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Administrative data

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.

.