Registration Dossier

Administrative data

Description of key information

Repeated Dose Oral Toxicity:

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be non-toxic to living organisms when dosed repeatedly via oral route. The No Observed Adverse Effect Level can be considered to be 500mg/kgbw/day. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be classified under the category “Not Classified”.

Repeated Dose Inhalation Toxicity

A short-term toxicity study need not be conducted as because exposure of humans via inhalation route in production and/or use is not likely based on the provided thorough and rigorous exposure assessment. The estimated vapor pressure of the test chemical was 3.49E-10 mm Hg.Hence, this endpoint can be considered for waiver

Repeated Dose dermal Toxicity

A short-term toxicity study need not be conducted as because exposure of humans via dermal route in production and/or use is not likely based on the provided thorough and rigorous exposure assessment.The acute dermal LD50 of the test chemical can be considered to be >2000 mg/kgbw. Hence, this endpoint was considered for waiver.

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
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
Remarks:
Weight of evidence approach based on various test chemicals
Justification for type of information:
Weight of evidence approach based on various test chemicals
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: Weight of evidence approach based on various test chemicals
Principles of method if other than guideline:
Weight of evidence approach based on various test chemicals
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
other: 2. Sprague- Dawley; 3. Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: 2. NaCl Solution; 3. Feed Basic diet, Laboratory Diet No. 5
Details on oral exposure:
2. Details on oral exposure
VEHICLE
- Justification for use and choice of vehicle (if other than water): Since the test chemical dissolve only a little in water and may not be reabsorbed by the intestinal tract, the effect which was seen in the subcutaneous tissue of rats could well be associated with the physical properties of the compounds
- Concentration in vehicle: 200 and 300 mg/kgbw/day
- Amount of vehicle (if gavage): 0.9%
3. PREPARATION OF DOSING SOLUTIONS: Fresh diets were prepared containing the test chemical at concentrations calculated on the basis of body weight and food intake data to achieve the intended mg/kg/day intakes of 0, 250, 500 or 1000 mg/Kg/day.
DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Basic diet, Laboratory Diet No. 5
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Basic diet, Laboratory Diet No. 5
- Concentration in vehicle: 0, 250, 500 and 1500 mg/kg/day
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
3. Diets were analysed after preparation and accepted for use if the result was within 10% of the desired value.
Duration of treatment / exposure:
2. 20 weeks
3. 2 weeks
Frequency of treatment:
2. twice weekly for life
3. daily
Remarks:
Study 2.
0, 200, 300 mg/kg/day
Remarks:
study 3: 0,250,500,1000 mg/kg/day
No. of animals per sex per dose:
2. Total number of animals 240 animals
0 mg/kgbw/week,40 male and 40 females
200 mg/kgbw/week,40 male and 40 females
300 mg/kgbw/week ,40 male and 40 females
3. Total: 40
0 mg/kg/day: 5 male, 5 female
250 mg/kg/day: 5 male, 5 female
500 mg/kg/day: 5 male, 5 female
1500 mg/kg/day: 5 male, 5 female
Control animals:
yes, concurrent vehicle
Details on study design:
no data available
Positive control:
no data available
Observations and examinations performed and frequency:
2. Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:Twice daily
- Cage side observations checked in table [No.?] were included.: The test animals were checked twice daily for mortality and morbidity.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as gfood/kg body weight/day: Not specified


3. CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. No data available
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: On the first day of treatment and twice weekly throughout the study.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as gfood/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY: No data available
- 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 available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Measured over the intervals between weighings.
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination
- Anaesthetic used for blood collection: Yes, barbiturate anaesthesia was used.
- Animals fasted: Overnight fasting (with water available)
- How many animals: In control and high dose group
- Parameters checked in table [No.?] were examined: Red blood cells, haemoglobin, methaemoglobin, packed cell volume; Heinz bodies and different type of leucocytes, reticulocytes, neutrophils, e
osinophils, lymphocytes and monocytes were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At termination
- Animals fasted: No data available
- How many animals: All the 40 animals
- Parameters checked in table [No.?] were examined. urea, glucose, total protein and albumin content, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and lactic dehydrogenase were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: During the last week of treatment urine was collected over a 6-hours period, urine produced in a 6-hr period without water, in a 4- hour period commencing after 16 hours without water and in a 2- hours period immediately after an oral water load of 25 ml/kg body weight.
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined: Specific gravity, Volume, pH, Cell excretion was
examined. The renal concentrating and diluting ability were assessed by measuring the volume and specific gravity of urine produced in a 6-hr period without water, in a 4-hr period commencing after 16hr without water and in a 2-hr period immediately after an oral water load of 25 ml/kg body weight. A urinary cell count was made using the latter sample.
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER:
Organ weight: Yes, Brain, pituitary, heart, stomach, caecum (with and without its contents), kidneys, adrenals, gonads, spleen, thyroid and liver were weighed.
Sacrifice and pathology:
2. GROSS PATHOLOGY: Yes, Complete autopsies were performed on all animals and the organs were fixed in 10% buffered formalin.
HISTOPATHOLOGY: Yes , Paraplast sections from the liver, kidneys and urinary bladder and macroscopically observed abnormal tissue were routinely stained with haematoxylin and eosin
3. GROSS PATHOLOGY: Yes, all macroscopic abnormalities were noted
Organ weight: Yes, Brain, pituitary, heart, stomach, caecum (with and without its contents), kidneys, adrenals, gonads,spleen, thyroid and liver were weighed.
HISTOPATHOLOGY: Yes, Tissue that appeared abnormal was preserved in 10% buffered formalin.
Paraffin-wax sections of these tissues from the control rats and those given the highest dietary level were stained with haematoxylin and eosin for histopathological investigation. This investigation indicated the need to examine, at the intermediate dose level, the intestine and thyroids. Hence sections of these were prepared and examined.Organ and tissue examined: Brain, pituitary, heart, stomach, caecum (with and without its contents), kidneys, adrenals, gonads, spleen, thyroid and liver skin, eye and optic nerve, Harderian gland, salivary glands, trachea,oesophagus, pancreas, rectum, colon, urinary bladder, urethra, spinal cord, skeletal muscle, lymph nodes, aorta, vena cava, thymus, lung,prostate, epididymis, seminal vesicles, uterus, vagina and mammary glands and any other tissue that appeared abnormal were examined.
Statistics:
2. For statistical evaluation, only those animals were considered which had been histologically examined (effective number of animals). Survival data are from the beginning of treatment.
3. Statistical analysis of body weight, food intake, water intake, dietary substance intake, haematological examinations and organ weight were performed by using t-test, urine analysis by using (sum of ranks test, (Wilcoxon, 1945) and clinical chemistry by using the exact test of Fisher, 1934.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
2. Dose levels of 600 and 400 mg/kg body wt. of test chemical were toxic and not well tolerated by the rats which showed diarrhoea and short average survival.Therefore, after 2 and 12 weeks, respectively, treatment was discontinued for 1 week.
3. Green staining of fur, extremities and faeces was observed, the intensity of colouring related to the dose. The faeces, particularly those of the 1500 mg/kg/day dose group, were very soft and moist.
Mortality:
mortality observed, treatment-related
Description (incidence):
2. Dose levels of 600 and 400 mg/kg body wt. of test chemical were toxic and not well tolerated by the rats which showed short average survival. Therefore, after 2 and 12 weeks, respectively, treatment was discontinued for 1 week.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
2. Dose levels of 600 and 400 mg/kg body wt. of test chemical were toxic and not well tolerated by the rats which showed rapid weight loss. Therefore, after 2 and 12 weeks, respectively, treatment was discontinued for 1 week.
3. The mean body weight and the body weight gain were greater than those of the controls for all the male groups treated for 13wk. The differences in mean body weights were statistically significant for the males given 250 and 1500 mg/kg/day.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
3. The food Intakes of the treated females did not differ consistently from those of the controls, but high-dose males consumed more food than the controls throughout the study,with the average intakes being 8% higher than the controls for food.Lower dose males showed similar but less marked trends towards higher food intakes.
Calculation of the average colouring intake shows that the dose levels achieved were close to the proposed values.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
3. The water intakes of the treated females did not differ consistently from those of the controls, but high-dose males consumed more water than the controls throughout the study, with the average intakes being 23% higher than the controls for water.Lower dose males showed similar but less marked trends towards higher water intakes.Calculation of the average colouring intake shows that the dose levels achieved were close to the proposed values.
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
3. Haematological examination showed no difference between treated and control groups at wk 2 and13. At wk 6 high-dose males had a higher reticulocyte count and a lower total leucocyte count than the controls. The total leucocyte count of the 500 mg/kg/day group was also lower than that of the controls at this time. At wk 6 the high-dose females showed a higher reticulocyte count and packed cell volume, and a lower haemoglobin concentration than the control
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
3. There were a few isolated differences between the test and control groups in the results of serum analysis, including lower values for glucose concentration and lactic dehydrogenase activity in the serum of female rats given 500 or 1500 mg/kg/day for 13 wk
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
3. The results of the urine studies showed various differences between treated and control groups. The most frequent difference was in specific gravity measurements, particularly for high-dose females under conditons of water deprivation. Semi-quantitative tests showed a trend, on all occasions, towards more animals with higher levels of urinary protein in treated groups . At wk 13 more high-dose females than controls showed a positive reaction for ketones; similarly at the intermediate dose of the same sex more high-dose animals showed traces of blood.
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
3. The most consistent finding in the organ weights and relative organ weights was of slightly higher caecal weights at the highest dose level. This was evident in both sexes, when the caecum was weighed with or without its contents at wk 13. With the earlier examinations the changes were most obvious in the weight of the empty caecum of the females. There was a similar finding in the empty caecal weights at wk 13 for those animals given 500 mg/kg.The remaining organ-weight differences from the control were not dose related and were confined to either the absolute or relative weights. At the highest dose level there was a tendency for slightly higher values for kidney weight at wk 13 but this reached statistical significance only in the male absolute values. At 1500 mg/kg the stomach weight of males at wk 13 was higher than that of the controls but this was not repeated in the relative values and a change in the opposite direction was found in the corresponding females. At wk 2 the weight of the thyroids from the males at the two highest dose levels was less than that of the controls.
This was not seen in the females at the same time or in either sex at the later examinations
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
2. No significant effects were observed at the 200 and 300mg/kgbw/week of treated group compare to control.
3. Green colouring of gastro-intestinal tract were observed in all the treated animals as compared to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
2. No significant effects were observed at the 200 and 300mg/kgbw/week of treated group compare to control.
3. Histopathological examination of the tissues preserved at autopsy revealed increases in the numbers of prominent lymph nodes of the gastro-intestinal tract in female rats fed 1500 mg/kg/day for 2 or 6 wk. This effect was not seen in the females at wk 13 or in the males at any time. There was an increased incidence of a mild degree of thyroid degeneration in the females fed the highest dietary level. The only other histological finding was a slight increase in the number of animals showing protein casts in the kidneys among the males fed the highest dietary concentration for 13 wk.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
mortality
urinalysis
Critical effects observed:
no
System:
other: not specified
Conclusions:
Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be non-toxic to living organisms when dosed repeatedly via oral route. The No Observed Adverse Effect Level can be considered to be 500mg/kgbw/day. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be classified under the category “Not Classified”.
Executive summary:

