Registration Dossier
Registration Dossier
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EC number: 204-524-2 | CAS number: 122-14-5
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Studies of bacterial mutation (Ames tests), mamalian cell mutation in vitro and mammalian cell clastogenicity in vitro are available for fenitrothion.
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:
- Not reported: published study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Fenitrothion technical grade
Batch No.: 00106
Purity: 94.7% - Target gene:
- Various; reversion to histidine and tryptophan independence
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium, other: TA100NR
- Remarks:
- nitroreductase-deficient
- Species / strain / cell type:
- E. coli WP2 uvr A
- Species / strain / cell type:
- S. typhimurium, other: TA100 1,8-DNP6
- Remarks:
- transacetylase deficient
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from Sprague-Dawley rats treated intraperitoneally with polychlorinated biphenyls (PCB)
- Test concentrations with justification for top dose:
- 0, 100, 200, 500, 1000, 2000, 5000 ug/plate (limit concentration)
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- benzo(a)pyrene
- methylmethanesulfonate
- other: 2-aminoanthracene, 2, 80 ug/plate
- Details on test system and experimental conditions:
- Fenitrothion was tested using strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, TA100 NR (nitroreductase-deficient strain) and TA100 1,8 -DNP6 (transacetylase-deficient strain)); and Escherichia coli WP2uvrA. Purified samples of fenitrothion and aminofenitrothion (AM-FNT) were tested using strains TA98, TA100, TA100 NR and TA100 1,8 -DNP6. Fenitrooxon (FNO), nitrosofenitrothion, nitrosofenitrooxon, aminofenitrooxon (AM-FNO) and 3-methyl-4-nitrophenol (NMC), were tested using strains TA98 and TA100. Test chemicals were dissolved in DMSO and tests were conducted using a pre-incubation method with and without metabolic activation. Negative control (DMSO, 100 ul /plate), positive and insensitive controls were also tested with and without metabolic activation. S9 mix, a mixture of cofactors and the liver S9 from Sprague-Dawley rats treated intraperitoneally with polychlorinated biphenyls (PCB), were used for metabolic activation.
- Statistics:
- Not required
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Remarks:
- weak mutagenicity was observed only in TA100 and it was enhanced by the addition of S9 mix
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium, other: TA100NR
- Remarks:
- nitroreductase deficient
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium, other: TA100 1,8-DNP6
- Remarks:
- transacetylase deficient strain
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- Decreased compared to TA100
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- Fenitrothion showed weak mutagenicity in TA100 without S9 and its mutagenicity was slightly enhanced by the addition of S9. The mutagenic activity of the technical-grade sample of fenitrothion did not differ from that of the purified sample. The mutagenicity of fenitrothion was not detected in TA100 NR, and was decreased in TA100 1,8-DNP6.
- Conclusions:
- Fenitrothion was found to be non-mutagenic in TA98, TA1535, TA1537 and WP2uvrA both with and without S9 mix, while weak mutagenicity was observed only in TA100 and it was enhanced by the addition of S9 mix. The mutagenicity was not observed in a nitroreductase-deficient strain, TA100 NR, and it decreased in a transacetylase-deficient strain, TA100 1,8-DNP6. The results suggest that the bacterial nitroreductase activity is necessary for fenitrothion to express the mutagenicity in TA100.
- Executive summary:
The mutagenic potenitial of fenitrothion was investigated in an Ames test. Fenitrothion was tested using strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, TA100 NR (nitroreductase-deficient strain) and TA100 1,8 -DNP6 (transacetylase-deficient strain)); and Escherichia coli WP2uvrA. Purified samples of fenitrothion and aminofenitrothion (AM-FNT) were tested using strains TA98, TA100, TA100 NR and TA100 1,8 -DNP6. Fenitrooxon (FNO), nitrosofenitrothion, nitrosofenitrooxon, aminofenitrooxon (AM-FNO) and 3-methyl-4-nitrophenol (NMC), were tested using strains TA98 and TA100. Test chemicals were dissolved in DMSO and tests were conducted using a pre-incubation method with and without metabolic activation. Negative control (DMSO, 100 ul /plate), positive and insensitive controls were also tested with and without metabolic activation. S9 mix, a mixture of cofactors and the liver S9 from Sprague-Dawley rats treated intraperitoneally with polychlorinated biphenyls (PCB), were used for metabolic activation. Fenitrothion was found to be non-mutagenic in TA98, TA1535, TA1537 and WP2uvrA both with and without S9 mix, while weak mutagenicity was observed only in TA100 and it was enhanced by the addition of S9 mix. The mutagenicity was not observed in a nitroreductase-deficient strain, TA100 NR, and it decreased in a transacetylase-deficient strain, TA100 1,8-DNP6. The results suggest that the bacterial nitroreductase activity is necessary for fenitrothion to express the mutagenicity in TA100.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25 March 1986 - 23 May 1986
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell gene mutation test using the Hprt and xprt genes
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 00106
Purity: 94.7% - Target gene:
- HPRT
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Kanechlor 400-induced male SD rat liver S9 fraction
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO 1%
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- other: N-methyl-N’-nitro-N-nitrosoguanidine (-S9)
- Details on test system and experimental conditions:
- In the main gene mutation test, cultures of V79 cells were treated with fenitrothion at concentrations of 10e-5 M, 3×10e-5 M, 10e-4 M and 3×10e-4 M with and without S9. Fenitrothion was dissolved in dimethyl sulphoxide (DMSO). Negative (sovent) controls (DMSO 1%) and positive controls (N-methyl-N’-nitro-N-nitrosoguanidine 3×10e-6 M; 9,10 -dimethyl-1,2 -benzanthracene 3×10e-5 M) were run concurrently. After incubation for five hours at 37°C, the cells were washed and cultured to determine cytotoxicity and to allow for expression of the mutant phenotype at 37°C for 7 days. After the expression period, the cells were innoculated to dishes with and without 6-thioguanine (6-TG) and cultivated for 6 or 7 days to determine the number of mutants and plating efficiency. Colonies formed were fixed, Giemsa-stained and counted. The number of colonies for each dish was counted and the mutation frequency and the plating efficiency were calculated.
- Rationale for test conditions:
- To determine appropriate concentrations for use in the gene mutation test, a preliminary cytotoxicity test was performed using concentrations of 10e-3 to 10e-5 M with a dilution factor of 3 in the presence and absence of metabolic activation system (S9 mix).
- Evaluation criteria:
- Not reported
- Statistics:
- Appropriate statisitcal methods were used to compare the control and treated groups
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- precipitation also observed
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Small increases in the mutation frequencies are considered to be within the range of variation of the spontaneous mutation frequency, and no reproducible dose-response relationship were observed both in the presence and absence of metabolic activation. Fenitrothion was concluded not mutagenic under the test conditions.
- Executive summary:
The mutagenic potential of fenitrothion was investigated in an HPRT assay using V79 cells. To determine appropriate concentrations for use in the gene mutation test, a preliminary cytotoxicity test was performed using concentrations of 10e-3 to 10e-5 M with a dilution factor of 3 in the presence and absence of metabolic activation system (S9 mix). In the main study, cultures of V79 cells were treated with fenitrothion at concentrations of 10e-5 M, 3×10e-5 M, 10e-4 M and 3×10e-4 M with and without S9. Fenitrothion was dissolved in dimethyl sulphoxide (DMSO). Negative (sovent) controls (DMSO 1%) and positive controls (N-methyl-N’-nitro-N-nitrosoguanidine 3×10e-6 M; 9,10 -dimethyl-1,2 -benzanthracene 3×10e-5 M) were run concurrently. After incubation for five hours at 37°C, the cells were washed and cultured to determine cytotoxicity and to allow for expression of the mutant phenotype at 37°C for 7 days. After the expression period, the cells were innoculated to dishes with and without 6-thioguanine (6-TG) and cultivated for 6 or 7 days to determine the number of mutants and plating efficiency. Colonies formed were fixed, Giemsa-stained and counted. The number of colonies for each dish was counted and the mutation frequency and the plating efficiency were calculated.
