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EC number: 258-038-0 | CAS number: 52605-52-4
Toxicological information
Repeated dose toxicity: oral
Currently viewing:
Administrative data
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- Experimental data fro various test chemicals
- Justification for type of information:
- WoE for the target CAS is summarized based on data from various test chemicals
Cross-reference
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- 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 is from J-check
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test (OECD TG422) was performed to evaluate the toxic nature of the test chemical upon repeated dosing by oral route.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data
- Age at study initiation: 10 weeks old / Recovery: 0, 500 mg/kg/day
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%):No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
IN-LIFE DATES: From: To: No data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- Male:42 days
Female: 42- 58 days (from 14 days before mating to day 5 of lactation) - Frequency of treatment:
- No data available
- Remarks:
- Doses / Concentrations:
0, 80, 200, 500 mg/kg/day
Basis:
actual ingested - No. of animals per sex per dose:
- No data available
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- No data available
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data
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
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: Yes
- 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: 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
- 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:
- Sacrifice and pathology
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- No data
- Statistics:
- No data
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No effect
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Male: Decrease in the body weight gain (500 mg/kg/day, tendency), Decrease in the rate of body weight gain (500 mg/kg/day)
Female: Decrease in the body weight (500 mg/kg/day), Decrease in the body weight gain (200, 500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the rate of body weight gain (Recovery 500 mg/kg/day) - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Male: No effect
Female: Decrease in the food consumption (200 and 500 mg/kg/day) - Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Male: Decrease in the WBC (200 and 500 mg/kg/day, tendency), Decrease in the RET (500 mg/kg/day), Decrease in the percentage of Eosinophil (500 mg/kg/day)
Female: Decrease in the Hct (500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the WBC (500 mg/kg/day, tendency), Decrease in the percentage of Lymphocyte (500 mg/kg/day, tendency), Decrease in the RBC (Recovery 500 mg/kg/day), Increase in the MCHC (Recovery 500 mg/kg/day) - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Male: Decrease in the AST (200 mg/kg/day), Decrease in the ALT (200 and 500 mg/kg/day), Decrease in the creatinine (500 mg/kg/day), Decrease in the beta-glb (500 mg/kg/day)
Female: No effect - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No effect
- 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):
- Male: Decrease in the spleen weight (Absolute and Relative) (200 mg/kg/day), Increase in the spleen weight (Absolute) (Recovery 500 mg/kg/day, tendency), Increase in the spleen weight (Relative) (Recovery 500 mg/kg/day), Decrease in the testes weight (Absolute) (Recovery 500 mg/kg/day)
Female: Decrease in the spleen weight (Absolute and Relative) (500 mg/kg/day) - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No effect
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Male: No effect
Female: Atrophy of white pulp in the spleen (500 mg/kg/day) - Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality: No effect
Body weight and weight gain:
Male: Decrease in the body weight gain (500 mg/kg/day, tendency), Decrease in the rat
e of body weight gain (500 mg/kg/day)
Female: Decrease in the body weight (500 mg/kg/day), Decrease in the body weight gain (200, 500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the rate of body weight gain (Recovery 500 mg/kg/day)
Food consumption and compound intake:
Male: No effect
Female: Decrease in the food consumption (200 and 500 mg/kg/day)
Food efficiency: No data
Water consumption and compound intake: No data
Opthalmoscopic examination: No data
Haematology
Male: Decrease in the WBC (200 and 500 mg/kg/day, tendency), Decrease in the RET (500 mg/kg/day), Decrease in the percentage of Eosinophil (500 mg/kg/day)
Female: Decrease in the Hct (500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the WBC (500 mg/kg/day, tendency), Decrease in the percentage of Lymphocyte (500 mg/kg/day, tendency), Decrease in the RBC (Recovery 500 mg/kg/day), Increase in the MCHC (Recovery 500 mg/kg/day)
Clinical chemistry
Male: Decrease in the AST (200 mg/kg/day), Decrease in the ALT (200 and 500 mg/kg/day), Decrease in the creatinine (500 mg/kg/day), Decrease in the betaglb (500 mg/kg/day)
Female: No effect
Urinanalysis: No effect
Neurobehaviour: No data
Organ weights
Male: Decrease in the spleen weight (Absolute and Relative) (200 mg/kg/day), Increase in the spleen weight (Absolute) (Recovery 500 mg/kg/day, tendency), Increase in the spleen weight (Relative) (Recovery 500 mg/kg/day), Decrease in the testes weight (Absolute) (Recovery 500 mg/kg/day)
Female: Decrease in the spleen weight (Absolute and Relative) (500 mg/kg/day)
Gross pathology: No effect
Histopathology
Male: No effect
Female: Atrophy of white pulp in the spleen (500 mg/kg/day) - Dose descriptor:
- NOAEL
- Effect level:
- 80 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant changes were noted
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse effect level (NOAEL) for the test chemical is considered to be 80 mg/Kg bw/day in male and female Crl:CD (SD) rats.
- Executive summary:
Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test (OECD TG422) was performed to evaluate the toxic nature of the test chemical upon repeated dosing by oral route. The test was performed onmale and female Crl:CD (SD) rats at dose levels of 0, 80, 200, 500 mg/kg/day. The animals were observed for clinical signs, body weight, food consumption, urinalysis, hematological and blood biochemistry parameters, gross and histopathological changes. On the basis of observations made, the No Observed Adverse effect level (NOAEL) for the test chemical is considered to be 80 mg/Kg bw/day in male and femaleCrl:CD (SD) rats.
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- WoE of repeated dose oral toxicity study for CAS no 52605-52-4
- Author:
- Sustainability Support Services (Europe) AB
- Year:
- 2 018
- Bibliographic source:
- WoE report, Sustainability Support Services (Europe) AB, 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- WoE for the target CAS is summarized based on data from various test chemicals
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazinium chloride
- EC Number:
- 258-038-0
- EC Name:
- 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazinium chloride
- Cas Number:
- 52605-52-4
- Molecular formula:
- C13H18Cl2N2.ClH
- IUPAC Name:
- 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazin-1-ium chloride
- Details on test material:
- - Name of the test chemical: 1-(3-chlorophenyl)-4-(3-chloropropyl) piperazine hydrochloride
- Molecular formula: C13H18Cl2N2ClH
- Molecular weight: 309.6661 g/mol
- Substance tpe: Organic
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 2. TEST ANIMALS
- Source: No data
- Age at study initiation: 10 weeks old / Recovery: 0, 500 mg/kg/day
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%):No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
IN-LIFE DATES: From: To: No data
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 2. Male:42 days
Female: 42- 58 days (from 14 days before mating to day 5 of lactation) - Frequency of treatment:
- No data available
Doses / concentrations
- Remarks:
- 2. Doses / Concentrations:
0, 80, 200, 500 mg/kg/day
Basis:
actual ingested
- No. of animals per sex per dose:
- No data available
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- No data available
Examinations
- Observations and examinations performed and frequency:
- 2. CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data
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
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: Yes
- 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: 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
- 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:
- 2. Sacrifice and pathology
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- No data
- Statistics:
- No data
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No effect
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 2. Male: Decrease in the body weight gain (500 mg/kg/day, tendency), Decrease in the rate of body weight gain (500 mg/kg/day)
Female: Decrease in the body weight (500 mg/kg/day), Decrease in the body weight gain (200, 500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the rate of body weight gain (Recovery 500 mg/kg/day) - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- 2. Male: No effect
Female: Decrease in the food consumption (200 and 500 mg/kg/day) - Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 2. Male: Decrease in the WBC (200 and 500 mg/kg/day, tendency), Decrease in the RET (500 mg/kg/day), Decrease in the percentage of Eosinophil (500 mg/kg/day)
Female: Decrease in the Hct (500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the WBC (500 mg/kg/day, tendency), Decrease in the percentage of Lymphocyte (500 mg/kg/day, tendency), Decrease in the RBC (Recovery 500 mg/kg/day), Increase in the MCHC (Recovery 500 mg/kg/day) - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 2. Male: Decrease in the AST (200 mg/kg/day), Decrease in the ALT (200 and 500 mg/kg/day), Decrease in the creatinine (500 mg/kg/day), Decrease in the beta-glb (500 mg/kg/day)
