Fenitrothion

Endpoint summary

Description of key information

Studies of acute oral, inhalation and dermal toxicity are available for fenitrothion.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 December 2009 - 1 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Fenitrothion TG (SMT, sumithion)
Brown liquid
Lot No.: 070502

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIO, Korea
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 173.3-217.8 g
- Fasting period before study: overnight (~16 hours)
- Housing: Individual
- Diet: ad libitum except prior to dosing
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3-22.4
- Humidity (%): 27.8-65.1
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 December 2009 To: 14 January 2010

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was administered undiluted.

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 30 minutes, 1, 2, 4 and 6 hours after dosing and subsequently daily
- Frequency of weighing: Days 0, 1, 3, 7 and 14 (terminal)
- Necropsy of survivors performed: yes

Statistics:

Not required

Preliminary study:

No details

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two deaths occurred at 2000 mg/kg bw in the initial group of three females (Day 1 or 2). There was no mortality in either of the two groups of three females administered 300 mg/kg bw.

Clinical signs:

other: Clinical signs were observed in all rats at 2000 mg/kg bw and included reduced activity, lacrimation, salivation, tremor, chromaturia and perineal staining. All signs had resolved by Day 9. Signs at 300 mg/kg bw included perineal soiling, lacrimation, s

Gross pathology:

There were no treatment-related findings at necropsy.

Summary of mortality

Group	Dose level (mg/kg bw)	Number of rats	Mortality
1	2000	3F	2/3
2	300	3F	0/3
3	300	3F	0/3

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of fenitrothion was found to be >300 -<2000 mg/kg bw;= fenitrothion therefore meets the criteria for classification for acute oral toxicity in Category 4 according to the CLP Regulation.

Executive summary:

The acute oral toxicity of fenitrothion was investigated in an Acute Toxic Class study according to OECD 423. Three females were initally administered a dose of 2000 mg/kg bw and observed for 14 days.  Due to mortality in this group, two additional groups of three females were administered 300 mg/kg bw in sequence, according to the study guideline. Two deaths occurred at 2000 mg/kg bw in the initial group of three females (Day 1 or 2).  There was no mortality in either of the two groups of three females administered 300 mg/kg bw. Clinical signs were observed in all rats at 2000 mg/kg bw and included reduced activity, lacrimation, salivation, tremor, chromaturia and perineal staining; all signs had resolved by Day 9.  Signs at 300 mg/kg bw included perineal soiling, lacrimation, salivation and tremor; all signs had resolved by Day 5. Transient slight reductions in bodyweight were seen in surviving animals of both dose groups. There were no treatment-related findings at necropsy. The acute oral LD50 of fenitrothion was found to be >300 -<2000 mg/kg bw; fenitrothion therefore meets the criteria for classification for acute oral toxicity in Category 4 according to the CLP Regulation.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

August 1, 1972 - September 30, 1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

In-house method, comparable to OECD 401

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Fenitrothion
Batch No.: 417
Purity: 97.2%

Species:

mouse

Strain:

other: dd

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: 10% Tween-80

Details on oral exposure:

Fenitrothion was suspended in 10% Tween-80 and administered orally to groups of 8 male and 8 female dd mice at dose levels of of 0 (vehicle), 500, 700, 980, 1370, 1920 mg/kg bw using a constant dose volume of 20 mL/kg bw.

Doses:

0 (vehicle), 500, 700, 980, 1370, 1920 mg/kg bw

No. of animals per sex per dose:

8

Control animals:

yes

Remarks:

Vehicle control

Details on study design:

Mortality and signs of toxicity were observed for 7 days

Statistics:

Not required

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 030 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 040 mg/kg bw

Based on:

test mat.

Mortality:

Deaths occurred at dose levels of >=700 mg/kg bw in males and females. Most deaths occurred within 24 hours of dosing.

Clinical signs:

other: Clinical signs including reduced spontaneous activity, dyspnoea, ataxia and lacrimation were observed from 30 minutes after dosing with 700 mg/kg bw. At higher dose levels, irregular respiration, salivation, slight tremor and clonic convulsion were also

Gross pathology:

No data

Summary of mortality

Males			Females
Dose level (mg/kg bw)	Mortality	Time of death	Dose level (mg/kg bw)	Mortality	Time of death
500	0/8	-	500	0/8	-
700	1/8	Day 1 (1)	700	1/8	Day 1 (1)
980	4/8	Day 1 (4)	980	3/8	Day 1 (3)
1370	6/8	Day 1 (6)	1370	6/8	Day 1 (5), Day 2 (1)
1920	8/8	Day 1 (8)	1920	8/8	Day 1 (5), Day 2 (3)

Interpretation of results:

study cannot be used for classification

Conclusions:

LD50 values of 1030 and 1040 mg/kg bw were calculated for males and females, respectively. Classification for acute oral toxicity under CLP is assigned on the basis of data in the rat.

Executive summary:

The acute oral toxicity of fenitrothion was investigated in the mouse. Groups of eight male and female dd mice were gavaged with fenitrothion (suspended in 10% Tween 80) at dose levels of 0 (vehicle), 500, 700, 980, 1370 or 1920 mg/kg bw, using a constant dose volume of 20 mL/kg bw. Mice were observed for 7 days after dosing. Deaths occurred at dose levels of >=700 mg/kg bw in males and females.  Most deaths occurred within 24 hours of dosing. Clinical signs including reduced spontaneous activity, dyspnoea, ataxia and lacrimation were observed from 30 minutes after dosing with 700 mg/kg bw.  At higher dose levels, irregular respiration, salivation, slight tremor and clonic convulsion were also observed. LD50 values of 1030 and 1040 mg/kg bw were calculated for males and females, respectively.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

A modern, GLP- and guideline-compliant study is available for fenitrothion and is supported by older data.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

Fenitrothion
Batch No.: 40805
Purity: 96.6%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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 %

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

Preliminary study:

Not reported

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:

other: 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 exci

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.

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	-

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 210 mg/m³ air

Quality of whole database:

A modern, GLP- and guideline-compliant study is available for fenitrothion.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

August 1, 1972 - September 30, 1972

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

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Fenitrothion
Batch No.: 417
Purity: 97.2%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Fenitrothion was applied without any vehicle to 9 cm2 of the dorsal area of Sprague-Dawley rats (groups of 8 males and 8 females) at dose levels of 310, 625, 1250, 2500 and 5000 mg/kg bw.

Duration of exposure:

No details

Doses:

310, 625, 1250, 2500 and 5000 mg/kg bw

No. of animals per sex per dose:

8

Control animals:

not required

Details on study design:

Animals were observed for 21 days for mortality and clinical signs.

Statistics:

Not required

Sex:

male

Dose descriptor:

LD50

Effect level:

890 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

1 200 mg/kg bw

Based on:

test mat.

Mortality:

Deaths occurred in both sexes at dose levels of >=625 mg/kg bw; within 2 to 10 days.

Clinical signs:

other: At 310 mg/kg bw, clinical signs were limited to slight hyperexcitability. At 625 mg/kg bw, urinary incontinence, muscular twitch, rapid respiration, hyperexcitability and exophthalmus were observed, and were more severe at >=1250 mg/kg bw.

Gross pathology:

No data

Other findings:

No data

Summary of mortality

Males			Females
Dose level (mg/kg bw)	Mortality	Time of death	Dose level (mg/kg bw)	Mortality	Time of death
310	0/8	-	310	0/8	-
625	1/8	Day 6 (1)	625	1/8	Day 5 ( 1)
1250	7/8	Day 3 (1), Day 4 (1), Day 5 (2) Day 6 (2), Day 10 (1)	1250	5/8	Day 2 (1), Day 3 (1), Day 4 (1) Day 6 (2)
2500	8/8	Day 3 (2), Day 5 (2), Day 6 (1) Day 8 (1), Day 10 (2)	2500	7/8	Day 2 (2), Day 3 (1), Day 4 (2) Day 6 (2)
5000	8/8	Day 2 (2), Day 3 (2), Day 4 (4)	5000	8/8	Day 2 (2), Day 3 (2), Day 4 (3), Day 5 (1)

Interpretation of results:

study cannot be used for classification

Remarks:

Not sufficiently reliable

Conclusions:

The acute dermal LD50 of fenitrothion was calculated to be 890 and 1200 mg/kg bw in males and females, respectively.

