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Administrative data

Description of key information

Acute oral Toxicity: 

In Acute oral toxicity,LDL0 value for target substance Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) was considered to be 142.5 mg/kg bw and MLD value was considered to be 75 mg/kg bw,and for differentstudies available on structurally similar read across substance was considered to be 55 mg/kg bw. All these studies concluded that the LD50 value is between 50- 300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) can be classified as “Category III” for acute oral toxicity.

Acute Inhalation Toxicity: 

Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5)has very low vapour pressure (0.000413 Pa =3.097754308e-6 mmHg),So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute dermal Toxicity: 

The acute dermal toxicity dose (LD50) for Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) was based on data available for the structurally and functionally similar read across chemicals. The LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) cannot be classified for acute dermal 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:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Acute oral toxicity study of test chemical Benzene-1,4-diammonium sulphate (16245-77-5) was performed in rodents.
GLP compliance:
not specified
Test type:
other:
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzene-1,4-diammonium sulphate- Molecular formula: C6H8N2.H2O4S- Molecular weight: 206.221 g/mol- Smiles notation: S(=O)(=O)(O)O.c1(ccc(cc1)N)N - InChl : 1S/C6H8N2.H2O4S/c7-5-1-2-6(8)4-3-5;1-5(2,3)4/h1-4H,7-8H2;(H2,1,2,3,4)- Substance type: organic- Physical state: Solid
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
142.5 mg/kg bw
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
female
Dose descriptor:
LDLo
Effect level:
142.5 mg/kg bw
Based on:
test mat.
Remarks on result:
other: converted value from the Source chemical (conversion factor: 1.90)
Mortality:
mortality was observed
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Based on data on benzene-1,4 -diamine (Source chemical), benzene-1,4 -diammonium sulphate is considered as toxic if swallowed. The converted LDLo is 142.5 mg/kg bw.
Executive summary:

Benzene-1,4 -diamine induced deaths at 100 and 75 mg/kg and severe clinical signs at 50 mg/kg after a single administration by the oral route to female Sprague-Dawley rats. No mortality and no clinical signs were noted at 25 mg/kg, whereas orange traces in the bedding were observed, probably related to orange-coloured urine. In conclusion, the minimal lethal dose (LDLo) was 75 mg/kg, the maximal non-lethal dose was 50 mg/kg and the no observed adverse effect level (NOAEL) was 25 mg/kg.Based on this data, benzene-1,4 -diammonium sulphate is considered as toxic if swallowed. The converted LDLo is 142.5 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
142.5 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from study report

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
WoE report is based on two acute oral toxicity studies as- 1.and 2. 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
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzene-1,4-diammonium sulphate- Molecular formula: C6H8N2.H2O4S- Molecular weight: 206.221 g/mol- Smiles notation: S(=O)(=O)(O)O.c1(ccc(cc1)N)N - InChl : 1S/C6H8N2.H2O4S/c7-5-1-2-6(8)4-3-5;1-5(2,3)4/h1-4H,7-8H2;(H2,1,2,3,4)- Substance type: organic- Physical state: Solid
Species:
other: 1. rabbit 2. rat
Strain:
other: 1. not specified 2.Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
1. not specified2. 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 : MaleMean : 249.20 g (= 100 %)Minimum : 243.9 g (- 2.13 %)Maximum : 255.3 g (+ 2.45 %)Total No. of animals : 5FemaleMean : 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
Type of coverage:
other: 1. dermal 2.semiocclusive
Vehicle:
other: 1.not specified 2.Distilled water
Details on dermal exposure:
1. not specified2. 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. TEST MATERIAL - Amount(s) applied (volume or weight with unit): 2000 mg/kg bw - Constant volume or concentration used: No data available - For solids, paste formed: Yes VEHICLE - Amount(s) applied (volume or weight with unit): No data available - Concentration (if solution): No data available - Lot/batch no. (if required): No data available - Purity: No data available
Duration of exposure:
1. not specified2. 24 hours
Doses:
1. 4000 mg/kg bw2. A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
No. of animals per sex per dose:
1. not specified2. 10 (5/sex).
Control animals:
not specified
Details on study design:
1. not specified2. - 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, 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. Evaluation of Dermal Reaction:Dermal reaction was observed daily for study period of 14 days. 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.
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Sex:
male/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. No Mortality observed at 4000 mg/kg2. Sex : MaleGroup I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.Sex : FemaleGroup I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Clinical signs:
1.not specified 2. Sex : MaleGroup 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. Sex : FemaleGroup 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.
Body weight:
1. not specified2. Sex : MaleGroup 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 : FemaleGroup 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 pathology:
1. not specified2. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
Other findings:
1. not specified2.- Other observations:Evaluation of Dermal ReactionSex : MaleGroup 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 : FemaleGroup 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.
Interpretation of results:
other: not classified
Conclusions:
According to CLP regulation,the test chemical Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.
Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the Acute dermal toxicity of the test chemical Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5).The studies are as mentioned below:

