Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 202-855-7 | CAS number: 100-47-0
- 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
Endpoint summary
Administrative data
Description of key information
Several sub-acute and sub-chronic studies (up to 90 days) are available for the oral and inhalation route.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 40 mg/kg bw/day (nominal)
- Remarks:
- Basis:
actual ingested - No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 40 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: mortality; body weight; gross pathology; behavior
- Critical effects observed:
- not specified
- Conclusions:
- Application or 40 mg benzonitrile/kg/d for 28 days did not cause any adverse effect in Wistar rats.
- Executive summary:
Application or 40 mg benzonitrile/kg/d for 28 days did not cause any adverse effect in Wistar rats.
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1994
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 2 weeks
- Frequency of treatment:
- daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 22 mg/kg bw/day (nominal)
- Dose / conc.:
- 66 mg/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Dose / conc.:
- 600 mg/kg bw/day (nominal)
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Dose descriptor:
- dose level: LD100
- Effect level:
- 2 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: animals died within 2 days
- Dose descriptor:
- LOAEL
- Effect level:
- 600 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No mortality; ataxia, hypoactivity; histopathology: karyomegaly and necrosis in hepatocytes
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Critical effects observed:
- not specified
- Conclusions:
- Application of 2000 mg benzonitrile/kg/day in mouse leads to symptoms of poisoning. All animals died within 2 days. At 600 mg/kg/d no mortality was reported but ataxia and hypoactivity was reported. Histopathology revealed karyomegaly and necrosis in hepatocytes. The NOAEL was 200 mg/kg.
- Executive summary:
Application of 2000 mg benzonitrile/kg/day in mouse leads to symptoms of poisoning. All animals died within 2 days. At 600 mg/kg/d no mortality was reported but ataxia and hypoactivity was reported. Histopathology revealed karyomegaly and necrosis in hepatocytes. The NOAEL was 200 mg/kg.
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1994
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 14 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 11 mg/kg bw/day (nominal)
- Dose / conc.:
- 33 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Dose descriptor:
- dose level: LD100
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: Application of 1000 mg/kg/day in rat leads to symptoms of poisoning (ataxia, loss of motor functions, salivation). All animals died within 5 days. Pathological examination revealed tubular vacuolar degeneration in 9/10 animals.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no kidney damage was reported.
- Critical effects observed:
- not specified
- Conclusions:
- Application of 1000 mg/kg/day in rat leads to symptoms of poisoning (ataxia, loss of motor functions, salivation). All animals died within 5 days. Pathological examination revealed tubular vacuolar degeneration in 9/10 animals. At 300 mg/kg/d no mortality and no kidney damage was reported.
- Executive summary:
Application of 1000 mg/kg/day in rat leads to symptoms of poisoning (ataxia, loss of motor functions, salivation). All animals died within 5 days. Pathological examination revealed tubular vacuolar degeneration in 9/10 animals. At 300 mg/kg/d no mortality and no kidney damage was reported.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 37.5 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 75 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 600 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 37.5 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no data
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEL in a 90 day oral gavage study was reported to be 37.5 in female and male mice.
- Executive summary:
The NOAEL in a 90 day oral gavage study was reported to be 37.5 in female and male mice.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 19 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 37.5 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 75 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 37.5 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: nephropathy
- Dose descriptor:
- NOAEL
- Effect level:
- 75 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: Nephropathy
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEL in a 90 day oral gavage study was reported to be 37.5 and 75 mg/kg/day in female and male rats, respectively.
- Executive summary:
The NOAEL in a 90 day oral gavage study was reported to be 37.5 and 75 mg/kg/day in female and male rats, respectively.
