Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

Data available for the target chemicals was reviewed to determine the toxic nature of the test chemical Reaction mass of Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2). The studies are as mentioned below:

In a repeated-dose toxicity study, 0, 31.25, 62.5, 125, 250 or 500 mg/kg/day of test chemical was administered to 10 male and 10 female B6C3F1 mice per dose via gavage 5 days/week for 90 days. No mortality was observed. Dose-related increases in splenomegaly, and extramedullary hematopoiesis and hemosiderosis of the spleen were observed in the mice when given greater than 31.25 mg/kg/day of test chemical . Splenomegaly was reported as minimal in 4/10 mice, and extramedullary hematopoiesis and hemosiderois were reported as mild in 1/10 mice.Compound-related effects were noted in the spleen, liver, and kidney of male and female mice. The incidence and/or severity of the lesions increased with increasing dose levels, where treatment-related effects were present in all groups of treated mice at doses greater than 31.25 mg/kg/day. Therefore the NOAEL was considered to be 31.25 mg/kg/day in B6C3F1 mice for 13 weeks by oral gavage.

In a 90 day oral toxicity study, rats were administered test chemical at doses: 0, 300, 1500 or 7500 ppm (0, 65, 319 or 1756 mg/kg/day for males and 0, 91, 467 or 2316 mg/kg/day for females) The NOAEL for test chemical was determined to be 65 mg/kg/day for males rat and 467 mg/kg/day for females rat. While LOAEL for 5-amino-4-chloro-2-phenyl-2,3-dihydropyridazin-3-one (Chloridazon) was 319 mg/kg/day for males based on decreased body weight and gain, decreased food consumption and increased liver weight and decreased cholesterol and triglycerides and 2316 mg/kg/day for females rat based on slight decrease in body weight and gain, decreased food consumption and possibly decreased cholesterol and triglycerides.

Based on the data available for the test chemical Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) is not likely to be toxic by oral route as per the criteria mentioned in CLP regulation.

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 particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron to 75 micron which is much larger size range compared to the inhalable particulate matter. The study need not to be conducted because the melting point of the test chemical is above 300°C has very low vapour pressure, 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, Thus, exposure to inhalable dust, mist and vapour of the chemical Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dermal study;

The acute toxicity value for substance Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) (as provided in section 7.2.3) is in range of >2000mg/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 Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) 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:

repeated dose toxicity: oral, other

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 mention below

Principles of method if other than guideline:

WoE derived based on the experimental data from structurally and functionally similar read across chemicals

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material : Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates- Molecular formula :C8H22NO12P.Mo.W- Molecular weight : 635.02 g/mol- Smiles notation : CN(C)c1ccccc1_O=[Mo](=O)(O{-})O{-}_O=[W](=O)(O{-})O{-}_OP(O)(O)=O- Substance type: Organic- Physical state : Solid

Species:

other: 1,mouse 2,rat

Strain:

other: 1,B6C3F1 2, not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

1,TEST ANIMALS- Source: Charles River Breeding Laboratories- Age at study initiation: 6-8 weeks- Weight at study initiation: No data available- Fasting period before study: N/A- Housing: Five animals per sex were housed in polycarbonate cages in a controlled environment. - Diet (e.g. ad libitum): NIH-07 diet, ad libitum- Water (e.g. ad libitum):Tap water, ad libitum- Acclimatization period: 2 weeksENVIRONMENTAL CONDITIONS- Temperature (°F): 70-74°F- Humidity (%): 48-71%- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): 12-hr dark/12-hr light2, not specified

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE- Justification for use and choice of vehicle (if other than water): Corn oil- Concentration in vehicle: 0, 31.25, 62.5, 125, 250 and 500 mg/kg/day- Amount of vehicle (if gavage): 5 ml corn oil/kg- Lot/batch no. (if required): No data available- Purity: No data availableOther details: Gavage solutions were prepared fresh once every week and stored in brown bottles at 4°C. Doses were adjusted weekly for changes in body weights.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1,13 Weeks2,90 days

Frequency of treatment:

1,Once daily, 5 days per week2, Daily

Remarks:

Doses / Concentrations:0, 31.25, 62.5, 125, 250 or 500 mg/kg/dayBasis:actual ingested

Remarks:

