Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral repeated dose toxicity

20 CD rats per sex per dose level were exposed to sodium cumene sulfonate at 0, 0.005, 0.05 and 0.5% in the diet. Mean administered doses were 0, 2.6, 26 and 270 mg/kg bw for males and 0, 3.6, 36 and 375 mg/kg bw for females. Taking into account the content of active ingredient, 42.3%, these doses equate to 1.1, 11 and 114 mg a.i./kg bw and 1.5, 15 ad 159 mg a.i./kg bw, respectively. Endpoints were mortality, body and organ weight, food consumption, haematology, and histopathology. No treatment related effects were observed in males at up to the highest dose (114 mg a.i./kg bw). The only effect observed was an 11.7% decrease in body weight gain in females at the highest dose (159 mg a.i./kg bw). The study report stated that this decrease in body weight gain was within the established ranges for animals of this species and age and was therefore not considered an adverse effect by the authors. The feed efficiency of the high dose females was statistically higher than the controls. The decrease in body weight gain of the high dose females was not associated with any histopathologic or other effects. In light of the palatability issues seen in the previously discussed study, this slight decrease in body weight gain may be explained as a palatability effect Also, the intervals between the dose levels in this study are large (factor of 10), while OECD 408 prefers 2-4 fold intervals and prefers an additional group if the factors are > 6-10.

A NOAEL for sodium cumene sulfonate is therefore >114 mg a.i./kg bw for males and >159 mg a.i./kg bw in femalesif the slight decrease in body weight gain is not considered toxicologically significant.

 

Dermal repeated dose toxicity

 The NOAEL was 800 mg/kg bw per day, on the basis of epidermal hyperplasia.

 

The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be NOAELin mg/cm2 = ((dose in mg/kg bw)x (average animal weight in kg)) /

Treated surface in cm2) NOAELtest* 0.25/44.5= NOAELmodified The highest dose not causing irritation/corrosion was 800 mg/kg bw in dermal toxicity study in rats

The modified dose descriptor would be:

 

 NOAELmodified=800 mg/kg*0.25 kg/44.5cm2=4.49mg/cm2

 

  

Inhalation repeated dose toxicity

 The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat             

114 mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat    4.96 mg/m3

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Principles of method if other than guideline:
20 CD rats per sex per dose level were exposed to sodium cumene sulfonate at 0, 0.005, 0.05 and 0.5% in the diet. Mean administered doses were 0, 2.6, 26 and 270 mg/kg bw for males and 0, 3.6, 36 and 375 mg/kg bw for females. Taking into account the content of active ingredient, 42.3%, these doses equate to 1.1, 11 and 114 mg a.i./kg bw and 1.5, 15 ad 159 mg a.i./kg bw, respectively. Endpoints were mortality, body and organ weight, food consumption, haematology, and histopathology.
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
Test Substance
CAS Number: 28348-53-0
Identity: Cumene sulfonic acid, sodium salt
Purity: 42.3%
Remarks: Substances tested are aqueous solutions; % purity equates to chemical content
Species:
rat
Strain:
Crj: CD(SD)
Details on species / strain selection:
20 CD rats per sex per dose level were exposed to sodium cumene sulfonate at 0, 0.005, 0.05 and 0.5% in the diet
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-CD rats
- Age at study initiation: newly weaned
- Weight at study initiation: 41-60 g
- Fasting period before study: no data
- Housing: metal wire screen cages (5 to a cage)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 degrees centigrade
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
20 CD rats per sex per dose level were exposed to sodium cumene sulfonate at 0, 0.005, 0.05 and 0.5% in the diet. Mean administered doses were 0, 2.6, 26 and 270 mg/kg bw for males and 0, 3.6, 36 and 375 mg/kg bw for females. Taking into account the content of active ingredient, 42.3%, these doses equate to 1.1, 11 and 114 mg a.i./kg bw and 1.5, 15 ad 159 mg a.i./kg bw, respectively. Endpoints were mortality, body and organ weight, food consumption, haematology, and histopathology.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
in ad libitum diet
Remarks:
Doses / Concentrations:
0, 0.005, 0.05 and 0.5 % in diet
No. of animals per sex per dose:
20 per sex per dose group
Control animals:
yes
Details on study design:
20 CD rats per sex per dose level were exposed to sodium cumene sulfonate at 0, 0.005, 0.05 and 0.5% in the diet. Mean administered doses were 0, 2.6, 26 and 270 mg/kg bw for males and 0, 3.6, 36 and 375 mg/kg bw for females. Taking into account the content of active ingredient, 42.3%, these doses equate to 1.1, 11 and 114 mg a.i./kg bw and 1.5, 15 ad 159 mg a.i./kg bw, respectively.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Observations: general appearance and behaviour
- Time schedule: no data


DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: weekly for the first week only