Referenceopen allclose all
2000 mg/kg: All animals died within 2 days
600 mg/kg:
- No mortality
- Ataxia, hypoactivity
- histopathology: karyomegaly and necrosis in hepatocytes
200 mg/kg: No effects
1000 mg/kg/day:
- Symptoms of poisoning: ataxia, loss of motor functions, salivation
- All animals died within 5 days;
- Pathology: tubular vacuolar degeneration in 9/10 animals
300 mg/kg/d:
- No mortality; no kidney damage
No substance related deaths occurred in both male and female mice. Both sexes in the 300 and 600 mg/kg bw dose group showed hyperactivity and ataxia. Female mice of the 600 mg/kg bw dose group displayed delayed startle responses to acoustic signals. Body weight gain of the male and female mice of the 600 mg/kg bw dose group was reduced by 21.5 % and 14.6 %, respectively, compared to the control. At the end of the experiment male and female mice in the 75 mg/kg bw dose groups and higher dose groups had significantly increased relative and absolute liver weights. In female mice of the 37.5 mg/kg bw dose group only the absolute liver weight was increased. Histopathological examinations of male mice of the 300 and 600 mg/kg bw dose groups as well as of female mice of the 600 mg/kg bw dose group revealed centrilobular hypertrophy of liver cells, increase of Kupffer cells, mineralization and cell necrosis. Kidneys of male and female mice of the three and two highest dose groups, respectively, displayed dose-related dilations of the tubuli of the inner cortex. The maximum tolerated dose for male and female mice was reported to be 37.5 mg/kg bw (no further details reported; NTP, 1994).
Over a total observation period of 13 weeks no deaths occurred. Hyperactivity and aggressiveness could be observed in rats dosed at 150 and 300 mg/kg bw. Female rats of the 300 mg/kg dose group showed a reduced strength in the hind legs and delayed response to thermic stimuli. Body weight gain of the male and female rats of this dose group was reduced by 10.6 % and 6.7 %, respectively, compared to the control. At the end of the experiment male rats in the 75 mg/kg bw dose groups and higher dose groups had significantly increased relative and absolute kidney weights. Histopathology showed a dose-dependent degeneration and enlargement of the tubuli in males of the 75 mg/kg bw dose group and higher. According to the authors these alterations are similar to the “hydrocarbon-nephropathy”. In female rats of the two highest dose groups kidney alterations are characterized by vacuolar degeneration of the cortex tubuli. The no effect level for nephropathy for male and female rats was 37, 5 mg/kg bw and 75 mg/kg bw, respectively (no further details reported; NTP, 1994). A possible α-2u-globulin nephropathy was not discussed.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 37.5 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1977
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Remarks:
- Original reference in foreign language (Russian)
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- exposure to 0.07 (+/- 0.01) mg/l air for 4 h/d (5 d/week; 4.5 month) in a 750 l chamber; dynamic method.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- not specified
- Sex:
- male
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 hours/day
- Frequency of treatment:
- 5 days/week; 4.5 month
- Dose / conc.:
- 70 mg/m³ air (nominal)
- Remarks:
- Basis: nominal conc.
- No. of animals per sex per dose:
- 10 per age (young/adult/old)
- Control animals:
- yes
- Dose descriptor:
- conc. level: 70 mg/m³
- Effect level:
- 70 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: decrease of haemoglobin
- Critical effects observed:
- not specified
- Conclusions:
- Subchronic exposure to Benzonitrile causes effects like a significant decrease in the number of red blood cells, decrease in haemoglobin and increase in the number of leucocytes. In contrast to acute exposure no age-dependency was found at a concentration of 0.07 mg/l in this study.
- Executive summary:
In an inhalation toxicity study groups of 10 male albino rats of different ages (young, adult and old: body weight ranging from 60 to 370 g) were exposed to benzonitrile for 4 h in a 750 l chamber 5 days/week for 4.5 months at a concentrations of 0.07 mg/l air.
A significant decrease in the number of red blood cells, a decrease in haemoglobin and an increase in the number of leucocytes were observed. In contrast to acute exposure no age-dependency was found in this study.
Due to the poor documentation it is not possible to assess the relevance and reliability of this study.
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1961
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- inhalation of 460 ppm benzonitrile for 3 consecutive days (6 h/d). Observation period 14-21 days
- GLP compliance:
- no
- Limit test:
- no
- Species:
- other: cats, rabbits, guinea pigs, rats, mice
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 6 h /d
- Frequency of treatment:
- 3 consecutive days
- Dose / conc.:
- 1 937 mg/m³ air (nominal)
- Remarks:
- Doses / Concentrations: 460 ppm
Basis: nominal conc. - No. of animals per sex per dose:
- total of 2 cats, 2 rabbits, 2 guinea pigs, 4 rat (2/sex), 10 mice (5/sex)
- Control animals:
- not specified
- Dose descriptor:
- conc. level: 1937 mg/m³
- Effect level:
- 1 937 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- Critical effects observed:
- not specified
- Conclusions:
- Exposure of cats, rabbits, guinea pigs, rats and mice to 460 ppm benzonitril (1.9 mg/l) for 3 days (6h/d) results in species specific adverse effects. One of 2 cats died after 7 days. Rabbits and guinea pigs were did not show any symtomes. One of 3 rats died after the third exposure days. 8/10 mice died during the exposure period.