1.Acute Dermal toxicity study was conducted in rabbits using test chemical at the concentration of 4000 mg/kg bw. No Mortality observed at 4000 mg/kg. Therefore, LD50 was considered to be >4000 mg/kg bw, when rabbits were treated with test chemical by dermal application to the skin.

2.The acute dermal toxicity profile of test chemical in Sprague Dawley rats.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.Hence, The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with test chemical  by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above summarised studies, Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) cannot be classified for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from peer-reviewed journal

Additional information

Acute Oral Toxicity: 

Data available for the structurally similar read across chemicals has been reviewed to determine the acute oral toxicity of the Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5).The studies are as mentioned below:

The experimental study mentioned in study report for the target chemical Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5)was designed and conducted for acute oral toxicity.Benzene-1,4 -diamine induced deaths at 100 and 75 mg/kg and severe clinical signs at 50 mg/kg after a single administration by the oral route to female Sprague-Dawley rats. No mortality and no clinical signs were noted at 25 mg/kg, whereas orange traces in the bedding were observed, probably related to orange-coloured urine. In conclusion, the minimal lethal dose (LDLo) was 75 mg/kg, the maximal non-lethal dose was 50 mg/kg and the no observed adverse effect level (NOAEL) was 25 mg/kg.Based on this data, benzene-1,4 -diammonium sulphate is considered as toxic if swallowed. The converted LDLo is 142.5 mg/kg bw.

The above study is supported by another experimental study mentioned in study report for thestructurally similar read across substancewas designed and conducted for acute oral toxicity.Under the designated experimental conditions of the study, a single administration of the test substance by the oral route to female Sprague-Dawley rats induced deaths at 100 and 75 mg/kg and severe clinical signs at 50 mg/kg. No mortality and no clinical signs were noted at 25 mg/kg, whereas orange traces in the bedding were observed, probably related to orange-coloured urine. In conclusion, the minimal lethal dose of the test substance following single oral gavage to fasted rats was 75 mg/kg, the maximal non-lethal dose was 50 mg/kg and the no observed adverse effect level (NOAEL) was 25 mg/kg.

Both these experimental studies are again supported with the structurally similar read across substance.In a acute oral toxicity study, rat were treated with test chemical in the concentration of 55 mg/kg bw orally. 50% mortality was observed in treated rats at 55 mg/kg bw. Convulsions or Effect On Seizure Threshold and Mydriasis (Pupillary Dilation) in Eye were observed in treated rats. Changes in Structure or Function of Salivary Glands were observed in treated rats. Therefore,LD50 was considered to be 55 mg/kg bw,when rat were treated with test chemical orally.

Thus, based on the above summarised studies onBenzene-1,4-diammonium sulphate (CAS no.: 16245-77-5)and it’s structurally similar read across substance, it can be concluded that LD50 value is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) can be classified as “Category III” for acute oral toxicity.

Acute Inhalation Toxicity: 

Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5)has very low vapour pressure (0.000413 Pa =3.097754308e-6 mmHg),So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute dermal Toxicity: 

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the Acute dermal toxicity of the test chemical Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5).The studies are as mentioned below:

1.Acute Dermal toxicity study was conducted in rabbits using test chemical at the concentration of 4000 mg/kg bw. No Mortality observed at 4000 mg/kg. Therefore, LD50 was considered to be >4000 mg/kg bw, when rabbits were treated with test chemical by dermal application to the skin.

2.The acute dermal toxicity profile of test chemical in Sprague Dawley rats.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.Hence, The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with test chemical  by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above summarised studies, Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies on Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5)and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is between 50-300 mg/kg bw for acute oral toxicity and >2000 mg/kg bw acute dermal toxicity.Thus, comparing this value with the criteria of CLP regulation,Benzene-1,4-diammonium sulphate (CAS no.: 16245-77-5) can be classified as “Category III” for acute oral toxicity and cannot be classified for acutedermal toxicity.For Acute inhalation toxicity wavier was added so, not possible to classify.