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EC number: 203-464-4 | CAS number: 107-12-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 981
- Report date:
- 1981
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Remarks:
- Current study is similar to the guideline study. The measurement of thyroid hormones in dams is a new endpoint which has been added to the guideline in 2018, and has not been conducted in this study.
- Principles of method if other than guideline:
- One hundred untreated, sexually mature, virgin female Charles River COBS CD rats were used to determine teratogenic potential of the substance. The rats were approximately 14-weeks old at the time of mating. Rats were acclimated for a minimum of 10 days prior to the start of study. Animals were individually housed, except during mating. Temperature and humidity were maintained, 12-hour light and dark cycle was also controlled. Purina, certified rodent chow (5002) and tap water were provided ad libitum.
Mating.
One female and one male rat of the same strain were placed together for mating. The occurrence of copulation was determined by daily inspection for copulatory plug or by vaginal smear for sperm. The day that evidence of mating was detected was designated day 0 of gestation and the females were returned to an individual cage.
Caesarean section.
On day 20 of gestation all animals were sacrificed by carbon dioxide inhalation. Immediately following sacrifice the uterus were excised and weight prior to removal of the foetuses. The number and the location of viable and non-viable foetuses, early and late resorptions and the number of total implantations and corpora lutea were recorded. The abnormal and thoracic cavities and organs of dams were examined for grossly evident morphological changes. All foetuses were individually weight and examined for external malformations and variations, including the palate. Each foetus were externally sexed and numbered and tagged for identification.
Positive control.
Aquasol® Vitamin A was used a positive control. Fourteen sexually active female Charles River COBS CD rats were approximately 17 weeks of age at the time of mating used in the study. Vitamin A was administered orally by gavage as a single dose on day 10 of gestation at 100, 000 I.U./rat and constant volume of 2 ml/rat. The negative control group received Mazola® corn oil at constant volume of 10 ml/mg as a single daily dose from days 6 through 19 of gestation. A 100 % survival was seen in both groups. There was a mass located in the right lateral neck region in one dam (Vitamin A group), which has been identified by histopathology as mammary adenocarcinoma. A slight decrease was observed in mean maternal body weight gain over the entire gestation period. Malformations were observed in 100% of the litters examined in Vitamin A treated group, which was statistically significant. The following malformations were noted in 96.3% of examined foetuses: eye anomalies, cleft palate, facial papillae and other head anomalies, scoliosis, vertebral variations and increased incidence of 14th rudimentary ribs. - GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Propiononitrile
- EC Number:
- 203-464-4
- EC Name:
- Propiononitrile
- Cas Number:
- 107-12-0
- Molecular formula:
- C3H5N
- IUPAC Name:
- propanenitrile
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Identification: Propionitrile
Lot number: PCN sample dated October 10th, 1979 @ 1000 HRS
Batch number: PCN sample dated October 10th, 1979 @ 1000 HRS
Physico-chemical properties: Dark amber liquid, MP-91.8 °C, BP 97.2 °C
Purity: >90%
Supplier: Monsanto Company, St Louis, Missouri
Date received: November 6th, 1979
Shelf life: Stable indefinitely
Storage conditions: Ambient temperature, closed container
Test animals
- Species:
- rat
- Strain:
- other: COBS CD
- Details on test animals or test system and environmental conditions:
- One hundred untreated, sexually mature, virgin female Charles River COBS CD rats were used to determine teratogenic potential of the substance. The rats were approximately 14-weeks old at the time of mating. Rats were acclimated for a minimum of 10 days prior to the start of study. Animals were individually housed, except during mating. Temperature and humidity were maintained, 12-hour light and dark cycle was also controlled. Purina, certified rodent chow (5002) and tap water were provided ad libitum.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- One female and one male rat of the same strain were placed together for mating. The occurrence of copulation was determined by daily inspection for copulatory plug or by vaginal smear for sperm. The day that evidence of mating was detected was designated day 0 of gestation and the females were returned to an individual cage.
- Duration of treatment / exposure:
- Single dose administered on days 6 through 19 of gestation.
- Frequency of treatment:
- Daily as a single dose
- Duration of test:
- Days 0 through 20 of gestation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 20 mg/kg bw/day
- Dose / conc.:
- 40 mg/kg bw/day
- Dose / conc.:
- 80 mg/kg bw/day
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- Prior to and during the treatment animals were observed daily for mortality, overt changes in appearance and behaviour and weight changes. Animals were observed daily for mortality and clinical signs of toxicity on days 6 through 20 of gestation. Any dam not surviving to the scheduled sacrifice date was necropsied to determine the cause of death.
Maternal individual body weights were recorded on days 0, 6, 9, 12, 16 and 20 of gestation. Maternal tissue were preserved for microscopic examination in 10% neutral buffered formalin when deemed necessary by gross findings. - Ovaries and uterine content:
- Uterus weights have been reported for individual animals in all treatment and control groups.
- Fetal examinations:
- All foetuses were individually weighed and examined for external malformations and variations.
Morphological observations. All external, visceral and skeletal malformations and developmental and genetic variations were recorded.
Malformations observed: scoliosis with associated rib anomalies, bent ribs, hydrophthalmia, diaphragmic hernia, abdominal closure defect, foetal anasarca.
Total malformations of both foetuses and litters were recorded, including external, soft and skeletal tissue malformations.
Variations - developmental and genetic observed: 27 presacral vertebrae, 14th rudimentary bibs, 14th full ribs, 12 full pair of ribs with 13th rudimentary ribs, reduced ossification of scull, sternebrae 5 and /or 6 and other sternebrae unossidied, hyoid body and pubis unossidied, sternebrae misaligned, renal papillae not developed and /or distended ureter. - Statistics:
- All statistical analysis compared the treatment groups to the control group with the level of significance at p<0.05. The male to female foetal sex distribution and the number of litters with malformations were compared using Chi-square test criterion with Yates correction for 2 x 2 contingency tables and /or Fisher's exact probability test to judge significance of the difference.
The number of early and late resorptions and post implantation loss were compared by the Mann-Whitney U-test to determine the significant difference.
The mean number of viable foetuses, total implantations, corpora lutea and mean foetal body weights were compared by analysis of variance (one-way classification) Bartlett's test for homogeneity of variances and the appropriate t-test (for equal or unequal variances) using Dunnett's multiple comparisons tables to determine the significant difference. - Historical control data:
- This laboratory has historical control data on the incidence of foetal malformations and variations in this strain from the source. This laboratory has historical control data (768 animals) on the incidence of foetal malformations and variations in this strain from the source. As reported, 0 animals have died, 1 anomaly that delivered, 767 animals examined at C-section, 57 of nongravid,710 of gravid, 4 dams with only resorptions, 706 dams with live foetuses, 13.2 live foetuses/dam, 0.9 post implantation loses/dam, 14.1 implantations/dam, 15.7 of corpora lutea/dam. Foetal male : female ratio of 4710:4687. Mean foetal body weight 3.6 g.
Diaphragmic hernia was observed in foetuses in historical control.
A slight increase in the number of foetuses and litters with sternebrae and/or unossified was noted in the 40 mg/kg/day, and this number was nearly comparable to historical control.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no biologically meaningful differences in the appearance or behaviour of rats in the 20 and 40 mg/kg/day substance treated groups comparing to the control. Occasional instances of hair loss, primarily from the forelimbs, and matted haircoat were noted with similar frequency in all dosage groups.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One animal died in the 80 mg/kg/day dosage group on gestation day 9. The cause of death could not be determined at necropsy examination for this animal. Survival was 100% in the remaining treatment groups and the control group.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- There was a slight to moderate reduction in mean maternal body weight gain over the entire treatment period observed in the 80 mg/kg/day treatment group.