- Executive summary:
Exposure of cats, rabbits, guinea pigs, rats and mice to 460 ppm benzonitril (1.9 mg/l) for 3 days (6h/d) results in species specific adverse effects. One of 2 cats died after 7 days. Rabbits and guinea pigs were did not show any symtomes. One of 3 rats died after the third exposure days. 8/10 mice died during the exposure period.
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1961
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Inhalation of 97 ppm benzonitrile for 2 weeks (5 d/w, 6 h/d) . Observation period 14-21 days
- GLP compliance:
- no
- Limit test:
- no
- Species:
- other: cats, rabbits, guinea pigs, rats, mice
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 6 h /d
- Frequency of treatment:
- 2 weeks, 5 d/w
- Dose / conc.:
- 408 mg/m³ air (nominal)
- Remarks:
- Doses / Concentrations: 97 ppm
Basis: nominal conc. - No. of animals per sex per dose:
- total of 2 cats, 2 rabbits, 2 guinea pigs, 4 rat (2/sex), 10 mice (5/sex)
- Control animals:
- not specified
- Dose descriptor:
- conc. level: 408 mg/m³
- Effect level:
- 408 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- mortality
- Critical effects observed:
- not specified
- Conclusions:
- Inhalation of 97 ppm benzonitrile for 6 h/d caused mortality in 2/10 mice after day 2 and 9 of exposure. In cats, rabbits, guinea pigs and rats 97 ppm did not cause mortality or any gross abnormalities during a 2 week exposure .
- Executive summary:
Inhalation of 97 ppm benzonitrile for 6 h/d caused mortality in 2/10 mice after day 2 and 9 of exposure. In cats, rabbits, guinea pigs and rats 97 ppm did not cause mortality or any gross abnormalities during a 2 week exposure .
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1977
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- exposure of rats of different ages to 0.07 mg/l air for 4 h/d (5 d/week; 4.5 month); assessment of morphological changes in internal organ
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Remarks on MMAD:
- MMAD / GSD: no details reported
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 h/day
- Frequency of treatment:
- 5 days/week for 4.5 months
- Dose / conc.:
- 70 mg/m³ air (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- not specified
- Dose descriptor:
- dose level: 70 mg/m³
- Effect level:
- 70 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: some age-dependent changes in lungs, liver, adrenal gland and spleen were reported
- Critical effects observed:
- not specified
- Conclusions:
- Reputed dose exposure to Benzonitrile by inhalation caused histopathological changes of the inner organs. The degree of the changes varied distinctly between young, adult and aged rats.
- Executive summary:
In a subchronic repeated dose inhalation toxicity study groups of 5 male albino rats of different age (young, adult and old: body weight ranging from 60 to 370 g) were exposed to benzonitrile for 4 h, 5 days/week for 4.5 months at a concentrations of 0.07 mg/l air.
Benzonitrile caused significant histopathological changes in visceral organs of adult but not in young rats.
Due to the poor documentation it is not possible to assess the relevance and reliability of this study.
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: Russian guideline
- Principles of method if other than guideline:
- Russian methods and guidelines
- GLP compliance:
- no
- Limit test:
- no
- Species:
- other: rabbits and rats
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 4 h/day
- Frequency of treatment:
- 5 days/week for 4.5 months
- Dose / conc.:
- 10 mg/m³ air (nominal)
- Remarks:
- Basis: nominal conc.
- Dose / conc.:
- 70 mg/m³ air (nominal)
- Remarks:
- Basis: nominal conc.
