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EC number: 247-323-5 | CAS number: 25899-50-7
- 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

Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1992-09-22 to 1994-03-31
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The protocol is considered to be acceptable even if this study does not follow any guidance and even if the integral report.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Subacute inhalation toxicity
- GLP compliance:
- yes
- Remarks:
- EPA TSCA (40 CFR 792) and OECD GLP
- Limit test:
- no
Test material
- Reference substance name:
- (Z)-pent-2-enenitrile
- EC Number:
- 247-323-5
- EC Name:
- (Z)-pent-2-enenitrile
- Cas Number:
- 25899-50-7
- Molecular formula:
- C5H7N
- IUPAC Name:
- (2Z)-pent-2-enenitrile
- Details on test material:
- - Name of test material (as cited in study report): 2-pentenenitrile, (Z)-
- Physical state: light yellow liquid
- Stability under test conditions: no data
- Storage condition of test material: no data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CRL:CD BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, New York
- Age at study initiation: born approximately 1992-07-20
- Weight at study initiation: no data
- Housing: stainless steel, wire-mesh cages suspended above cageboard
- Diet: Purina Certified Rodent Chow ad libitum except during exposure
- Water: Tap water from Wilmington Suburban Water Corporation ad libitum except during exposure
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature: 23 +/- 2 °C
- Humidity: 50 +/- 10 %
- Air changes (per hr):
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: From: 1992-09-23 To: 1992-11-21
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: No data
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Method of holding animals in test chamber: rats were individually restained in perforated, stainless steel or polycarbonate cylinders with conical
nose pieces. The restainers were inserted into to face plate of a 150-L stainless steel exposure chamber sot that only the nose of each rat protruded
into the chamber
- Source and rate of air: Vapors of stripped 2-pentenenitrile were dynamically generated by infusing stripped 2-pentenenitrile into a heated
Instatherm three-neck mixing flask at a particular rate controlled by a Harvard Apparatus Compact Infusion Pump. Nitrogen, introduced into the
heated three-neck mixing flask, directed the resulting gas into the exposure chamber. Dilution air was delivered to the top of the chamber. The
stripped 2-pentenenitrile vapor was dispersed using a stainless steel baffle.
- Temperature, humidity in air chamber: targeted at 23 +/- 2 °C; 50 +/- 10 %
- Air flow rate: targeted at a rate of 33 to 35 L/min
Chamber oxygen concentrations were targeted to at least 19 % and measured with a Biosystems Model 3100R Oxygen Monitor.
- Treatment of exhaust air: test atmosphere was exhausted through a bubbler filled with 50 % H2O and 50 % acetonitrile, a cold trap filter filled with
dry ice, and a MSA filter prior to discharge into a fume hood.
TEST ATMOSPHERE
- Brief description of analytical method used: the atmospheric concentrations of the two principle components, cis-2-pentenenitrile and cis-2-methyl-2-butenenitrile, were monitored at approximately 45-minute intervals using a gas chromatographic analysis. Single or duplicate samples of
chamber atmospheres were automatically sampled and analyzed with a computer driven Hewlett-Packard Model 5880A Gas Gromatograph equipped with a flame ionization detector. The atmospheric concentrations of the two components were determined by comparing the detector response of
samples with standard curves. Standards were prepared prior to exposure by quantitatively diluting the components in air. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Gas chromatographic analysis of the chamber atmosphere (see above)
- Duration of treatment / exposure:
- 28 days (20 exposures)
- Frequency of treatment:
- 6 hours/day, 5 days/week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 3, 30, 100 and 300 ppm
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0, 3.2, 31, 102 and 292 ppm
Basis:
analytical conc.
- No. of animals per sex per dose:
- 15 animals/sex/dose:
- 5 animals/sex/dose for the subacute toxicity group
- 5 animals/sex/dose for the on-week neurotoxicity group
- 5 animals/sex/dose for the four-week neurotoxicity group - Control animals:
- yes
- Details on study design:
- Post-exposure period: 1 or 4 weeks for the neurotoxicity satellite groups, none for the other groups
- Positive control:
- For neuropathology test: data were collected for rats exposed to amphetamine, carbaryl, DDT or acrylamide.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at each weight interval
BODY WEIGHT: Yes
- Time schedule for examinations: at least twice a week
FOOD CONSUMPTION: Yes, weekly determination for the subactute toxicity group
FOOD EFFICIENCY: Yes
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on the day following the 20th exposure
- Anaesthetic used for blood collection: Yes (carbon dioxyde)
- Animals fasted: Males were not fasted prior to the evaluation, however females were fasted overnight after being allowed access to food for approximately two hours follwing removal from the exposure chambers.
