2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conducted at a GLP accredited laboratory to GLP
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
- Fasting period before study: overnight
Route of administration:
oral: gavage
Details on oral exposure:
14 day were monitored
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 female
Details on study design:
Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of SDIPB at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.
Preliminary study:
Using available information on the toxicity of the test item, 2000mg/kg was chosen as the starting dose. One rat was dosed once only by gavage. In the absence of toxicity at 2000 mg/kg dose (1.74 ml/kg), a total of five animals were treated at a dose level of 2000 mg/kg in the stduy.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight.
Other findings:
No abnormalities were noted at necropsy.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute oral median lethal dose (LD50) of the SDIPB in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bw.
Executive summary:

To cover the endpoint acute oral toxicity of substance SDIPB, fixed dose method was applied to female Wistar strain rats according to OECD Guideline 420, and EU method B.1 bis. Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of SDIPB at a dose level of 2000 mg/kg bw. The acute oral median lethal dose (LD50) of the SDIPB in the female Wistar strain rat was estimated to be > 2000 mg/kg bw.

SDIPB should not be classified as acute oral toxicity according to CLP regulation and DSD criteria.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
April 10 - 24, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline not specified, but with detailed documentation
Reference:
Composition 0
Qualifier:
no guideline followed
Guideline:
other: no information about guideline available
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: albino, COX-SD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lab Supply Company
- Age at study initiation: no data
- Weight at study initiation: 217 - 240 grams
- Fasting period before study: not fasted
- Housing:individually in metal, wire-bottomed cages elevated above the droppings
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: From: April 10, 1980 To: April 24, 1980
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: DeVilbiss Nebulizer and glass chamber
- Exposure chamber volume: 57 liters
- Method of holding animals in test chamber: none
- Source and rate of air: 24 liters per minute (test sample carried in at an air flow of 3 liter/minute; joined by auxiliary air flow of 21 liter/minute)
- Method of conditioning air: 11 minute period to equilibrium to 99% concentration
- System of generating particulates/aerosols: DeVilbiss Nebulizer
- Method of particle size determination: no data
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data


TEST ATMOSPHERE
- Brief description of analytical method used: no analytical performed
- Samples taken from breathing zone: no


VEHICLE
- Composition of vehicle (if applicable): no vehicle


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: none provided
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
>= 232 min
Remarks on duration:
plus an 11 minute period to equilibrate to 99% of concentration
Concentrations:
6.41 mg/liter of air
No. of animals per sex per dose:
5 males and 5 females; single dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at regular intervals during the first day and once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,histopathology, other: behavior and stool
- Upon removal from the chamber, the animals were cleaned with lukewarm water to remove any test material having accumulated on their coats and dried with toweling. Animals were then placed in individual cages.
- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Preliminary study:
none reported
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.41 mg/L air (nominal)
Exp. duration:
232 min
Mortality:
No deaths
Clinical signs:
One animal displayed a pronounced case of soft stool on Day 6 an returned to normal in two days. Otherwise no gross signs of test compound induced adverse effects were observed in the remaining nine animals
Body weight:
Slight weight gains in two animals at 7 and 14 days. The body weights for the remaining 8 animals showed gains within limits of expectation.
Gross pathology:
Five animals showed slight mottling or slight to moderate congestion of the lungs. The remaining five showed tissues to be not remarkable
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Ammonium xylene sulphonate at 6.41 mg/L did not result in mortality and half of the exposed animals showed only slight to moderate congestion of the lungs.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
6 410 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
April 7-21, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline test; GLP compliance, full documentation
Reference:
Composition 0
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Michigan
- Age at study initiation: 5 months
- Weight at study initiation: nakes 2944-3091g and females 2915-3155g
- Fasting period before study: no data
- Housing: individually in hanging stainless steel wire mesh cages
- Diet: up to 125 g/day
- Water: ad libitum
- Acclimation period: minimum of 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled but no values reported
- Humidity (%): controlled but no values reported
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
- other: The animals were maintained in accordance with the recommendations contained in the D.H.H.S. Publication "Guuide for the Care and Use of Laboratory Animals".

