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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Overall, both positive and negative results have been observed with AITC in genotoxicity tests in bacterial and mammalian cells in vitro in the absence of metabolic activation, with positive results occurring usually at or near cytotoxic concentrations.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Principles of method if other than guideline:
The mutagenicity of isothiocyanates and related compounds was tested by the method of Ames et al. with some modifications.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Metabolic activation system:
S-9 Mix
Species / strain:
other: TA1535, TA1537,TA1538
Metabolic activation:
not specified
Vehicle:
DMSO
Species / strain:
other: TA100, TA98
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity:
not specified
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Species / strain:
other: TA1535, TA1537, TA1538
Metabolic activation:
not specified
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Additional information on results:
There was no activating effect on mutagenicity by the pretreatment of these samples with S-9 Mix.
Conclusions:
It was found that all of the isohiocyanates tested showed mutagenicity on Salmonella typhimurium TA100, though the degree varied with each sample. Especially, allyl isothiocyanate have the highest potency among these compunds.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Reference:
Composition 0
Principles of method if other than guideline:
Results from the testing of 108 coded chemicals in Chinese hamster ovary (CHO) cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented. All chemicals were tested with and without exogenous metabolic activation, using protocols designed to allow testing up to toxic doses.
GLP compliance:
not specified
Type of assay:
in vitro mammalian cell transformation assay
Test material information:
Composition 1
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
Weakly positive
Cytotoxicity:
not specified
Conclusions:
The aberration test was weakly positive, with increases primarily in simple deletions. A chromosome aberration test in Chinese hamster cells with and without S9 was also reported by Kamasaki et al. (1982).
Endpoint:
genetic toxicity in vitro, other
Remarks:
Sister Chromatid Exchange
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Reference:
Composition 0
Principles of method if other than guideline:
Results from the testing of 108 coded chemicals in Chinese hamster ovary (CHO) cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented. All chemicals were tested with and without exogenous metabolic activation, using protocols designed to allow testing up to toxic doses.
GLP compliance:
not specified
Type of assay:
sister chromatid exchange assay in mammalian cells
Test material information:
Composition 1
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
S9 Mix
Conclusions:
In the SCE test without S9, there was evidence for a trend, but no responses were elevated 20% over the control level. With S9, a more convincing increase in SCEs was seen. Polyploid cells were noted at 0.16 pg/ml or more without S9 and at 0.5 pg/ml or more with S9.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Principles of method if other than guideline:
The mutagenicity test was conducted in the Salmonella/microsome mutagenicity assay on plates according to the method of Ames (Ames et al., 1975), with the S. typhimurium histidine (-) mutants, TA98 and TA100.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Vehicle:
DMSO
Species / strain:
other: TA 98 and TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Conclusions:
In the mutation test none of the flavorings exhibited significant induction of his + revertants in Salmonella typhimurium TA98 or TA100, either with or without rat liver microsome as the metabolic activation system.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Principles of method if other than guideline:
CH cell line B241 was used it for the chromosome test in culture stages between the 5th and 8th passages. Exponentially growing cells at one day after seeding were exposed to each of the chemicals for 24 h, and then incubated another 24 h without the chemicals followed by treatment with colchicine (1 x 10 - 7 M) for 2-3 h.
GLP compliance:
not specified
Type of assay:
other: chromosome aberration test
Test material information:
Composition 1
Vehicle:
Chemicals were dissolved in DMSO at a concentration of 50 mM and then were diluted with the medium.
Species / strain:
other: Chinese-hamster B241 cells
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity:
not specified
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Conclusions:
The results of the chromosome test showed significant increases in chromosome aberrations in the Chinese-hamster B241 cells by 8 out of the 9 agents, regardless of the presence or absence of S9 mix. In particular, trcinnamaldehyde (tr-CA) and allylisothiocyanate (AITC) exhibited high potentials for inducing aberrations. The total frequency of the aberrations indicated a dose dependent increase at a certain dose range.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Principles of method if other than guideline:
reverse mutations in Eschericia coli WP67
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Species / strain:
other: Wp67 (trp uvrA polA)
Metabolic activation:
with and without
Species / strain:
other: WP67 (trp uvrA polA)
Metabolic activation:
with
Genotoxicity:
positive
Additional information on results:
The authors noted that the degree of mutagenicity was related to the source and protein content of the metabolic activation system. Microsomal fractions from the liver of phenobarbital-treated rats, goats and monkeys were reported to be more active at a lower protein content than those prepared from mice and hamsters.
Conclusions:
AITC induced reverse mutations in Eschericia coli WP67 (trp uvrA polA) only in the presence of metabolic activation in an assay with 120 minutes incubation (Rihová, 1982). Bacteriotoxicity was higher in the absence of metabolic activation than in the presence. The authors noted that the degree of mutagenicity was related to the source and protein content of the metabolic activation system. Microsomal fractions from the liver of phenobarbital-treated rats, goats and monkeys were reported to be more active at a lower protein content than those prepared from mice and hamsters.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Principles of method if other than guideline:
induction of chromosomal aberrations in Chinese hamster ovary cells
GLP compliance:
not specified
Type of assay:
other: chromosomal aberration
Test material information:
Composition 1
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Conclusions:
An induction of chromosomal aberrations in Chinese hamster ovary cells which were exposed to AITC concentrations up to 10 nmol/l (0.99 ng/ml) without metabolic activation was reported by Kasamaki et al. (1982) and Kasamaki and Urasawa (1985).
Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)

