Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 January 1985 - 20 March 1986
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:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
traditional method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Fenitrothion
Batch No.: 40805
Purity: 96.6%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Nominal concentration of the test material in the chamber air (mg/m3)

Group I: vehicle only (vehicle control)
Group II: vehicle only (negative control)
Group III: 6.57
Group IV: 16.4
Group V: 65.7
Group VI: 1640
Group VII: 3280

Mean concentration measured (mg/m3)
Group III: 3.91
Group IV: 8.90
Group V: 38.2
Group VI: 1,010
Group VII: 2,210

Median aerodynamic diameter: 0.59 to 0.82 µm
Chamber air temperature: 28.4 to 30.8 °C
Relative humidity: 59.8 to 90.3 %

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: corn oil
Mass median aerodynamic diameter (MMAD):
>= 0.59 - <= 0.82 µm
Remark on MMAD/GSD:
Particle size adequately small: in the respirable range
Details on inhalation exposure:
Fenitrothion was dissolved in corn oil and administered by inhalation of a test atmosphere containing dust generated from the test substance; single administration, 4-hour whole body exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Remarks on duration:
Standard exposure period
Concentrations:
Mean measured concentrations were 3.91, 8.90, 38.2, 1010 and 2210 mg/m3.
No. of animals per sex per dose:
20/sex: each group had a main group for general observation, body weight, cholinesterase activity and pathological examination, and a satellite group for assessment of cholinesterase activity only.
Control animals:
yes
Remarks:
Two control groups; control and non-exposed
Details on study design:
Fenitrothion was dissolved in corn oil and administered by inhalation of a test atmosphere containing dust generated from the test substance; single administration, 4-hour whole body exposure, two control groups (vehicle and negative controls) and five test groups of Sprague-Dawley rats. Each exposure group had a main group for general observation, body weight, cholinesterase activity and pathological examination, and a satellite group for assessment of cholinesterase activity only.
Statistics:
Not required

Results and discussion

Preliminary study:
Not reported
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 210 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
One male exposed to 2210 mg/m3 died on Day 6. There were no further mortalities.
Clinical signs:
Irregular respiration, hyperpnoea, nasal discharge, muscular fibrillation, intermittent tremors, reduced spontaneous activity, lacrimation, salivation and urinary incontinence were observed in both sexes at >= 1010 mg/m3 and above. Males also showed excitation, tonic convulsion, ataxia and soft faeces. Signs of toxicity were observed from 30 minutes after the initiation of exposure and resolved within 9 days of exposure in surviving rats.
Body weight:
Slight transient reductions in body weight or weight gain was seen at >=1010 mg/m3.
Gross pathology:
Necropsy did not reveal any effects of treatment.
Other findings:
Inhibition of cholinesterase activity was observed 1-7 days after exposure. Plasma cholinesterase activity was reduced in males and females exposed to >=8.90 mg/m3; erythrocyte cholinesterase activity was reduced in males of groups exposed to >=1010 mg/m3 and in females exposed to >= 38.2 mg/m3. Brain cholinesterase activity was reduced in males and females exposed to >= 1010 mg/m3.

Any other information on results incl. tables

Summary of mortality

Exposure level

 

Males

Females

Cumulative Mortality

Time of death

Cumulative Mortality

Time of death

3.91 mg/m3

0

-

0

-

8.90 mg/m3

0

-

0

-

38.2 mg/m3

0

-

0

-

1010 mg/m3

0

-

0

-

2210 mg/m3

1

Day 6 (1)

0

-

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute inhalation LC50 of fenitrothion was found to be >2.21 mg/L (reported to be the maximum attainable concentration). Classification for acute inhalation toxicity is not required according to CLP criteria.
Executive summary:

The acute inhalation toxicity of fenitrothion was investigated in a study in the rat. Groups of Sprague-Dawley rats (20/sex) were exposed for four hours (whole body) to mean measured concentrations of 3.91, 8.90, 38.2, 1010 and 2210 mg/m3 (MMAD 0.59 -0.82 um). One male exposed to 2210 mg/m3 died on Day 6.  There were no further mortalities. Irregular respiration, hyperpnoea, nasal discharge, muscular fibrillation, intermittent tremors, reduced spontaneous activity, lacrimation, salivation and urinary incontinence were observed in both sexes at >= 1010 mg/m3 and above.  Males also showed excitation, tonic convulsion, ataxia and soft faeces.  Signs of toxicity were observed from 30 minutes after the initiation of exposure and resolved within 9 days of exposure in surviving rats. Slight transient reductions in body weight or weight gain was seen at >=1010 mg/m3. Inhibition of cholinesterase activity was observed 1-7 days after exposure.  Plasma cholinesterase activity was reduced in males and females exposed to >=8.90 mg/m3; erythrocyte cholinesterase activity was reduced in males of groups exposed to >=1010 mg/m3 and in females exposed to >= 38.2 mg/m3.  Brain cholinesterase activity was reduced in males and females exposed to >= 1010 mg/m3. Gross necropsy did not reveal any effects of treatment. The acute inhalation LC50 of fenitrothion was found to be >2210 mg/m3 (>2.21 mg/L; reported to be the maximum attainable concentration).  Classification for acute inhalation toxicity is not required according to CLP criteria.