Ammonium (xylenes and 4-ethylbenzene)sulfonates

Endpoint summary

Description of key information

The HYDROTOPES Category comprises the following 6 substances:
STS - Sodium toluene 4-sulphonate (CAS 657-84-1, EC 211-522-5)
SXS - Sodium (xylenes and 4-ethylbenzene) sulfonates (EC 701-037-1)
NH4XS - Ammonium (xylenes and 4-ethylbenzene) sulfonates (EC 943-024-5)
SCS - Sodium p-cumenesulphonate (CAS 15763-76-5, EC 239-854-6)
KCS - Potassium p-cumenesulphonate (CAS 164524-02-1, EC 629-764-9)
NH4CS - Ammonium p-cumenesulphonate (CAS 680972-33-2, EC 811-484-5) 
In addition CaXS (Calcium Xylenesulphonate, CAS 28088-63-3, EC 248-829-9) was evaluated for complete the assessment despite it is not registered under REACH.

The acute oral toxicity has been tested at least for each member of the hydrotropes subgroup (toluene, xylene and cumene).

The LC50 values in rats ranging from 3000 to 16000 mg/Kg bw, depending on the tested dose. No deaths related to the test item occurred up to the highest tested doses for each available test.

There is only one test for acute inhalation toxicity for NH4XS which did not show clinical effects following inhalation exposure.

The acute dermal toxicity is available for xylene and cumene sulphonates with a LD50 values greater than 2000 mg/kg bw.

The available data on the substances in the category show that they are all negative regarding acute toxicity.

Across the hydrotropes category, toxicity results are consistent across the toluene, xylene and cumene sulfonates and their various salts.

All results consistently indicate no evidence for oral, dermal and inhalation toxicity for Hydrotopes category members.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: Read across from another member of the category

Adequacy of study:

supporting study

Study period:

April 6 to May 6, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Crl:CD BR VAF/Plus

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Michigan
- Age at study initiation: 8 weeks
- Weight at study initiation: 180-248g males and 163-206g females
- Fasting period before study: 20 hr- Housing: individually in hanging stainless steel wire mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days minimum

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

IN-LIFE DATES: From: April 6 To: May 6

Randomization
Fourteen animals free from disease or physical abnormalities and of the appropriate body weight range were arbiti'arily chosen from a stock group of animals
and madee available for selection. Ten rabbits were randomized using a computer-generated sequence of random numbers. Each rabbit was jdentified by a Monel metal ear tag bearing the individual animal number.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: no vehicle usedMAXIMUM DOSE VOLUME APPLIED: 20 mL/kg single oral dose

Doses:

2500, 3000, 3300, 3500, 4000 and 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: 1,2 and 4 hours after dosing then twice daily for 13 additional days for observations. Weighing occurred on day 0, on day 9 and at study termination.- Necropsy of survivors performed: yes- Other examinations performed: pharmacotoxic signs

Statistics:

Using Rosiello, Essigmann and Wogan. 1977. Rapid and accurate determination of the median lethal dose (LD50) and its error with a small computer. Journal of Toxicology and Environmental Health, 3, 797-809.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 3 346 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 3 196 - <= 3 503

Mortality:

0 in controls, 0 at 2500, 2 at 3000, 4 at 3300, 6 at 3500 and all 10 at both 4000 and 5000 mg/kg bwMales - LD50 = 3450 (3306-3599) mg/kgFemales LD50 = 3217 (2978-3475) mg/kg

Clinical signs:

other: The predominate observations were decreased activity, anogenital staining, ptosis and prostration. These observations were noted typically noted 1-4 hours after dosing, except anogenital staining which was noted between study days 2 and 5.

Gross pathology:

The predominate observation was red diffuse discoloration of the mucosa glandular stomach. Also red discouloration at the limited ridge of the glandular stomach, tan foci of the glandular stomach or spleen, and red multifocal foci of the thymus. Except for one animal at 3000 dose, these findings were limiited to animals that died during the study.

The test article, SAR 33-55, was admjnistered once orally by gavage to 30 male and 30 female fasted Olarles River CJ)8 BR rats at dosage levels of 2.500, 3.000, 3.300, 3.500, 4.000 and 5.000 mg/kg. Each group was comprised of five males and five females. The test article was administered as a solution in deionized water at a constant dosage volume of 20 ml/kg.

Criteria evaluated for treatment effect during the 15-day study period included mortality, pharmacotoxic signs, body weight, and gross necropsy examinations.

Mortality was observed at dosages of 3,000 mg/kg bw and greater during the 4-hour post-dose observation interval on study day 1, -ana on study day 2.

All the animals at 4,000 and 5,000 mg/kg died on study. No mortality was obsetved at 2,500 mg/kg.

The predominant signs were decreased activity, anogenital stalmns. ptosis and prostration.

No remarkable changes in body weights of the surviving animals were observed. The predominate post-mortem observation was trace to moderate red diffuse discoloration of the mucosa of the glandular stomach.

This observation was noted in animals that had died on study.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for male and female rats is greater than 3.346 mg/kg bw based on active ingredient.

Executive summary:

The acute Oral Toxicity of Calcium Xylene sulphonate was assessed following official method OECD 401, Acute Oral Toxicity. The test was performed on both males and females Wistar rats and the the test article was admjnistered once orally by gavage at dosage levels of 2.500, 3.000, 3.300, 3.500, 4.000 and 5.000 mg/kg. The test article was administered as a solution in deionized water at a constant dosage volume of 20 ml/kg.

