Trisodium 8-hydroxypyrene-1,3,6-trisulphonate

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

90 days toxicity study was conducted in rats with test substance fed at dietary levels of 50,500 and 5000mg/kg/day. (100, 1000, 10000 ppm) Therefore No Observed Adverse Effect Level (NOAEL) for repeated oral administration of test substance in rats was considered to be 500mg/kg bw for 90 days by oral feed.

 

Repeated dose toxicity: 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 Solvent Green 7 also known as Pyranine; trisodium 8-hydroxypyrene-1,3,6-trisulfonate (6358-69-6 ) which is reported as 0.0001860153mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical trisodium 8-hydroxypyrene-1,3,6-trisulfonate is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: dermal

In a two year study 60 mice were applied once a week with 3.5 mg substance (0.05 ml of a 7% solution) for 2 years. The No Observed Adverse Effect Level (NOAEL) for repeated dermal exposure to test substance  in 60 mice for 2 years is 3.5 mg (0.05 ml of a 7% solution)

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:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

data from secondary literature

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

To determine the repeated dose – oral toxicity of the test chemical .

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: feed

Vehicle:

other: feed

Details on oral exposure:

no data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
50, 500, 5000 mg/kgb.w

No. of animals per sex per dose:

no data

Control animals:

not specified

Details on study design:

no data

Positive control:

no data

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: : Yes
Time schedule: No data

BODY WEIGHT: Yes
Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
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

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

HAEMATOLOGY: Yes
Time schedule for collection of blood: No data
Anesthetic 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: Yes
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 / No / No data: Yes
Time schedule for collection of urine: No data
Metabolism cages used for collection of urine: No data
Animals fasted: Yes / No / No data: 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:

Sacrifice and pathology
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

no data

Statistics:

no data

Clinical signs:

no effects observed

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Growth was slightly retarded in males of 5000 mg/kg/day group compare to control

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No toxic effects observed at thos dose level.

Remarks on result:

other: No toxic effect were observed

Critical effects observed:

not specified

Conclusions:

90 days toxicity study was conducted in rats with test substance fed at dietary levels of 100, 1000, 10000 ppm. The No Observed Adverse Effect Level (NOAEL) for repeated oral administration of test substance is considered to be 500mg/kg bw.

Executive summary:

Sub chronic toxicity study was conducted for test substance for its possible toxic effects. The test substance was exposed to male and female rats by oral feed at the dose concentration of 50,500 and 5000 mg/kg/day(100, 1000, 10000 ppm) for 90 days . The animals were observed for clinical sign, mortality, food consumption, body weight, hematology, clinical chemistry, urine analysis, organ weight histopathology and gross pathology. Growth was slightly retarded in males of the 5000 mg/kg/day. No significant effect were observed in clinical sign, mortality, food consumption, body weight, hematology, clinical chemistry, urine analysis, organ weight histopathology and gross pathology of 50 and 500 mg/kg/day group. Therefore No Observed Adverse Effect Level (NOAEL) for repeated oral administration of test substance in rats was considered to be 500mg/kg bw for 90 days by oral feed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from 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

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Remarks:

combined repeated dose and carcinogenicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

The study was performed to determine the repeated dose – dermal toxicity of the test chemical.

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

other: topical application

Vehicle:

water

Details on exposure:

TEST MATERIAL
Amount(s) applied (volume or weight with unit): 3.5 mg
substance
Concentration (if solution): (0.05 ml of a 7% solution)
Constant volume or concentration used: yes/no: Yes

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

2 years

Frequency of treatment:

applied once a week

Remarks:

Doses / Concentrations:
3.5 mg substance (0.05 ml of a 7% solution)
Basis:
no data

No. of animals per sex per dose:

60 mice (sex not specified)

Control animals:

not specified

Details on study design:

no data

Positive control:

no data

Observations and examinations performed and frequency:

no data

Sacrifice and pathology:

no data

Other examinations:

Animals were observed for skin tumours and systemic toxicity

Statistics:

no data

Clinical signs:

not specified

Dermal irritation:

no effects observed

Mortality:

not specified

Body weight and weight changes:

not specified

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:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

Animals were observed for skin tumours and systemic toxicity

Dose descriptor:

NOAEL

Effect level:

3.5 other: mg (0.05 ml of 7% solution)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No signs of toxicity observed after 2 years

Remarks on result:

other: No toxic effects were observed

Critical effects observed:

not specified

Conclusions:

In a two year study 60 mice were applied once a week with 3.5 mg substance (0.05 ml of a 7% solution) for 2 years. The No Observed Adverse Effect Level (NOAEL) for repeated dermal exposure to test substance in 60 mice for 2 years is 3.5 mg (0.05 ml of a 7% solution)

Executive summary:

Two year toxicity study was performed to determine the repeated dose – dermal toxicity of the test chemical .60 mice were applied once a week with 3.5 mg substance (0.05 ml of a 7% solution) for 2 years. No toxicity was observed after 2 years. One mouse out of 60 developed a benign skin tumour (fibroma) near the application site. No control group was used in this study. The No Observed Adverse Effect Level (NOAEL) for repeated dermal exposure to test substance in 50 male mice for 2 years is 3.5 mg (0.05 ml of a 7% solution)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3.5 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

Data is from publication

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Various data available for the test chemical was reviewed to determine the toxic nature of Solvent Green 7 also known as Pyranine; trisodium 8-hydroxypyrene-1,3,6-trisulfonate (6358-69-6 ) upon repeated exposure by oral route. The studies are as summarized below:

