Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEC
Value:
25 mg/m³
AF for dose response relationship:
1
Justification:
NOAEC valued used as POD
AF for differences in duration of exposure:
2
Justification:
substance specific duration adjustment: the degree of severity does not increase with longer duration of exposure based on the inhalation study (EU RAR), therefore AF of 2 is proposed instead of 6.
AF for interspecies differences (allometric scaling):
1
Justification:
inhalatory route of exposure
AF for other interspecies differences:
1
Justification:
metabolic rate scaling for nhalation exposure
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Justification:
AF for breathing volumes
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: EU RAR

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: OECL as recommended by SCOEL (2011)
Dose descriptor:
NOAEC
Value:
0.5 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: EU RAR
Overall assessment factor (AF):
4
Dose descriptor starting point:
LOAEC
Value:
5 mg/m³
AF for remaining uncertainties:
4
Justification:
EU RAR approach:
LOAEC from subacute study was taken as POD. Therefore, the AF for duration was 2, only to adjust for 8-hour exposure. Additional uncertainty is covered by AF 2 - LOAEC/NAEC.

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEC
Value:
25 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
7.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Experimental studies with repeated dose dermal exposure to butynediol are not available. Dermal risk assessment is based on subacute inhalation study.

100% absorption is assumed in both cases. Kinetics of absorption and bioavailability are more similar for inhalation and dermal routes, for the oral route (EU RAR).

The starting point is NOAEC of 25 mg/m3 which cooresponds to an intake of 7.2 mg/kg/day (respiratory rate of 0.8 L/min.kg for rat, 6 hours a day).

AF for dose response relationship:
1
Justification:
NOAEC as POD
AF for differences in duration of exposure:
2
Justification:
substance specific duration adjustment: the degree of severity does not increase with longer duration of exposure based on the inhalation study (EU RAR), therefore AF of 2 is proposed instead of 6.
AF for interspecies differences (allometric scaling):
4
Justification:
human exposure route dermal, animal exposure route inhalatory (ECHA guidance)
AF for other interspecies differences:
1
Justification:
covered by allometric scaling
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.6 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
other: LD50 dermal
Value:
659 mg/kg bw/day
AF for dose response relationship:
5
Justification:
lethal dose used as POD
AF for interspecies differences (allometric scaling):
4
Justification:
human route of exposure dermal, animal route of exposure dermal (ECHA Guidance)
AF for other interspecies differences:
1
Justification:
covered by allometric scaling
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population