Mortality was observed at dosages of 3.000 mg/kg bw and greater during the 4-hour post-dose observation interval on study day 1 and on study day 2.

All the animals at 4.000 and 5.000 mg/kg died on study. No mortality was obsetved at 2.500 mg/kg.  The predominant signs were decreased activity, anogenital stalmns. ptosis and prostration.  No remarkable changes in body weights of the surviving animals were observed. The predominate post-mortem observation was trace to moderate red diffuse discoloration of the mucosa of the glandular stomach.

 

 

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 346 mg/kg bw

Quality of whole database:

Sufficient to meet requirements, similar to OECD 401

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 10 - 24, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: albino, COX-SD

Sex:

male/female

Details on test animals or test system 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 dataENVIRONMENTAL 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

Vehicle:

other: unchanged (no vehicle)

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

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6.41 mg/L air (nominal)

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: 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:

GHS criteria not met

Conclusions:

LC50 > 6.41 mg/L based on test material

Executive summary:

The acute inhalation toxicity of Ammonium (xylenes and 4-ethylbenzene) sulfonates was assessed following official method OECD 403, Acute Inhalation Toxicity. One animal displayed a pronounced case of soft stool on Day 6 an returned to normal in two days. No gross signs of test compound induced adverse effects were observed in the remaining nine animals, there was no mortality and half of the exposed animals showed only slight to moderate congestion of the lungs.
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. Five animals showed slight mottling or slight to moderate congestion of the lungs. The remaining animals did not showed remarkable effects.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

6 410 mg/m³ air

Quality of whole database:

Sufficient to meet requirements

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

other: Read across from another member of the category

Adequacy of study:

supporting study

Study period:

April 7-21, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system 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

Randomization
Fourteen animals free from disease or physical abnormalities and of the appropriate body weight range were arbiti'arily chosen from a stock group of animals
and madee available for selection. Ten rabbits were randomized using a computer-generated sequence of random numbers. Each rabbit was jdentified by a Monel metal ear tag bearing the individual animal number.

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Mortality:

none

Clinical signs:

other: 4 of the 10 animals displayed no visible abnormal signs. Erythema was noted on day 3 in six animals with desquamation additionally obsserved on day 9 in one animal.

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.

Five male and five female New Zealand White rabbits were administered a single dermal dose of the test article, SAR 33-55. undiluted as received, at a dosage level of

2,000 mll/kg. The test article was applied to the shaven, intact skin on the baclc of each rabbit. The test site of each rabbit was then wrapped Wlth gauze bandaging and secured

with Elastoplast tape. A collar (E-lay Saf-T ShiCfd) was a1so placed on each rabbit. The exposure period was 24 hours. Follow the exposure period, the bandaging materials and collar were removed, the test Sites were washed with tepid tap water and dried with disposable paper towels.

Criteria evaluated for treatment effect during the 15-day study period included mortality. pharmacotoxical signs (including observations of the test site). body weight, and gross necropsy examinations.

All animals survived to study termination.

The predominate pharmacotoxic finding observed was erythema of the treated skin.

This finding was observed in 6 of 10 animals on study day 3 and persisted to termination in all but two of these animal.

Body weight loss was noted in eight animals during study week 2 post-mortem examination, the predominate finding was red discoloration of the treated skin of four animal.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 is > 2000 mg/kg bw based on test material.

Executive summary:

The acute dermal toxicity of Calcium xylene sulphonate was assessed following official method OECD 402, Acute dermal Toxicity.
There was no mortality in tested group, 4 of the 10 animals displayed no visible abnormal signs. Erythema was noted on day 3 in six animals with desquamation additionally obsserved on day 9 in one animal. Body weight loss was noted in eight animals during study week 2 post-mortem examination. 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. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Sufficient to meet requirements

Additional information

There are a total of 11 acute toxicity studies on the hydrotrope category substances, six by the oral route, four by the dermal route and one by inhalation.

 

The key acute oral study is a 1994 GLP study with CaXS which is generally equivalent to OECD 401 guideline. The LD50 was recorded as 3346 mg/kg bw. The other 5 oral studies show comparable results. GHS criteria is not met.

 

The key acute dermal toxicity is a 1994 GLP study with CaXS which is generally equivalent to OECD 402. Six rabbits (3 with shaved and abraded skin and 3 with intact shaved skin) were exposed to 2000 mg/kg bw. There were no deaths but primary irritation was reported at the site of exposure. Body weights were normal at 14 days and there were no gross pathology or histopathology noted at sacrifice. The dermal LD50 is reported as >2000 mg/kg bw. The other three acute dermal studies reported comparable results. GHS criteria is not met.

 

The key acute inhalation study is a 1980 (non-GLP) study with ammonium xylene sulphonate. This is a 232-minute, limit test, involving exposure of male and female rats 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 of the 10 had slight weight gains at days 7 and 14, and 5 of the 10 showed slight mottling or a moderate congestion of lungs at necropsy. GHS criteria is not met.

Justification for classification or non-classification

The available studies with oral, dermal and inhalation exposure demonstrate that the members of the hydrotrope category should not be classified regarding acute toxicity according to CLP Regulation.