In the first experiment without metabolic activation, the mutation frequencies of the fenitrothion-treated groups were statistically significantly higher than that of the negative control group, but no concentration-dependent increase was observed. The result in the second experiment with two negative control groups showed no significant differences. In the first experiment with metabolic activation, the mutation frequencies of the fenitrothion-treated groups were partly higher than that of the negative control group, but no concentration-dependent increase was observed. In the second experiment, a small increase was observed at the highest concentration in the mutation frequency, but these values were within the range of historical control data [range (0.8-7.7) ×10-6; average (4.3 +/- 2.0) ×10e-6 (n=12)]. Small increases in the mutation frequencies are considered to be within the range of variation of the spontaneous mutation frequency, and no reproducible dose-response relationship were observed both in the presence and absence of metabolic activation. Fenitrothion was concluded not mutagenic under the test conditions.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 April 1988 - 7 June 1988
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 60553
Purity: 96.7% - Target gene:
- Not applicable (clastogenicity study)
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Remarks:
- CHO-K!
- Cytokinesis block (if used):
- Colcemid (0.1 ug/mL) was added to cultures two hours prior to harvest
- Metabolic activation:
- with and without
- Metabolic activation system:
- Kanechlor-400 induced male SD rat liver S9
- Test concentrations with justification for top dose:
- 3, 10 and 30 µg/ml, for 8, 16 or 24 hours
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO 0.5%
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- cyclophosphamide
- mitomycin C
- Statistics:
- Appropriate statistical methods were uased to compare the control and test material groups.
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Remarks:
- CHO-K1
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not determined
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Fenitrothion does not have any clastogenic potential against CHO-K1 cells under the conditions tested.
- Executive summary:
The potential clastogenicity of fenitrothion was investigated in CHO-K1 cells. A preliminary cytotoxicity test was performed to determine the concentrations to be used in the main study. The concentrations ranged from 1 -300 µg/mL with and without metabolic activation. In the chromosomal aberration test, Chinese hamster ovary cells (CHO-K1) were treated with fenitrothion (dissolved in DMSO) at concentrations of 3, 10 and 30 µg/mL for periods of 8, 16 or 24 hours in the absence of metabolic activation. In the presence of metabolic activation, cells were exposed to concentrations of 75, 150 and 300 µg/mL for 2 hours, with further culture in a fresh medium for 14 or 22 hours after removal of the test chemical. The cells were harvested, fixed, stained and analyzed in a blind manner. Negative control (DMSO) and positive controls (MMC, B(a)P, cyclophosphamide) were also tested. Mitotic indices were determined by counting more than 1000 cells. The number of structural aberrations and the frequencies of cells with structural aberrations were obtained by observation of 100 cells from each duplicate culture at each experimental point, and also the frequencies of polyploid cells were determined by observation of an additional 200 cells. Fenitrothion did not induce any significant increase in the number of total chromosome aberrations or in the frequency of cells with structural aberrations in the presence or absence of metabolic activation. A slight increase in the incidence of polyploid cells was observed in one culture of the 8 -hour treatment group at a concentration of 10 µg/ml in the absence of metabolic activation. However, no significant increase of polyploid cells was observed in other cultures and time- or concentration-dependency was not observed. Thus it was concluded that the increase was spontaneous. Positive control chemicals induced marked increases both in the number of total chromosome aberrations and in the frequency of cells with chromosomal aberrations. Fenitrothion does not have any clastogenic potential against CHO-K1 cells under the conditions tested.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 17 October 1975
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- In house method (Ames test), significant deficiencies compared to OECD 471
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 31184
Purity: 98.5% - Target gene:
- Various; reversion to histidine and tryptopgan independence
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- S. typhimurium TA 1537
- Species / strain / cell type:
- S. typhimurium TA 1538
- Species / strain / cell type:
- E. coli, other:
- Details on mammalian cell type (if applicable):
- W-3102
- Metabolic activation:
- with and without
- Metabolic activation system:
- Liver, lung, kidney, testis and brain homogenate from male SD rats intraperitoneally injected with 3-methylcholanthrene (20 mg/kg) for 24 hr and liver homogenate from male ICR mice pretreated with 1% sodium phenobarbital in drinking water for one week
- Test concentrations with justification for top dose:
- 10, 100, 1000, 10000 ug/plate (exceeds limit concentration)
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: N-methyl-N’-nitro-N-nitrosoguanidine; 2-aminoanthracene
- Remarks:
- NNG: used for all strains without metabolic activation; 2-AA used for all strains with metabolic activation
- Details on test system and experimental conditions:
- Salmonella typhimurium (strains TA1535 his G-, TA1537 his D-, TA1538 his C- uvr B-) and Escherichia coli (W3102 trp E -) cultures were treated with fenitrothion) dissolved in dimethyl sulfoxide (DMSO) (10 ul /plate or 100 ul/tube without metabolic activation, 100 ul/plate with metabolic activation) at dose levels of 10, 100, 1000 (with and without metabolic activation) and 10000 (without metabolic activation) ug/plate or 10, 100, 1000 ug/ ml (without metabolic activation). Negative control (DMSO, 10000 ug/plate or 100 ul/tube) and positive controls (N-methyl-N’-nitro-N-nitrosoguanidine (NTG): 10, 100, 1000 ug/ plate; 2-aminoanthracene: 100, 1000 ug/ plate) were also tested with and without metabolic activation.
Three plates were used for each treatment,
1) Without metabolic activation; a) Bacterial cells were inoculated on the minimal plate and the test chemicals were applied onto a paper disk. Plates were incubated at 37°C for 48 hours. The number of revertant colonies per plate was counted. b) Bacterial suspension were mixed with the test chemicals. The mixture was incubated at 37°C for 1 hour. Bacterial cells were washed and plated to determine the viability and the mutation frequency, respectively. Reverse mutant cells and viable cells were counted respectively, and mutation frequency was calculated.
2) With metabolic activation; The metabolizing mixture containing the homogenate (Liver, lung, kidney, testis and brain homogenate from male Sprague Dawley rats intraperitoneally injected with 3-methylcholanthrene (20 mg/kg) for 24 hr and liver homogenate from male ICR mice pretreated with 1% sodium phenobarbital in drinking water for one week), bacterial cells and the test chemicals was shaken for 30 min at 37°C. The whole mixture was plated and incubated for 48 hours at 37°C. The number of revertant colonies per plate was counted. - Statistics:
- Not required
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli, other: W-3102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Fenitrothion did not show any increase in the number of revertant colonies with or without metabolic activation in any of the strains investigated.
- Executive summary:
The mutagenic potential of fenitrothion was investigated in a non-standard Ames test. Salmonella typhimurium strains TA1535, TA1537 and TA1538; and E. coli strain W3102 were exposed in triplicate to fenitrothion (dissolved in DMSO) at concentrations of 10, 100, 1000 or 10000 ug/plate in the absence or presence of metabolic activation (homogenates of liver, lung, kidney, testis and brain homogenate from male SD rats intraperitoneally injected with 3-methylcholanthrene (20 mg/kg) for 24 hr and liver homogenate from male ICR mice pretreated with 1% sodium phenobarbital in drinking water for one week). Fenitrothion did not show any increase in the number of revertant colonies with or without metabolic activation in any of the strains investigated. Positive control substances (2 -AA, NTG) showed marked increases in the numbers of revertant colonies. There is no evidence of mutagenicity in this study.
