1-phenyl-3-pyrazolidone

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

The toxicity of test substance was tested in rats by oral exposure for 17 weeks at the dose concentration of 0, 50, 250 or 500 mg/kg bw. No adverse effects were observed at dose range of 300-500 mg/kg/day.

 

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 1-phenyl-3-pyrazolidone (92-43-3), which is reported as 0.00944 Pa. Also considering the particle size distribution of the substance the majority of the particles were found to be in the size of 150 micrometer which is much larger size range compared to the inhalable particu late matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 1-hydroxybenzotriazole is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dose toxicity: dermal

The acute toxicity value for 1-phenyl-3-pyrazolidone (92-43-3) (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 1-phenyl-3-pyrazolidone shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 1-phenyl-3-pyrazolidone 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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication.

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:

Weight of evidence prepared from various publication mention below
1,To evaluate the toxic potential of test substance in male and female rats by oral feed for 17 weeks.
2,To evaluate the toxic potential of test substance in male rats by oral gavage

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

T and had access to food and water at all times.TEST ANIMALS

TEST ANIMALS
- Housing: he animals were housed individually in wire cages
- Diet (e.g. ad libitum): Rodent diet ad libitum
- Water (e.g. ad libitum): water ad libitum

Route of administration:

oral: feed

Vehicle:

other: Rodent diet

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency):The compound was fed in the diet and fresh diets were made and distributed weekly.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Not specified.

Duration of treatment / exposure:

1,17 weeks
2, Not specified

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
1000, 2500 and 10000 ppm, corresponding to an average daily intake of 0, 50, 250 or 500 mg/kg bw
Basis:
no data

Remarks:

0and 300 mg/kg/day

No. of animals per sex per dose:

Total number of animals 80
0 mg/kg/day-10 male and 10 female
50 mg/kg/day-10 male and 10 female
250 mg/kg/day-10 male and 10 female
500 mg/kg/day-10 male and 10 female

Control animals:

yes, plain diet

Details on study design:

Groups of 10 male and 10 female Osborne-Mendel rats were given diets containing phenethyl phenylacetate at a concentration of 0, 1000, 2500 or 10000 ppm, corresponding to an average daily intake of 0, 50, 250 or 500 mg/kg bw, for 17 weeks. The compound was fed in the diet and fresh diets were made and distributed weekly. The rat's weight, food intake and general condition were recorded every week.

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD 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: Yes

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: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Haematological examinations were made at termination of the subacute studies
- Parameters checked in table [No.?] were examined. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits

CLINICAL CHEMISTRY: Not specified

URINALYSIS: Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified

IMMUNOLOGY: Not specified


OTHER: The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes , At the termination of the experiments the rats were sacrificed and exsanguinated.

HISTOPATHOLOGY: Yes , The tissues of all the rats were examined macroscopically at the time of sacrifice. These organs, the remaining abdominal and
thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 % buffered formalin-saline solution for histopathological
examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.

Other examinations:

Tissues from rats dying during the experiment were examined for gross changes and were preserved if autolysis was not advanced. Organs were not weighed but abnormalities and the suspected reason for death were noted

Statistics:

Not specified

Clinical signs:

no effects observed

Description (incidence and severity):

No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.

Mortality:

no mortality observed

Description (incidence):

No mortality were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Weekly measurement of body weight showed no significant difference between test and control animals.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Weekly measurement of food intake showed no significant difference between test and control animals.

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Description (incidence and severity):

At termination, haematological examination revealed no effects due to treatment. No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

At necropsy, no difference between test and control animals in the weights of major organs was reported.

Gross pathological findings:

no effects observed

Description (incidence and severity):

No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Gross examination of tissues from all animals revealed no remarkable changes, and histological examination of three to four animals of each sex at the high dose and from the control group revealed no treatment-related lesions.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

500 other: mg/kg bw/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 obnserved at this dose.

Dose descriptor:

NOAEL

Effect level:

300 other: mg/kg/day

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant effect were observed at this dose

Remarks on result:

other: No toxic potential was observed

Critical effects observed:

not specified

Conclusions:

The toxicity of test substance was tested in rats by oral exposure for 17 weeks at the dose concentration of 0, 50, 250 or 500 mg/kg bw. No adverse effects were observed at dose range of 300-500 mg/kg/day.