0, 300, 1500 or 7500 ppm (0, 65, 319 or 1756 mg/kg/day for males and 0, 91, 467 or2316 mg/kg/day for females)

No. of animals per sex per dose:

1,Control: 10 males, 10 females31.25 mg/kg/day: 10 males, 10 females62.2 mg/kg/day: 10 males, 10 females125 mg/kg/day: 10 males, 10 females250 mg/kg/day: 10 males, 10 females500 mg/kg/day: 10 males, 10 females

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Observations and examinations performed and frequency:

1,DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: twice daily (once in the morning and once in the afternoon) for morbidity and mortalityBODY WEIGHT: YesTime schedule for examinations-WeeklyCAGE SIDE OBSERVATIONS: Yes - Time schedule: Twice daily - Cage side observations checked in table [No.?] were included.DETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: WeeklyBODY WEIGHT: Yes - Time schedule for examinations: WeeklyFOOD 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: No- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: NoFOOD 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: NoWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No- Time schedule for examinations:No dataOPHTHALMOSCOPIC EXAMINATION: No- Time schedule for examinations:No data- Dose groups that were examined:No dataHAEMATOLOGY: No- Time schedule for collection of blood:No data- Anaesthetic used for blood collection: No data- Animals fasted: No data- How many animals:No data- Parameters checked in table [No.?] were examined.No dataCLINICAL CHEMISTRY: No- Time schedule for collection of blood:No data- Animals fasted: No data- How many animals:No data- Parameters checked in table [No.?] were examined. No dataURINALYSIS: No- Time schedule for collection of urine:- Metabolism cages used for collection of urine: No data- Animals fasted: No data- Parameters checked in table [No.?] were examined. No dataNEUROBEHAVIOURAL EXAMINATION: No- Time schedule for examinations:- Dose groups that were examined:- Battery of functions tested: sensory activity / grip strength / motor activity / other:OTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: YesAll rats, including those that died during the study and those that survived to study termination, were necropsied and all gross lesions were recorded.HISTOPATOLOGY: YesTissues and organs were collected from each animal and fixed in 10% neutral buffered formalin. The fixed tissues were embedded in paraffin, sectioned at 5-6 um, and stained with hematoxylin and eosin. Selected tissues were stained with Perl's iron stain to confirm the presence of hemosiderin.

Statistics:

No data available

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

No mortality observed. Decrease in motor activity occurred in female mice at ≥125 mg/kg/day and in male mice in all treated groups, and lasted throughout the day.

Mortality:

mortality observed, treatment-related

Description (incidence):

No mortality observed. Decrease in motor activity occurred in female mice at ≥125 mg/kg/day and in male mice in all treated groups, and lasted throughout the day.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Mean body weights of all treated male mice were about 8% lower than the controls. Little difference in mean body weights was observed between treated and control female mice.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Splenomegaly was present in all mice receiving ≥125 mg/kg/day, in 7 of 10 male and 8 of 10 females at 62.5 mg/kg/day, and 4 of 10 male and 4 of 10 female mice at 31.25 mg/kg/day.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Comp.-related effects were noted in spleen,liver & kidney of male & female mice.The incidence &/or severity of the lesions increased with increasing dose levels,where treatment-related effects were present in all groups of treated mice at doses >31.65 mg

Histopathological findings: neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Hyperplasia of the bone marrow and hematopoiesis in the spleen were observed in all rats in a dose-related manner

Dose descriptor:

NOAEL

Effect level:

31.25 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effct were observed

Remarks on result:

other: No toxic effect were observed

Dose descriptor:

NOAEL

Effect level:

65 other: mg/kg/day

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant effect were observed

Remarks on result:

other: No toxic effect were observed

Dose descriptor:

NOAEL

Effect level:

467 other: mg/kg/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No significant effct were observed

Remarks on result:

other: No toxic effct were observed

Critical effects observed:

not specified

Conclusions:

The No Observed Adverse Effect level (NOAEL) for the test chemical Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates in test animals were considered to be in range of 31.25-467 mg/Kg bw.