Referenceopen allclose all
Summary of results
Chemical |
Dose (mg/plate) |
Revertant colonies/plate |
|||||
Salmonella typhimurium |
|||||||
TA100 |
TA100 NR |
TA100 1,8-DNP6 |
|||||
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
||
Fenitrothion (technical) |
0 |
94 |
87 |
114 |
100 |
108 |
105 |
100 |
113 |
122 |
107 |
104 |
126 |
120 |
|
200 |
138 |
173 |
101 |
111 |
127 |
131 |
|
500 |
192 |
323 |
110 |
105 |
141 |
145 |
|
1000 |
203t |
380 |
105t |
104 |
152t |
160 |
|
2000 |
173t |
315t |
97t |
103 |
154t |
184 |
|
5000 |
142t |
173t |
90t |
101 |
174t |
215 |
|
Fenitrothion (purified) |
0 |
81 |
79 |
87 |
83 |
96 |
89 |
100 |
116 |
121 |
81 |
93 |
104 |
104 |
|
200 |
153t |
164 |
88 |
96 |
113t |
112 |
|
500 |
224t |
341 |
102 |
105 |
125t |
128 |
|
1000 |
224t |
388t |
89t |
82 |
123t |
141 |
|
2000 |
222t |
463t |
86t |
89 |
135t |
146 |
|
5000 |
221t |
255t |
80t |
91 |
134t |
154 |
|
MMS |
100 |
413 |
- |
468 |
- |
514 |
- |
B(a)P |
5 |
- |
827 |
- |
949 |
- |
964 |
2NF |
2 |
485 |
- |
154 |
- |
176 |
- |
1,8-DNP |
0.01 |
473 |
- |
771 |
- |
151 |
- |
t: evidence of toxicity
Chemical |
Dose (mg/ plate) |
Revertant colonies/plate |
|||||||
Salmonella typhimurium |
Escherichia coli |
||||||||
TA98 |
TA1535 |
TA1537 |
WP2uvrA |
||||||
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
||
Fenitrothion (technical) |
0 |
37 |
38 |
10 |
10 |
11 |
21 |
16 |
15 |
100 |
32 |
36 |
9 |
10 |
8 |
14 |
19 |
21 |
|
200 |
34 |
38 |
8 |
14 |
10 |
17 |
18 |
25 |
|
500 |
34 |
44 |
9 |
15 |
5 |
12 |
25 |
20 |
|
1000 |
31 |
40 |
7 |
13 |
4t |
4t |
24 |
22 |
|
2000 |
26 |
37 |
9 |
9 |
3t |
3t |
22 |
21 |
|
5000 |
21 |
39 |
7 |
8 |
3t |
3t |
23 |
25 |
|
Fenitrothion (purified) |
0 |
25 |
44 |
- |
- |
- |
- |
- |
- |
100 |
28 |
32 |
- |
- |
- |
- |
- |
- |
|
200 |
30 |
35 |
- |
- |
- |
- |
- |
- |
|
500 |
25 |
44 |
- |
- |
- |
- |
- |
- |
|
1000 |
35t |
42 |
- |
- |
- |
- |
- |
- |
|
2000 |
22t |
37 |
- |
- |
- |
- |
- |
- |
|
5000 |
22t |
37 |
- |
- |
- |
- |
- |
- |
|
2NF |
1 |
355 |
- |
- |
- |
- |
- |
- |
- |
2 |
- |
- |
- |
- |
- |
- |
250 |
|
|
B(a)P |
5 |
- |
687 |
- |
- |
- |
160 |
- |
- |
Sodium azide |
0.5 |
- |
- |
341 |
- |
- |
- |
- |
- |
2AA |
2 |
- |
- |
- |
141 |
- |
- |
- |
- |
80 |
- |
- |
- |
- |
- |
- |
- |
479 |
|
9AA |
80 |
- |
- |
- |
- |
1474 |
- |
- |
- |
t: evidence of toxicity
Chemical |
Dose (mg/plate) |
Revertant colonies/plate |
|||||||
Salmonella typhimurium |
|||||||||
TA100 |
TA100NR |
TA100 1,8-DNP6 |
TA98 |
||||||
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
-S9 |
+S9 |
||
FNO |
0 |
71 |
66 |
- |
- |
- |
- |
23 |
34 |
3 |
71 |
69 |
- |
- |
- |
- |
31 |
39 |
|
10 |
78 |
63 |
- |
- |
- |
- |
25 |
41 |
|
30 |
83 |
69 |
- |
- |
- |
- |
24 |
36 |
|
100 |
83 |
72 |
- |
- |
- |
- |
20 |
40 |
|
300 |
91 |
101 |
- |
- |
- |
- |
36 |
49 |
|
1000 |
165 |
204 |
- |
- |
- |
- |
33 |
43 |
|
Nitroso- fenitrothion |
0 |
93 |
89 |
- |
- |
- |
- |
26 |
40 |
2 |
106 |
86 |
- |
- |
- |
- |
38 |
40 |
|
5 |
133 |
86 |
- |
- |
- |
- |
32 |
44 |
|
10 |
118t |
92 |
- |
- |
- |
- |
4t |
38 |
|
20 |
73t |
113 |
- |
- |
- |
- |
Tox |
53 |
|
50 |
Tox |
111 |
- |
- |
- |
- |
- |
56 |
|
100 |
- |
103 |
- |
- |
- |
- |
- |
59 |
|
200 |
- |
117 |
- |
- |
- |
- |
- |
58 |
|
500 |
- |
Tox |
- |
- |
- |
- |
- |
151 |
|
Nitroso- fenitrooxon |
0 |
71 |
66 |
- |
- |
- |
- |
23 |
34 |
3 |
82 |
57 |
- |
- |
- |
- |
38 |
38 |
|
10 |
90 |
72 |
- |
- |
- |
- |
29 |
42 |
|
30 |
42t |
99 |
- |
- |
- |
- |
17t |
40 |
|
100 |
Tox |
106 |
- |
- |
- |
- |
Tox |
49 |
|
300 |
- |
97 |
- |
- |
- |
- |
- |
48 |
|
1000 |
- |
Tox |
- |
- |
- |
- |
- |
Tox |
|
AM-FNT |
0 |
83 |
64 |
104 |
97 |
132 |
112 |
30 |
46 |
2 |
86 |
85 |
104 |
115 |
126 |
121 |
- |
- |
|
5 |
96 |
118 |
109 |
145 |
124 |
137 |
- |
- |
|
10 |
92 |
158 |
102 |
189 |
131 |
161 |
- |
- |
|
20 |
78 |
225 |
110 |
244 |
119 |
181 |
- |
- |
|
50 |
79 |
294 |
118 |
304 |
115 |
216 |
- |
- |
|
100 |
88 |
355 |
113 |
332 |
119 |
205 |
32 |
65 |
|
200 |
- |
- |
- |
- |
- |
- |
25 |
76 |
|
500 |
38t |
344 |
94t |
373 |
123t |
220 |
29 |
69 |
|
1000 |
Tox |
285t |
Tox |
393 |
89t |
261 |
15t |
58 |
|
5000 |
- |
- |
- |
- |
- |
- |
Tox |
Tox |
|
AM-FNO |
0 |
71 |
66 |
- |
- |
- |
- |
23 |
34 |
3 |
77 |
63 |
- |
- |
- |
- |
37 |
46 |
|
10 |
64 |
60 |
- |
- |
- |
- |
35 |
41 |
|
30 |
70 |
64 |
- |
- |
- |
- |
26 |
38 |
|
100 |
61 |
115 |
- |
- |
- |
- |
26 |
37 |
|
300 |
83 |
221 |
- |
- |
- |
- |
25 |
63 |
|
1000 |
96 |
290 |
- |
- |
- |
- |
34 |
60 |
|
NMC |
0 |
94 |
100 |
- |
- |
- |
- |
27 |
49 |
50 |
85 |
103 |
- |
- |
- |
- |
31 |
49 |
|
100 |
88 |
92 |
- |
- |
- |
- |
24 |
42 |
|
200 |
86 |
47 |
- |
- |
- |
- |
31 |
40 |
|
500 |
100 |
61 |
- |
- |
- |
- |
27 |
35 |
|
1000 |
45 |
38 |
- |
- |
- |
- |
12 |
26 |
|
2000 |
Tox |
Tox |
- |
- |
- |
- |
Tox |
3 |
|
t: evidence of toxicity
Tox: excessive toxicity, not scored
Summary of findings (-S9)
Chemical |
Concentration |
Experiment 1 |
Experiment 2 |
||||
Survival (%) |
Plating efficiency (%) |
Mutation frequency (/10e6) |
Survival (%) |
Plating efficiency (%) |
Mutation frequency (/10e6) |
||
DMSO |
1.0% |
100 |
105.6 |
1.6 |
100 |
75.0 |
4.9 |
|
- |
- |
- |
|
88.8 |
5.3 |
|
Fenitrothion |
10e-5M |
111 |
98.4 |
4.4* |
89 |
88.6 |
5.3 |
3x10e-5M |
94 |
101.8 |
5.6** |
97 |
97.8 |
6.5 |
|
10e-4M |
81 |
110.0 |
7.6** |
80 |
89.6 |