- How many animals: all rats/sex/concentration assigned to the subacute toxicity group
- Parameters checked in table 7.5.3/1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:
- Animals fasted: Males were not fasted prior to the evaluation, however females were fasted overnight after being allowed access to food for approximately two hours follwing removal from the exposure chambers.
- How many animals: all rats/sex/concentration assigned to the subacute toxicity group
- Parameters checked in table 7.5.3/1 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: overnight following the 20th exposure (test days 29)
- How many animals: all rats/sex/concentration assigned to the subacute toxicity group
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table 7.5.3/1 were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to exposure, on test days 11 and 18, and 4 days following the last exposure (test day 32)
- Dose groups that were examined: 10 rats/sex/dose (rats assigned to the one-week and four-week recovery neurotoxicity group)
- Battery of functions tested:
Functional observational battery (FOB): each rat was evaluated in 3 environments: while in its home cage, upon removal from its home cage, and in a free-roaming space. Rats were counterbalanced by sex and dose groups over time to minimize the influence of uncontrolled factors.
Motor activity (MA) : rats were counterbalanced by sex and dose groups over time to minimize the influence of uncontrolled factors. - Sacrifice and pathology:
- 5 animals/sex/concentration were sacrificed on test day 29 (phenobarbital anesthesia and exsanguination) and evaluated for gross and microscopic morphological change:
-GROSS PATHOLOGY: see table 7.5.3/2
- HISTOPATHOLOGY: see table 7.5.3/2
After approximately one-week of recovery, 5 rats/sex/concentration were sacrificed and evaluated for gross pathology andneuropathology.
The remaining rats were sacrificed after approximately a four-week recovery period and were similarly evaluated for gross pathology andneuropathology. - Other examinations:
- Neuropathological assessment included gross examination of the neuromuscular system, and histopathological evaluation was performed on the following tissues/sections: brain (5 different levels of the anterio-posterior axis), spinal cord (cervical and lumbar), dorsal root ganglia (cervical and lombar), dorsal/ventral root fibers (cervical and lumbar), Gasserian ganglia, proximal sciatic and tibial nerves, and skeletal muscle (gastrocnemius).
- Statistics:
- Body weights and body weight gains were analyzed by a one-way analysis of variance. When the corresponding F-test for difference among test group means was significant, pairwise comparisons between test and control groups were made with the Dunnett‘s test. Incidence of clinical observation was evaluated by the Fisher‘s Exact test with a Bonferroni correction and the Cochran-Armitage test for trend.
Descriptions of the statistical procedures used to evaluate clinical pathology data, neurobehavioral data, neuropathology data, and pathology data are located in the report.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Compound-related mortality did not occur over the course of the exposure period or during the recovery period. The incidences and type of clinical observations were similar to control for males and females exposed to 3, 30, 100, or 300 ppm.
BODY WEIGHT AND WEIGHT GAIN
A compound-related decrease in body weight and body weight gain occurred in males at exposure concentrations of 3, 30, 100, and 300 ppm and in females at exposure concentrations of 30, 100 and 300 ppm. The lower body weight may be due in part to lower food consumption and lower food
efficiency that were observed in males at concentrations of 30 ppm and above, and in females at 300 ppm. The boby weight reduction is low in males at 3 ppm, therefore at this concentration this effect is not considered as adverse.
HAEMATOLOGY
Compound-related hematological alterations were not observed at any exposure concentration in either males or females.
CLINICAL CHEMISTRY
Serum sorbitol dehydrogenase activity was decreased in 100 and 300 ppm males and females, and in 30 ppm females. In addition, serum aspartate
aminotransferase activity was significantly decreased in the 100 and 300 ppm females. The mechanism(s) related to the decreases in serum enzyme
activity have not been determined, however, the decreased activities were considered to be compound-related and potentially adverse.
URINALYSIS
Females exposed to 300 ppm also had increased urine volume and decreased urine osmolality, which were consistent with diuresis. Diuresis was not apparent in males.
NEUROBEHAVIOUR
There were no compound-related changes in FOB or MA parameters at any exposure concentration in either males or females. There were no
compound-related gross or microscopic morphological changes in nervous tissue at any exposure concentration in either males or females.
