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EC number: 202-855-7 | CAS number: 100-47-0
- Life Cycle description
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- Endpoint summary
- Appearance / physical state / colour
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- 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
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- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
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- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
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Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Several negative Ames tests are available including a GLP guideline study according to OECD 471 (Microtest, 1988). A negative Sister Chromatide exchange assay (NTP, 1988) and a negative mouse lymphoma mutagenesis assay (Microbiological Associates, 1982) was reported as well as ambiguous results in in vitro Chromosome Aberration (NTP, 1988) and Chromosomal loss studies (Whittaker, 1990).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial gene mutation assay
- Species / strain / cell type:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-Mix from Aroclor 1254 induced rat liver
- Test concentrations with justification for top dose:
- 0.08, 0.4, 2, 10 and 50 mg/ml of treatment solutions
Final concentration (µg/plate) 8, 40, 200, 1000, and 5000 - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-nitrofluorene, sodium azide, 9-aminoacridine, 2-aminoanthracene
- Key result
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results (migrated information):
negative
Benzonitrile was unable to induce mutation in five strains of Salmonella typhimurium when tested up to 5000 µg/plate, either in the absence or presence of a rat liver metabolic activation system. - Executive summary:
In a reverse gene mutation assay in bacteria, with five strains (TA98, TA100, TA1535, TA1537 and TA1538) of S. typhimurium were exposed to Benzonitrile (98.56%) in sterile analytical grade anhydrous dimetyl sulphoxide (DMSO) at concentrations of 0.08, 0.4, 2, 10 and 50 µg/plate in the presence and absence of mammalian metabolic activation of a rat liver post-mitochondrial fraction (S-9).
Benzonitril was tested up to limit concentration of 5000 µg/plate. No evidence of toxicity was observed in a range-finder experiments, and the same series of concentrations was therefore retained for treatment of the remaining strains in both experiments. The mean numbers of revertant colonies on negative control plates all fell within acceptable ranges, and were significantly elevated by positive control treatments.
No Benzonitrile treatment of any strain, either in the absence or presence of S-9, resulted in the two-fold (strains TA98 and TA100) or three-fold (strains TA 1535, TA1537 and TA 1538) increases in revertant numbers sufficient to indicate that an induction of mutation had occurred.
This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1996
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 (Arocol 1254 iduced rat or hamster liver)
- Test concentrations with justification for top dose:
- 33 - 3333 µg/plate
- Key result
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:
negative
Benzonitrile does not induce reverse mutation in Salmonella Typhimurium. - Executive summary:
Benzonitrile does not induce reverse mutation in Salmonella Typhimurium.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1984
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 (Arocol 1254 iduced rat or hamster liver)
- Test concentrations with justification for top dose:
- 33 - 3333 µg/plate
- Key result
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results:
negative
Benzonitrile does not induce reverse mutation in S. typhimurium up to 3333 µg/plate when used with and without metabolic activation. - Executive summary:
Benzonitrile does not induce reverse mutation in S. typhimurium up to 3333 µg/plate when used with and without metabolic activation.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix from Phenobarbital & 5,6-Benzoflavon induced rat liver
- Test concentrations with justification for top dose:
- 20 - 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from 625 µg/plate
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results:
negative
Benzonitrile does not induce reverse mutation in S. typhimurium TA 1535 up to 7500 µg/plate when used without metabolic activation. - Executive summary:
Benzonitrile does not induce reverse mutation in S. typhimurium TA 1535 up to 7500 µg/plate when used without metabolic activation.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1988
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Remarks:
- (data collection)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium, other: no details reported
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-Mix from Aroclor 1254 induced rat or hamster liver
- Test concentrations with justification for top dose:
- no data
- Species / strain:
- other: S. typhimurium TA 1535, TA 97, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Zeiger et.al (1988) found benzonitrile to have no possitive effect in a histidine reversion test using Salmonella typhimurium.
- Executive summary:
Zeiger et.al (1988) found benzonitrile to have no possitive effect in a histidine reversion test using Salmonella typhimurium.