5.6 |
|
3x10e-4M p |
66 |
114.0 |
6.4** |
70 |
80.0 |
8.3 |
|
MNNG |
3x10e-6M |
86 |
76.5 |
1063.5** |
76 |
60.6 |
1234.3** |
*significantly different to controls (p<0.05); **p<0.01
Summary of findings (+S9)
Chemical |
Concentration |
Experiment 1 |
Experiment 2 |
||||
Survival (%) |
Plating efficiency (%) |
Mutation frequency (/10e6) |
Survival (%) |
Plating efficiency (%) |
Mutation frequency (/10e6) |
||
DMSO |
1.0% |
100 |
112.6 |
3.3 |
100 |
85.4 |
0.8 |
- |
- |
- |
- |
97.0 |
2.7 |
||
Fenitrothion |
10e-5M |
94 |
100.6 |
6.6* |
92 |
100.0 |
4.0 |
3x10e-5M |
98 |
97.0 |
6.2 |
89 |
92.6 |
3.2 |
|
10e-4M |
87 |
82.2 |
6.5 |
89 |
107.4 |
2.5 |
|
3x10e-4M p |
64 |
101.4 |
7.2* |
62 |
90.2 |
5.2* |
|
DMBA |
3x10e-5M |
85 |
106.2 |
178.0** |
82 |
71.6 |
260.2** |
*significantly different to controls (p<0.05); **p<0.01
Summary of clastogenicity (-S9)
8 hr treatment |
|||||||||||||||
Treatment |
µg/mL |
Cells scored |
Chromosomal aberration |
Total aberrations |
Cells with aberrations(%) |
Polyploid (%)
|
MI (%) |
||||||||
ctg |
ctb |
cte |
csg |
csb |
cse |
Oth |
+ G |
- G |
+ G |
- G |
|||||
DMSO |
0.5 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
8.0 |
% |
100 |
0 |
1 |
0 |
0 |
1 |
1 |
0 |
3 |
3 |
3 |
3 |
1.5 |
9.6 |
|
Fenitrothion |
3 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3.5 |
6.7 |
100 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
3 |
7.0 |
||
10 |
100 |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
3 |
2 |
3 |
2 |
3 |
7.0 |
|
100 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
6* |
8.2 |
||
30 |
100 |
1 |
1 |
0 |
0 |
0 |
1 |
0 |
3 |
2 |
2 |
2 |
2.5 |
2.4 |
|
100 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
1.5 |
2.6 |
||
MMC |
0.05 |
100 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
0.5 |
3.5 |
|
|
100 |
1 |
1 |
2 |
0 |
0 |
2 |
0 |
6 |
5 |
5 |
5 |
3 |
4.2 |
16 hr treatment |
|||||||||||||||
Treatment |
µg/mL |
Cells scored |
Chromosomal aberration |
Total aberrations |
Cells with aberrations(%) |
Polyploid (%)
|
MI (%) |
||||||||
ctg |
ctb |
cte |
csg |
csb |
cse |
Oth |
+ G |
- G |
+ G |
- G |
|||||
DMSO |
0.5 |
100 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
1 |
1 |
1 |
1 |
7.5 |
% |
100 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
1 |
6.5 |
|
Fenitrothion |
3 |
100 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
2 |
6.6 |
100 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
2 |
7.0 |
||
10 |
100 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
0 |
6.9 |
|
100 |
0 |
0 |
1 |
0 |
0 |
1 |
0 |
2 |
2 |
2 |
2 |
0 |
6.1 |
||
30 |
100 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
3 |
1 |
3 |
1 |
1.5 |
4.2 |
|
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
4.0 |
||
MMC |
0.05 |
100 |
2 |
11 |
12 |
0 |
0 |
0 |
1 |
26** |
24** |
21** |
19** |
0.5 |
2.8 |
100 |
4 |
8 |
11 |
0 |
0 |
0 |
0 |
23** |
19** |
18** |
16** |
1 |
3.8 |
||
24 hr treatment |
|||||||||||||||
Treatment |
µg/mL |
Cells scored |
Chromosomal aberration |
Total aberrations |
Cells with aberrations(%) |
Polyploid (%)
|
MI (%) |
||||||||
ctg |
ctb |
cte |
csg |
csb |
cse |
Oth |
+ G |
- G |
+ G |
- G |
|||||
DMSO |
0.5 |
100 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
2 |
1 |
2 |
1 |
1.5 |
6.2 |
% |
100 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
0.5 |
5.0 |
|
Fenitrothion |
3 |
100 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
2 |
2 |
2 |
2 |
1 |
6.1 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1.5 |
5.5 |
||
10 |
100 |
0 |
7 |
0 |
0 |
0 |
1 |
0 |
8 |
8 |
2 |
2 |
3.5 |
6.0 |
|
100 |
1 |
0 |
0 |
0 |
1 |
1 |
0 |
3 |
2 |
3 |
2 |
1 |
5.8 |
||
30 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
2.0 |
|
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2.5 |
2.4 |
||
MMC |
0.05 |
100 |
6 |
15 |
29 |
0 |
0 |
3 |
0 |
53** |
47** |
41** |
37** |
1 |
3.4 |
100 |
5 |
13 |
23 |
0 |
1 |
1 |
0 |
43** |
38** |
37** |
34** |
1 |
2.9 |
||
ctg: chromatid gaps
ctb: chromatid breaks
cte: chromatid exchanges
csg: chromosome gaps
csb: chromosome breaks
cse: chromosome exchanges
Oth: others (fragmentations and cells with more than 9 aberrations)
+G: aberrations including gaps
-G: aberrations excluding gaps
*p<0.05; **p<0.01
Summary of clastogenicity (+S9)
2 hr treatment and 14 hr culture |
|||||||||||||||
Treat-ment |
Dose (µg/ml) |
Cells scored |
Chromosomal aberrations |
Total aberrations |
Cells with aberrations (%) |
Polyploidy (%)
|
MI (%) |
||||||||
ctg |
ctb |
cte |
csg |
csb |
cse |
Oth |
+ G |
- G |
+ G |
- G |
|||||
DMSO |
0.5 |
100 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
2 |
1 |
2 |
1 |
1.5 |
3.3 |
% |
100 |
3 |
0 |
0 |
0 |
0 |
1 |
0 |
4 |
1 |
4 |
1 |
2 |
2.6 |
|
Fenitrothion |
75 |
100 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
3 |
1 |
3 |
1 |
1.5 |
3.8 |
|
100 |
2 |
1 |
2 |
0 |
1 |
1 |
0 |
7 |
5 |
5 |
4 |
2.5 |
4.4 |
|
150 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2.5 |
3.0 |
|
|
100 |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
2 |
2 |
2 |
2 |
1 |
2.7 |
|
300 |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
1.7 |
|
|
100 |
0 |
1 |
2 |
0 |
0 |
0 |
0 |
3 |
3 |
2 |
2 |
1.5 |
2.2 |
|
B(a)P |
20 |
100 |
1 |
5 |
32 |
0 |
0 |
0 |
0 |
38** |
37** |
33** |
32** |
1 |
3.2 |
|
100 |
2 |
5 |
34 |
0 |
0 |
1 |
0 |
42** |
40** |
37** |
35** |
1.5 |
2.4 |
|
2 hr treatment and 22 hr culture |
