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EC number: 202-856-2 | CAS number: 100-48-1
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 013
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
- Reference substance name:
- Isonicotinonitrile
- EC Number:
- 202-856-2
- EC Name:
- Isonicotinonitrile
- Cas Number:
- 100-48-1
- Molecular formula:
- C6H4N2
- IUPAC Name:
- pyridine-4-carbonitrile
Constituent 1
- Specific details on test material used for the study:
- purity 99.65%
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Remarks:
- Crl:CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 9 weeks old at initiation of dosing
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Remarks:
- dissolved
- Details on exposure:
- 5 mL/kg dosing volume
- Duration of treatment / exposure:
- males - 42 days dosing period
females - 42-50 days (from 14 days before mating to day 4 of lactation)
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 4 mg/kg bw/day (nominal)
- Dose / conc.:
- 20 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- Males:
7 rats/group (control and high dose groups of main study) + 5 rats/group (control and high dose
groups of recovery)
12 rats/group (low and middle dose groups of main study)
Females:
12 rats/group (all groups of main study) + 5 rats/group (control and high dose groups of recovery,
satellite without mating) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Sacrifice and pathology:
Males: day 43 of treatment and day 15 of recovery
Females: day 5 of lactation
Females (satellite): day 15 of recovery
Offspring: day 4 after birth
Examinations
- Parental animals: Observations and examinations:
- Mortality: At 100 mg/kg: Males = none; Females = 1/12 (gestation day 22, under parturition)
Clinical Signs: At 100 mg/kg: soiled perigenitalial region (M/F); decreased fecal volume (M/F)
Body weight: At 100 mg/kg, decreased weight gain initial period (MF, RF)
Food consumption: At 100 mg/kg, decreased in week 1, increased in week 2 (M/F)
Hematology: At 100 mg/kg, decreased RBC, decreased eosinophil%; increased MCH; increased MCHC (M only); increased MCV (M tendency, RM), increased RET (MF, RM), increased Plt (F only); decreased neutrophil%, increased lymphocyte% (F only)
Blood chemistry: TP inc, Alb inc, A/G inc, T-Bil inc (MF), T-Cho inc, PL inc, Glu dec, BUN dec, Cl dec (M), ALP inc, K inc, TG dec, ALT dec (F) - Oestrous cyclicity (parental animals):
- 100 mg/kg dose: prolonged estrous cycle, abnormal parturition (2/11)
- Litter observations:
- Decreased birth index, decrease number of live pups on postnatal days 0 and 4.
- Postmortem examinations (parental animals):
- Organ weight: 20 mg/kg group: liver A, R inc (M), liver R inc (F)
100 mg/kg group: liver A,R inc (MF, RM, RF); kidney A, R inc (MF); kidney A inc (RM,RF), epididymis A dec (M, RM[tendency]), epididymis R dec (M, RM[tendency])
Pathology:
20 mg/kg dose:
Liver: centrilobular hepatocyte hypertrophy (M 1/12, F 2/12), centriolobular fatty change (M 1/12).
Kidney: eosinophilic body in proximal tubule (M 7/12).
100 mg/kg dose:
Dead female (F 1/12)
Liver: centrilobular necrosis, centriolbular fatty change, centrilobular single cell necrosis, anisonucleosis
Kidney: tubular necrosis, hyaline cast
Survivals
Liver: centrilobular hepatocyte hypertrophy (M 7/7, F 11/11, RM 1/5, RF 1/5), centrilobular fatty change (M 7/7, F 9/11, RM 2/5, RF 5/5), centrilobular single cell necrosis (F 2/11), inflammatory cell nest (F 6/11, RF 5/5), anisonucleosis (F 10/11, RF 5/5), extramedullary hemapoiesis (F 2/11)
Kidney: eosinophilic body in proximal tubule (M 7/7, RM 5/5), tubular necrosis / hyaline cast (F 1/11)
Spleen: extramedullary hematopiesis (F 2/11)
Testis: tubular atrophy (M 1/7)
Epididymis: debris of spermatic elements (M 1/7)
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- At 100 mg/kg: soiled perigenitalial region (M/F); decreased fecal volume (M/F)
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- At 100 mg/kg: Males = none; Females = 1/12 (gestation day 22, under parturition)
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- At 100 mg/kg, decreased weight gain initial period (MF, RF)
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- At 100 mg/kg, decreased in week 1, increased in week 2 (M/F)
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At 100 mg/kg, decreased RBC, decreased eosinophil%; increased MCH; increased MCHC (M only); increased MCV (M tendency, RM), increased RET (MF, RM), increased Plt (F only); decreased neutrophil%, increased lymphocyte% (F only)
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- TP inc, Alb inc, A/G inc, T-Bil inc (MF), T-Cho inc, PL inc, Glu dec, BUN dec, Cl dec (M), ALP inc, K inc, TG dec, ALT dec (F)
- Urinalysis findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Description (incidence and severity):
- prolonged estrous cycle
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- abnormal parturition (2/11)
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive function (oestrous cycle)
- reproductive performance
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 100 mg/kg bw/day (nominal)
- Organ:
- cauda epididymis
- testes
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- decreased birth index, decrease number of live pups on days 0 and 4
- Gross pathological findings:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- mortality
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- yes
- Lowest effective dose / conc.:
- 100 mg/kg bw/day (nominal)
- Treatment related:
- yes
- Relation to other toxic effects:
- not specified
Applicant's summary and conclusion
- Conclusions:
- For reproductive and developmental toxicity, the endpoint for a NOAEL/NOEL was a decreased weight of epididymis and tublar atrophy of a rat, and abnormalities of delivery and a decrease in number of pups born in the 100 mg/kg dosed group. NOAEL/NOEL = 20 mg/kg/day
- Executive summary:
For reproductive and developmental toxicity, the endpoint for a NOAEL/NOEL was a decreased weight of epididymis and tublar atrophy of a rat, and abnormalities of delivery and a decrease in number of pups born in the 100 mg/kg dosed group. NOAEL/NOEL = 20 mg/kg/day
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