Executive summary:

Repeated dose toxicity: Oral

Data available for the target chemicals was reviewed to determine the toxic nature of the test chemical Reaction mass of Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2). The studies are as mentioned below:

In a repeated-dose toxicity study, 0, 31.25, 62.5, 125, 250 or 500 mg/kg/day of test chemical was administered to 10 male and 10 female B6C3F1 mice per dose via gavage 5 days/week for 90 days. No mortality was observed. Dose-related increases in splenomegaly, and extramedullary hematopoiesis and hemosiderosis of the spleen were observed in the mice when given greater than 31.25 mg/kg/day of test chemical . Splenomegaly was reported as minimal in 4/10 mice, and extramedullary hematopoiesis and hemosiderois were reported as mild in 1/10 mice.Compound-related effects were noted in the spleen, liver, and kidney of male and female mice. The incidence and/or severity of the lesions increased with increasing dose levels, where treatment-related effects were present in all groups of treated mice at doses greater than 31.25 mg/kg/day. Therefore the NOAEL was considered to be 31.25 mg/kg/day in B6C3F1 mice for 13 weeks by oral gavage.

In a 90 day oral toxicity study, rats were administered test chemical at doses: 0, 300, 1500 or 7500 ppm (0, 65, 319 or 1756 mg/kg/day for males and 0, 91, 467 or 2316 mg/kg/day for females) The NOAEL for test chemical was determined to be 65 mg/kg/day for males rat and 467 mg/kg/day for females rat. While LOAEL for 5-amino-4-chloro-2-phenyl-2,3-dihydropyridazin-3-one (Chloridazon) was 319 mg/kg/day for males based on decreased body weight and gain, decreased food consumption and increased liver weight and decreased cholesterol and triglycerides and 2316 mg/kg/day for females rat based on slight decrease in body weight and gain, decreased food consumption and possibly decreased cholesterol and triglycerides.

 Based on the data available for the test chemical Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) is not likely to be toxic by oral route as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

31.25 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

Weight of evidence prepared for test chemical based on the summary of qualified publication.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

other justification

Justification for data waiving:

other:

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

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Data available for the target chemicals was reviewed to determine the toxic nature of the test chemical Reaction mass of Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2). The studies are as mentioned below:

In a repeated-dose toxicity study, 0, 31.25, 62.5, 125, 250 or 500 mg/kg/day of test chemical was administered to 10 male and 10 female B6C3F1 mice per dose via gavage 5 days/week for 90 days. No mortality was observed. Dose-related increases in splenomegaly, and extramedullary hematopoiesis and hemosiderosis of the spleen were observed in the mice when given greater than 31.25 mg/kg/day of test chemical . Splenomegaly was reported as minimal in 4/10 mice, and extramedullary hematopoiesis and hemosiderois were reported as mild in 1/10 mice. Compound-related effects were noted in the spleen, liver, and kidney of male and female mice. The incidence and/or severity of the lesions increased with increasing dose levels, where treatment-related effects were present in all groups of treated mice at doses greater than 31.25 mg/kg/day. Therefore the NOAEL was considered to be 31.25 mg/kg/day in B6C3F1 mice for 13 weeks by oral gavage.

In a 90 day oral toxicity study, rats were administered test chemical at doses: 0, 300, 1500 or 7500 ppm (0, 65, 319 or 1756 mg/kg/day for males and 0, 91, 467 or 2316 mg/kg/day for females) The NOAEL for test chemical was determined to be 65 mg/kg/day for males rat and 467 mg/kg/day for females rat. While LOAEL for 5-amino-4-chloro-2-phenyl-2,3-dihydropyridazin-3-one (Chloridazon) was 319 mg/kg/day for males based on decreased body weight and gain, decreased food consumption and increased liver weight and decreased cholesterol and triglycerides and 2316 mg/kg/day for females rat based on slight decrease in body weight and gain, decreased food consumption and possibly decreased cholesterol and triglycerides.

Based on the data available for the test chemical Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) is not likely to be toxic by oral route as per the criteria mentioned in CLP regulation.

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 particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron to 75 micron which is much larger size range compared to the inhalable particulate matter. The study need not to be conducted because the melting point of the test chemical is above 300°C has very low vapour pressure, 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, Thus, exposure to inhalable dust, mist and vapour of the chemical Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dermal study;

The acute toxicity value for substance Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) (as provided in section 7.2.3) is in range of >2000mg/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 Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2) exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver. 

Based on the observations made for test chemical , Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2)does not 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 observations made for test chemical chemicals, Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates(101357-72-2)does not 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.