ORGAN WEIGHTS
Differences in absolute and relative organ weights in males were considered to be secondary to decreased body weight. In females, a compound-
related increase in absolute and relative liver weights occurred at 300 ppm, and an increase in relative liver weights occurred at 100 ppm, however,
microscopic morphological changes were not evident.
HISTOPATHOLOGY: NON-NEOPLASTIC
Compound-related microscopic effects were observed in the nose of both male and female rats exposed to 30 ppm and above. These changes
consisted of primary olfactory epithelial degeneration with secondary necrotic exudate, regeneration/metaplasia, and vacuolation of the olfactory
nerve bundles.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 3 ppm
- Sex:
- male
- Basis for effect level:
- other: based on the lower body weights considered to be adverse from 30 ppm.
- Dose descriptor:
- NOAEL
- Effect level:
- 3 ppm
- Sex:
- female
- Basis for effect level:
- other: based on microscopic nasal lesions observed in female rats at 30 ppm and above, and on the changes in sorbitol dehydrogenase activity at 30 ppm and above
- Dose descriptor:
- NOAEL
- Effect level:
- 300 ppm
- Sex:
- male/female
- Basis for effect level:
- other: for neurotoxicity. No effects were observed.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
No remarks
Applicant's summary and conclusion
- Conclusions:
- NOAEL Males = 3 ppm based on the lower body weights.
NOAEL Females = 3 ppm based on microscopic nasal lesions observed in female rats at 30 ppm and above, and on the changes in sorbitol
dehydrogenase activity at 30 ppm and above.
NOAEL for neurotoxicity = 300 ppm in both males and females. - Executive summary:
This study was conducted to determine the potential subacute toxicity and neurotoxicity from repeated inhalation exposure to stripped 2-pentenenitrile. CRL:CD®BR Rats (15/sex/group) were exposed nose-only to cis-2-pentenenitrile vapor for 6 hours/day over approximately a 4-week period (total of 20 exposures) at concentrations of 0, 3, 30, 100 and 300 ppm. Each exposure group was subdivided into 3 replicates of 5 rats. For each group, 1 replicate was designated for evaluation of subacute toxicity, and the other 2 replicates were designated for neurobehavioral evaluation and neuropathology. One air-exposed control group was subjected to the same treatment and evaluation as the test groups.
The lower body weight may be due in part to lower food consumption and lower food efficiency that were observed in males at concentrations of 30 ppm and above, and in females at 300 ppm.
Compound-related mortality did not occur over the course of the exposure period or during the recovery period. The incidences and type of clinical observations were similar to control for males and females exposed to 3, 30, 100, or 300 ppm. A compound-related decrease in body weight and body weight gain occurred in males at exposure concentrations of 3, 30, 100, and 300 ppm. At 3 ppm, the body weight reduction observed in males is very low and therefore, this effect was not considered as adverse at this concentration.
Compound-related hematological alterations were not observed at any exposure concentration in either males or females. Serum sorbitol dehydrogenase activity was decreased in 100 and 300 ppm males and females, and in 30 ppm females. In addition, serum aspartate aminotransferase activity was significantly decreased in the 100 and 300 ppm females. The mechanism(s) related to the decreases in serum enzyme activity have not been determined, however, the decreased activities were considered to be compound-related and potentially adverse. Females exposed to 300 ppm also had increased urine volume and decreased urine osmolality, which were consistent with diuresis. Diuresis was not apparent in males.
There were no compound-related changes in FOB or MA parameters at any exposure concentration in either males or females. There were no compound-related gross or microscopic morphological changes in nervous tissue at any exposure concentration in either males or females.
Differences in absolute and relative organ weights in males were considered to be secondary to decreased body weight. In females, a compound-related increase in absolute and relative liver weights occurred at 300 ppm, and an increase in relative liver weights occurred at 100 ppm, however, microscopic morphological changes were not evident. Compound-related microscopic effects were observed in the nose of both male and female rats exposed to 30 ppm and above. These changes consisted of primary olfactory epithelial degeneration with secondary necrotic exudate, regeneration/metaplasia, and vacuolation of the olfactory nerve bundles.
The no-observed-adverse-effect level (NOAEL) is 3 ppm cis-2-pentenenitrile for male rats based on the lower body weights. For females, the NOAEL was 3 ppm based on microscopic nasal lesions observed in female rats at 30 ppm and above, and on the changes in sorbitol dehydrogenase activity at 30 ppm and above. Since, no neurotoxicity was observed on rats, the NOAEL for this endpoint was 300 ppm in both males and females.
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