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Toxicological information

Genetic toxicity: in vivo

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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:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
no
Type of assay:
mammalian erythrocyte micronucleus test

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
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

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.