Data available from different studies were reviewed to determine the repeated dose oral toxicity of test chemical. The studies are as mentioned below:

Sprague-Dawley rats received intragastric administration of the test chemical for their lifetime. The animals were exposed at the 600 and 400 mg/kg body weight/week. The dose levels of 600 and 400 mg/kg body wt. of the test chemical was not well tolerated by the rats which showed rapid weight loss, diarrhoea and short average survival. Therefore, after 2 and 12 weeks, respectively, treatment was discontinued for 1 week. As no improvement in the general health of the rats was found after a further 6 weeks, half of the original dose levels was used for the remaining treatment. Macroscopic alterations and microscopic observations were similar in experimental and control rats and were unrelated to the treatment. Age dependent alterations included amyloidosis of the kidneys and liver. Tumours found in the treated groups and not seen in controls were either isolated observations or were within the incidence of tumours commonly known to occur spontaneously in these animals. The urinary bladder and kidneys were free of neoplastic growth in the test chemical treated rats. Therefore NOAEL was considered to be 300mg/kg bw/week for the test chemical in male and female Sprague-Dawley rats by oral gavage for chronic study.

This is supported by the results of another Repeated dose sub-acute toxicity study performed to determine the toxic nature of the test chemical in rats. Wistar male and female rats were treated with the test chemical in the concentration of 0, 250, 500 and 1500 mg/kg/day orally in diet for 2 weeks. The animals were observed for clinical signs, mortality, body weight and food intake, hematology, clinical chemistry, urinalysis, gross and histopathological changes. All rats receiving the test chemical showed green staining of fur and extremities, and the urine and faeces were also coloured, with the intensity of colouring related to the dose. The faeces, particularly those of the highest dose group, were very soft and moist. The mean body weight and the bodyweight gain were greater than those of the controls for all the male groups treated for 13week. The differences in mean body weights were statistically significant for the males given 250 and 1500 mg/kg/day. The food and water intakes of the treated females did not differ consistently from those of the controls, but high-dose males consumed more food and water than the controls throughout the study, with the average intakes being 8 and 23% higher than the controls for food and water, respectively. Haematological examination showed no difference between treated and control groups at week 2 and 13. At week 6 high-dose males had a higher reticulocyte count and a lower total leucocyte count than the controls.There were a few isolated differences between the test and control groups in the results of serum analysis, including lower values for glucose concentration and lactic dehydrogenase activity in the serum of female rats given 500 or 1500 mg/kg/day for 13 week. The results of the urine studies showed various differences between treated and control groups. The most frequent difference was in specific gravity measurements, particularly for high-dose females under conditions of water deprivation. Semi-quantitative tests showed a trend, on all occasions, towards more animals with higher levels of urinary protein in treated groups. The most consistent finding in the organ weights and relative organ weights was of slightly higher caecal weights at the highest dose level. This was evident in both sexes, when the caecum was weighed with or without its contents at week 13. The remaining organ-weight differences from the control were not dose related and were confined to either the absolute or relative weights. There were few gross findings in the tissues during the post-mortem examination. The only significant difference in incidence between the test and control groups was a green colouring of the gastro-intestinal tract of all animals fed the test diets. Histopathological examination of the tissues preserved at autopsy revealed increases in the numbers of prominent lymph nodes of the gastro-intestinal tract in female rats fed 1500 mg/kg/day for 2 or 6 week. This effect was not seen in the females at week 13 or in the males at any time. There was an increased incidence of a mild degree of thyroid degeneration in the females fed the highest dietary level. Therefore, No Observed Adverse Effect level (NOAEL) was considered to be 500 mg/kg/day when Wistar male and female rats were treated with the test chemical for 2 weeks.

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be non-toxic to living organisms when dosed repeatedly via oral route. The No Observed Adverse Effect Level can be considered to be 500mg/kgbw/day. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be classified under the category “Not Classified”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Klimisch Rating 2

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Endpoint conclusion
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:
short-term repeated dose toxicity: dermal
Data waiving:
exposure considerations
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
Quality of whole database:
waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose Oral toxicity:    

Data available from different studies were reviewed to determine the repeated dose oral toxicity of test chemical. The studies are as mentioned below:

Sprague-Dawley rats received intragastric administration of the test chemical for their lifetime. The animals were exposed at the 600 and 400 mg/kg body weight/week. The dose levels of 600 and 400 mg/kg body wt. of the test chemical was not well tolerated by the rats which showed rapid weight loss, diarrhoea and short average survival. Therefore, after 2 and 12 weeks, respectively, treatment was discontinued for 1 week. As no improvement in the general health of the rats was found after a further 6 weeks, half of the original dose levels was used for the remaining treatment. Macroscopic alterations and microscopic observations were similar in experimental and control rats and were unrelated to the treatment. Age dependent alterations included amyloidosis of the kidneys and liver. Tumours found in the treated groups and not seen in controls were either isolated observations or were within the incidence of tumours commonly known to occur spontaneously in these animals. The urinary bladder and kidneys were free of neoplastic growth in the test chemical treated rats. Therefore NOAEL was considered to be 300mg/kg bw/week for the test chemical in male and female Sprague-Dawley rats by oral gavage for chronic study.

