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Administrative data

Description of key information

There are 6 acute oral, 4 acute dermal and one acute inhalation studies, a number of which are guideline GLP studies, for different hydrotrope substances.

By EU criteria these hydrotrope substance are deemed "practically non-toxic" for 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:
1982-08-25 to 1982-09-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation
Justification for type of information:
Please see Category Approach
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Winkelmann, Borchen, Germany- Age at study initiation: not mentioned- Weight at study initiation: 141 g (males); 117 g (females), mean weights- Fasting period before study: 16 hours- Housing: 1 - 5 animals in Makrolon cages, type III- Diet (e.g. ad libitum): R10 Complete feed for rats ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany- Water (e.g. ad libitum): Drinking water ad libitum- Acclimation period: 4 - 8 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 ± 1- Humidity (%): 60 ± 5- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg
Doses:
7000 mg/kg bw (highest technically feasable concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Examination of clinical signs up to 6 hours after the treatment and daily observations thereafter; bodyweights were determined before treatment, and 1, 7 and 14 days after treatment.- Necropsy of survivors performed: yes, 3 male and 3 female animals- Other examinations performed: no
Statistics:
The means of the body weights were calculated. The LD50 was determined according to Litchfield and Wilcoxon and reported with 95% confidence limits (J. Pharmacol. Exp. Ther. 96, 1949, 99)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 000 mg/kg bw
Mortality:
male: 0/5female 2/5
Clinical signs:
One hour after application piloerection, slight ataxia, lateral position and increased water intake was noted. After 24 hours the surviving animals were free of symptoms.
Body weight:
The treatment had no influence on body weight gain.
Gross pathology:
Post mortem reddening of the gastric mucosa was observed, the surviving animals showed no pathological changes in organs at necropsy.

Table: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

7000

0/5

2/5

2/10

1 1/2

5/5

5/5

10/10

 

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 to male and female Wistar rats was greater than 7000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
7 000 mg/kg bw
Quality of whole database:
Sufficient to meet requirements

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:
other: Guideline not specified, but with detailed documentation
Justification for type of information:
Please see Category Approach
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
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 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
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 dataTEST ATMOSPHERE- Brief description of analytical method used: no analytical performed- Samples taken from breathing zone: noVEHICLE- Composition of vehicle (if applicable): no vehicleTEST ATMOSPHERE (if not tabulated)- Particle size distribution: no dataCLASS 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
Key result
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 sulfonate 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
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:
experimental study
Adequacy of study:
key study
Study period:
1968-04-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to the OECD Guideline, Pre GLP study. Not a full study report.
Justification for type of information:
Please see Category Approach
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
6 animals were used for study instead of 10 (5 male and 5 female animals)
Principles of method if other than guideline:
None
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Not available- Age at study initiation: Not available- Weight at study initiation: 2703 grams (Abraded skin), 2730 grams (Intact skin)- Fasting period before study: Not available- Housing: Not available- Diet (e.g. ad libitum): Not available- Water (e.g. ad libitum): Not available- Acclimation period: Not availableENVIRONMENTAL CONDITIONS- Temperature (°C): Not available- Humidity (%): Not available- Air changes (per hr): Not available- Photoperiod (hrs dark / hrs light): Not availableIN-LIFE DATES: 1968-04-23
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
TEST SITE- Area of exposure: Not available- % coverage: Not available- Type of wrap if used: Not availableREMOVAL OF TEST SUBSTANCE- Washing (if done): Not available- Time after start of exposure: Not availableTEST MATERIAL- Amount(s) applied (volume or weight with unit): 2 ml/kg bw- Concentration (if solution): Not available- Constant volume or concentration used: yes- For solids, paste formed: Not availableVEHICLE- Amount(s) applied (volume or weight with unit): Not available- Concentration (if solution): Not available- Lot/batch no. (if required): Not available- Purity: Not available
Duration of exposure:
Not available
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Total 6 animals were taken for the study. Sex was not mentioned.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Not available- Necropsy of survivors performed: Not available- Other examinations performed: Clinical signs, body weight
Statistics:
None
Preliminary study:
None
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
0/3 (Abraded skin), 0/3 (Intact skin)
Clinical signs:
Sodium Cumene Suphonate elicited moderate primary irritation on the test sites.
Body weight:
Normal body weight gain.
Gross pathology:
Not available
Other findings:
- Organ weights: None- Histopathology: None- Potential target organs: None- Other observations: None

None

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The LD50 > 2000 mg/kg bw and test substance is considered practically non toxic.
Executive summary:

The LD50 was >2000 mg/kg bw. This test substance is practically non toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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 1982 study with sodium cumene sulphonate which follows OECD 401 guideline but not GLP. It is a limit test of 5 males and 5 females exposed at 7000 mg/kg bw . Two female rats died. There were some clinical signs of stress following dosing but all animals were free of clinical symptoms at 24 hours. There were no effects on body weights and no pathological changes at the 14 day necropsy. The LD50 was recorded as greater than 7000 mg/kg bw and per EU criteria the test substance was deemed "practically non-toxic". The other 5 oral studies show comparable results.

 

The key acute dermal toxicity is a 1968 study with sodium cumene sulphonate which is generally equivalent to OECD 402. It was a limit test. 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.

 

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. The conclusion was reported as "practically nontoxic".

Justification for classification or non-classification

The available studies with oral, dermal and inhalation exposure demonstrate that the members of the hydrotrope category are of low acute toxicity. No classification is warranted.