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Postpartum finding revealed hydrometra in one dam in the 20 mg/kg/day group. One dam in the 80 mg/kg/day group also developed hydrometra with an associated pouch (2 mm x 3 mm) containing a clear fluid extending from the right oviduct. In the 40 mg/kg/day group one dam had a mottled kidney.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In the 40 mg/kg day group one dam presented with subcutaneous hard mass (1 cm x 1 cm). The mass was removed from the left longitudinal region and histopathological examinations revealed it to be adenocarcinoma derived from mammary gland tissue.
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant post implantation loss reported only in the 80 mg/kg/day dose group, which accounted for 40 early and late resorptions in total.
- Total litter losses by resorption:
- effects observed, treatment-related
- Description (incidence and severity):
- Dams in the 80 mg/kg/day dose group had a statistically significant high number of early resorptions (total of 40 late and early resorptions) compared to the control group.
- Early or late resorptions:
- effects observed, treatment-related
- Description (incidence and severity):
- Dams in the 80 mg/kg/day dose group had a statistically significant high number of resorptions (1 late resorptions and 39 early resorptions) compared to the control group (17 resorptions, all of which were early).
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- A reduced mean maternal body weight gain was noted in the 80 mg/kg/day treatment group.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 40 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- early or late resorptions
- pre and post implantation loss
- total litter losses by resorption
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight reduction in mean foetal body weight observed in the 40 mg/kg/day group and a statistically significant reduction (p<0.01) in the 80 mg/kg/day treatment group.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight reduction in mean foetal body weight observed in the 40 mg/kg/day group and a statistically significant reduction (p<0.01) in the 80 mg/kg/day treatment group.
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Description (incidence and severity):
- There were no biologically meaningful or statistically significant differences in the number of litters with malformation in any of the treatment groups comparing to the control.
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- There was a moderate increase in the number of foetuses and litters with sternebrae ( 5 and/ or 6 unossified) and a slight increase in the number of foetuses and litters with sternebrae (1 and/ or 2, 3, and 4 unossified) in the 80 mg/kg/day group.
- Visceral malformations:
- no effects observed
- Other effects:
- not specified
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
Fetal abnormalities
- Key result
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- skeletal: sternum
- Description (incidence and severity):
- Moderate increase in the number of foetuses and litters with sternebrae ( 5 and/ or 6 unossified) and a slight increase in the number of foetuses and litters with sternebrae (1 and/ or 2, 3, and 4 unossified) in the 80 mg/kg/day group.
Overall developmental toxicity
- Key result
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 80 mg/kg bw/day
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In a reliable prenatal toxicity study the substance did not produce a teratogenic response when administered orally (via gavage) to pregnant rats at doses of up to 80 mg/kg bw/day.
- Executive summary:
Pregnant Charles River COBS CD rats were used to determine the teratogenic potential of the substance. Dose levels of 20, 40 and 80 mg/kg bw/day was administered orally by gavage as a single daily dose on gestation days 6 to 19. The control group received the vehicle (distilled water) only on a comparable regime. Caesarean sections were performed on all surviving dams on gestation day 20. There were no biologically meaningful differences in appearance, behaviour or mean maternal body weight gain in the 20 and 40 mg/kg bw/day treatment groups. There were no significant differences observed in the incidence of malformations in any of the substance treatment groups when compared to the vehicle control group. There was 100% survival in the control group and the low and mid dose groups. One animal died in the 80 mg/kg bw/day treatment group on gestation day 9, however the cause of death could not be determined. A reduced mean maternal body weight gain was noted over the entire treatment period in the high dose group. There was a statistically significant increase in the number of early resorptions and a corresponding increase in the number of post-implantation losses in the high dose group. A slight decrease in mean foetal body weight was observed in the mid dose group which was comparable to the control group. The reduction in mean foetal body weight reached statistical significance in the high dose group. An increase in the number of foetuses and litters with reduced ossification of sternebrae was noted in the high dose group. This effect was attributed to maternal toxicity and parallels the reduced mean foetal weight observed in this high dose group. The substance was considered to not produce a teratogenic response when administered to pregnant rats at dose levels of up to 80 mg/kg bw/day.
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