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: week 6 and week 12
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: 10 males and 10 females from each dose group

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: terminally
- Animals fasted: No data
- How many animals: 10 males and 10 females from each dose group


URINALYSIS: Yes
- Time schedule for collection of urine: urinalysis from pooled samples from 10 males and 10 females from each dose group in 7th week.
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data


NEUROBEHAVIOURAL EXAMINATION: No


OTHER: kidney funcion from samples of 10 males and 10 females in 13th week. Serum protein electrophoresis of 10 males and 10 females of control and high dose groups at 13 weeks. Liver enzyme activity at termination.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
20 CD rats per sex per dose level were exposed to sodium cumene sulfonate at 0, 0.005, 0.05 and 0.5% in the diet. Mean administered doses were 0, 2.6, 26 and 270 mg/kg bw for males and 0, 3.6, 36 and 375 mg/kg bw for females. Taking into account the content of active ingredient, 42.3%, these doses equate to 1.1, 11 and 114 mg a.i./kg bw and 1.5, 15 ad 159 mg a.i./kg bw, respectively. Endpoints were mortality, body and organ weight, food consumption, haematology, and histopathology. No treatment related effects were observed in males at up to the highest dose (114 mg a.i./kg bw). The only effect observed was an 11.7% decrease in body weight gain in females at the highest dose (159 mg a.i./kg bw). The study report stated that this decrease in body weight gain was within the established ranges for animals of this species and age and was therefore not considered an adverse effect by the authors. The feed efficiency of the high dose females was statistically higher than the controls. The decrease in body weight gain of the high dose females was not associated with any histopathologic or other effects. In light of the palatability issues seen in the previously discussed study, this slight decrease in body weight gain may be explained as a palatability effect Also, the intervals between the dose levels in this study are large (factor of 10), while OECD 408 prefers 2-4 fold intervals and prefers an additional group if the factors are > 6-10. A NOAEL for sodium cumene sulfonate is therefore >114 mg a.i./kg bw for males and >159 mg a.i./kg bw in females if the slight decrease in body weight gain is not considered toxicologically significant.
Dose descriptor:
NOAEL
Effect level:
> 114 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
Dose descriptor:
NOAEL
Effect level:
> 159 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
female
Basis for effect level:
body weight and weight gain
clinical signs
Critical effects observed:
not specified
Conclusions:
A NOAEL for sodium cumene sulfonate is >114 mg a.i./kg bw for males and >159 mg a.i./kg bw in females if the slight decrease in body weight gain is not considered toxicologically significant.
Executive summary:

20 CD rats per sex per dose level were exposed to sodium cumene sulfonate at 0, 0.005, 0.05 and 0.5% in the diet. Mean administered doses were 0, 2.6, 26 and 270 mg/kg bw for males and 0, 3.6, 36 and 375 mg/kg bw for females. Taking into account the content of active ingredient, 42.3%, these doses equate to 1.1, 11 and 114 mg a.i./kg bw and 1.5, 15 ad 159 mg a.i./kg bw, respectively. Endpoints were mortality, body and organ weight, food consumption, haematology, and histopathology. No treatment related effects were observed in males at up to the highest dose (114 mg a.i./kg bw). The only effect observed was an 11.7% decrease in body weight gain in females at the highest dose (159 mg a.i./kg bw). The study report stated that this decrease in body weight gain was within the established ranges for animals of this species and age and was therefore not considered an adverse effect by the authors. The feed efficiency of the high dose females was statistically higher than the controls. The decrease in body weight gain of the high dose females was not associated with any histopathologic or other effects. In light of the palatability issues seen in the previously discussed study, this slight decrease in body weight gain may be explained as a palatability effect Also, the intervals between the dose levels in this study are large (factor of 10), while OECD 408 prefers 2-4 fold intervals and prefers an additional group if the factors are > 6-10. A NOAEL for sodium cumene sulfonate is therefore >114 mg a.i./kg bw for males and >159 mg a.i./kg bw in females if the slight decrease in body weight gain is not considered toxicologically significant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
114 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
A NOAEL for sodium cumene sulfonate is >114 mg a.i./kg bw for males and >159 mg a.i./kg bw in females if the slight decrease in body weight gain is not considered toxicologically significant.
Sufficient to meet requirements

In the (Q)SAR study, NOAEL for Repeated dose oral toxicity was 385 mg/kg bw/day (No adverse effects on the highest dose tested) for S-allyl O-pentyl dithiocarbonate. This HESS QSAR grouping method contains simple categories for Repeated dose oral toxicity.This method is relevant for Repeated dose oral toxicity endpoints in mammals. The database include a set of 75 chemicals that have been evaluated for their repeated dose oral toxicity potential.
NOAEL= 385 mg/kg bw/day
System:
other: slight decrease in body weight gain

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
4.96 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Inhalation exposure:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
114 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 4.96 mg/m3
NOAEC of 4.96 mg/m3 was established based on no effects in rats.