This is supported by the results of another Repeated dose sub-acute toxicity study performed to determine the toxic nature of the test chemical in rats. Wistar male and female rats were treated with the test chemical in the concentration of 0, 250, 500 and 1500 mg/kg/day orally in diet for 2 weeks. The animals were observed for clinical signs, mortality, body weight and food intake, hematology, clinical chemistry, urinalysis, gross and histopathological changes. All rats receiving the test chemical showed green staining of fur and extremities, and the urine and faeces were also coloured, with the intensity of colouring related to the dose. The faeces, particularly those of the highest dose group, were very soft and moist. The mean body weight and the bodyweight gain were greater than those of the controls for all the male groups treated for 13week. The differences in mean body weights were statistically significant for the males given 250 and 1500 mg/kg/day. The food and water intakes of the treated females did not differ consistently from those of the controls, but high-dose males consumed more food and water than the controls throughout the study, with the average intakes being 8 and 23% higher than the controls for food and water, respectively. Haematological examination showed no difference between treated and control groups at week 2 and 13. At week 6 high-dose males had a higher reticulocyte count and a lower total leucocyte count than the controls.There were a few isolated differences between the test and control groups in the results of serum analysis, including lower values for glucose concentration and lactic dehydrogenase activity in the serum of female rats given 500 or 1500 mg/kg/day for 13 week. The results of the urine studies showed various differences between treated and control groups. The most frequent difference was in specific gravity measurements, particularly for high-dose females under conditions of water deprivation. Semi-quantitative tests showed a trend, on all occasions, towards more animals with higher levels of urinary protein in treated groups. The most consistent finding in the organ weights and relative organ weights was of slightly higher caecal weights at the highest dose level. This was evident in both sexes, when the caecum was weighed with or without its contents at week 13. The remaining organ-weight differences from the control were not dose related and were confined to either the absolute or relative weights. There were few gross findings in the tissues during the post-mortem examination. The only significant difference in incidence between the test and control groups was a green colouring of the gastro-intestinal tract of all animals fed the test diets. Histopathological examination of the tissues preserved at autopsy revealed increases in the numbers of prominent lymph nodes of the gastro-intestinal tract in female rats fed 1500 mg/kg/day for 2 or 6 week. This effect was not seen in the females at week 13 or in the males at any time. There was an increased incidence of a mild degree of thyroid degeneration in the females fed the highest dietary level. Therefore, No Observed Adverse Effect level (NOAEL) was considered to be 500 mg/kg/day when Wistar male and female rats were treated with the test chemical for 2 weeks.

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be non-toxic to living organisms when dosed repeatedly via oral route. The No Observed Adverse Effect Level can be considered to be 500mg/kgbw/day. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be classified under the category “Not Classified”.

Repeated Dose Inhalation Toxicity

A short-term toxicity study need not be conducted as because exposure of humans via inhalation route in production and/or use is not likely based on the provided thorough and rigorous exposure assessment. The estimated vapor pressure of the test chemical was 3.49E-10 mm Hg.Hence, this endpoint can be considered for waiver

Repeated Dose dermal Toxicity

A short-term toxicity study need not be conducted as because exposure of humans via dermal route in production and/or use is not likely based on the provided thorough and rigorous exposure assessment.The acute dermal LD50 of the test chemical can be considered to be >2000 mg/kgbw. Hence, this endpoint was considered for waiver.

Justification for classification or non-classification

Based on the available results, the test chemical can be considered to be comparatively non-toxic when exposed repeatedly via oral, dermal and inhalation route to living organisms. Hence, the test chemical can be considered to be "Not Classified" as per CLP Regulation.