Executive summary:

In a non-guideline acute dermal toxicity study, Fenitrothion was applied without any vehicle to 9 cm2 of the dorsal area of Sprague-Dawley rats (groups of 8 males and 8 females) at dose levels of 310, 625, 1250, 2500 and 5000 mg/kg bw. Animals were observed for 21 days for mortality and clinical signs. Deaths occurred in both sexes at dose levels of >=625 mg/kg bw; within 2 to 10 days. At 310 mg/kg bw, clinical signs were limited to slight hyperexcitability.  At 625 mg/kg bw, urinary incontinence, muscular twitch, rapid respiration, hyperexcitability and exophthalmus were observed, and were more severe at >=1250 mg/kg bw. The acute dermal LD50 of fenitrothion was calculated to be 890 and 1200 mg/kg bw in males and females, respectively. Due to deficiencies in reporting, the study is not considered to be sufficiently reliable as a basis for classification.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 December 2009 - 1 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Fenitrothion TG (SMT, sumithion)
Brown liquid
Lot no.: 070502

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIO, Korea
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 280.8-303.3 g (M); 224.8 - 247.9 g (F)
- Fasting period before study: No
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.2-22.4
- Humidity (%): 27.8-65.1
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 Dec 2009 To: 5 Jan 2010

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 6 cm
- Type of wrap if used: Gauze, plastic film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2000 mg/kg bw (undiluted)

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 30 minutes, 1, 2, 4 and 6 hours on the day of dosingand daily thereafter
- Frequency of weighing: Days 0, 1, 3, 7 and 14 (terminal)
- Necropsy of survivors performed: yes

Statistics:

None

Preliminary study:

Not reported

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths occurred

Clinical signs:

other: There were no signs of toxicity

Gross pathology:

Necropsy did not reveal any effects of treatment

Other findings:

None

Summary of mortality

Dose level (mg/kg bw)	Number of rats	Mortality
0	5M / 5F	-
2000	5M / 5F	-

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of fenitrothion was found to be >2000 mg/kg bw. Fenitrothion does not therefore require classification for acute dermal toxicity according to the CLP Criteria.

Executive summary:

The acute dermal toxicity of fenitrothion was investigated in a study in the rat, performed in compliance with OECD 402. Groups of rats were exposed to fenitrothion for 24 hours under occlusive conditions at dose levels of 0 (control) or 2000 mg/kg bw and observed for 14 days. There was no mortality in this study and no signs of systemic toxicity or local irritation. Bodyweights were unaffected by treatment and gross necropsy did not reveal any effects. The acute dermal LD50 of fenitrothion was therefore found to be >2000 mg/kg bw under the conditions of this study.  Fenitrothion does not therefore require classification for acute dermal toxicity according to the CLP Criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

A modern, GLP- and guideline-compliant study is available for fenitrothion. An older study is available but is not considered to be reliable due to methodological limitations.

Additional information

Acute oral toxicity

The acute oral toxicity of fenitrothion was investigated in an Acute Toxic Class study according to OECD 423. Three females were initally administered a dose of 2000 mg/kg bw and observed for 14 days.  Due to mortality in this group, two additional groups of three females were administered 300 mg/kg bw in sequence, according to the study guideline. Two deaths occurred at 2000 mg/kg bw in the initial group of three females (Day 1 or 2).  There was no mortality in either of the two groups of three females administered 300 mg/kg bw. Clinical signs were observed in all rats at 2000 mg/kg bw and included reduced activity, lacrimation, salivation, tremor, chromaturia and perineal staining; all signs had resolved by Day 9.  Signs at 300 mg/kg bw included perineal soiling, lacrimation, salivation and tremor; all signs had resolved by Day 5. Transient slight reductions in bodyweight were seen in surviving animals of both dose groups. There were no treatment-related findings at necropsy. The acute oral LD50 of fenitrothion was found to be >300 -<2000 mg/kg bw; fenitrothion therefore meets the criteria for classification for acute oral toxicity in Category 4 according to the CLP Regulation.