- Endpoint:
- in vitro cytogenicity / micronucleus study
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- 2003
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Remarks:
- documentation insufficient for assessment; interpretation of results is questionable (2x increase in the number of MNs is considered a positive effect; no dose-effect-relationship)
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- MN assay was performed in vitro (V79 cells) according to Matsuoka et al. (Matsuoka A, Yamazaki N, Suzuki T, Hayashi M, Sofuni T (1992) Evaluation of the micronucleus test using a Chinese hamster cell line as an alternative to the conventional in vitro chromosomal aberration test. Mutat Res 272:223–236)
- GLP compliance:
- no
- Type of assay:
- in vitro mammalian cell micronucleus test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Additional strain / cell type characteristics:
- not specified
- Test concentrations with justification for top dose:
- 0.001, 0.005, 0.01, 0.1, 1, 10, 100 µM
- Vehicle / solvent:
- 0.04% DMSO
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: vincristine
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- other: ambigous statements
- Conclusions:
- Interpretation of results:
ambiguous
The authors conclude that Benzonitril exhibits a weak, but definitely positive test result at concentrations below cytotoxicity. A small (2x) increase in the number of micronucleus was considered a positive effect. Based on the limited available data and the small increase in the number of MNs this conclusion is not considered to be reliable. - Executive summary:
In a mammalian cell cytogenetics assay [in vitro micronucleus (MN)], V79 cell cultures were exposed to benzonitrile in DMSO at concentrations of 0.001, 0.005, 0.01, 0.1, 1, 10, 100, 1000 µM (data for 1 mM not shown) without metabolic activation. Positive controls induced the appropriate response (data not shown). The authors reported an induced 2-fold increase over background as evidence of Ch’some aberration . Results are presented as graphs, only. The control value is 6-7 MN/1000 cells. The maximum increase in MN is 12/1000 cells at 1 µM. Higher concentrations do not increase the number of MNs. A clear dose response has not been shown. In addition, according to OECD 487 the micronuclei frequencies of solvent/vehicle control and untreated cultures are typically between 5-25 micronuclei/1000. Thus the slight increase in the number of MN cannot be regarded as positive result. This study is classified as unacceptable. This study does not satisfy the requirement for Test Guideline In vitro mammalian cytogenetics [OECD 487] for in vitro cytogenetic mutagenicity data.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1988
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix from Arocol 1245 induced rat liver
- Test concentrations with justification for top dose:
- without metabolic activation: 200 - 1500 µg/ml
with metabolic activation: 200 - 3000 µg/ml
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 1500 µg/ml
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Remarks:
- 11% aberration vs 1-3% control
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3000 µg/ml
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results:
ambiguous with metabolic activation
At a concentration of 1005-1993 µg/ml (with metabolic activation) benzonitrile increased the rate of chromosomal aberration up to 11% (3% basic, 9% complex) compared to 1-3% DMSO. A concentration of 1993 µg/ml was cytotoxic. - Executive summary:
At a concentration of 1005-1993 µg/ml (with metabolic activation) benzonitrile increased the rate of chromosomal aberration up to 11% (3% basic, 9% complex) compared to 1-3% DMSO. A concentration of 1993 µg/ml was cytotoxic.
- Endpoint:
- in vitro DNA damage and/or repair study
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1990
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 481 (Genetic Toxicology: Saccharomyces cerevisiae, Mitotic Recombination Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- mitotic recombination assay with Saccharomyces cerevisiae
- Species / strain / cell type:
- Saccharomyces cerevisiae
- Additional strain / cell type characteristics:
- other: D61.M
- Metabolic activation:
- not specified
- Test concentrations with justification for top dose:
- up to 2190µg/ml
- Key result
- Species / strain:
- Saccharomyces cerevisiae
- Metabolic activation:
- not specified
- Genotoxicity:
- ambiguous
- Remarks:
- negative under standard conditions; positive under customized conditions (16h 0°C)
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results:
ambiguous
Benzonitrile did not induce chromosomal losses under standard conditions (16h, 30°C) up to 2190 µg/ml. Under modified test conditions (4h 30°C + 16h, 0°C) a significant increase in chromosomal losses was reported. - Executive summary:
Benzonitrile did not induce chromosomal losses under standard conditions (16h, 30°C) up to 2190 µg/ml. Under modified test conditions (4h 30°C + 16h, 0°C) a significant increase in chromosomal losses was reported.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1982
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Additional strain / cell type characteristics:
- other: TK+/-
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 (Arocol 1254 induced rat liver)
- Test concentrations with justification for top dose:
- 0.5-1.07 µl/ml (without metabolic activation)
0.39-0.8 µl/ml (with metabolic activation) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- viability without metabolic activation: 71-11%; with: 104-39%
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results:
negative
Benzonitrile did not significantly increase the mutation rate in mouse lymphoma L5178Y cells up to cytotoxic concentrations. - Executive summary:
Benzonitrile did not significantly increase the mutation rate in mouse lymphoma L5178Y cells up to cytotoxic concentrations.
- Endpoint:
- in vitro DNA damage and/or repair study
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1988
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- sister chromatid exchange assay in mammalian cells
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix from Arocol 1254 induced rat liver
- Test concentrations with justification for top dose:
- 5 - 166.7 µg/ml
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 166.7 µg/ml
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results:
negative
Benzonitrile did not induce a significant increase of sister-chromatide exchange in CHO-cells up to cytotoxic concentrations. - Executive summary:
Benzonitrile did not induce a significant increase of sister-chromatide exchange in CHO-cells up to cytotoxic concentrations.