|||||||||||||||
Treat-ment |
Dose (µg/ml) |
Cells scored |
Chromosomal aberrations |
Total aberrations |
Cells with aberrations (%) |
Polyploidy (%)
|
MI (%) |
||||||||
ctg |
ctb |
cte |
csg |
csb |
cse |
Oth |
+ G |
- G |
+ G |
- G |
|||||
DMSO |
0.5 |
100 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
2 |
6.3 |
% |
100 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
1.5 |
6.1 |
|
Fenitrothion |
75 |
100 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
1.5 |
6.1 |
100 |
0 |
2 |
0 |
0 |
0 |
2 |
0 |
4 |
4 |
4 |
4 |
1 |
6.0 |
||
150 |
100 |
0 |
0 |
1 |
0 |
0 |
1 |
1 |
3 |
3 |
3 |
3 |
2 |
2.7 |
|
100 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
2 |
2.6 |
||
300 |
100 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
2 |
2 |
2 |
2 |
1.5 |
2.5 |
|
100 |
0 |
1 |
2 |
0 |
0 |
0 |
0 |
3 |
3 |
1 |
1 |
1 |
1.7 |
||
CP |
40 |
100 |
5 |
10 |
39 |
0 |
2 |
0 |
1 |
57** |
52** |
32** |
29** |
1 |
2.4 |
100 |
3 |
10 |
31 |
0 |
2 |
1 |
1 |
48** |
45** |
34** |
32** |
1.5 |
1.9 |
||
ctg: chromatid gaps
ctb: chromatid breaks
cte: chromatid exchanges
csg: chromosome gaps
csb: chromosome breaks
cse: chromosome exchanges
Oth: others (fragmentations and cells with more than 9 aberrations)
+G: aberrations including gaps
-G: aberrations excluding gaps
*p<0.05; **p<0.01
Summary of results without metabolic activation
Chemical |
Dose (mg/ plate) |
Revertant colonies/plate |
|||
E. coli |
S. typhimurium |
||||
W-3102 |
TA1535 |
TA1537 |
TA1538 |
||
DMSO |
10000 |
23.0 |
13.3 |
10.7 |
46.7 |
Fenitrothion |
10 |
16.6 |
10.7 |
21.0 |
46.7 |
100 |
30.0 |
7.30 |
16.3 |
29.7 |
|
1000 |
27.3 |
12.3 |
14.3 |
30.7 |
|
10000 |
32.0 |
12.6 |
17.0 |
42.3 |
|
NTG |
10 |
12.7 |
800 |
16.6 |
45.7 |
100 |
1000 |
2000 |
38.2 |
72.3 |
|
1000 |
2500 |
4000 |
84.1 |
140 |
|
Summary of results with metabolic activation
Strain |
Chemical |
Dose (mg/ plate) |
Revertant colonies/plate |
|||||
Rat |
Mouse |
|||||||
Liver |
Lung |
Kidney |
Testis |
Brain |
Liver |
|||
TA1535 |
DMSO |
10000 |
13.0 |
13.3 |
16.1 |
9.0 |
14.0 |
16.2 |
Fenitrothion |
10 |
15.0 |
20.7 |
19.7 |
13.0 |
18.7 |
17.0 |
|
100 |
15.0 |
22.7 |
19.0 |
7.0 |
23.3 |
16.3 |
||
1000 |
16.3 |
17.0 |
20.7 |
11.3 |
21.3 |
15.7 |
||
2-AA |
100 |
76.3 |
53.0 |
15.3 |
5.0 |
5.7 |
131 |
|
1000 |
138 |
62.3 |
15.7 |
7.3 |
7.0 |
170 |
||
TA1538 |
DMSO |
10000 |
46.2 |
43.1 |
38.8 |
34.8 |
40.8 |
37.6 |
Fenitrothion |
10 |
51.7 |
71.3 |
36.7 |
36.6 |
38.3 |
45.3 |
|
100 |
44.3 |
75.0 |
33.3 |
33.3 |
28.0 |
31.3 |
||
1000 |
40.3 |
56.7 |
34.7 |
34.7 |
27.3 |
24.0 |
||
2-AA |
100 |
272 |
57.0 |
116 |
105 |
69.0 |
1000 |
|
1000 |
1500 |
101 |
161 |
38.3 |
46.6 |
1800 |
||
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Studies of micronucleus formation and clastogenicity in vivo are available for fenitrothion.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 23 March 1982 - 14 April 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- no
- Type of assay:
- mammalian erythrocyte micronucleus test
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 00106
Purity: 96.8% - Species:
- mouse
- Strain:
- ICR
- Details on species / strain selection:
- Standard species/strain used for regulatory studies
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Laboratory Animals (Japan)
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 33-45 g
- Diet: ad libitum)
- Water: e.g. ad libitum
- Acclimation period: one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-25
- Humidity (%): 50-70
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): 12-12
IN-LIFE DATES: From: 23 March 1982 To: 14 April 1982 - Route of administration:
- intraperitoneal
- Vehicle:
- Corn oil
- Details on exposure:
- Groups of 6 male ICR mice (7 to 8 weeks old) each received a single intraperitoneal injection of fenitrothion in corn oil at dose levels of 200, 400, 800 and 1600 mg/kg bw (10 mL kg/bw)
- Duration of treatment / exposure:
- Single intraperitoneal injection
- Frequency of treatment:
- Single intraperitoneal injection
- Post exposure period:
- 24 hours
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Vehicle (corn oil) control
- Dose / conc.:
- 200 mg/kg bw/day
- Remarks:
- Single intraperitoneal injection
- Dose / conc.:
- 400 mg/kg bw/day
- Remarks:
- Single intraperitoneal injection
- Dose / conc.:
- 800 mg/kg bw/day
- Remarks:
- Single intraperitoneal injection
- Dose / conc.:
- 1 600 mg/kg bw/day
- Remarks:
- Single intraperitoneal injection
- No. of animals per sex per dose:
- 6 males
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Mitomycin C, 4 mg/kg bw
- Tissues and cell types examined:
- Polychromatic bone marrow erythrocytes
- Details of tissue and slide preparation:
- Mice were sacrificed 24 hours after administration. Bone marrow cells were obtained from a femur, fixed, stained (Giemsa) and analyzed in a blind manner. A thousand erythrocytes were observed and the incidence of micronucleated cells as well as the ratio of polychromatic erythrocytes to whole erythrocytes were examined from each animal. The micronucleated cells in 1000 polychromatic erythrocytes were also counted
- Evaluation criteria:
- Not reported
- Statistics:
- The incidence of micronucleated cells was assessed according to Kastenbaum & Bowman; the t-test was used for assessment of the PCE:NCE ratio.
