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

Endpoint summary

Description of key information

Skin irritation

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

 

The acute dermal irritation study was conducted for the read across chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.    Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.

 

The above result was further supported by a Patch test reported by safety assessment report for another similar read across substance which was conducted on humans in accordance with IMDG code (2002) to assess the irritation potential of test chemical. About 50 mg was applied under occlusive conditions to the inner arm of 5 male volunteers for 6 hours. The test site was observed for erythema and edema till 14 days post dosing. Since the chemical did not produce any skin lesions, the test chemical was considered as not irritating to the skin.

 

Based on the above summarized studies for target chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

 

Eye irritation

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

 

An ocular irritation test was conducted on rabbits by peer reviewed journal to determine the eye irritation potential of read across chemical. The chemical did not induce any ocular lesions during the study. Hence the test chemical was considered as not irritating.

 

The above results were further supported by another eye irritation study reported by safety assessment report on rabbits for another read across substance.When the chemical was instilled into the eyes of each rabbit, no signs of eye irritation were observed. Hence the test chemical was considered as not irritating to the rabbits’ eyes.

 

Based on the above summarized studies for target chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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 skin irritation studies as- WoE-2 and WoE-3.
Skin irritation study of test chemical was conducted on rats and humans to assess its skin irritating effects.

GLP compliance:

not specified

Species:

other: 1.Rat 2.Human

Strain:

other: 1.Sprague-Dawley 2.Not specified

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: No data available
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.
- Weight at study initiation: The weight range of approximately 221.7 to 255.3 grams at initiation of dosing.
Body weights at the start :
Male
Mean : 249.20 g (= 100 %)
Minimum : 243.9 g (- 2.13 %)
Maximum : 255.3 g (+ 2.45 %)
Total No. of animals : 5
Female
Mean : 225.60 g (= 100 %)
Minimum : 221.7 g (- 1.73 %)
Maximum : 230.5 g (+ 2.17 %)
Total No. of animals : 5
- Identification: Each rat was individually identified by the cage number.
- Fasting period before study: No data available
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- 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 22.5 degree centigrade.
- Humidity (%): 53.2% to 58.8%
- 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: 20-07-2017 to 04-08-2017

2.male: age 27-48

2.

Type of coverage:

other: 1.semiocclusive 2.occlusive

Preparation of test site:

other: 1. clipped 2. Not specified

Vehicle:

other: 1. water 2. unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

1.2000 mg/kg bw
2.ca. 50 mg/patch (direct) on an inner arm

Duration of treatment / exposure:

1.24 hours
2.6 hours

Observation period:

1. 14 days
2.14 days

Number of animals:

1.10 (5/sex).
2.5(male)

Details on study design:

1.TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : Dermal reaction was observed daily for study period of 14 days.

SCORING SYSTEM: Draize Method.

OTHER OBSERVATIONS
Type and Frequency of Tests, Analyses and Measurements

Viability:Twice daily.

Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 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 pre-test (prior to administration of the test item), day 7 and at termination on day 14.

Gross Pathology:
Necropsy was performed on animals surviving at the end of the study. 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 (day 15).

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
2. Not specified

Irritation parameter:

erythema score

Basis:

mean

Time point:

14 d

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

14 d

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

1.Overall result:
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.


2. No skin irritation was observed in treated group,

Other effects:

1.Other effects:
Clinical Signs of Toxicity and Mortality
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.

Body Weight
Sex : Male
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.58% and 18.09% respectively.

Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.54% and 9.72% respectively.

Gross Pathological Findings
Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.

2.No skin irritation was observed in treated group,

1.

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Male

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	5	1 - 5	Day 0 - Day 14	0/5

 

Sex : Female

 

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	5	6 - 10	Day 0 - Day 14	0/5

 

 

Table No. II

Summary of Evaluation of Dermal Reaction

Test System : Sprague Dawley Rat

Sex : Male 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No dermal reaction observed	5	1 - 5	Day 0 - Day 14	0/5

 

Sex : Female

 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No dermal reaction observed	5	6 - 10	Day 0 - Day 14	0/5

 

 

Table No.III

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Male

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	249.20	270.66	8.58	294.34	8.77	18.09
		± SD	4.57	9.96	2.02	9.37	1.21	1.70

 

Sex : Female

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	225.60	238.12	5.54	247.52	3.98	9.72
		± SD	3.57	5.80	1.18	5.22	2.68	1.96

 

 

 Table No.IV

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Male

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	1 - 5	TS	No abnormality detected

 

Sex : Female

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	6 - 10	TS	No abnormality detected

TS = Terminal Sacrifice

 

 2. Not specified                       

 

Interpretation of results:

other: Not irritating

Conclusions:

The test chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) was considered as not irritating.

Executive summary:

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

 

The acute dermal irritation study was conducted for the read across chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.    Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.

 

The above result was further supported by a Patch test reported by safety assessment report for another similar read across substance which was conducted on humans in accordance with IMDG code (2002) to assess the irritation potential of test chemical. About 50 mg was applied under occlusive conditions to the inner arm of 5 male volunteers for 6 hours. The test site was observed for erythema and edema till 14 days post dosing. Since the chemical did not produce any skin lesions, the test chemical was considered as not irritating to the skin.

 

Based on the above summarized studies for target chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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 and functionally 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 eye irritation studies as- WoE-2 and WoE-3.
An eye irritation study of test chemical was conducted on rabbits to assess its eye irritating effects.

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

1.not specified
2.10% solution

Duration of treatment / exposure:

not specified

Observation period (in vivo):

not specified

Duration of post- treatment incubation (in vitro):

not specified

Number of animals or in vitro replicates:

not specified

Details on study design:

not specified

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No ocular lesions were observed in traeted rabbits.

Interpretation of results:

other: not Irritating

Conclusions:

The chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) was considered as not irritating.

Executive summary:

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

 

An ocular irritation test was conducted on rabbits by peer reviewed journal to determine the eye irritation potential of read across chemical. The chemical did not induce any ocular lesions during the study. Hence the test chemical was considered as not irritating.

 

The above results were further supported by another eye irritation study reported by safety assessment report on rabbits for another read across substance.When the chemical was instilled into the eyes of each rabbit, no signs of eye irritation were observed. Hence the test chemical was considered as not irritating to the rabbits’ eyes.

 

Based on the above summarized studies for target chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

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

 

The acute dermal irritation study was conducted for the read across chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.    Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.

 

The above result was further supported by a Patch test reported by safety assessment report for another similar read across substance which was conducted on humans in accordance with IMDG code (2002) to assess the irritation potential of test chemical. About 50 mg was applied under occlusive conditions to the inner arm of 5 male volunteers for 6 hours. The test site was observed for erythema and edema till 14 days post dosing. Since the chemical did not produce any skin lesions, the test chemical was considered as not irritating to the skin.

 

Based on the above summarized studies for target chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

 

Eye irritation

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

 

An ocular irritation test was conducted on rabbits by peer reviewed journal to determine the eye irritation potential of read across chemical. The chemical did not induce any ocular lesions during the study. Hence the test chemical was considered as not irritating.

 

The above results were further supported by another eye irritation study reported by safety assessment report on rabbits for another read across substance.When the chemical was instilled into the eyes of each rabbit, no signs of eye irritation were observed. Hence the test chemical was considered as not irritating to the rabbits’ eyes.

 

Based on the above summarized studies for target chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8)  and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical  is unlikely to cause skin and eye irritation. Hence Benzenesulfonamide, 4-methyl-, reaction products with formaldehyde and melamine (CAS No: 97808-67-8)  can be classified under the category “Not Classified” for skin and eye as per CLP.