Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine

Endpoint summary

Description of key information

Acute oral toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8). The studies are as mentioned below:

1. The acute oral toxicity study was conducted by using test chemical in groups of 5 male and 5 female Fischer 344 rats at the dose concentration range from 2150 to 10,000 mg/kg bw. The given test chemical was dissolved in corn oil and administered via oral gavage route. Five dose levels of test chemical were included in each study. LD50 values were determined by probit analysis (Finney, 1964) and were based on deaths occurring within 14 days after administration. 50% mortality observed at 3161 mg/kg bw in male rats and 3828 mg/kg bw in female rats. Therefore, LD50 was considered to be 3161 mg/kg bw, with 95% confidence limit of 1344-4722 mg/kg bw in male rats and 3828 mg/kg bw, with 95% confidence limit of 2787-5255 mg/kg bw in female rats, when groups of 5 male and 5 female Fischer 344 rats were treated with test chemical via oral gavage route.

2.The acute oral toxicity study was designed and conducted to determine the acute oral toxicity profile of test chemical in Sprague Dawley rats. Initially, 3 female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional 3 female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 of test chemical was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

Thus, based on the above summarised studies, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across chemical, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine is not likely to be toxic in the dose range of >2000 - 3828 mg/Kg bw, for acute oral toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute 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

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

WoE report is based on 2 acute oral toxicity studies as- WoE-2 and WoE-3.
Acute Oral toxicity test was carried out to study the effects of the test chemicals on rodents.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

other: 1. rat 2. rat

Strain:

other: 1. Fischer 344 2. Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS
- Source: Frederick Cancer Research Center (Frederick, Md.)
- Age at study initiation: 10-week-old rats
2. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used at the commencement of its dosing.
- Weight at study initiation: Body weight range was 198.9 to 215.1 grams.
Body weights at the start : Female Mean : 205.26 g (= 100 %); Minimum : 198.9 g (- 3.10 %); Maximum : 215.1 g (+ 4.79 %)
- Identification: Each female rat was individually identified by the picric acid marking.
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 21.9 degree centigrade.
- Humidity (%): 56.3% to 59.8%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
IN-LIFE DATES: 14-07-2017 to 02-08-2017

Route of administration:

other: 1. oral: gavage 2. oral: gavage

Vehicle:

other: 1. corn oil 2. 1% aqueous Tween 80

Details on oral exposure:

1. not specified
2. VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg, 2000 mg/kg and 2000 mg/kg
- Justification for choice of vehicle: 1) One of the widely used suspending agent in the toxicological evaluations,
2) Test item was insoluble in water. Uniformly dispersed suspension of the test item was possible in 1% aqueous Tween 80.
3) Extremely safe with LD50 = 38 g/kg body weight.
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.

Doses:

1. Range from 2150 to 10,000 mg/kg bw
2. Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 mg/kg
Dose Group II : 2000 mg/kg

No. of animals per sex per dose:

1. groups of 5 male and 5 female
2. Three females were used at each step.

Control animals:

not specified

Details on study design:

1. not specified
2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality and morbidity, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Body weights: Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.
Gross Pathology: Necropsy was performed on all animals at the end of the study period on day 15. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique.
Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Statistics:

1. LD50 values were determined by probit analysis (Finney, 1964)
2. No data

Preliminary study:

1. not specified
2. No data

Sex:

male

Dose descriptor:

LD50

Effect level:

3 161 mg/kg bw

Based on:

test mat.

95% CL:

1 344 - 4 722

Remarks on result:

other: 50% mortality observed

Sex:

female

Dose descriptor:

LD50

Effect level:

3 828 mg/kg bw

Based on:

test mat.

95% CL:

2 787 - 5 255

Remarks on result:

other: 50% mortality observed

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

1. 50% mortality observed at 3161 mg/kg bw in male rats and 3828 mg/kg bw in female rats.
2. Group I Step I : Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.
Group I Step II : Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.
Group II Step I : Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Group II Step II :Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.

Clinical signs:

other: 1. not specified 2. Group I Step I : Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. Group I Step II : Animals treated at the dose level of 300 mg/kg body weight did

Gross pathology:

1. not specified
2. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.

Other findings:

1. not specified
2. No data available

Interpretation of results:

other: Not classified

Conclusions:

The test chemcial Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) is not likely to be toxic atleast in the dose range of >2000 - 3828 mg/Kg bw for acute oral toxicity.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8). The studies are as mentioned below:

1. The acute oral toxicity study was conducted by using test chemical in groups of 5 male and 5 female Fischer 344 rats at the dose concentration range from 2150 to 10,000 mg/kg bw. The given test chemical was dissolved in corn oil and administered via oral gavage route. Five dose levels of test chemical were included in each study. LD50 values were determined by probit analysis (Finney, 1964) and were based on deaths occurring within 14 days after administration. 50% mortality observed at 3161 mg/kg bw in male rats and 3828 mg/kg bw in female rats. Therefore, LD50 was considered to be 3161 mg/kg bw, with 95% confidence limit of 1344-4722 mg/kg bw in male rats and 3828 mg/kg bw, with 95% confidence limit of 2787-5255 mg/kg bw in female rats, when groups of 5 male and 5 female Fischer 344 rats were treated with test chemical via oral gavage route.

2.The acute oral toxicity study was designed and conducted to determine the acute oral toxicity profile of test chemical in Sprague Dawley rats. Initially, 3 female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional 3 female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 of test chemical was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

Thus, based on the above summarised studies, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across chemical, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine is not likely to be toxic in the dose range of >2000 - 3828 mg/Kg bw, for acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 828 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from database.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8). The studies are as mentioned below:

1. The acute oral toxicity study was conducted by using test chemical in groups of 5 male and 5 female Fischer 344 rats at the dose concentration range from 2150 to 10,000 mg/kg bw. The given test chemical was dissolved in corn oil and administered via oral gavage route. Five dose levels of test chemical were included in each study. LD50 values were determined by probit analysis (Finney, 1964) and were based on deaths occurring within 14 days after administration. 50% mortality observed at 3161 mg/kg bw in male rats and 3828 mg/kg bw in female rats. Therefore, LD50 was considered to be 3161 mg/kg bw, with 95% confidence limit of 1344-4722 mg/kg bw in male rats and 3828 mg/kg bw, with 95% confidence limit of 2787-5255 mg/kg bw in female rats, when groups of 5 male and 5 female Fischer 344 rats were treated with test chemical via oral gavage route.

2.The acute oral toxicity study was designed and conducted to determine the acute oral toxicity profile of test chemical in Sprague Dawley rats. Initially, 3 female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional 3 female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 of test chemical was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

Thus, based on the above summarised studies, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across chemical, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine is not likely to be toxic in the dose range of >2000 - 3828 mg/Kg bw, for acute oral toxicity.

Justification for classification or non-classification

Based on the above experimental studies on Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS no.: 97808-67-8) and it’s structurally similar related read across substances, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine cannot be classified for acute oral toxicity.