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EC number: 221-698-5 | CAS number: 3195-78-6
Toxicological information
Developmental toxicity / teratogenicity
Currently viewing:
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 969
- Report date:
- 1969
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Pregnant female rats were treated by dermal application from day 7 to day 16 of gestation
On gestation day 21 rats were sacrified and foetuses were removed by cesarean
Maternal examinations: Cage side observation, body weight, food consumption, organ examination
Fetal examinations: body weight, sex ration, still birth/growth retarded feteouses, external examination, soft tissue examination, skeletal examination
Further investigations: number of pregnancy, resorption rate, litter size - GLP compliance:
- no
- Remarks:
- study performed prior to implementation of GLP
- Limit test:
- no
Test material
- Reference substance name:
- N-methyl-N-vinylacetamide
- EC Number:
- 221-698-5
- EC Name:
- N-methyl-N-vinylacetamide
- Cas Number:
- 3195-78-6
- Molecular formula:
- C5H9NO
- IUPAC Name:
- N-ethenyl-N-methylacetamide
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: SPF Wistar K
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: centraal proefdierendedrijf (central laboratory animal market) TNO, Zeist, Netherlands
- Weight at study initiation: 189g
- Housing: after cohabitation individual housing
- Diet: Altromin VM 1025, ad libitum
- Drinking: tap water, ad libitum
- Temperature: 22-23°C
- Humidity: 55-60%
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- water
- Remarks:
- bidestillated
- Details on exposure:
- TEST SITE
- Area of exposure: on the clipped back and flank - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Length of cohabitation: over night
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy - Duration of treatment / exposure:
- day 7 to day 16 of gestation
- Frequency of treatment:
- once daily
- Duration of test:
- until gestation day 21
Doses / concentrationsopen allclose all
- Dose / conc.:
- 400 mg/kg bw/day (nominal)
- Remarks:
- 0.08 mL
- Dose / conc.:
- 800 mg/kg bw/day (nominal)
- Remarks:
- 0.16 mL
- Dose / conc.:
- 1 600 mg/kg bw/day (nominal)
- Remarks:
- 0.32 mL
- Dose / conc.:
- 3 200 mg/kg bw/day (nominal)
- Remarks:
- 0.63 mL
- No. of animals per sex per dose:
- 20 female animals
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once per day
BODY WEIGHT: Yes
- Time schedule for examinations: once per day
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: Yes - Ovaries and uterine content:
- - On gestation day 21 rats were sacrified and foetuses were removed by cesarean
- The uterus and uterine content was examined after termination: Yes
Examinations included:
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes (50% of the foetuses), fixed in Bouin´sche solution followed by makroskopic examination (cross section analysis)
- Skeletal examinations: Yes (50% of the foetuses), fixed in 70% alcohol, dissected, eviscerated, brightened in KOH and dyed in Alizarinred S
- Head examinations: no data - Statistics:
- no data
- Indices:
- number of pregnancy, resorption rate, litter size, body weight, sex ration, still birth/growth retarded feteouses
- Historical control data:
- no data
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 1600 mg/kg bw/day and 3200 mg/kg bw/day: coat sparse and anaemic acren
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 1600 mg/kg bw/day: 1/20
3200 mg/kg bw/day: 8/20 - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 800 mg/kg bw/day: only slight influences
1600 mg/kg bw/day: body weight increased only slightly
3200 mg/kg bw/day: body weight decreased - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- 800 mg/kg bw/day and 1600 mg/kg bw/day: reduced food consumption during the first treatment days
3200 mg/kg bw/day: reduced food consumption during the treatment period - 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
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Description (incidence and severity):
- No organ abnormalities.
Bloody secretion in abdominal cavity and thoracic cavity, light brown liquid in liver and stomach. - Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- 400 mg/kg bw/day: no effect
800 mg/kg bw/day: resorptions instead of fetuses in 2/20* animals
1600 mg/kg bw/day: resorptions instead of fetuses in 7/19* animals
3200 mg/kg bw/day: resorptions instead of fetuses in 7/10* animals
Control group: resorptions instead of fetuses in 1/18* animals
* animal pregnant and survived until gestation day 21. Dose-dependent increased resorption rate also seen in delivering animals, especially in the 800 mg/kg bw/day, 1600 mg/kg bw/day, 3200 mg/kg bw/day dose group. - Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- effects observed, treatment-related
- Description (incidence and severity):
- 3200 mg/kg bw/day: Pregnancy did not occur in 10/20 animals despite sperm in vaginal smear
Control group: Pregnancy did not occur in 2/20 animals despite sperm in vaginal smear - Other effects:
- no effects observed
- Description (incidence and severity):
- Placenta: size and macroscopic examinations were considered to be within a normal range.
Effect levels (maternal animals)
- Basis for effect level:
- other: effect type not specified
- Remarks on result:
- other: No NOAEL derived.
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 400 mg/kg bw/day: slightly decreased body weight (within the normal range)
800 mg/kg bw/day: slightly decreased body weight (within the normal range)
1600 mg/kg bw/day: markly decreased body weight
3200 mg/kg bw/day: markly decreased body weight
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified - Reduction in number of live offspring:
- effects observed, treatment-related
- Description (incidence and severity):
- Still birth/growth retarded fetuses:
400 mg/kg bw/day: within the normal range
800 mg/kg bw/day: within the normal range
1600 mg/kg bw/day: within the normal range
3200 mg/kg bw/day: increased - Changes in sex ratio:
- effects observed, treatment-related
- Description (incidence and severity):
- 400 mg/kg bw/day: balanced and within the normal range
800 mg/kg bw/day: balanced and within the normal range
1600 mg/kg bw/day: balanced and within the normal range
3200 mg/kg bw/day: increased number of male offspring - Changes in litter size and weights:
- effects observed, treatment-related
- Description (incidence and severity):
- 400 mg/kg bw/day: comparable to control group
800 mg/kg bw/day: decreased in relation to increased resorption rate
1600 mg/kg bw/day: decreased in relation to increased resorption rate
3200 mg/kg bw/day: decreased in relation to increased resorption rate - Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Description (incidence and severity):
- No external abnormalities and no organ abnormalities appeared in fetuses used for skeletal examination.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- 400 mg/kg bw/day: within the normal range
800 mg/kg bw/day: within the normal range
1600 mg/kg bw/day: within the normal range
3200 mg/kg bw/day: within the normal range - Visceral malformations:
- not specified
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Cross section analysis:
Fetuses with oneside microphthalmia and anophthalmos:
400 mg/kg bw/day: 1%
800 mg/kg bw/day: 3.6%
1600 mg/kg bw/day: 6.4%
3200 mg/kg bw/day: 14.3%
Control group: 1.1%
Applicant's summary and conclusion
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.
