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EC number: 258-038-0 | CAS number: 52605-52-4
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- 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 authoritative database J-check
Data source
Reference
- Reference Type:
- other: Authoritative database
- Title:
- Combined repeated dose and reproduction / developmental screening for test chemical
- Author:
- Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation
- Year:
- 2 010
- Bibliographic source:
- Japan chemicals collborative knowledge database (J-check),2010
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: 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 and reproduction / developmental screening was performed for test chemical
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1-methylpiperazine
- EC Number:
- 203-639-5
- EC Name:
- 1-methylpiperazine
- Cas Number:
- 109-01-3
- Molecular formula:
- C5H12N2
- IUPAC Name:
- 1-methylpiperazine
- Test material form:
- other: Liquid
- Details on test material:
- - Name of test material (as cited in study report):1-Methylpiperazine
- Molecular formula :C5H12N2
- Molecular weight :100.163g/mol
- Smiles notation :N1(CCNCC1)C
- InChl (if other than submission substance):1S/C5H12N2/c1-7-4-2-6-3-5-7/h6H,2-5H2,1H3
- Substance type:Organic
- Physical state: Liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD (SD)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Not specified
- Duration of treatment / exposure:
- Male: 42 days / - Female: 42 - 58 days (from 14 days before mating to day 5 of lactation)
- Frequency of treatment:
- daily
- Duration of test:
- 58 days
Doses / concentrations
- Remarks:
- 0,80,200,500mg/kg bw /day
- No. of animals per sex per dose:
- Not specified
- Control animals:
- not specified
- Details on study design:
- Not specified
Examinations
- Maternal examinations:
- Clinical signs, Body weight, food consumption, Organ weights, Gross pathology, Histopathology, Hematology, Food chemistry, Urinalysis
Reproductive performance - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data
- Skeletal examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data
- Head examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data - Statistics:
- Not specified
- Indices:
- Not specified
- Historical control data:
- Not specified
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- 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):
- no effects observed
- 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
- 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
- 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
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- No overall adverese effects were observed on rats (male/female) including reproductive performance.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- urinalysis
- other: No overall adverese effects were observed on rats (male/female) including reproductive performance.
- Remarks on result:
- other: No overall adverese effects were observed on rats (male/female) including reproductive performance.
Maternal abnormalities
- Abnormalities:
- not specified
- Localisation:
- not specified
Results (fetuses)
- Fetal body weight changes:
- not specified
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Skeletal malformations:
- not specified
- Visceral malformations:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- No overall adverse effects observed.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: No overall adverse effects observed.
- Remarks on result:
- other: No overall adverse effects observed.
Fetal abnormalities
- Abnormalities:
- not specified
- Localisation:
- other: not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The No Observed Adverse effect level (NOAEL) in relation to developmental toxicity for the test chemical was considered to be 500 mg/Kg bw/day in male and female Crl:CD (SD) rats for both P0 and F1 generation.
- 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 on male 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 and reproductive performance.
in male decrease in the body weight gain (500 mg/kg/day, tendency), Decrease in the rate of body weight gain (500 mg/kg/day)was observed while in 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) .in Female decrease in the food consumption (200 and 500 mg/kg/day) dose grop while 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)In female atrophy of white pulp in the spleen (500 mg/kg/day) was observed .No overall adverese effects were observed on rats (male/female) including reproductive performance.
On the basis of observations made, TheNo Observed Adverse effect level (NOAEL) in relation to reproductive toxicity for the test chemical was considered to be 500 mg/Kg bw/day in male and female Crl:CD (SD) rats for both P0 and F1 generation.
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