Executive summary:

Various data available for the test chemical was reviewed to determine the toxic nature of 1-phenyl-3-pyrazolidone (92-43-3) upon repeated exposure by oral route. The studies are as summarized below:

Repeated dose toxicity: Oral

Repeated dose oral study for test substance was assessed for its possible toxic potential. For this purpose Subchronic study for 17 weeks was conducted on Osborne-Mendel male and female rats. The test material was exposed at the concentration of 0, 50, 250 and 500 mg/kg bw (1000.2500 and 10000ppm)by oral feed. The animal’s weight, food intake and general condition were recorded every week. Haematological examinations were made at termination of the subacute studies. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 ~o buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. No mortality observed. No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control in clinical sign, Body weight, Food intake , Haematology, organ weight ,gross and histopathology . Hence the NOAEL was considered to be 500 mg/kg bw for test substance in male and female rats by oral feed for 17 weeks study. 

Repeated dose oral toxicity study was performed to determine the toxic nature of test substance. The test chemical was dissolved in saline at dose level of 0 or 300 mg/kg/day and fed by the oral intubation route of exposure for 7 days to male albino rats. The rats were killed 1 hrs after the last of 7 daily administrations. The animals were observed for clinical chemistry parameters including liver and plasma lipids and triglyceride and free fatty acid. No change in plasma FFA levels was observed 90 minutes after the last of 7 daily administrations of test substance. Similarly, liver and plasma triglyceride levels of test substance treated animals were comparable to those of the saline-treated control group. Based on the observations made, no observed adverse effect level (NOAEL) for male rats is considered to be 300 mg/Kg/day when they were treated orally and repeatedly for 7 days with test substance.

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:

Weight of evidence prepared from various publication mention below.

Repeated dose toxicity: inhalation - systemic effects

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

Endpoint conclusion

Endpoint conclusion:

no study available

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 1-phenyl-3-pyrazolidone (92-43-3) upon repeated exposure by oral route. The studies are as summarized below:

Repeated dose toxicity: Oral

Repeated dose oral study for test substance was assessed for its possible toxic potential. For this purpose Subchronic study for 17 weeks was conducted on Osborne-Mendel male and female rats. The test material was exposed at the concentration of 0, 50, 250 and 500 mg/kg bw (1000.2500 and 10000ppm)by oral feed. The animal’s weight, food intake and general condition were recorded every week. Haematological examinations were made at termination of the subacute studies. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 ~o buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin. No mortality observed. No significant effect were observed at doses 0, 50, 250 or 500 mg/kg bw in treated group compare to control in clinical sign, Body weight, Food intake , Haematology, organ weight ,gross and histopathology . Hence the NOAEL was considered to be 500 mg/kg bw for test substance in male and female rats by oral feed for 17 weeks study. 

Repeated dose oral toxicity study was performed to determine the toxic nature of test substance. The test chemical was dissolved in saline at dose level of 0 or 300 mg/kg/day and fed by the oral intubation route of exposure for 7 days to male albino rats. The rats were killed 1 hrs after the last of 7 daily administrations. The animals were observed for clinical chemistry parameters including liver and plasma lipids and triglyceride and free fatty acid. No change in plasma FFA levels was observed 90 minutes after the last of 7 daily administrations of test substance. Similarly, liver and plasma triglyceride levels of test substance treated animals were comparable to those of the saline-treated control group. Based on the observations made, no observed adverse effect level (NOAEL) for male rats is considered to be 300 mg/Kg/day when they were treated orally and repeatedly for 7 days with test substance.

 

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 1-phenyl-3-pyrazolidone (92-43-3), which is reported as 0.00944 Pa. Also considering the particle size distribution of the substance the majority of the particles were found to be in the size of 150 micrometer which is much larger size range compared to the inhalable particu late matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 1-hydroxybenzotriazole is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dose toxicity: dermal

The acute toxicity value for 1-phenyl-3-pyrazolidone (92-43-3) (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 1-phenyl-3-pyrazolidone shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 1-phenyl-3-pyrazolidone shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available from the test chemical, 1-phenyl-3-pyrazolidone (92-43-3) not likely to exhibit repeated dose dermal toxicity. Hence the test chemical is not likely to classify as a repeated dose dermal toxicity as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available from the test chemical, 1-phenyl-3-pyrazolidone (92-43-3) not likely to exhibit repeated dose dermal toxicity. Hence the test chemical is not likely to classify as a repeated dose dermal toxicity as per the criteria mentioned in CLP regulation.