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Mortality at 1600 mg/kg bw; altered PCE ratio at 800 mg/kg bw
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- All mice administered 1600 mg/kg bw fenitrothion died before scheduled sacrifice.
- Conclusions:
- Fenitrothion did not induce micronuclei in the bone marrow cells of mice under the conditions of this study.
- Executive summary:
In a mouse bone marrow micronucleus assay, groups of 6 male ICR mice (7 to 8 weeks old) each received a single intraperitoneal injection of fenitrothion in corn oil at dose levels of 200, 400, 800 and 1600 mg/kg bw (10 mL/kg bw). All animals at 1600 mg/kg bw died before the scheduled sacrifice. Mice were sacrificed 24 hours after administration. Bone marrow cells were obtained from a femur, fixed, stained (Giemsa) and analysed in a blind manner. A thousand erythrocytes were observed and the incidence of micronucleated cells as well as the ratio of polychromatic erythrocytes to whole erythrocytes were examined from each animal. The micronucleated cells in 1000 polychromatic erythrocytes were also counted. Negative controls (corn oil) and positive controls (mitomycin C 4 mg/kg bw; 10 mL/kg bw) were similarly assessed. All mice administered 1600 mg/kg bw fenitrothion died before scheduled sacrifice. A significantly increased PCE ratio in mice at 800 mg/kg bw indicated adequate exposure of the target tissue. A statistically significant increase in the incidence of micronucleated PCEs was seen in the low dose group, but is not considered to be of biological relevance in the absence of similar findings in the other dose groups. The PCE ratio was significantly increased in the high dsoe group, indicating exposure of the target tissue. Fenitrothion did not induce micronuclei in the bone marrow cells of mice under the conditions of this study.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 15 April 1982 - 25 May 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- GLP compliance:
- no
- Type of assay:
- mammalian bone marrow chromosome aberration test
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 00106
Purity: 96.8% - Species:
- mouse
- Strain:
- ICR
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shizuoka Agricultural Coopertaive Association for Laboratory Animals
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 33-45 g
- Housing:
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-25
- Humidity (%): 50-70
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 15 April 1982 To: 25 May 1982 - Route of administration:
- intraperitoneal
- Vehicle:
- Corn oil
- Details on exposure:
- Groups of 6 male ICR mice (7 to 8 weeks old) each received a single intraperitoneal injection of fenitrothion, in corn oil at dose levels of 200, 400 and 800 mg/kg bw (10 mL/kg bw). Mice were injected with 4 mg/kg of colchicine 2 hours before sacrifice.
- Duration of treatment / exposure:
- Single intraperitoneal injection
- Frequency of treatment:
- Single injection
- Post exposure period:
- 6, 24, 48 hours
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Control (corn oil)
- Dose / conc.:
- 200 mg/kg bw/day (actual dose received)
- Remarks:
- Single intraperitoneal injection
- Dose / conc.:
- 400 mg/kg bw/day (actual dose received)
- Remarks:
- Single intraperitoneal injection
- Dose / conc.:
- 800 mg/kg bw/day (actual dose received)
- Remarks:
- Single intraperitoneal injection
- No. of animals per sex per dose:
- 6 males
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Mitomycin C (4 mg/kg bw)
- Tissues and cell types examined:
- Bone marrow cells
- Details of tissue and slide preparation:
- Bone marrow cells were harvested, fixed, stained (Giemsa) and analyzed in a blind manner. Fifty well-spread metaphases from each animal were observed under microscope.
- Evaluation criteria:
- No details
- Statistics:
- Appropriate statistical methods (chi-squared test) were used to compare the control and test groups.
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Remarks:
- Toxicity not detailed, but predicted on the basis of the preliminary study
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- In the fenitrothion treated groups, there was no significant increase in frequencies of chromosomal aberrations compared with the corresponding vehicle control value.
- Conclusions:
- Fenitrothion did not induce chromosomal aberrations in bone marrow cells of mice under the conditions of this study.
- Executive summary:
The potential of fenitrothion to cause chromosomal aberrations was investigated in a study in the mouse. Groups of 6 male ICR mice (7 to 8 weeks old) each received a single intraperitoneal injection of fenitrothion, in corn oil at dose levels of 200, 400 and 800 mg/kg bw. Mice were injected with 4 mg/kg bw of colchicine 2 hours before sacrifice. Bone marrow cells were harvested, fixed, stained (Giemsa) and analyzed in a blind manner. Fifty well-spread metaphases from each animal were observed under microscope. In the fenitrothion treated groups, there was no significant increase in frequencies of chromosomal aberrations compared with the corresponding vehicle control value. The positive control (mitomycin C 4 mg/kg bw) produced significant increases in the proportion of cells with chromosomal aberrations. Fenitrothion did not induce chromosomal aberrations in bone marrow cells of mice under the conditions of this study.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 9 September 1982 - 17 December 1982
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- GLP compliance:
- no
- Type of assay:
- mammalian bone marrow chromosome aberration test
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 00106
Purity: 96.8% - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Standard strain / species used in regulatory studies
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 80-160 g
- Diet :ad libitum
- Water: ad libitum
- Acclimation period: One week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-25
- Humidity (%): 50-70
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 9 September 1982 To: 17 December 1982 - Route of administration:
- oral: gavage
- Vehicle:
- Cottonseed oil
- Details on exposure:
- A preliminary acute toxicity test was conducted to determine the dose levels to be used in the chromosomal aberration test. Rats were treated with fenitrothion at dose levels of 400, 800, 1200 and 1600 mg/kg bw. In the chromosomal aberration test, dose levels of 100, 200, 400 mg//kg bw (single treatment) or 20, 40, 80 mg/kg bw (5 consecutive doses with a 24 hour interval) were used. Rats were injected with 4 mg/kg bw colchicine 2 hours before sacrifice.
- Duration of treatment / exposure:
- The study used single doses and also five repeated daily doses
- Frequency of treatment:
- The study used single doses and also five repeated daily doses
- Post exposure period:
- 6, 24, 48 hours (single dose)
6 hours (repeated dose) - Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Vehicle (cottonseed oil), single dose
- Dose / conc.:
- 100 mg/kg bw/day
- Remarks:
- Single dose
- Dose / conc.:
- 200 mg/kg bw/day
- Remarks:
- Single dose
- Dose / conc.:
- 400 mg/kg bw/day
- Remarks:
- Single dose
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Vehicle (cottonseed oil): 5 consecutive daily doses
- Dose / conc.:
- 20 mg/kg bw/day
- Remarks:
- 5 consecutive daily doses
- Dose / conc.:
- 40 mg/kg bw/day
- Remarks:
- 5 consecutive daily doses
- Dose / conc.:
- 80 mg/kg bw/day
- Remarks:
- 5 consecutive daily doses
- No. of animals per sex per dose:
- 6 males
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide, 60 mg/kg bw
- Tissues and cell types examined:
- Bone marrow cells
- Details of tissue and slide preparation:
- Bone marrow cells were then harvested, fixed, stained (Giemsa) and analyzed in a blind manner. Fifty well-spread metaphases from each animal were observed under a microscope.
- Evaluation criteria:
- Not reported
- Statistics:
- Appropriate statistical methods (chi-squared test) were used to compare the control and treated groups.
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Remarks:
- Toxicity was not reported but can be predicted based on the results of the range-finding study
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Fenitrothion did not induce chromosomal aberrations in bone marrow cells of rats, under the conditions of this study.
