Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.8 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):
7
Modified dose descriptor starting point:
other: Allometric scaling is taken into account because a dog study was used as a point of departure.
DNEL value:
0.79
Explanation for the modification of the dose descriptor starting point:
No local effects observed.
AF for dose response relationship:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for differences in duration of exposure:
1
Justification:
point of departure chronic dog study; lowest NOAEL.
AF for interspecies differences (allometric scaling):
1.4
Justification:
default factor dogs -> humans
AF for other interspecies differences:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for intraspecies differences:
5
Justification:
default worker
AF for the quality of the whole database:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for remaining uncertainties:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 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):
7
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
other: Allometric scaling is taken into account because a dog study was used as a point of departure.
DNEL value:
0.79
Explanation for the modification of the dose descriptor starting point:
no local effects observed
AF for dose response relationship:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for interspecies differences (allometric scaling):
1.4
Justification:
default factor dogs -> humans
AF for other interspecies differences:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for intraspecies differences:
5
Justification:
default worker
AF for the quality of the whole database:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for remaining uncertainties:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)

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:
2.2 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):
7
Modified dose descriptor starting point:
NOAEL
DNEL value:
15.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Lactofen is not irritating to the skin or eye in recent guideline complient studies.
AF for dose response relationship:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for differences in duration of exposure:
1
Justification:
point of departiure derived from a chronic dog study. Additional chronic studies are available
AF for interspecies differences (allometric scaling):
1.4
Justification:
default factor dogs -> humans
AF for other interspecies differences:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for intraspecies differences:
5
Justification:
default factor worker
AF for the quality of the whole database:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for remaining uncertainties:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11 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):
35
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
DNEL value:
15.8 mg/kg bw/day
AF for dose response relationship:
5
Justification:
According to REACH Guidance a factor of 5 can be used; since the compound is not irritating the factor is justified.
AF for interspecies differences (allometric scaling):
1.4
Justification:
default factor dogs -> humans
AF for other interspecies differences:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for intraspecies differences:
5
Justification:
default factor worker
AF for the quality of the whole database:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)
AF for remaining uncertainties:
1
Justification:
Lowest NOAEL was used (different studies, subacute to chronic are available in different species mice, rats, dogs monkeys)

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Starting point systemic toxicity:

Different studies (sub-acute - chronic) in different species (mice, rat, dogs and monkeys) are summarized by EPA. The short evaluations are available via the internet. The lowest NOAEL reported is 0.79 mg/kg in a one-year study in dogs. At higher doses increased incidence of proteinaceous casts in the kidney and statistically significant decreases in the absolute weight of thyroid and adrenal glands was reported in males.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Due to strictly controlled conditions applied in the manufacturing process in the EU, and direct, complete export of product, no relevant exposure to humans and the environment has to be expected. The relevant studies were sponsored by the receipient of the product.