Registration Dossier
Registration Dossier
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EC number: 203-254-2 | CAS number: 104-94-9
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- repeated dose toxicity: oral
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed publication
Data source
Reference
- Reference Type:
- publication
- Title:
- Interlaboratory comparison of the CB6F1-Tg rasH2 rapid carcinogenicity testing model
- Author:
- R.R. Maronpot, K. Mitsumori , P. Mann , M. Takaoka , S. Yamamoto , T. Usui , H. Okamiya , S. Nishikawa, T. Nomura
- Year:
- 2 000
- Bibliographic source:
- Toxicology 146 (2000) 149–159
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Details of guidelines not mentioned in publication.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- p-anisidine
- EC Number:
- 203-254-2
- EC Name:
- p-anisidine
- Cas Number:
- 104-94-9
- Molecular formula:
- C7H9NO
- IUPAC Name:
- 4-methoxyaniline
- Reference substance name:
- 4-methoxyaniline (Synonym: p-anisidine)
- IUPAC Name:
- 4-methoxyaniline (Synonym: p-anisidine)
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- CAS No: 104-94-9
Chemical Name: 4-methoxyaniline (Synonym: p-anisidine)
Nature of chemical: Organic
Constituent 1
Constituent 2
Test animals
- Species:
- mouse
- Strain:
- CB6F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Central Institute for Experimental Animals (Kawasaki, Japan)
- Age at study initiation:≈6 week old
- Weight at study initiation: No data available
Housing: housed in polycarbonate cages (singly housed for males and 5:cage
for females) with absorbent hardwood bedding
- Diet (e.g. ad libitum): NIH-07 open formula diet (ad libitum)
- Water (e.g. ad libitum): (ad libitum)
- Acclimation period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): continuous temperature monitoring.
- Humidity (%): continuous humidity monitoring.
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12-h light:12-h dark cycle
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: Feed
- Details on oral exposure:
- Rate of preparation of diet (frequency): p-Anisidine admixed with feed at concentrations of 0.450 and 0.225%
- Mixing appropriate amounts with (Type of food): NIH-07 open formula diet - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 18 months
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
321.428 And 642.857 mg/kg (0.225 and 0.450%)
Basis:
nominal in diet
- No. of animals per sex per dose:
- 60 animal/sex/dose
- Control animals:
- yes
Examinations
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- No data available
- Statistics:
- No data available
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical signs: No clinical sighs observed in animals during study. Mortality: all animals were necropsied
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Clinical signs: No clinical sighs observed in animals during study. Mortality: all animals were necropsied
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- In male decrease in body weight and in female only in low dose mice decrease in body weight observed.
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Gross lesions included dark red spleens and small lung nodules in a few mice.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- no significant dose-related trends for either pulmonary or splenic tumors
- Details on results:
- In a combined repeated dose & carcinogenicity study using the test chemical p- anisidine the No Observed Adverse Effect Level (NOAEL) was found tobe at 642.857 mg/kg concentration of p-anisidine administered daily over an 18 month period.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 642.857 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Gross pathology and histopathology evaluations
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In a combined repeated dose & carcinogenicity study using the test chemical p- anisidine the No Observed Adverse Effect Level (NOAEL) was found tobe at 642.857 mg/kg concentration of p-anisidine administered daily over an 18 month period.
- Executive summary:
Repeated dose toxicity test was performed on CB6F1 males and female at two different laboratories in Japan and USA. p-anisidine was mixed with feed and given to animals at two different concentrations as 321.428 and 642.857 mg/kg and observed for 18 months. After 18 months all mice were necropsied and observed histopathologically. Standard hematoxylin and Eosin-stained slides were also evaluated.
After 18 months no clinical effects were observed in male and female mice. Decrease in body weight in males and some females of low dose concentration were also observed. On gross pathology dark red spleens and small lung nodules in a few mice and no significant dose-related trends for either pulmonary or splenic tumors were observed. Some effects were also observed in control also.
So on the basis of above experimental results it was concluded that the No Observed Adverse Effect Level (NOAEL) at 642.857 mg/kg concentration of p-anisidine
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