- Executive summary:
The potential of fenitrothion to cause chromosomal aberrations was investigated in a study in the rat. A preliminary acute toxicity test was conducted to determine the dose levels to be used in the chromosomal aberration test. Rats were treated with fenitrothion at dose levels of 400, 800, 1200 and 1600 mg/kg bw. In the chromosomal aberration test, dose levels of 100, 200, 400 mg//kg bw (single treatment) or 20, 40, 80 mg/kg bw (5 consecutive doses with a 24 hour interval) were used. Rats were injected with 4 mg/kg bw colchicine 2 hours before sacrifice. In fenitrothion treated groups, there was no significant increase in frequencies of chromosomal aberrations compared with the negative control values. The positive control (cyclophosphamide 60 mg/kg bw) produced significant amounts of chromosomal aberrations at 6 and 24 hours after administration. Fenitrothion did not induce chromosomal aberrations in bone marrow cells of rats, under the conditions of this study.
Referenceopen allclose all
Summary of findings
Treatment |
Dose level (mg/kg bw) |
Time |
No. mice |
No. cells |
PCEs (%) |
Micronucleated erythrocytes (%) |
Micronucleated PCEs (%) |
Corn oil |
10 ml/kg |
24h |
6 |
6000 |
30.9 |
0.08 |
0.18 |
Fenitrothion |
200 |
24h |
6 |
6000 |
36.0 |
0.25* |
0.25 |
400 |
24h |
6 |
6000 |
36.8 |
0.10 |
0.17 |
|
800 |
24h |
6 |
6000 |
44.4** |
0.18 |
0.30 |
|
MMC |
4 |
24h |
6 |
6000 |
31.0 |
1.45** |
4.75** |
**significantly different to controls (p<0.01)
PCE: polychromatic erythrocyte
Summary of findings
Chemical |
Dose (mg/kgbw) |
Time after injection |
No. mice |
No. cells |
Cells with aberration (%) |
No. of aberrations |
||||
G |
B |
E |
m.a. |
P |
||||||
Corn oil |
-b) |
6 |
6 |
300 |
0.7 |
1 |
1 |
0 |
0 |
0 |
Fenitrothion |
200 |
6 |
6 |
300 |
1.0 |
2 |
1 |
0 |
0 |
0 |
400 |
6 |
6 |
300 |
0.0 |
0 |
0 |
0 |
0 |
0 |
|
800 |
6 |
6 |
300 |
1.0 |
2 |
1 |
0 |
0 |
0 |
|
MMC |
4 |
6 |
6 |
300 |
30.3** |
27 |
25 |
94 |
5 |
0 |
Corn oil |
- |
24 |
6 |
300 |
1.7 |
4 |
1 |
0 |
0 |
0 |
Fenitrothion |
200 |
24 |
6 |
300 |
0.0 |
0 |
0 |
0 |
0 |
0 |
400 |
24 |
6 |
300 |
0.0 |
0 |
0 |
0 |
0 |
0 |
|
800 |
24 |
6 |
300 |
0.7 |
2 |
0 |
0 |
0 |
0 |
|
MMC |
4 |
24 |
6 |
300 |
66.3** |
187 |
190 |
95 |
26 |
9 |
Corn oil |
- |
48 |
6 |
300 |
0.3 |
1 |
0 |
0 |
0 |
0 |
Fenitrothion |
200 |
48 |
6 |
300 |
0.7 |
2 |
0 |
0 |
0 |
0 |
400 |
48 |
6 |
300 |
0.0 |
0 |
0 |
0 |
0 |
0 |
|
800 |
48 |
6 |
300 |
0.7 |
2 |
0 |
0 |
0 |
0 |
|
MMC |
4 |
48 |
6 |
300 |
16.3** |
11 |
2 |
19 |
11 |
18 |
G: gaps
B: breaks
E: exchanges
P: pulverised
m.a.: multiuple aberrations
**significantly different to controls (p<0.01)
Summary of findings
Chemical |
Dose (mg/kg bw) |
Time |
No. rats |
No. cells |
Cell with aberrations (%) |
No. of aberrations |
||||
G |
B |
E |
m.a. |
P |
||||||
-control |
- |
6h |
6 |
300 |
0.7 |
1 |
1 |
0 |
0 |
0 |
Fenitrothion |
100 |
6h |
6 |
300 |
1.0 |
2 |
1 |
0 |
0 |
0 |
200 |
6h |
6 |
300 |
0.7 |
2 |
0 |
0 |
0 |
0 |
|
400 |
6h |
6 |
300 |
1.3 |
4 |
0 |
0 |
0 |
0 |
|
+control |
60 |
6h |
6 |
300 |
22.0** |
59 |
23 |
6 |
0 |
0 |
-control |
- |
24h |
6 |
300 |
0.7 |
2 |
0 |
0 |
0 |
0 |
Fenitrothion |
100 |
24h |
6 |
300 |
0.7 |
2 |
0 |
0 |
0 |
0 |
200 |
24h |
5c) |
300 |
0.4 |
1 |
0 |
0 |
0 |
0 |
|
400 |
24h |
6 |
300 |
1.3 |
4 |
0 |
0 |
0 |
0 |
|
+control |
60 |
24h |
6 |
300 |
44.7** |
105 |
62 |
45 |
42 |
2 |
-control |
- |
48h |
6 |
300 |
0.7 |
2 |
0 |
0 |
0 |
0 |
Fenitrothion |
100 |
48h |
6 |
300 |
0.0 |
0 |
0 |
0 |
0 |
0 |
200 |
48h |
6 |
300 |
0.3 |
1 |
0 |
0 |
0 |
0 |
|
400 |
48h |
6 |
300 |
1.0 |
1 |
2 |
0 |
0 |
0 |
|
CP |
60 |
48h |
6 |
300 |
1.0 |
1 |
2 |
4 |
0 |
0 |
-control |
- |
6h |
6 |
300 |
0.3 |
1 |
0 |
0 |
0 |
0 |
Fenitrothion |
20 x5 |
6h |
6 |
300 |
1.0 |
2 |
1 |
0 |
0 |
0 |
40 x5 |
6h |
6 |
300 |
0.3 |
0 |
1 |
0 |
0 |
0 |
|
80 x5 |
6h |
6 |
300 |
1.0 |
2 |
1 |
0 |
0 |
0 |
|
**significantly different to controls (p<0.01)
G: gaps
B: breaks
E: exchanges
P: pulverisation
m.a.: multiple aberrations
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Mode of Action Analysis / Human Relevance Framework
A weakly positive response reported in S. typhiumurium TA100 was shown to be bacterial-specifc (nitroreductase-dependent) and is not considered to be relevant to humans.
Additional information
Studies in vitro
In the key Ames test, fenitrothion was tested using strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, TA100 NR (nitroreductase-deficient strain) and TA100 1,8 -DNP6 (transacetylase-deficient strain)); andEscherichia coliWP2uvrA. Purified samples of fenitrothion and aminofenitrothion (AM-FNT) were tested using strains TA98, TA100, TA100 NR and TA100 1,8 -DNP6. Test chemicals were dissolved in DMSO and tests were conducted using a pre-incubation method with and without metabolic activation. Negative control (DMSO, 100 ul /plate), positive and insensitive controls were also tested with and without metabolic activation. S9 mix, a mixture of cofactors and the liver S9 from Sprague-Dawley rats treated intraperitoneally with polychlorinated biphenyls (PCB), were used for metabolic activation. Fenitrothion was found to be non-mutagenic in TA98, TA1535, TA1537 and WP2uvrA both with and without S9 mix, while weak mutagenicity was observed only in TA100 and it was enhanced by the addition of S9 mix. The mutagenicity was not observed in a nitroreductase-deficient strain, TA100 NR, and it decreased in a transacetylase-deficient strain, TA100 1,8-DNP6. The results suggest that the bacterial nitroreductase activity is necessary for fenitrothion to express the mutagenicity in TA100.