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
4.96 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Inhalation exposure:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
114 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 4.96 mg/m3

NOAEC of 4.96 mg/m3 was established based on no effects in rats.

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
other: published data
Adequacy of study:
weight of evidence
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 411 (Subchronic Dermal Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
As per OECD 411 with the exception of clinical signs recorded weekly, no food consumption, no ophthalmoscopy, clinical
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
CAS Number: 1300-72-7
Identity: Xylene sulfonic acid, sodium salt
Purity: 65%
Remarks: purity 65% (11.5% ortho, 38% meta and 15.5% para).
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Germantown, NY
- Age at study initiation: 6 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 1 animal per cage; polycarbonate cage with stainless steel rack (rotated every 2 weeks); heat-treated hardwood chips and spun-bonded polyester cage filters changed weekly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 24.5
- Humidity (%): 20 to 67
- Air changes (per hr): 10 minimum
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Vehicle:
ethanol
Details on exposure:
TEST SITE
- Area of exposure: clipped interscapular skin
- % coverage: no data
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: once at start of study


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 300 microliters
- Concentration (if solution): 0, 5, 15, 44, 133, 400 mg/mL
- Constant volume or concentration used: yes


VEHICLE
- Justification for use and choice of vehicle (if other than water): ethanol because test material beads up rather than spreads out when applied neat
- Amount(s) applied (volume or weight with unit): 300 microliters of combined test material and vehicle
- Concentration (if solution): 50% solution of ethanol i water
- Lot/batch no. (if required): no data
- Purity: no data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
HPLC on each dose at beginning, middle and end of the study
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days per week
Remarks:
Doses / Concentrations:
5, 15, 44, 133 and 400 mg/ml (vehicle 50% ethanol, volume applied 0.3 ml) which averaged approximately 6, 20, 60, 170 and 500 mg a.i./kg for males and
10, 30, 90, 260 and 800 mg a.i./kg for females taking into consideration the 65% purity of the substance; solutions/suspensions were prepared every 2
weeks; feeding ad libitum.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Details on study design:
Dose selection rationale: wide range of doses for screening
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: 10 males and 10 females at each dose for special hematology and clinical chemistry study
- Post-exposure recovery period in satellite groups: no data
- Section schedule rationale (if not random): random
Positive control:
no data
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked in table were not included.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: weekly


BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No


WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 5 and 21 (from satellite group) and at end of study for all animals
- Anaesthetic used for blood collection: Yes / carbon dioxide
- Animals fasted: No data
- How many animals: 10 per dose; males and females
- Parameters checked in table [No.1] were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 5 and 21 (from satellite group) and at end of study for all animals
- Animals fasted: No data
- How many animals: 10 per dose; males and females
- Parameters checked in table [No.1] were examined.


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Kaplan-Meier method
Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY - no treatment related effects

BODY WEIGHT AND WEIGHT GAIN - no treatment related effects


FOOD CONSUMPTION - protocol indicates measurements conducted, but not reported


HAEMATOLOGY - no treatment related effects


CLINICAL CHEMISTRY - no treatment related effects


ORGAN WEIGHTS - decrease seen in liver weights of males but not accompanied by histopathology changes; a liver enzyme increase was observed in males at day 5 but not at a later time period.


GROSS PATHOLOGY - no treatment related effects


HISTOPATHOLOGY: NON-NEOPLASTIC - protocol indicates examinations conducted, but not reported


OTHER FINDINGS - epidermal hyperplasia of the application site in both males and females at the highest dose
Dose descriptor:
NOAEL
Effect level:
>= 800 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
female
Basis for effect level:
other: other: overall effects: other: epidermal hyperplasia at highest dose in males
Critical effects observed:
not specified
Conclusions:
Results
Value: NOAEL = 400 mg/ml which equals 800 mg/kg bw active ingredient (a.i.)
NOAEL = (800 mg active ingredient/kg bw).
Executive summary:

Results

Value: NOAEL = 400 mg/ml which equals 800 mg/kg bw active ingredient (a.i.)

