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EC number: 203-704-8 | CAS number: 109-78-4
- 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: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study sufficient documented, meets generally scientific principles, acceptable for assessment - Evaluated small, but adequate, groups of male and female rats for a subchronic duration - Doses carefully calculated in drinking water - Only reported results were slight but significant increases in absolute weights of brain and heart - Numerical data not provided for these changes in the manuscript
Data source
Reference
- Reference Type:
- publication
- Title:
- Toxicological evaluation and pharmacokinetic profile of beta-hydroxypropionitrile in rats.
- Author:
- Sauerhoff MW, Braun WH, Ramsey JC
- Year:
- 1 976
- Bibliographic source:
- J. Toxicol. Environ. Health 2(1): 31-44
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Ninety-Day Toxicity Study: Male/female Sprague-Dawley rats were treated orally with drinking water, containing sufficient Ethylene cyanohydrin (beta-Hydroxy-propionitrile) to provide dose-levels of 0 (control), 270, 90, 30, 10 mg/kg bw (body weight) per day for 90 days.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- 3-hydroxypropiononitrile
- EC Number:
- 203-704-8
- EC Name:
- 3-hydroxypropiononitrile
- Cas Number:
- 109-78-4
- Molecular formula:
- C3H5NO
- IUPAC Name:
- 3-hydroxypropanenitrile
- Details on test material:
- Name of test material (as cited in study report): beta-Hydroxypropionitrile (beta-HPN)
- Substance type: aliphatic nitrile
- Physical state: colourlesss liquid
- Analytical purity: > 99% (by 1H-NMR)
Test substance: purified by fractional destillation and analyzed by 1H-NMR
Impurities: Ethylene glycol 0.2 +/- 0.1 wt %
Acrylonitrile 0.3 +/- 0.2 wt %
Formic acid 0.3 +/- 0.2 wt %
Acrylamide < 0.01 wt %
ß-Hydroxypropionamide 0.1 +/- 0.1 wt % (*)
a-Hydroxypropionitrile 0.12 +/- 0.03 wt % (*)
(*) probable composition of these compounds.
- Purity test date: no data
- Lot/batch No.: no data
- Stability under test conditions: stable in water under test conditions
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Spartan Research Animals Inc., Haslett, Michigan
- Age at study initiation: 6-7 weeks old
- Weight at study initiation: male: 235g; female: 195g
- Fasting period before study: no data
- Housing: individual housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
no data
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: no data
VEHICLE
- Concentration in vehicle: "To provide a constant dose of Ethylene cyanohydrine in drinking water (270, 90, 30, 10, 0 mg/kg bw a day) weekly
adjustments were made in the concentration of the test substance in drinking water to correct changes in water consumption and body weight
(bw)."
- Purity: "Fresh solutions were supplied twice a week. Water solutions, prepared on day 4, 40, and 80 of the study, were analyzed for the test
substance using gas chromatography. The anticipated concentrations of the test substance were confirmed." - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- GC-Analysis of Ethylene cyanohydrin in water solutions, administered as drinking water to the test animals.
GC-conditions: coloumn, Porapak Q; temperature: 210°C, flow: helium 40cc/min; detector: flame ionization 280°C; injector: 230°C. - Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- continuously in drinking water
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0; 10; 30; 90 and 270 mg/kg bw/day
Basis:
nominal in water
- No. of animals per sex per dose:
- 10 male, 10 female Sprague Dawley rats
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Post-exposure period: no
- Dose selection rationale: no data
- Rationale for animal assignment (if not random): randomly - Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No changes in physical appearance or demeanor were observed in any of the rats
DETAILED CLINICAL OBSERVATIONS: Yes
Table with mean cleanical chemistry values (BUN, AP; SGPT) respectiv. with mean hematologic values (RBC, Hb, Neutrophils, Lymphocytes) for the
rats (in dependance of the dosis group) is shown in table2 respectiv. table3 as an attachement in the field "attached documents".
- Time schedule for examinations of morbidity and mortality: No deaths occurred during the subchronic toxicity study.