Referenceopen allclose all
Negative (solvent) and positive control treatments were included for all strains in both experiments. The mean numbers of revertant colonies on negative control plates all fell within acceptable ranges, and were significantly elevated by positive control treatments. No Benzonitrile treatment of any tester strain, either in the absence or presence of S-9, resulted in the two-fold (strains TA98 and TA100) or three-fold (strains TA 1535, TA1537 and TA 1538) increases in revertant numbers sufficient to indicate that an induction of mutation had occurred. It is concluded that Benzonitrile was unable to induce mutation in five strains of Salmonella typhimurium when tested up to 5000 µg/plate, either in the absence or presence of a rat liver metabolic activation system.
A genetic assay for histidine reversion testing using Salmonella typhimurium was found to be negative.
1) benzonitrile exhibited no cytotoxicity in V79 cells, in terms of Neutral red uptake, even when tested up to high medium concentrations (1 mM; data not shown)
2) With 50 mM benzonitrile, the tubulin cytoskeleton was completely destroyed, presumably as a result of general cytotoxicity, as the cells began to detach from the surface.
In a first experiment with metabolic activation a total of 72% of the cell had chromosomal aberrations (64% basic, 8% complex) at 1495 µg/ml. In a second experiment with metabolic activation this severe effect could not be verified. The incubation at 1005 – 1993 µg/ml led to an increase in Chromosomal aberration of up to 11% (3% basic, 9% complex). The DMSO control was 3, 1, and 2%. The highest concentration tested (1993 µg/ml) caused cytotoxicity. However, without additional data it cannot be verified that aberrations only occur at cytotoxic concentrations.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Description of key information
One negative in vivo micronucleus test in mice (NTP, 1995) is available.
Based on the in vivo study Benzonitrile was not classified for genetic toxicity.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2000
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Duration of treatment / exposure:
- 13 weeks (micronucleus test at the end of a 90 day study)
- Frequency of treatment:
- daily
- Post exposure period:
- no data
- Dose / conc.:
- 600 mg/kg bw/day (nominal)
- Remarks:
- Basis: actual ingested
- No. of animals per sex per dose:
- 9-10 males; 7-10 females
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- systemic toxicity at 37.5 mg/kg/d (females) and 75 mg/kg/d (males)
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Conclusions:
- Interpretation of results: negative
Benzonitrile did not increase the rate of micronuclei in polychromatic erythrocytes in a micronucleus test conducted at the end of a 90 day study in mice. - Executive summary:
At the end of a sub-chronic oral toxicity study in 7-10 B6C3F1-mice/sex/dose a micronucleus test was conducted. Exposure to benzonitrile did not increase the rate of micronuclei in polychromatic erythrocytes at doses up to 600 mg/kg/d. This micronucleus test conducted at the end of a 90 day study is valid according to OECD 474. Systemic adverse effects were reported at 37.5 mg/kg/d. Benzonitrile is considered to be not mutagenic in vivo.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Additional information from genetic toxicity in vivo:
Benzonitrile did not induce an increase in bacterial reverse mutation (Microtest, 1988), a significantly increase in the mutation rate in mouse lymphoma L5178Y cells (Microbiological Associates, 1982) or a significant increase of sister-chromatide exchange in CHO-cells (NTP, 1988) up to cytotoxic concentrations.
Ambiguous results were reported in a Chromosome Aberration assay (NTP, 1988). In a first experiment with metabolic activation a total of 72% of the cell had chromosomal aberrations (64% basic, 8% complex) at 1495 µg/ml. In a second experiment with metabolic activation this severe effect could not be verified. The incubation at 1005 – 1993 µg/ml led to an increase in chromosomal aberration of up to 11% (3% basic, 9% complex). The DMSO control was 3, 1, and 2%. The highest concentration tested (1993 µg/ml) caused cytotoxicity. However, without additional data it cannot be verified that aberrations only occur at cytotoxic concentrations.
Ambiguous results were also reported in a chromosomal loss assay in S. cerevidiae (Whittaker, 1900). Under standard conditions (incubation for 16h at 30°C) benzoniotrile did not increase the rate of chromosomal losses. However, the use of modified conditions (incubation for 4h at 30°C followed by 16 h at 0°C) led to a significant increase of chromosomal losses. According to the authors this increase is caused by an interaction with the spindle apparatus. It is difficult to judge the significance of the effect observed under non-standard conditions.
In addition to in vitro data the results of an in vivo micronucleus test were reported (NTP, 1995, cited in BG Chemie 2000). This test was conducted at the end of a sub-chronic oral toxicity study in 7-10 B6C3F1-mice/sex/dose. Exposure to benzonitrile did not increase the rate of micronuclei in polychromatic erythrocytes at doses up to 600 mg/kg/d. This micronucleus test is valid according to OECD 474 because systemic adverse effects were already reported at 37.5 mg/kg/d. Benzonitrile is considered to be not mutagenic in vivo.
Justification for selection of genetic toxicity endpoint
in vivo study
Justification for classification or non-classification
Based on the available data it can be concluded that the potential genetic toxicity of benzonitrile is low. A classification is not warranted.
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