The acute oral toxicity of fenitrothion was investigated in a further study in the rat. Groups of eight male and female Sprague-Dawley rats were gavaged with fenitrothion (suspended in 10% Tween 80) at dose levels of0 (vehicle), 52, 73, 102, 143 (males only), 200, 280, 392, 550, 770, 1080 (females only) and 1510 (females only) mg/kg bw, using a constant dose volume of 10 mL/kg bw. Rats were observed for 7 days after dosing.Deaths occurred at dose levels of >=200 mg/kg bw in males and >=392 mg/kg bw in females.  Most deaths occurred within 24 hours of dosing. Clinical signs including muscular twitch, tremor, ataxia, dacryohaemorrhoea, salivation, exophthalmus and urinary incontinence developed from 10-30 minutes after dosing at 72-102 mg/kg bw. Clinical signs increased in severity at higher dose levels.  Recovery of surviving females was slower compared to males. LD50 values of 330 and 800 mg/kg bw were calculated for males and females, respectively.  Fenitrothion is therefore classified in Category 4 for acute oral toxicity according to the CLP Criteria.

The acute oral toxicity of fenitrothion was investigated in a study in the mouse. Groups of eight male and female dd mice were gavaged with fenitrothion (suspended in 10% Tween 80) at dose levels of0 (vehicle), 500, 700, 980, 1370 or 1920 mg/kg bw, using a constant dose volume of 20 mL/kg bw. Mice were observed for 7 days after dosing.Deaths occurred at dose levels of >=700 mg/kg bw in males and females.  Most deaths occurred within 24 hours of dosing. Clinical signs including reduced spontaneous activity, dyspnoea, ataxia and lacrimation were observed from 30 minutes after dosing with 700 mg/kg bw.  At higher dose levels, irregular respiration, salivation, slight tremor and clonic convulsion were also observed. LD50 values of 1030 and 1040 mg/kg bw were calculated for males and females, respectively.

Acute inhalation toxicity

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.

Acute dermal toxicity

The acute dermal toxicity of fenitrothion was investigated in a study in the rat, performed in compliance with OECD 402. Groups of rats were exposed to fenitrothion for 24 hours under occlusive conditions at dose levels of 0 (control) or 2000 mg/kg bw and observed for 14 days. There was no mortality in this study and no signs of systemic toxicity or local irritation. Bodyweights were unaffected by treatment and gross necropsy did not reveal any effects. The acute dermal LD50 of fenitrothion was therefore found to be >2000 mg/kg bw under the conditions of this study.  Fenitrothion does not therefore require classification for acute dermal toxicity according to the CLP Criteria.

In a non-guideline acute dermal toxicity study, Fenitrothion was applied without any vehicle to 9 cm2 of the dorsal area of Sprague-Dawley rats (groups of 8 males and 8 females) at dose levels of 310, 625, 1250, 2500 and 5000 mg/kg bw. Animals were observed for 21 days for mortality and clinical signs. Deaths occurred in both sexes at dose levels of >=625 mg/kg bw; within 2 to 10 days. At 310 mg/kg bw, clinical signs were limited to slight hyperexcitability.  At 625 mg/kg bw, urinary incontinence, muscular twitch, rapid respiration, hyperexcitability and exophthalmus were observed, and were more severe at >=1250 mg/kg bw. The acute dermal LD50 of fenitrothion was calculated to be 890 and 1200 mg/kg bw in males and females, respectively. Due to deficiencies in reporting, the study is not considered to be sufficiently reliable as a basis for classification.

Justification for classification or non-classification

Fenitrothion has a harmonised classification for acute oral toxicity in Category 4. This is consistent with the available data: the key study reports an acute oral LD50 of >300 -<2000 mg/kg bw. No change is proposed to the harmonised classification.

Fenitrothion does not have a harmonised classification for acute inhalation toxicity. This is consistent with the available data: the key study reports an acute inhalation LC50 of >2.21 mg/L (MAC). No change is proposed to the harmonised classification.

Fenitrothion does not have a harmonised classification for acute dermal toxicity. This is consistent with the available data: the key study reports an acute dermal LD50 of >2000 mg/kg bw. No change is proposed to the harmonised classification.