Genetic toxicity in vivo

Description of key information

In vivo, the results were consistently negative in assays for micronucleus formation in mice and rats and unscheduled DNA synthesis in rats after oral application as well as in a dominant lethal mutation assay in mice after intraperitoneal injection.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
Only a single sex was used.
GLP compliance:
not specified
Test material information:
Composition 1
Species:
mouse
Strain:
B6C3F1
Sex:
male
Route of administration:
intraperitoneal
Vehicle:
Each chemical was prepared in the appropriate solvent (PBS for water soluble chemicals, corn oil for water-insoluble chemicals).
Duration of treatment / exposure:
Three consecutive day
Frequency of treatment:
Daily
Post exposure period:
48 hr after the third treatment, the surviving mice were euthanized
Dose / conc.:
37.5 mg/kg bw/day (nominal)
Dose / conc.:
75 mg/kg bw/day (nominal)
Dose / conc.:
150 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Groups of 5 mice were administered the test chemicals.
Control animals:
yes
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls valid:
yes
Conclusions:
AITC did not increase the number of micronuclei in bone marrow cells.
Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Principles of method if other than guideline:
Allylisothiocyanate (AITC) has been evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the livers of male rats in vivo. Specific Pathogen Free
outbred albino Hsd/Ola Sprague-Dawley rats were exposed by oral gavage to 37.5 or 125 mg/kg AITC in corn oil and hepatocytes assessed for UDS by autoradiography 2 and 14 h later.
GLP compliance:
not specified
Type of assay:
unscheduled DNA synthesis
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
Specific Pathogen Free outbred albino Hsd/Ola Sprague-Dawley rats were treated.
Sex:
male
Route of administration:
oral: gavage
Vehicle:
corn oil.
Details on exposure:
A dose level of 125 mg/kg bodyweight was found to be the maximum tolerated dose under the conditions of this test. Clinical signs occurred in the 250 and 500 mg/kg body weight dose groups accompanied by mortality of one and two of four animals in each group, respectively. A dosage of 125 mg/kg body weight was therefore chosen as the maximum for use in the DNA repair test.
Duration of treatment / exposure:
Once
Dose / conc.:
37.5 mg/kg bw/day (nominal)
Dose / conc.:
125 mg/kg bw/day (nominal)
Control animals:
yes, concurrent vehicle
Positive control(s):
Animals in the positive control group were treated with dimethylnitrosamine at 4 mg/kg for the 2 h expression or 2-acetylaminofluorene at 50 mg/kg for the 14 h expression.
Tissues and cell types examined:
Hepatocytes were isolated from each rat by enzymatic dissociation of the liver.
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls valid:
yes
Positive controls valid:
yes
Conclusions:
AITC did not induce UDS at either dose level at either time point. These data are consistent with all other evidence indicating that AITC does not act as a genotoxin in vivo.
Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
yes
Remarks:
lower number of animals and of dose levels used, limited report of experimental observations.
GLP compliance:
not specified
Type of assay:
rodent dominant lethal assay
Test material information:
Composition 1
Species:
mouse
Strain:
Swiss
Sex:
male/female
Route of administration:
intraperitoneal
Dose / conc.:
3.8 mg/kg bw/day (nominal)
Dose / conc.:
19 mg/kg bw/day (nominal)
No. of animals per sex per dose:
7 male rats/ 3.8 mg/kg
9 male rats/19 mg/kg
Control animals:
yes, concurrent vehicle
Conclusions:
AITC was investigated in a dominant lethal mutation assay. The substance was administered to male ICR/Ha Swiss mice as a single intraperitoneal injection at doses of 3.8 or 19 mg/kg bw. The incidence of early fetal death or pre-implantation losses in females mated with the treated males was not increased over a period of eight weeks
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Principles of method if other than guideline:
Allyl isothiocyanatc (AITC) was given in doses of 0, 10, 20, or 40 mg/kg (5 days/week) by oral intubation to male rats for up to 6 weeks.
GLP compliance:
not specified
Test material information:
Composition 1
Species:
rat
Strain:
other: Shoe: WIST
Sex:
male
Route of administration:
oral: gavage
Vehicle:
Paraffin oil
Duration of treatment / exposure:
Up to 6 weeks
Frequency of treatment:
daily
Dose / conc.:
10 mg/kg bw/day (nominal)
Dose / conc.:
20 mg/kg bw/day (nominal)
Dose / conc.:
40 mg/kg bw/day (nominal)
Control animals:
yes, concurrent vehicle
Conclusions:
Cell number, and the percentage of polychromatic erythrocytes and erythrocytes with micronuclei in the femoral marrow, indicative of the clastogenicity of chemicals, were not affected.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

According to the available information and in particular according to in vivo study results, AITC is not classified as genotoxic.