IN-LIFE DATES: From: April 7 To: April 21
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day prior to dosing, the hair was removed from the back of each rabbit with an electric clipper. The skin was left intact. The test material was applied once, as received, at a dose of 2000 mg/kg then spread evenly to cover 100% of the test site which was approximately 10% of the body surface. The test site was covered with a 1 x 1 inch gauze pad, wrapped with a gauze bandage, overwrapped with plastic wrap and then sealed with elastoplast tape. A collar was placed on each animal. The test site was washed 24 hours later with water and towel dried.
Duration of exposure:
24 hours
Doses:
2000 mg/Kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations at 1,2 and 4 hours on day one then twice daily for the next 13 days. weighing prior to dosing, on day 8 and at study termination.
- Necropsy of survivors performed: yes
- Other examinations performed: pharmacotoxic signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Remarks on result:
other: no mortality
Mortality:
none
Clinical signs:
4 of the 10 animals displayed no visible abnormal signs. Erythema was noted on day 3 in six animals with desquamation additionally observed on day 9 in one animal.
Body weight:
body weight loss was observed in 8 of the 10 animals during week 2 compared to week 1 weights; the loss being 2% or less. 3 of the animals had weight loss at the end of the study compared to thier starting weights; the loss being 2% or less.
Gross pathology:
No visible abnormalities in 6 of the 10 animals. The remaining 4 displayed focal or multifocal red discoloration of the treated skin with one animal additionally displaying desquamation of the same site.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The dermal LD50 is > 2000 mg/kg bw
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

The acute oral toxicity test was performed with SDIBP (Huntsman, 2012). In accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, read across data from the members of hydrotrophes ammonium xylene sulphonate (CAS No. 26447-10-9), and calcium xylene sulphonate (CAS No. 28088-63-3) were used for inhalation and dermal acute toxicity. To address the acute oral toxicity endpoint of SDIPB, the fixed dose method was applied to female Wistar strain rats according to OECD Guideline 420. Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of SDIPB at a dose level of 2000 mg/kg bw. The acute oral median lethal dose (LD50) of SDIPB in the female Wistar strain rat was estimated to be > 2000 mg/kg bw.

An acute inhalation study (Conoco,1980), limit test, with an exposure period of 232-minutes is available for ammonium xylene sulphonate (CAS No. 26447-10-9). Exposure of single dose of 6.41mg/L to male and female rats was performed with no vehicle and a 14-day post exposure observation period. There were no deaths at the 6.41 mg/L dose. Aerosolization was done by a DeVilbiss Nebulizer and exposures were in glass chambers. One of the 10 animals demonstrated clinical signs (soft stool), 2 out of 10 had slight weight gains at days 7 and 14, and 5 out of 10 showed slight mottling or a moderate congestion of lungs at necropsy. The conclusion was reported as "practically nontoxic".

The acute dermal study (calcium xylene sulphonate - CAS No. 28088 -63 -3) is a GLP compliant, guideline study (EPA OTS 798.1100) that exposed 10 adult rabbits (10 male, 10 female) for 24 hours (occluded) to one dosage level of 2000 mg/kg bw) followed by a full suite of observations and measures for 14 days (Ruetgers-Nease, 1994). In this limit test with no vehicle and clipped hair but intact skin, no adverse effects were recorded. 4 of the 10 animals displayed no visible abnormal signs. Erythema was noted on day 3 in six animals with desquamation additionally observed on day 9 in one animal. The dermal LD50 was determined to be higher than 2000 mg/kg bw.

The available acute oral toxicity study of SDIBP and read- across studies with inhalation and dermal exposure to the members of hydrotropes demonstrate that SDIBP has a low acute toxicity.

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.

Justification for classification or non-classification

The available acute toxicity study of SDIBP and read-across studies with inhalation and dermal exposure to the members of hydrotropes demonstrate that SDIBP is of low acute toxicity. SDIPB should not be classified for acute toxicity according to CLP regulation and DSD criteria.