Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.09 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
DNEL value:
1.32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
2.33 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for activity (*6.7/10) and breathing rate (*1/0.38) to give a corrected inhalation NOAEC of 2.33 mg/m3. As oral absorption is demonstrated to be almost complete, additional correction for the extent of inhalation absorption is not required.

AF for dose response relationship:
1
Justification:
Default AF value from ECHA guidance: the starting point is derived from a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default AF value from ECHA guidance: extrapolation from sub-chronic to long-term exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required: already taken into account in derivation of the corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default AF value from ECHA guidance
AF for intraspecies differences:
5
Justification:
Default AF value from ECHA guidance: workers
AF for the quality of the whole database:
1
Justification:
Default AF value from ECHA guidance: good quality database
AF for remaining uncertainties:
1
Justification:
Default AF value from ECHA guidance: no significant remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
1.32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
6.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for the extent of oral absorption (essentially complete) and dermal absorption (20% worst case) to give a corrected dermal NOAEL of 6.60 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Default AF value from ECHA guidance: starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default AF value from ECHA guidance: extrapolation from sub-chronic study to long-term exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF value from ECHA guidance: starting point is from a rat study
AF for other interspecies differences:
2.5
Justification:
Default AF value from ECHA guidance:
AF for intraspecies differences:
5
Justification:
Default AF value from ECHA guidance: workers
AF for the quality of the whole database:
1
Justification:
Default AF value from ECHA guidance: good quality database
AF for remaining uncertainties:
1
Justification:
Default AF value from ECHA guidance: no significant remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Fenitrothion is acutely toxic by the oral route, is not an irritant, but is a moderate skin sensitiser and classified as a skin sensitiser in Cat 1B. The critical effect of fenitrothion toxicity is the inhibition of cholinesterase activity; classification in STOT SE1 and STOT RE1 is proposed on the basis of the effects of fenitrothion on the nervous system. The relevant starting point for DNEL derivation is the NOAEL of 1.32 mg/kg bw/d for cholinesterase inhibition derived from the 90 -day oral rat study.

Inhalation DNELs

Systemic inhalation DNELs

Long-term systemic inhalation DNEL

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for activity (*6.7/10) and breathing rate (*1/0.38) to give a corrected inhalation NOAEC of 2.33 mg/m3. As oral absorption is demonstrated to be almost complete, additional correction for the extent of inhalation absorption is not required. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for additional interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall AF of 25. Application of the AF to the corrected starting point results in a long-term inhalation DNEL for workers of 0.09 mg/m3.

Short-term systemic inhalation DNEL

Fenitrothion is acutely toxic and is classified for acute oral toxicity. Classification for STOT SE1 is also proposed; therefore fenitrothion is considered to be 'high hazard' according to Appendix 3 of ECHA Practical Guide 15. The critical toxicological effect of fenitrothion is on the nervous system (inhibition of cholinesterase activity). A clear NOAEL for cholinesterase inhibition has not been demonstrated in a single dose study; therefore a separate short-term DNEL cannot be reliably derived. As a protective measure the short-term inhalation DNEL is therefore set at the level of the long-term inhalation DNEL, which is set on the basis of the same critical effect (cholinesterase inhibition).

Local inhalation DNELs

Fenitrothion is not a respiratory irritant or respiratory sensitiser; therefore no relevant hazard is identified. Local inhalation DNELs are not derived.

Dermal DNELs

Systemic dermal DNELs

Long-term systemic dermal DNEL

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for the extent of oral absorption (essentially complete) and dermal absorption (20% worst case) to give a corrected dermal NOAEL of 6.60 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for additional interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall AF of 100. Application of the AF to the corrected starting point results in a long-term dermal DNEL for workers of 0.07 mg/kg bw/d.

Short-term systemic DNEL

Fenitrothion is acutely toxic and is classified for acute oral toxicity. Classification for STOT SE1 is also proposed; therefore fenitrothion is considered to be 'high hazard' according to Appendix 3 of ECHA Practical Guide 15. The critical toxicological effect of fenitrothion is on the nervous system (inhibition of cholinesterase activity). A clear NOAEL for cholinesterase inhibition has not been demonstrated in a single dose study; therefore a separate short-term DNEL cannot be reliably derived. As a protective measure the short-term dermal DNEL is therefore set at the level of the long-term dermal DNEL, which is set on the basis of the same critical effect (cholinesterase inhibition).

Local dermal DNELs

Local dermal DNELs are not derived; a qualitative risk assessment is proposed. Fenitrothion is not classified for skin corrosion or skin irritation, but is a moderate skin sensitiser and classified for skin sensitisation in CLP Category 1B and is therefore considered to be moderate hazard according to ECHA Guidance (Appendix 3 of Practical Guide 3).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
DNEL value:
1.32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
1.15 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for breathing rate (*1/1.15) to give a corrected inhalation NOAEC of 1.15 mg/m3. As oral absorption is demonstrated to be almost complete, additional correction for the extent of inhalation absorption is not required.

