Lactofen

Toxicological Summary

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.

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.

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

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

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

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.