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EC number: 201-603-3 | CAS number: 85-41-6
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 999
- Reference Type:
- secondary source
- Title:
- Phthalimide - CAS No: 85-41-6
- Author:
- OECD SIDS
- Year:
- 2 005
- Bibliographic source:
- SIDS Initial Assessment Report for 20th SIAM, UNEP Publications
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD 422
- GLP compliance:
- yes
Test material
- 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: 99.9%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8 weeks for males and females
- 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
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24°C
- Humidity (%): 45-61%
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1% (w/v) methylcellulose-sodium
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Males, 46 days
Females, from 14 days before mating to day 3 post parturition - Frequency of treatment:
- one administration per day
- Duration of test:
- Duration of test: Males, 46 days
Females, from 14 days before mating to day 3 p.p.
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: every day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: every day
BODY WEIGHT: Yes
-Time schedule for examinations: male animals´ body weight was recorded on day 1, 2, 5, 7, 10, 14, 21, 28, 35, 42, 46; female animals´ body weight was recorded: before mating on day 1, 2, 5, 7, 10, 14; during gestation on day 0, 1, 3, 5, 7, 10, 14, 17, 20 after parturition on day 0, 1, 4
FOOD CONSUMPTION:
- At every body weight check (24hr consumption), except day 0 of gestation and day 0 of parturition for female
-NECROPSY: autopsy: to all animals
-Regarding to urinalysis, hematology, blood chemical and organs, please refer to endpoint summary 7.5.1 - Fetal examinations:
- -CLINICAL AND PATHOLOGICAL OBSERVATIONS FOR PUPS
general appearance: every day
-MORTALITY: every day
-BODY WEIGHT: on day 0, 1, 4
-AUTOPSY: on day 4 or when died on major organs by gross observation
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
One female in the 500 mg/kg bw/day dose group did not deliver until day 26 of gestation. Autopsy of the females revealed dilatation of the uterus and vagina, and five implantation sites. Body weights and food consumption were decreased in one female dosed with 1000 mg/kg bw/day which demonstrated abnormal findings on histopathological examination.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 500 mg/kg bw/day
- Basis for effect level:
- body weight and weight gain
- changes in pregnancy duration
- food consumption and compound intake
- histopathology: non-neoplastic
- pre and post implantation loss
- Dose descriptor:
- other: NOEL teratogenicity
- Effect level:
- 250 mg/kg bw/day
- Basis for effect level:
- other: effect type not specified
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
Eight of its pups were dead or cannibalized, and the surviving nine pups showed body weight loss. Male and female pups of the 500 and 1000 mg/kg bw/day groups showed lower body weights or body weight gains in the lactation period at day 4 (not at day 0, and 1). No pups with malformation were found in any group. No changes in pathological findings were observed in offspring
Effect levels (fetuses)
- Dose descriptor:
- NOEL
- Effect level:
- 250 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- fetal/pup body weight changes
Overall developmental toxicity
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 250 mg/kg bw/day
- Treatment related:
- not specified
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
Any other information on results incl. tables
Tab1 Developmental performance and observation on pups F1 after exposure to phthalimide
| Dose (mg/kg bw) | 0 | 250 | 500 | 100 |
| No. of pregnant animals | 12 | 12 | 12 | 12 |
| No. of corpora lutea | 17±2 | 18±3 | 18±2 | 18±2 |
| No. of implantation sites | 16±2 | 17±2 | 16±4 | 16±3 |
| Implantation index (%) | 93±8 | 96±7 | 94±11 | 86±19 |
| No. of pups born | 14±2 | 16±2 | 14±5 | 15±3 |
| Delivery index (%) | 91±7 | 94±7 | 86±27 | 98±3** |
| Live pups born | 14±2 | 15±2 | 16±3 | 15±3 |
| Live birth index (%) | 100±0 | 99±3 | 100±2 | 99±2 |
| Sex ratio (M/F) | 1.2±0.6 | 1.4±0.6 | 1.1±0.8 | 1.2±0.6 |
| Gestation length (day) | 23±1 | 23±1 | 23±1 | 22±1 |
| Gestation index (%) | 100 | 100 | 91.7 | 100 |
| Body weight of pups (g) | ||||
| Male Day 0 | 6.9±0.4 | 6.8±0.7 | 6.7±0.5 | 6.4±0.6 |
| Male Day 4 | 11±0.9 | 11±1.6 | 10±0.8* | 10±1.9* |
| Female Day 0 | 6.6±0.4 | 6.4±0.6 | 6.3±0.5 | 6.1±0.6 |
| Female Day 4 | 10±0.8 | 10±1.5 | 9±0.7** | 9±1.7* |
Values are expressed as mean ± SD. Significantly different from 0 mg/kg group; *:p<0.05, **:p<0.01
The influence of phthalimide on developmental performance was as follows: no influence on no. of dead pups, no. of pups born, sex ratio, gestation length, gestation index, nursing index, live pups on day 4. Male and female pups of the 500 and 1000 mg/kg bw/day groups showed lower body weights or body weight gains in the lactation period
Applicant's summary and conclusion
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