Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

The No Observed adverse effect level (NOAEL) for  test chemical  is considered to be in a dose range of 1000mg/kg bw in rats for subchronic study

Repeated dose study: Inalation

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 Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate (17372-87-1)which is reported as 8.62571e-13 mmHg at 25 C. Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron -10 micron which is much larger size range compared to the inhalable particulate matter .Thus, exposure to inhalable dust, mist and vapour of the chemical Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate is highly unlikely. Therefore this study is considered for waiver.

Repeated dose study: Dermal

The acute toxicity value for Disodium 2-(2, 4, 5, 7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate (17372-87-1) (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 Disodium 2-(2, 4, 5, 7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl) benzoate shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate 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: Refer below principle

Principles of method if other than guideline:

Weight of evidence prepared based on the data from various publication

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: 1,Charles River CD Sprague-Dawley 2,Crl:CD (SD)

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

1,TEST ANIMALS
- Source:
Female rats: Charles River Breeding Laboratories, Portage, Michigan.
Male rats: Langshaw Farms, Augusta, Michigan
- Age at study initiation: 18 weeks
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: The animals were housed in wire bottomed cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow No. 5002 ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: 4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 ± -15.5 ˚C
- Humidity (%): 50 ± 15%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hrs light/dark cycle

IN-LIFE DATES: From: To: No data

2,Details on test animal
TEST ANIMALS
- Source: No data
- Age at study initiation: 9 weeks
- Weight at study initiation: No data

Route of administration:

oral: gavage

Details on route of administration:

No data

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with water as vehicle at dose levels of 0, 100, 500 or 1500 mg/kg body weight and prepared daily

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

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: 0, 100, 500 or 1500 mg/kg bw
- Amount of vehicle (if gavage): 10 mL/Kg
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

1,14 days
2,Male: 42 days / - Female: 41 - 47 days (from 14 days before mating to day 4 of lactation)

Frequency of treatment:

Daily from 6-15 days of gestation

Remarks:

0, 100, 500 or 1500 mg/kg bw

Remarks:

Test group: 0, 40, 200 or 1000 mg/Kg/day
Recovery group: 0, 1000 mg/kg/day

No. of animals per sex per dose:

1,Total: 100 females
0 mg/Kg bw: 25 females
100 mg/Kg bw: 25 females
500 mg/Kg bw: 25 females
1500 mg/Kg bw: 25 females

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: During the study period
- Cage side observations checked in table [No.?] were included. Mortality

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: body weights were recorded on days 6, 9, 12 and 16 of gestation

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

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: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- 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 data

CLINICAL CHEMISTRY: No data
- 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 data

URINALYSIS: Yes
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: No data

Other examinations:

No data

Statistics:

No data

Clinical signs:

not specified

Description (incidence and severity):

No data

Mortality:

mortality observed, non-treatment-related

Description (incidence):

1,Survival was 100% in the controls and the groups receiving 100 and 500 mg/kg of dye. Six rats in the high-dose group (1500 mg/kg) died during the dosing period.
2, No mortality were observed at dose level of 0, 40, 200 or 1000 mg/Kg/day of treated group compare to control.

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

There were slight reductions in body-weight gains in 1500 mg/Kg bw group, compared with controls, throughout the dosing period

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:

effects observed, treatment-related

Description (incidence and severity):

Orange discoloration of the urine was noted in all treated rats during the treatment period.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

1,At autopsy, green discoloration of the amniotic fluid was noted in 1, 10 and 16 rats in the 100, 500 and 1500 mg/kg/day groups, respectively, and the small intestines were green in colour in many rats in the 500 mg/Kg group.
2,No effects were observed at dose level of 0, 40, 200 or 1000 mg/Kg/day of treated group compare to control.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

1 500 mg/kg bw (total dose)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No significant effects were noted at the mentioned dose level

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 this dose

Remarks on result:

other: No toxic effect were observed

Critical effects observed:

not specified

Conclusions:

The No Observed adverse effect level (NOAEL) for  test chemical  is considered to be in a dose range of 1000mg/kg bw in rats for subchronic study

Executive summary:

Data available for the test chemicals was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

In another combined repeated dose repro-devp. Screen was performed to determine the toxic nature of test chemical upon repeated exposure by oral route.An aqueous solution of the dye was administered by garage to groups of 25 Charles River Sprague-Dawley rats at doses of 100, 500 and 1500 mg/kg on days 6- 19 of gestation. A control group received water on a comparable basis. Individual doses were determined on the basis of body weights recorded on days 6, 9, 12 and 16 of gestation.Survival was 100% in the controls and the groups receiving 100 and 500 mg/kg of dye. Six rats in the high-dose group (1500 mg/kg) died during the dosing period. There were slight reductions in body-weight gains in 1500 mg/Kg bw group, compared with controls, throughout the dosing period.Orange discoloration of the urine was noted in all treated rats during the treatment period.At autopsy, green discoloration of the amniotic fluid was noted in 1, 10 and 16 rats in the 100, 500 and 1500 mg/kg/day groups, respectively, and the small intestines were green in colour in many rats in the 500 mg/Kg group. Based on the above observations made, the No Observed adverse effect level (NOAEL) for test chemical is considered to be 1500 mg/kg bw.

In yet another combined repeated dose and reproduction / developmental screening, study was performed to evaluate the toxic nature of Pigment Orange 13. Male and female Crl:CD (SD) rats were used in the study. The test compound was dissolved in water and used at dose levels of 0, 40, 200 or 1000 mg/Kg/day. The male rats were treated for 42 days and female rats were treated for 41-47 days. Recovery group of 0 and 1000 mg/Kg/day was also included in the study. The treated animals were noted for clinical signs, functional battery observations, body weight, food consumption, urinanalysis, hematology, blood chemistry, organ weight changes and histopathology. No adverse effects were noted in the various parameters studied. Based on the observations made, The No Observed Adverse Effect Level (NOAEL) for the test chemical is considered to be 1000 mg/Kg/day when male and female Crl: CD (SD) rats were exposed for subchronic toxicity study duration .              

Based on the data available, the No Observed adverse effect level (NOAEL) for  test chemical  is considered to be in a dose range of 1000mg/kg bw in rats for subchronic study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

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

Quality of whole database:

Waiver

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

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

 

The data available for the test chemicals Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate (17372-87-1) was reviewed to determine the toxic nature upon repeated exposure by oral, dermal and inhalation route. The studies are as mentioned below:

 

Repeated dose toxicity: Oral

In another combined repeated dose repro-devp. Screen was performed to determine the toxic nature of test chemical upon repeated exposure by oral route.An aqueous solution of the dye was administered by garage to groups of 25 Charles River Sprague-Dawley rats at doses of 100, 500 and 1500 mg/kg on days 6- 19 of gestation. A control group received water on a comparable basis. Individual doses were determined on the basis of body weights recorded on days 6, 9, 12 and 16 of gestation.Survival was 100% in the controls and the groups receiving 100 and 500 mg/kg of dye. Six rats in the high-dose group (1500 mg/kg) died during the dosing period. There were slight reductions in body-weight gains in 1500 mg/Kg bw group, compared with controls, throughout the dosing period.Orange discoloration of the urine was noted in all treated rats during the treatment period.At autopsy, green discoloration of the amniotic fluid was noted in 1, 10 and 16 rats in the 100, 500 and 1500 mg/kg/day groups, respectively, and the small intestines were green in colour in many rats in the 500 mg/Kg group. Based on the above observations made, the No Observed adverse effect level (NOAEL) for test chemical is considered to be 1500 mg/kg bw.

 

In yet another combined repeated dose and reproduction / developmental screening, study was performed to evaluate the toxic nature of Pigment Orange 13. Male and female Crl:CD (SD) rats were used in the study. The test compound was dissolved in water and used at dose levels of 0, 40, 200 or 1000 mg/Kg/day. The male rats were treated for 42 days and female rats were treated for 41-47 days. Recovery group of 0 and 1000 mg/Kg/day was also included in the study. The treated animals were noted for clinical signs, functional battery observations, body weight, food consumption, urinanalysis, hematology, blood chemistry, organ weight changes and histopathology. No adverse effects were noted in the various parameters studied. Based on the observations made, The No Observed Adverse Effect Level (NOAEL) for the test chemical is considered to be 1000 mg/Kg/day when male and female Crl: CD (SD) rats were exposed for subchronic toxicity study duration .              

 

Based on the data available, the No Observed adverse effect level (NOAEL) for  test chemical  is considered to be in a dose range of 1000mg/kg bw in rats for subchronic study.

 

Repeated dose study: Inhalation

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 Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate (17372-87-1)which is reported as 8.62571e-13 mmHg at 25 C. Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron -10 micron which is much larger size range compared to the inhalable particulate matter .Thus, exposure to inhalable dust, mist and vapour of the chemical Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dose study: Dermal

The acute toxicity value for Disodium 2-(2, 4, 5, 7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate (17372-87-1) (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 Disodium 2-(2, 4, 5, 7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl) benzoate shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

 

Based on the data available and applying the weight of evidence approach, the test chemical 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 and applying the weight of evidence approach, the test chemical 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.