Repeated dose toxicity: Oral

 Sub chronic toxicity study was conducted for test substance for its possible toxic effects. The test substance was exposed to male and female rats by oral feed at the dose concentration of 50,500 and 5000 mg/kg/day(100, 1000, 10000 ppm) for 90 days . The animals were observed for clinical sign, mortality, food consumption, body weight, hematology, clinical chemistry, urine analysis, organ weight histopathology and gross pathology. Growth was slightly retarded in males of the 5000 mg/kg/day. No significant effect were observed in clinical sign, mortality, food consumption, body weight, hematology, clinical chemistry, urine analysis, organ weight histopathology and gross pathology of 50 and 500 mg/kg/day group. Therefore No Observed Adverse Effect Level (NOAEL) for repeated oral administration of test substance in rats was considered to be 500mg/kg bw for 90 days by oral feed.

Repeated dose toxicity test were performed for test chemical on mice with different concentrations from 0.1, 0.25,0.5 or 1.0% (130,325,650,1300 mg/kg bw/d) for 80 wk. 30 males and 30 females was used for the treatment and group of 60 mice of each sex as control. The general condition and behaviour of the animals were observed frequently and any mouse that showed signs of ill-health was isolated, to be returned to its cage on recovery or to be killed if its condition deteriorated. The mice were weighed at the start of the experiment, at wk 3 and then at intervals of 2 wk until wk 73 of the experiment. Blood sample were taken at week 28 and 55.At 80 wk, blood samples were collected from the aorta of all surviving mice during the autopsy. For haematology blood samples were collected and for urine sample from 6-hr period from three groups of five mice of each sex from the controls and the groups on the two highest dietary levels of test substance. Histopathology was also conducted. There were no dose-related effects on body-weight gain, haematology or organ weights. The incidence of histopathological findings, including tumours, was not altered by the feeding of test substance. Therefore, the endpoint for the repeated dose toxicity was found to be NOAEL at 1 % (1300 mg/kg/day) concentration of test substance to mice.

In the subchronic study that was conducted to determine the adverse effects, groups of 10 males and 10 females B6C3F1 mouse was fed diets containing 0, 6,000, 12,500, 25,000, 50,000, or 100,000 mg/kg test substance or 12 weeks and then given control diets for 1 week. The animals were observed twice per day and weighed weekly. Necropsies were performed on all animals. Gross and histopathological examinations were performed on all animals. Mean body weight gain was decreased compared to controls among male mice receiving the 100,000 mg/kg diet intake level. Decreases in body weight gain were also reported for female mice at all intake levels, and was dose related from 12,500 mg/kg diet to 100,000 mg/kg diet. Gross and histopathological examinations revealed no treatment related lesions in male or female mice at any intake level. Thus, on the basis of study results the NOAEL (No observed adverse effect level) was observed to be less than 6000 ppm and 50000 ppm.

Repeated dose toxicity: 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 Solvent Green 7 also known as Pyranine; trisodium 8-hydroxypyrene-1,3,6-trisulfonate (6358-69-6 ) which is reported as 0.0001860153mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical trisodium 8-hydroxypyrene-1,3,6-trisulfonate is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dose toxicity: dermal

Two year toxicity study was performed to determine the repeated dose – dermal toxicity of the test chemical .60 mice were applied once a week with 3.5 mg substance (0.05 ml of a 7% solution) for 2 years. No toxicity was observed after 2 years. One mouse out of 60 developed a benign skin tumour (fibroma) near the application site. No control group was used in this study. The No Observed Adverse Effect Level (NOAEL) for repeated dermal exposure to test substance in 50 male mice for 2 years is 3.5 mg (0.05 ml of a 7% solution).

Repeated dermal dose toxicity test was performed on Swiss Webster mice for 19.5 months. 50 animals per sex were used and the distilled water was the vehicle.100 female and 100 male mice were used in each control group. First the hair was removed and to the depilated area dosage was applied. Each mouse was observed daily for behavior, survival and visible or palable growth. No abnormalities were observed in treated group as compare with control group and no significant change was observed in gross or histopathology. Therefore, from the study it was found that the end point for the dermal repeated dose toxicity study was found to be No Observed Adverse effect level (NOAEL) at 1428.5 mg/kg of test substance treated to mice.

In a Subcutaneous repeated dose toxicity study, Shell or Carworth Farm E SPF male and female rats were treated with test substance in the concentration of 2000 mg/kg Twice-weekly. Skin and subcutaneous tissue were examined histopathologically. Type ll tissue reactions were observed i.e. insufficient progressive lesions in treated rats. In addition, test substance shows weak physicochemical properties which indicate a self-limiting reaction (type II). Therefore, NOAEL was considered to be 2000 mg/kg when Shell or Carworth Farm E SPF male and female rats were treated with test substance Subcutaneous for 10 weeks.

Based on the data available from the test chemical, olvent Green 7 also known as Pyranine; trisodium 8-hydroxypyrene-1,3,6-trisulfonate (6358-69-6 )not likely to exhibit repeated dose oral,dermal and inhalation toxicity. Hence the test chemical is not likely to classify as per the criteria mentioned in CLP regulation.

 

Justification for classification or non-classification

Based on the data available from the test chemical, olvent Green 7 also known as Pyranine; trisodium 8-hydroxypyrene-1,3,6-trisulfonate (6358-69-6 )not likely to exhibit repeated dose oral,dermal and inhalation toxicity. Hence the test chemical is not likely to classify as per the criteria mentioned in CLP regulation.

.