AF for dose response relationship:
1
Justification:
Default AF value from ECHA guidance: the starting point is derived from a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default AF value from ECHA guidance: extrapolation from sub-chronic to long-term exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required: already taken into account in derivation of the corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default AF value from ECHA guidance
AF for intraspecies differences:
10
Justification:
Default AF value from ECHA guidance: general population
AF for the quality of the whole database:
1
Justification:
Default AF value from ECHA guidance: good quality database
AF for remaining uncertainties:
1
Justification:
Default AF value from ECHA guidance: no significant remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.03 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
DNEL value:
1.32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
6.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for the extent of oral absorption (essentially complete) and dermal absorption (20% worst case) to give a corrected dermal NOAEL of 6.60 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Default AF value from ECHA guidance: starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default AF value from ECHA guidance: extrapolation from sub-chronic study to long-term exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF value from ECHA guidance: starting point is from a rat study
AF for other interspecies differences:
2.5
Justification:
Default AF value from ECHA guidance
AF for intraspecies differences:
10
Justification:
Default AF value from ECHA guidance: General Population
AF for the quality of the whole database:
1
Justification:
Default AF value from ECHA guidance: good quality database
AF for remaining uncertainties:
1
Justification:
Default AF value from ECHA guidance: no significant remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.007 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
DNEL value:
1.32 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1.32 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point is derived from an oral study and does not therefore required modification.

AF for dose response relationship:
1
Justification:
Default AF value from ECHA guidance: starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default AF value from ECHA guidance: extrapolation from sub-chronic study to long-term exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF value from ECHA guidance: starting point is from a rat study
AF for other interspecies differences:
2.5
Justification:
Default AF value from ECHA guidance
AF for intraspecies differences:
10
Justification:
Default AF value from ECHA guidance: general population
AF for the quality of the whole database:
1
Justification:
Default AF value from ECHA guidance: good quality database
AF for remaining uncertainties:
1
Justification:
Default AF value from ECHA guidance: no significant remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Fenitrothion is acutely toxic by the oral route, is not an irritant, but is a moderate skin sensitiser and classified as a skin sensitiser in Cat 1B. The critical effect of fenitrothion toxicity is the inhibition of cholinesterase activity; classification in STOT SE1 and STOT RE1 is proposed on the basis of the effects of fenitrothion on the nervous system. The relevant starting point for DNEL derivation is the NOAEL of 1.32 mg/kg bw/d for cholinesterase inhibition derived from the 90 -day oral rat study.

Inhalation DNELs

Systemic inhalation DNELs

Long-term systemic inhalation DNEL

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for breathing rate (*1/1.15) to give a corrected inhalation NOAEC of 1.15 mg/m3. As oral absorption is demonstrated to be almost complete, additional correction for the extent of inhalation absorption is not required. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for additional interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall AF of 25. Application of the AF to the corrected starting point results in a long-term inhalation DNEL for the general population of 0.02 mg/m3.

Short-term systemic inhalation DNEL

Fenitrothion is acutely toxic and is classified for acute oral toxicity. Classification for STOT SE1 is also proposed; therefore fenitrothion is considered to be 'high hazard' according to Appendix 3 of ECHA Practical Guide 15. The critical toxicological effect of fenitrothion is on the nervous system (inhibition of cholinesterase activity). A clear NOAEL for cholinesterase inhibition has not been demonstrated in a single dose study; therefore a separate short-term DNEL cannot be reliably derived. As a protective measure the short-term inhalation DNEL is therefore set at the level of the long-term inhalation DNEL, which is set on the basis of the same critical effect (cholinesterase inhibition).

Local inhalation DNELs

Fenitrothion is not a respiratory irritant or respiratory sensitiser; therefore no relevant hazard is identified. Local inhalation DNELs are not derived.

Dermal DNELs

Systemic dermal DNELs

Long-term systemic dermal DNEL

The starting point of 1.32 mg/kg bw/d from a 90-day oral rat study is corrected for the extent of oral absorption (essentially complete) and dermal absorption (20% worst case) to give a corrected dermal NOAEL of 6.60 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for additional interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall AF of 200. Application of the AF to the corrected starting point results in a long-term dermal DNEL for the general population of 0.03 mg/kg bw/d.

Short-term systemic DNEL

Fenitrothion is acutely toxic and is classified for acute oral toxicity. Classification for STOT SE1 is also proposed; therefore fenitrothion is considered to be 'high hazard' according to Appendix 3 of ECHA Practical Guide 15. The critical toxicological effect of fenitrothion is on the nervous system (inhibition of cholinesterase activity). A clear NOAEL for cholinesterase inhibition has not been demonstrated in a single dose study; therefore a separate short-term DNEL cannot be reliably derived. As a protective measure the short-term dermal DNEL is therefore set at the level of the long-term dermal DNEL, which is set on the basis of the same critical effect (cholinesterase inhibition).

Local dermal DNELs

Local dermal DNELs are not derived; a qualitative risk assessment is proposed. Fenitrothion is not classified for skin corrosion or skin irritation, but is a moderate skin sensitiser and classified for skin sensitisation in CLP Category 1B and is therefore considered to be moderate hazard according to ECHA Guidance (Appendix 3 of Practical Guide 3).

Oral DNELs

Systemic oral DNELs

Long-term systemic oral DNEL

The starting point is derived from an oral study and does not therefore required modification. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for additional interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall AF of 200. Application of the AF to the starting point results in a long-term oral DNEL for the general population of 0.007 mg/kg bw/d.

Short-term systemic oral DNEL

Fenitrothion is acutely toxic and is classified for acute oral toxicity. Classification for STOT SE1 is also proposed; therefore fenitrothion is considered to be 'high hazard' according to Appendix 3 of ECHA Practical Guide 15. The critical toxicological effect of fenitrothion is on the nervous system (inhibition of cholinesterase activity). A clear NOAEL for cholinesterase inhibition has not been demonstrated in a single dose study; therefore a separate short-term DNEL cannot be reliably derived. As a protective measure the short-term oral DNEL is therefore set at the level of the long-term oral DNEL, which is set on the basis of the same critical effect (cholinesterase inhibition).