Sodium 4-(2-methylprop-2-en-1-yl)benzenesulphonate

Endpoint summary

Description of key information

Repeated dose toxicity: via oral route;

The NOAEL was considered to be in a dose range of  220.0-1000 mg/kg body weight /day when male and  rats were treated wtih test substance  for chronic study.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9) which is reported as 0.0028427338 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical 4-(2-methylprop-2-en-1-yl) benzenesulfonate is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study;

The acute toxicity value for4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9)  (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 4-(2-methylprop-2-en-1-yl) benzenesulfonate shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4-(2-methylprop-2-en-1-yl) benzenesulfonate shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data from handbook or collection of data

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Weight of evidence prepared from various test chemical mention below
1,The subchronic repeated dose toxicity study of in rats was conducted to evaluate the adverse effects by oral route.
2,The objective of this study was to evaluate the subchronic toxicity of test substance in Wistar rats.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: 1,Sprague-Dawley 2,Wistar

Sex:

male/female

Route of administration:

oral: feed

Vehicle:

other: commercial chow

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: No data available

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): commercial chow
- Concentration in vehicle: 0, 0.02%, 0.1%, and 0.5% (equivalent to 0, 8.8, 44, 220 mg/kg bw/day )
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1,90 days
2,13 weeks

Frequency of treatment:

Daily

Dose / conc.:

0 other: mg/kg bw/day

Remarks:

0%

Dose / conc.:

8.8 other: mg/kg bw/day

Remarks:

(eqivalent to 0.02%)

Dose / conc.:

44 other: mg/kg bw/day

Remarks:

(eqivalent to 0.1%)

Dose / conc.:

220 other: mg/kg bw/day

Remarks:

(eqivalent to 0.5%)

Remarks:

0,100,330 and 1000mg/kg/day

No. of animals per sex per dose:

1,0.0 mg/kg bw/day :10 males and 10 females
8.8 mg/kg bw/day :10 males and 10 females
44.0 mg/kg bw/day :10 males and 10 females
220.0 mg/kg bw/day :10 males and 10 females

2,Test: 30 animals [15♂, 15♀]/ dose group)
Control: 30 animals [15♂, 15♀]

Control animals:

yes, concurrent no treatment

Positive control:

No data available

Observations and examinations performed and frequency:

1,CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Not specified
- Cage side observations checked in table [No.?] were included: Mortality was observed.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: Recorded weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption measurements were conducted during the entire test period and calculated weekly.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY: Not specified
- 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: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood studies were conducted at the beginning of the test and after 30, 60, and 90 days of testing.
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: 5 males and 5 females
- Parameters checked in table [No.?] were examined.: Blood studies, including determinations of hemoglobin concentration, erythrocyte count, hematocrit value, and total and differential leukocyte counts were conducted.

CLINICAL CHEMISTRY: Not specified
- Time schedule for collection of blood: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined.: Not specified

URINALYSIS: Yes
- Time schedule for collection of urine: Urine analysis were conducted at the beginning of the test and after 30, 60, and 90 days of testing.
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- How many animals: 5 males and 5 females
- Parameters checked in table [No.?] were examined.: Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations: Not specified
- How many animals: Not specified
- Dose groups that were examined: Not specified
- Parameters checked in table [No.?] were examined.: Not specified

OTHER:Not specified

2,CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Observations were carried out daily on all animals.
- Cage side observations checked: Mortality was observed.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
- Food consumption were recorded weekly.

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: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: recorded weekly.

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: week 6 and at termination of the study
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: 5 males and 5 females of each group.
- Parameters checked in table [No.?] were examined. No data available

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: week 6 and at termination of the study
- Animals fasted: Not specified
- How many animals: 5 males and 5 females of each group.
- Parameters checked in table [No.?] were examined. No data available

URINALYSIS: Yes
- Time schedule for collection of urine: week 6 and at termination of the study
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined.No data available

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations:Not specified
- Dose groups that were examined:Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other:Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations: Not specified
- How many animals: Not specified
- Dose groups that were examined: Not specified
- Parameters checked in table [No.?] were examined.Not specified

OTHER: No data available

Sacrifice and pathology:

At the end of the test period all animals were sacrificed by either inhalation, and each was subjected to complete autopsy.
GROSS PATHOLOGY: Yes
The body weight at autopsy was recorded along with the weights of the liver, kidneys, spleen, gonads, heart and brain.