BODY WEIGHT: Yes
- Time schedule for examinations: Mean Body weight development as a function of time (in dependance of the dosis group) is shown in figure 1 as an attachment in the field "attached documents".
other:
"Sporadic increases in food and water consumption were also not considered to be associated with treatment" - Sacrifice and pathology:
- GROSS PATHOLOGY: "Slight, but significant differences in the mean weights of the heart and brain of female rats receiving 270 and 90 mg/kg a day
were observed, but there were no gross or microscopic pathologic changes in these organs."
HISTOPATHOLOGY: No data - Other examinations:
- Hematologic evaluations and urinalysis were conducted on five rats/sex from the controls and those receiving 270 mg/kg ethylene
cyanohydrin a day.
At necropsy blood samples were collected from five rats/sex-dose for determination of the serum levels of blood urea nitrogen(BUN), alkaline
phosphatase (AP) activity, and serum glutamic pyruvic transaminase (SGPT) activity. - Statistics:
- An analysis of variance and Dunnetts test were used to determine whether Ethylen cyanohydrin induced significant alterations in body weight,
food consumption, water consumption, hematological values, clinical chemical parameters, organ weights and organ to body weight ratios. A level of significance of p<0.05 was considered indicative of significant difference between control and treated rats.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No changes in physical appearance or demeanor were observed in any of the rats and there were no deaths.
BODY WEIGHT AND WEIGHT GAIN
Compared with the control, the mean body weights of female rats receiving 30 and 90 mg/kg bw a day, Ethylene cyanohydrin were sporadically
elevated during the study. These non-dose related increases most likely were not due to the treatment.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Sporadic increases in food and water consumption were not considered to be associated with treatment.
OPHTHALMOSCOPIC EXAMINATION
no data
HAEMATOLOGY/CLINICAL CHEMISTRY
There were no treatment-related differences in the clinical chemistry or hematology parameters measured. (see: Attachment; table2 and 3)
URINALYSIS
No untowardeffects of Ethylene cyanohydrin were revealed by urinalysis including specific gravity, pH, sugar, protein, ketones, occult blood, and
bilirubin.
NEUROBEHAVIOUR
no data
ORGAN WEIGHTS
No significant differences occurred between the mean organ weights or organ to body weight ratios of male rats receiving Ethylene cyanohydrin and controls. Absolute, but not relative, brain and heart weights of females receiving 270 and 90 mg/kg bw a day were slightly but significantly p<0.05=
lower than controls. The weight differences in this tissues were not accompanied by pathologic alterations.
GROSS PATHOLOGY
Examinations were done grossly and microscopically on all tissues collected from 5 rats/sex from the control ,group and those receiving
270 mg/kg bw a day. The only alterations observed were considered to be spontaneous and unrelated to treatment with Ethylene cyanohydrin.
HISTOPATHOLOGY: NON-NEOPLASTIC
No effects
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
No effects
HISTORICAL CONTROL DATA (if applicable)
no data
OTHER FINDINGS
no data
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
No other treatment related effects were observed. Proposed mode of action - Cyanohydrin compounds are known to generate free cyanide ion. - While alpha-cyanohydrins tend to liberate cyanide more readily, beta- cyanohydrin compounds, like Ethylene cyanohydrin, are also believed to liberate cyanide ion in vivo - Free cyanide may have effects on oxygen-sensitive tissues, such as the brain and the heart - With this mechanism of action under consideration, the slight changes in absolute brain and heart weights reported additional weight. - The 90 mg/kg-day dose level was selected as a LOAEL. - The 30 mg/kg-day dose level was selected as a NOAEL.
Applicant's summary and conclusion
- Conclusions:
- Repeated dose toxicity study result: Ethylene cyanohydrin, administered in the drinking water for 90 days with dose levels ranging to 270 mg/kg bw resulted in no mortality in all dose groups. 90 and 270 mg/kg Ethylene cyanohydrin per day showed slight but significantly altered brain and heart
weights compared to the controls. No gross or microscopic pathologic changes in these organs.
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