NOAEL = (800 mg active ingredient/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
800 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The NOAEL was 800 mg/kg bw per day, on the basis of epidermal hyperplasia

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
other: published data
Adequacy of study:
weight of evidence
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 411 (Subchronic Dermal Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
As per OECD 411 with the exception of clinical signs recorded weekly, no food consumption, no ophthalmoscopy, clinical
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
CAS Number: 1300-72-7
Identity: Xylene sulfonic acid, sodium salt
Purity: 65%
Remarks: purity 65% (11.5% ortho, 38% meta and 15.5% para).
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Germantown, NY
- Age at study initiation: 6 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 1 animal per cage; polycarbonate cage with stainless steel rack (rotated every 2 weeks); heat-treated hardwood chips and spun-bonded polyester cage filters changed weekly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 24.5
- Humidity (%): 20 to 67
- Air changes (per hr): 10 minimum
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Vehicle:
ethanol
Details on exposure:
TEST SITE
- Area of exposure: clipped interscapular skin
- % coverage: no data
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: once at start of study


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 300 microliters
- Concentration (if solution): 0, 5, 15, 44, 133, 400 mg/mL
- Constant volume or concentration used: yes


VEHICLE
- Justification for use and choice of vehicle (if other than water): ethanol because test material beads up rather than spreads out when applied neat
- Amount(s) applied (volume or weight with unit): 300 microliters of combined test material and vehicle
- Concentration (if solution): 50% solution of ethanol i water
- Lot/batch no. (if required): no data
- Purity: no data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
HPLC on each dose at beginning, middle and end of the study
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days per week
Remarks:
Doses / Concentrations:
5, 15, 44, 133 and 400 mg/ml (vehicle 50% ethanol, volume applied 0.3 ml) which averaged approximately 6, 20, 60, 170 and 500 mg a.i./kg for males and
10, 30, 90, 260 and 800 mg a.i./kg for females taking into consideration the 65% purity of the substance; solutions/suspensions were prepared every 2
weeks; feeding ad libitum.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Details on study design:
Dose selection rationale: wide range of doses for screening
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: 10 males and 10 females at each dose for special hematology and clinical chemistry study
- Post-exposure recovery period in satellite groups: no data
- Section schedule rationale (if not random): random
Positive control:
no data
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked in table were not included.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: weekly


BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No


WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 5 and 21 (from satellite group) and at end of study for all animals
- Anaesthetic used for blood collection: Yes / carbon dioxide
- Animals fasted: No data
- How many animals: 10 per dose; males and females
- Parameters checked in table [No.1] were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 5 and 21 (from satellite group) and at end of study for all animals
- Animals fasted: No data
- How many animals: 10 per dose; males and females
- Parameters checked in table [No.1] were examined.


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Kaplan-Meier method
Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY - no treatment related effects

BODY WEIGHT AND WEIGHT GAIN - no treatment related effects


FOOD CONSUMPTION - protocol indicates measurements conducted, but not reported


HAEMATOLOGY - no treatment related effects


CLINICAL CHEMISTRY - no treatment related effects


ORGAN WEIGHTS - decrease seen in liver weights of males but not accompanied by histopathology changes; a liver enzyme increase was observed in males at day 5 but not at a later time period.


GROSS PATHOLOGY - no treatment related effects


HISTOPATHOLOGY: NON-NEOPLASTIC - protocol indicates examinations conducted, but not reported


OTHER FINDINGS - epidermal hyperplasia of the application site in both males and females at the highest dose
Dose descriptor:
NOAEL
Effect level:
>= 800 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
female
Basis for effect level:
other: other: overall effects: other: epidermal hyperplasia at highest dose in males
Critical effects observed:
not specified
Conclusions:
Results
Value: NOAEL = 400 mg/ml which equals 800 mg/kg bw active ingredient (a.i.)
NOAEL = (800 mg active ingredient/kg bw).
Executive summary:

Results

Value: NOAEL = 400 mg/ml which equals 800 mg/kg bw active ingredient (a.i.)

NOAEL = (800 mg active ingredient/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
4.49 mg/cm²
Study duration:
subchronic
Species:
rat
Quality of whole database:
The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be NOAELin mg/cm2 = ((dose in mg/kg bw)x (average animal weight in kg)) /
Treated surface in cm2) NOAELtest* 0.25/44.5= NOAELmodified The highest dose not causing irritation/corrosion was 800 mg/kg bw in dermal toxicity study in rats
The modified dose descriptor would be:
NOAELmodified =800 mg/kg*0.25 kg/44.5cm2=4.49mg/cm2

Additional information

Justification for classification or non-classification

Based on the hazard assessment of sodium cumenesulfonate e in section 2.1 and 2.2. in IUCLID 6., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99) and according to the criteria described in Directive 67/548 and in the CLP Regulation:

 

Directive 67/548

Repeated dose toxicity

R33 Danger of cumulative effects.

T; R48/23 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation.

T; R48/23/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin.

T; R48/23/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

T; R48/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin.

T; R48/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed.

T; R48/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure if swallowed.

Xn; R48/20 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation.

Xn; R48/20/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin.

Xn; R48/20/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and if swallowed.

Xn; R48/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin.

Xn; R48/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed.

Xn; R48/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure if swallowed

CLP

Repeated dose toxicity

STOT Rep. Exp. 1

STOT Rep. Exp. 2

H372: Causes damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

It is concluded that the substance sodium cumenesulfonate does not meet the criteria to be classified for human health hazards for Repeated dose toxicity