HISTOPATHOLOGY: Yes
Complete microscopic examinations were conducted. The following tissues and organs were studied: heart, liver, lung, pancreas, stomach (cardia, fundus, pylorus), small intestine (duodenum, ileum and jejunum), colon, spleen, lymph node, kidney, urinary bladder, testis or ovary, prostate or uterus, pituitary, adrenal, thyroid, parathyroid, skeletal muscle, bone marrow, and brain (cerebellum, cerebrum, and pons).

Other examinations:

No data available

Statistics:

Bartlett (1973) tests for homogeneity of variance were conducted on these data followed by an analysis of variance. Significant effects for treatments disclosed by the analysis of variance were further studied by the t- test. Data showing heterogeneity of variance were treated directly by the t-test, in which no assumption of homogeneity of variance was required.

Clinical signs:

no effects observed

Description (incidence and severity):

1,No abnormal reactions were noted.

Mortality:

no mortality observed

Description (incidence):

Two males at the 0.02% dietary level died in the early stages of the study. These deaths were attributed to respiratory illness, not to ingestion of the test material.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No statistically significant effects for treatments were disclosed.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Findings of test and control groups were comparable.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Description (incidence and severity):

No abnormalities resulted from ingestion of the test substance.

Clinical biochemistry findings:

not specified

Urinalysis findings:

no effects observed

Description (incidence and severity):

The results of urine analyses revealed no significant differences between test animals and control animals respecting the presence of reducing substances, protein, and microscopic elements.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Statistical analyses of organ:body weight and organ:brain weight ratios indicated there were no significant differences related to ingestion of the test substance.

Gross pathological findings:

no effects observed

Description (incidence and severity):

There were no gross pathologic findings which could be correlated with the ingestion of the test material.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Necropsy-findings in the animals which had died intercurrently, revealed no pathological changes attributable to the test substance. Neither did the animals which were sacrificed pursuant to protocol at the end of the study exhibit any such changes.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

220 other: mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

food consumption and compound intake

gross pathology

haematology

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

urinalysis

other: No effects were observed.

Remarks on result:

other: No toxic effect were observed

Dose descriptor:

NOAEL

Effect level:

1 000 other: mg/kg/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effect were observed at ths dose

Remarks on result:

other: No toxic effects were observed

Critical effects observed:

not specified

Conclusions:

The NOAEL was considered to be in a dose range of 220.0-1000 mg/kg body weight /day when male and rats were treated wtih test substance for chronic study.

Executive summary:

The data available for the test chemical was reviewed to determine the toxic nature of sodium 4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9)repeated exposure by oral route. The study is as mentioned below:

The subchronic repeated dose toxicity study of test substance in rats was conducted to evaluate the adverse effects by oral route. Test substance was fed to rats at dietary levels of 0.02%, 0.1%, and 0.5% (equivalent to 8.8, 44, 220 mg/kg bw/day ) for 90 days. No adverse effects were found upon the following parameters: growth, food consumption, food utilization, survival, hematologic values, urinary analytical values, organ weights, and organ:body weight ratios. There were no gross or microscopic tissue changes attributable to ingestion of the test material. Therefore, NOAEL was considered to be 220.0 mg/kg body weight /day when Sprague-Dawley rats were treated wtih test substance.