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Dose descriptor:
- conc. level: 70 mg/m³
- Effect level:
- 70 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: Reduced body weight, reduced activity of Cholinesterase activity; decrease of blood protein concentration; disturbance of detoxification in rat liver; increased urine production; anaemia; dystrophic and inflammatory changes in rat liver and lungs
- Dose descriptor:
- conc. level: 10 mg/m³
- Effect level:
- 10 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: decrease in body weight; increase in Cholinesterase and Cytochrom oxidase activity; all physiological effects were transient; no morphological changes in visceral organs;
- Critical effects observed:
- not specified
- Conclusions:
- Subchronic repeated exposure to 70 mg/m³ Benzonitril by inhalation for 4 h/day caused severe health effects in rats and rabbits. Effects at 10 mg/m³ were considered transient. Due to the poor documentation it is not possible to assess the reliability of this study.
- Executive summary:
20 rabbits and 20 rats were exposed to Benzonitrile at concentratons of 70 and 10 mg/m³ for 4 h/day, 5 days/week, 4.5 months. The clinical symptoms resemble those of Benzol intoxication. Effects at 10 mg/m³ were considered transient. The author concluded a threshold value of 10 mg/m³ and a maximum permissible concentration in the air of working areas of 1 mg/m³.
Due to the poor documentation it is not possible to assess the reliability of this study.
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1975
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: Russian guidelines
- Principles of method if other than guideline:
- Russian guidelines
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 h
- Frequency of treatment:
- 5 days/week for 4 weeks
- Dose / conc.:
- 70 mg/m³ air (nominal)
- Remarks:
- Doses / Concentrations: 0.07 +/- 0.01 mg/l
- No. of animals per sex per dose:
- no details reported
- Dose descriptor:
- conc. level: 70 mg/m³
- Effect level:
- 70 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: lower red cell blood count, as well as erythrocytes and leukocytes in the peripheral blood, shift of the albumin-globulin ratio through increase of the α-1, α-2 and β-globulin in the blood serum
- Critical effects observed:
- not specified
- Conclusions:
- Exposure of rats to 70 mg benzonitrile/m³ for 4 weeks (5 d/w) results in a lower red cell blood count, lower amount of erythrocytes and leukocytes in the peripheral blood and a shift of the albumin-globulin ratio through increase of the α-1, α-2 and β-globulin in the blood serum.
- Executive summary:
Exposure of rats to 70 mg benzonitrile/m³ for 4 weeks (5 d/w) results in a lower red cell blood count, lower amount of erythrocytes and leukocytes in the peripheral blood and a shift of the albumin-globulin ratio through increase of the α-1, α-2 and β-globulin in the blood serum.
Referenceopen allclose all
First transient effects in adult rats occur after 5 days, normalizing until the end of the first month (except some CNS effects). After 90 days there was a significant decrease in the number of red blood cells in adults, together with an decrease in haemoglobin and increase in the number of leucocytes.
The cats showed no symptoms during and after the first inhalation exposure but developed imbalance and jumpiness in the course of the following exposure. Moreover, mydriasis, inappetence and a reduction in body weightcould be observed. One cat died 7 days after exposure (pyic pleuropneumonia, Perikarditis fibrinosa). The surviving cat was free of symptoms after 5 days. Rabbits and guinea pigs did not display any symptoms. One of 4 rats died after the third exposure (abscess of the throat). The other rats remained free of symptoms. Mice showed temporary apathy, imbalance, lateral position (one animal) and narcosis. 6 and 2 mice died after the second and third exposure, respectively. Autopsy of these animals revealed atelectasis of the lungs in five cases and pronounced lobular pattern of the liver. In two further animals a significant increase in fat deposits in liver was detected.
Two out of 10 mice died after day 2 and 9 of exposure. All other animals survived. No abnormal findings were reported.
Changes in the inner organs are found to be age-depending in rats when exposed to 0.07 mg benzonitrile/l air, 4 h/day, 5 days/week for 4.5 months. There were no macroscopic changes in any age group and no significant histopahological changes in young rats. In adult and old rats changes in lungs, liver, adrenal gland and spleen were observed at different levels, including pericholangitis with granular epithelial dystrophy and accumulation of erythrocytes in the capillaries of the bile duct, necrosis of liver cells, hyperplasia of spleen follicles, and inflammation of the adrenal cortex.
