Fenitrothion

Genetic toxicity: in vivo

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

no

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Fenitrothion

EC Number:

204-524-2

EC Name:

Fenitrothion

Cas Number:

122-14-5

Molecular formula:

C9H12NO5PS

IUPAC Name:

O,O-dimethyl O-3-methyl-4-nitrophenyl phosphorothioate

Test material form:

liquid

Specific details on test material used for the study:

Fenitrothion
Batch No.: 00106
Purity: 96.8%

Test animals

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

Administration / exposure

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

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Remarks:

Vehicle (corn oil) control

Doses / concentrations 2

Dose / conc.:

200 mg/kg bw/day

Remarks:

Single intraperitoneal injection

Doses / concentrations 3

Dose / conc.:

400 mg/kg bw/day

Remarks:

Single intraperitoneal injection

Doses / concentrations 4

Dose / conc.:

800 mg/kg bw/day

Remarks:

Single intraperitoneal injection

Doses / concentrations 5

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

Examinations

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.

Results and discussion

Test results

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.