In order to evaluate the toxicological properties of chemical substance was administered orally to male and female Wistar rats 7 days/week for 13 weeks. The study was conducted according to OECD guideline 408. The dosage was 0, 100, 330 and 1000 mg/kg bw, and the vehicle (5% aqueous tylose) administration group was provided as a control. Animals were examined with respect to in-life-observations (viz. mortalities and clinical signs of toxicity, body weight and food-/water consumption were recorded.), clinical pathology (viz. haematology, clinical chemistry and urinalysis) and anatomic pathology (viz. organ weights, necropsy, histopathology.). Three mortalities (1♂, week 5, control group; 1♀, week 13, 330 mg/kg-group; 1♀, week 6, 1000 mg/kg-group) occurred intercurrently but were not substance related. No clinical signs of toxicity were seen in any group. Food- and water consumption were the same in test- and control groups. Haematology results (total and differential blood count) of test animals did not differ from controls throughout the experiment. The same holds for clinico-chemical parameters, except for protein content in serum in females of the 1000 mg/kg-group, which was increased as compared to controls. However, the level found was within the biological variability range on record for female rats of this age and was therefore not considered substance related. Necropsy-findings in the animals which had died intercurrently, revealed no pathological changes attributable to the test substance. Neither did the animals which were sacrificed pursuant to protocol at the end of the study exhibit any such changes. Differences in organ weights, if observable at all (e.g. spleen in♀'s), were small and not dose dependent. Histopathology did not reveal any organ change or–damage in any one of the dose groups. Based on the above study, the toxicologically no adverse effect amount by repetitive oral administration of test substance for 13 weeks was observed and hence under this test condition NOAEL was considered to be1000 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Weight of evidence prepared from various qualified publication.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The data available for the test chemical was reviewed to determine the toxic nature of sodium 4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9)repeated exposure by oral route. The study is as mentioned below:

Repeated dose toxicity: via oral route;

The subchronic repeated dose toxicity study of test substance in rats was conducted to evaluate the adverse effects by oral route. Test substance was fed to rats at dietary levels of 0.02%, 0.1%, and 0.5% (equivalent to 8.8, 44, 220 mg/kg bw/day ) for 90 days. No adverse effects were found upon the following parameters: growth, food consumption, food utilization, survival, hematologic values, urinary analytical values, organ weights, and organ:body weight ratios. There were no gross or microscopic tissue changes attributable to ingestion of the test material. Therefore, NOAEL was considered to be 220.0 mg/kg body weight /day when Sprague-Dawley rats were treated wtih test substance.

In order to evaluate the toxicological properties of chemical substance was administered orally to male and female Wistar rats 7 days/week for 13 weeks. The study was conducted according to OECD guideline 408. The dosage was 0, 100, 330 and 1000 mg/kg bw, and the vehicle (5% aqueous tylose) administration group was provided as a control. Animals were examined with respect to in-life-observations (viz. mortalities and clinical signs of toxicity, body weight and food-/water consumption were recorded.), clinical pathology (viz. haematology, clinical chemistry and urinalysis) and anatomic pathology (viz. organ weights, necropsy, histopathology.). Three mortalities (1♂, week 5, control group; 1♀, week 13, 330 mg/kg-group; 1♀, week 6, 1000 mg/kg-group) occurred intercurrently but were not substance related. No clinical signs of toxicity were seen in any group. Food- and water consumption were the same in test- and control groups. Haematology results (total and differential blood count) of test animals did not differ from controls throughout the experiment. The same holds for clinico-chemical parameters, except for protein content in serum in females of the 1000 mg/kg-group, which was increased as compared to controls. However, the level found was within the biological variability range on record for female rats of this age and was therefore not considered substance related. Necropsy-findings in the animals which had died intercurrently, revealed no pathological changes attributable to the test substance. Neither did the animals which were sacrificed pursuant to protocol at the end of the study exhibit any such changes. Differences in organ weights, if observable at all (e.g. spleen in♀'s), were small and not dose dependent. Histopathology did not reveal any organ change or–damage in any one of the dose groups. Based on the above study, the toxicologically no adverse effect amount by repetitive oral administration of test substance for 13 weeks was observed and hence under this test condition NOAEL was considered to be1000 mg/kg bw/day.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9) which is reported as 0.0028427338 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical 4-(2-methylprop-2-en-1-yl) benzenesulfonate is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study;

The acute toxicity value for4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9)  (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 4-(2-methylprop-2-en-1-yl) benzenesulfonate shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4-(2-methylprop-2-en-1-yl) benzenesulfonate shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

 

Based on the data available for the test chemical 4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9) not likely to exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the test chemical 4-(2-methylprop-2-en-1-yl) benzenesulfonate( 1208-67-9) not likely to exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.