Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.63
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

DNEL derivation for each of the relevant endpoints was based on the most conservative value obtained. Thus, DNELs represent the worst – case secenario.

In a repeated dose toxicity oral study combined with a reproduction/ developmental toxicity study, MTHPA caused primary local toxicity effects. All observed systemic effects were of secondary nature. Since local effects are independent of metabolic rate, an assessment factor of 1 (default factor 4) was applied for allometric scaling from rat to human. For the remaining interspecies differences an assessment factor of 1 was applied (default factor 2.5), as there is no evidence for differences in the general mode of action or kinetics. Due to the local nature of primary toxicity effects an assessment factor of 1 was used for extrapolation from subacute to chronic exposure (default factor 6). Finally, an assessment factor of 5 was applied for intraspecies differences (worker). As worker DNEL long term for dermal route and inhalation route was derived from the NOAEL long term oral, same assessment factors (as detailed above) were applied in the calculations of the DNEL long term dermal/ inhalation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.75
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

DNEL derivation for each of the relevant endpoints was based on the most conservative value obtained. Thus, DNELs represent the worst – case secenario. In a repeated dose toxicity oral study combined with a reproduction/ developmental toxicity study, MTHPA caused primary local toxicity effects. All observed systemic effects were of secondary nature. Since local effects are independent of metabolic rate, an assessment factor of 1 (default factor 4) was applied for allometric scaling from rat to human. For the remaining interspecies differences an assessment factor of 1 was applied (default factor 2.5), as there is no evidence for differences in the general mode of action or kinetics. Due to the local nature of primary toxicity effects an assessment factor of 1 was used for extrapolation from subacute to chronic exposure (default factor 6). Finally, an assessment factor of 10 was applied for intraspecies differences (general population). As worker DNEL long term for dermal route and inhalation route was derived from the NOAEL long term oral, same assessment factors (as detailed above) were applied in the calculations of the DNEL long term dermal/ inhalation.