Female: No effect - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No effect
- 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):
- 2. Male: Decrease in the spleen weight (Absolute and Relative) (200 mg/kg/day), Increase in the spleen weight (Absolute) (Recovery 500 mg/kg/day, tendency), Increase in the spleen weight (Relative) (Recovery 500 mg/kg/day), Decrease in the testes weight (Absolute) (Recovery 500 mg/kg/day)
Female: Decrease in the spleen weight (Absolute and Relative) (500 mg/kg/day) - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No effect
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 2. Male: No effect
Female: Atrophy of white pulp in the spleen (500 mg/kg/day) - Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- 2. Clinical signs and mortality: No effect
Body weight and weight gain:
Male: Decrease in the body weight gain (500 mg/kg/day, tendency), Decrease in the rat
e of body weight gain (500 mg/kg/day)
Female: Decrease in the body weight (500 mg/kg/day), Decrease in the body weight gain (200, 500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the rate of body weight gain (Recovery 500 mg/kg/day)
Food consumption and compound intake:
Male: No effect
Female: Decrease in the food consumption (200 and 500 mg/kg/day)
Food efficiency: No data
Water consumption and compound intake: No data
Opthalmoscopic examination: No data
Haematology
Male: Decrease in the WBC (200 and 500 mg/kg/day, tendency), Decrease in the RET (500 mg/kg/day), Decrease in the percentage of Eosinophil (500 mg/kg/day)
Female: Decrease in the Hct (500 mg/kg/day and Recovery 500 mg/kg/day), Decrease in the WBC (500 mg/kg/day, tendency), Decrease in the percentage of Lymphocyte (500 mg/kg/day, tendency), Decrease in the RBC (Recovery 500 mg/kg/day), Increase in the MCHC (Recovery 500 mg/kg/day)
Clinical chemistry
Male: Decrease in the AST (200 mg/kg/day), Decrease in the ALT (200 and 500 mg/kg/day), Decrease in the creatinine (500 mg/kg/day), Decrease in the betaglb (500 mg/kg/day)
Female: No effect
Urinanalysis: No effect
Neurobehaviour: No data
Organ weights
Male: Decrease in the spleen weight (Absolute and Relative) (200 mg/kg/day), Increase in the spleen weight (Absolute) (Recovery 500 mg/kg/day, tendency), Increase in the spleen weight (Relative) (Recovery 500 mg/kg/day), Decrease in the testes weight (Absolute) (Recovery 500 mg/kg/day)
Female: Decrease in the spleen weight (Absolute and Relative) (500 mg/kg/day)
Gross pathology: No effect
Histopathology
Male: No effect
Female: Atrophy of white pulp in the spleen (500 mg/kg/day)
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 80 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant changes were noted
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The No Observed Adverse effect level (NOAEL) for the test chemical is considered to be 80 mg/Kg bw/day in male and female Crl:CD (SD) rats.
- Executive summary:
Data available for the test chemical was reviewed to determine the toxic nature of the target chemical. The studies are as mentioned below:
Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test (OECD TG422) was performed to evaluate the toxic nature of the test chemical upon repeated dosing by oral route. The test was performed onmale and female Crl:CD (SD) rats at dose levels of 0, 80, 200, 500 mg/kg/day. The animals were observed for clinical signs, body weight, food consumption, urinalysis, hematological and blood biochemistry parameters, gross and histopathological changes. On the basis of observations made, the No Observed Adverse effect level (NOAEL) for the test chemical is considered to be 80 mg/Kg bw/day in male and femaleCrl:CD (SD) rats.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