Subchronic inhalation test using benzonitril on adult rats
Index |
5-days |
10-days |
30-days |
||||||
|
control |
test |
P |
control |
test |
P |
control |
test |
P |
Erythrocytes (in Mio.) |
8.5 ± 0.1 |
7.2 ± 0.4 |
< 0.05 |
8.0 ± 0.3 |
7.9 ± 0.3 |
|
8.0 ± 0.3 |
8.8 ± 0.3 |
|
Leukocytes (in thousands) |
10.9 ± 0.9 |
8.0 ± 0.7 |
< 0.05 |
11.0 ± 0.8 |
9.4 ± 0.8 |
|
10.5 ± 0.8 |
13.3 ± 1 |
< 0.05 |
The primary reaction of rat organs upon exposure to low level concentrations of benzonitrile occurs at an earlier stage in adult rats than in juvenile or older rats. The reaction is also earlier compensated.
The primary reaction shows in lower red cell blood count, as well as erythrocytes and leukocytes in the peripheral blood, the sum of the impacts, shift of the albumin-globulin ratio through increase of the α-1, α-2 and β-globulin in the blood serum. The character of the reaction does not change with the age of the animals.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Oral:
Subacute (14 days) studies are available in rat and mouse (NTP, 1994). Application of 1000 mg/kg/day in rat led to symptoms of poisoning (ataxia, loss of motor functions, salivation). All animals died within 5 days. Pathological examination revealed tubular vacuolar degeneration in 9/10 animals. At 300 mg/kg/d no mortality and no kidney damage was reported. Application of 2000 mg benzonitrile/kg/day in mouse led to symptoms of poisoning. All animals died within 2 days. At 600 mg/kg/d no mortality was reported but ataxia and hypoactivity was reported. Histopathology revealed karyomegaly and necrosis in hepatocytes. The NOAEL was 200 mg/kg.
According to Chaev and Foussard-Blanpin (1990) the application or 40 mg benzonitrile/kg/d for 28 days did not cause any adverse effect in Wistar rats.
Sub-chronic studies are available in rat and mouse (NTP, 1994). The NOAEL in a 90 day oral gavage study in rats was reported to be 37.5 and 75 mg/kg/day in females and males, respectively. The NOAEL in a 90 day oral gavage study in mice was reported to be 37.5 in both sexes.
Inhalation:
Results of long-term inhalation studies are available from Agaev (1975, 1977) and BASF (1961).
20 rabbits and 20 rats were exposed to benzonitrile at concentrations of 70 and 10 mg/m³ for 4.5 months (4 h/day, 5 days/week). The clinical symptoms resemble those of benzol intoxication. Effects at 10 mg/m³ were considered transient. The author concluded a threshold value of 10 mg/m³ and a maximum permissible concentration in the air of working areas of 1 mg/m³. In an inhalation toxicity study groups of 10 male albino rats of different ages (young, adult and old: body weight ranging from 60 to 370 g) were exposed to benzonitrile for 4 h in a 750 l chamber 5 days/week for 4.5 months at a concentrations of 0.07 mg/l air. A significant decrease in the number of red blood cells, a decrease in haemoglobin and an increase in the number of leucocytes were observed. In contrast to acute exposure no age-dependency was found in this study. Due to the poor documentation it is not possible to assess the relevance and reliability of these studies (Agaev, 1977). Exposure of rats to 70 mg benzonitrile/m³ for 4 weeks (5 d/w) results in a lower red cell blood count, lower amount of erythrocytes and leukocytes in the peripheral blood and a shift of the albumin-globulin ratio through increase of the α-1, α-2 and β-globulin in the blood serum (Agaev, 1975)
Exposure of cats, rabbits, guinea pigs, rats and mice to 460 ppm benzonitril (1.9 mg/l) for 3 days (6 h/d) results in species specific adverse effects (BASF, 1961). One of 2 cats died after 7 days. Rabbits and guinea pigs did not show any symptoms. One out of 3 rats died after the third exposure days. 8/10 mice died during the exposure period. Inhalation of 97 ppm benzonitrile for 6 h/d caused mortality in 2/10 mice after day 2 and 9 of exposure. In cats, rabbits, guinea pigs and rats 97 ppm did not cause mortality or any gross abnormalities during a 2 week exposure (BASF, 1961 (2)).
Justification for classification or non-classification
Based on the available data a classification for specific target organ toxicity is not warranted.
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.