In a supporting Ames test, fenitrothion was investigated in Salmonella typhimurium strains TA1535, TA1537 and TA1538; and E. colis train W3102. Strains were exposed in triplicate to fenitrothion (dissolved in DMSO) at concentrations of 10, 100, 1000 or 10000 ug/plate in the absence or presence of metabolic activation (homogenates of liver, lung, kidney, testis and brain homogenate from male SD rats intraperitoneally injected with 3-methylcholanthrene (20 mg/kg) for 24 hr and liver homogenate from male ICR mice pretreated with 1% sodium phenobarbital in drinking water for one week). Fenitrothion did not show any increase in the number of revertant colonies with or without metabolic activation in any of the strains investigated. Positive control substances (2 -AA, NTG) showed marked increases in the numbers of revertant colonies. There is no evidence of mutagenicity in this study.
The potential clastogenicity of fenitrothion was investigated in CHO-K1 cells. A preliminary cytotoxicity test was performed to determine the concentrations to be used in the main study. The concentrations ranged from 1 -300 µg/mL with and without metabolic activation. In the chromosomal aberration test, Chinese hamster ovary cells (CHO-K1) were treated with fenitrothion (dissolved in DMSO) at concentrations of 3, 10 and 30 µg/mL for periods of 8, 16 or 24 hours in the absence of metabolic activation. In the presence of metabolic activation, cells were exposed to concentrations of 75, 150 and 300 µg/mL for 2 hours, with further culture in a fresh medium for 14 or 22 hours after removal of the test chemical. The cells were harvested, fixed, stained and analyzed in a blind manner. Negative control (DMSO) and positive controls (MMC, B(a)P, cyclophosphamide) were also tested. Mitotic indices were determined by counting more than 1000 cells. The number of structural aberrations and the frequencies of cells with structural aberrations were obtained by observation of 100 cells from each duplicate culture at each experimental point, and also the frequencies of polyploid cells were determined by observation of an additional 200 cells. Fenitrothion did not induce any significant increase in the number of total chromosome aberrations or in the frequency of cells with structural aberrations in the presence or absence of metabolic activation. A slight increase of the incidence of polyploid cells was observed in one culture of the 8 -hour treatment group at a concentration of 10 µg/ml in the absence of metabolic activation. However, no significant increase of polyploid cells was observed in other cultures and time- or concentration-dependency was not observed. Thus it was concluded that the increase was spontaneous. Positive control chemicals induced marked increases both in the number of total chromosome aberrations and in the frequency of cells with chromosomal aberrations. Fenitrothion does not have any clastogenic potential against CHO-K1 cells under the conditions tested.
The mutagenic potential of fenitrothion was investigated in an HPRT assay using V79 cells. To determine appropriate concentrations for use in the gene mutation test, a preliminary cytotoxicity test was performed using concentrations of 10e-3 to 10e-5 M with a dilution factor of 3 in the presence and absence of metabolic activation system (S9 mix). In the main study, cultures of V79 cells were treated with fenitrothion at concentrations of 10e-5 M, 3×10e-5 M, 10e-4 M and 3×10e-4 M with and without S9. Fenitrothion was dissolved in dimethyl sulphoxide (DMSO). Negative (sovent) controls (DMSO 1%) and positive controls (N-methyl-N’-nitro-N-nitrosoguanidine 3×10e-6 M; 9,10 -dimethyl-1,2 -benzanthracene 3×10e-5 M) were run concurrently. After incubation for five hours at 37°C, the cells were washed and cultured to determine cytotoxicity and to allow for expression of the mutant phenotype at 37°C for 7 days. After the expression period, the cells were innoculated to dishes with and without 6-thioguanine (6-TG) and cultivated for 6 or 7 days to determine the number of mutants and plating efficiency. Colonies formed were fixed, Giemsa-stained and counted. The number of colonies for each dish was counted and the mutation frequency and the plating efficiency were calculated. In the first experiment without metabolic activation, the mutation frequencies of the fenitrothion-treated groups were statistically significantly higher than that of the negative control group, but no concentration-dependent increase was observed. The result in the second experiment with two negative control groups showed no significant differences. In the first experiment with metabolic activation, the mutation frequencies of the fenitrothion-treated groups were partly higher than that of the negative control group, but no concentration-dependent increase was observed. In the second experiment, a small increase was observed at the highest concentration in the mutation frequency, but these values were within the range of historical control data. Small increases in the mutation frequencies are considered to be within the range of variation of the spontaneous mutation frequency, and no reproducible dose-response relationship were observed both in the presence and absence of metabolic activation. Fenitrothion was concluded not mutagenic under the test conditions.
Studies in vivo
In a mouse bone marrow micronucleus assay, groups of 6 male ICR mice (7 to 8 weeks old) each received a single intraperitoneal injection of fenitrothion in corn oil at dose levels of 200, 400, 800 and 1600 mg/kg bw (10 mL/kg bw). All animals at 1600 mg/kg bw died before the scheduled sacrifice. Mice were sacrificed 24 hours after administration. Bone marrow cells were obtained from a femur, fixed, stained (Giemsa) and analysed in a blind manner. A thousand erythrocytes were observed and the incidence of micronucleated cells as well as the ratio of polychromatic erythrocytes to whole erythrocytes were examined from each animal. The micronucleated cells in 1000 polychromatic erythrocytes were also counted. Negative controls (corn oil) and positive controls (mitomycin C 4 mg/kg bw; 10 mL/kg bw) were similarly assessed. All mice administered 1600 mg/kg bw fenitrothion died before scheduled sacrifice. A significantly increased PCE ratio in mice at 800 mg/kg bw indicated adequate exposure of the target tissue. A statistically significant increase in the incidence of micronucleated PCEs was seen in the low dose group, but is not considered to be of biological relevance in the absence of similar findings in the other dose groups. The PCE ratio was significantly increased in the high dsoe group, indicating exposure of the target tissue. Fenitrothion did not induce micronuclei in the bone marrow cells of mice under the conditions of this study.
The potential of fenitrothion to cause chromosomal aberrations was investigated in a study in the mouse. Groups of 6 male ICR mice (7 to 8 weeks old) each received a single intraperitoneal injection of fenitrothion, in corn oil at dose levels of 200, 400 and 800 mg/kg bw. Mice were injected with 4 mg/kg bw of colchicine 2 hours before sacrifice. Bone marrow cells were harvested, fixed, stained (Giemsa) and analyzed in a blind manner. Fifty well-spread metaphases from each animal were observed under microscope.In the fenitrothion treated groups, there was no significant increase in frequencies of chromosomal aberrations compared with the corresponding vehicle control value. The positive control (mitomycin C 4 mg/kg bw) produced significant increases in the proportion of cells with chromosomal aberrations.Fenitrothion did not induce chromosomal aberrations in bone marrow cells of mice under the conditions of this study.
The potential of fenitrothion to cause chromosomal aberrations was investigated in a study in the rat. A preliminary acute toxicity test was conducted to determine the dose levels to be used in the chromosomal aberration test. Rats were treated with fenitrothion at dose levels of 400, 800, 1200 and 1600 mg/kg bw. In the chromosomal aberration test, dose levels of 100, 200, 400 mg//kg bw (single treatment) or 20, 40, 80 mg/kg bw (5 consecutive doses with a 24 hour interval) were used. Rats were injected with 4 mg/kg bw colchicine 2 hours before sacrifice.In fenitrothion treated groups, there was no significant increase in frequencies of chromosomal aberrations compared with the negative control values. The positive control (cyclophosphamide 60 mg/kg bw) produced significant amounts of chromosomal aberrations at 6 and 24 hours after administration.Fenitrothion did not induce chromosomal aberrations in bone marrow cells of rats, under the conditions of this study.
Justification for classification or non-classification
Fenitrothion has a harmonised classification but is not classified for germ cell mutagenicity. In the absence of relevant findings in the available studies, no change to this classification is proposed.
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