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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Toxicity Testing Reports of Environmental Chemicals
Author:
MHW Japan (1999). Toxicity Testing Reports of Environmental Chemicals 7, 97-124.
Year:
1999
Bibliographic source:
Chemicals Investigations Promoting Council 7:97-124.
Reference Type:
secondary source
Title:
Phthalimide - CAS No: 85-41-6
Author:
OECD SIDS
Bibliographic source:
SIDS Initial Assessment Report for 20th SIAM, UNEP Publications

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)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Phthalimide
EC Number:
201-603-3
EC Name:
Phthalimide
Cas Number:
85-41-6
Molecular formula:
C8H5NO2
IUPAC Name:
1H-isoindole-1,3(2H)-dione
Details on test material:
- Name of test material (as cited in study report): phthalimide
- Analytical purity: > 99%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks old (male and female rats)
- Weight at study initiation: 350-402 g for male, 195-257 g for female
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Carboxymethylcellulose sodium 1%
Duration of treatment / exposure:
Males, 46 days
Females, from 14 days before mating to day 3 of lactation (at least 38 days)
Frequency of treatment:
Once a day
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 250, 500, 1000 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: none

Examinations

Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS AND FREQUENCY
Clinical signs and mortality: every day

BODY WEIGHT: Yes
Body weight: male: day 1, 2, 5, 7, 10, 14, 21, 28, 35, 42, 46; female: before mating day 1, 2, 5, 7, 10, 14; during gestation: day 0, 1, 3, 5, 7, 10, 14, 17, 20; after parturition: day 0, 1, 4

FOOD CONSUMPTION
Food consumption: at every body weight check (24h consumption), except day 0 of gestation and day 0 of parturition for female water
consumption: not checked

URINALYSIS: Yes
Urinalysis: performed in all males at day 43-44; pH, protein, sugar, ketones, urobilinogen, bilirubin, occult blood, specific gravity, deposit and appearance

HAEMATOLOGY: Yes
Hematology: performed in all males at day 46; erythrocyte count, MCV, platelet count, leukocyte count, hemoglobin, hematocrit, MCH, mean corpuscular hemoglobin (MCHC), differential leukocyte count, PT (prothrombin time) and ATPP (activated partial thromboplastin time)

CLINICAL CHEMISTRY: Yes
Blood biochemical: Same sample as hematology was used; total protein, albumin, albumin/globulin (A/G) ratio, GOT, GPT, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholin esterase (Ch-E), gamma-GTP, total bilirubin, glucose, total cholesterol, triglyceride, phospholipids, urea nitrogen, creatinine, sodium, potassium, chlorine, calcium and inorganic phosphorus

NEUROBEHAVIOURAL EXAMINATION: No
OPHTHALMOSCOPIC EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes: brain, lung, heart, liver, kidneys, spleen, adrenal, pituitary gland, thymus, thyroids, testis, epididymides and ovaries, number of implants and corpora lutea
HISTOPATHOLOGY: Yes : lung, cecum, liver, kidney, testis, epididymis, prostate, spleen, mediastinal lymph node, renal lymph node, lumbar lymph node, pituitary gland, adrenal and skin

Results and discussion

Results of examinations

Details on results:
Males:
No effects of phthalimide were detected on general appearance, body weight, food consumption, organ weights, autopsy, gross pathology, urinalysis, hematological or biochemical parameters, or histopathological findings in males.

Females:
Histopathological examination revealed periportal fatty change in the liver, renal epithelial fatty change, and atrophy in the thymus in one female given 1000 mg/kg. No effects of phthalimide were detected on general appearance, body weight, food consumption, organ weights, autopsy gross pathology of females, or by histopathological examination of the other females.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: In one female given 1000 mg/kg bw/day body weight and food consumption were decreased, and histopathological examination revealed periportal fatty change in the liver, renal epithelial fatty change, and atrophy in the thymus
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Sex:
male

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion