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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.16 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
Value:
145 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
179 mg/m³
Explanation for the modification of the dose descriptor starting point:

The test substance is a waxy solid with a low vapor pressure (1.34 Pa at 25°C), therefore the exposure hazard via inhalation is unlikely for humans. As no route-specific data are available, a route-to-route extrapolation from an oral repeated dose study in rats (90 days, NTP, 2012) as a worst-case is justified. The oral NOAEL of 145 mg/kg bw/day was corrected for exposure days per week (7d/w to 5d/w; factor *7/5), absorption (assumption according to ECHA Guidance R.8: 50% absorbed oral, 100 % absorbed via inhalation; factor: 1/2), respiratory volume (factor *1/0.38) and respiratory volume for light activity within 8h (6.7m³/10m³; factor * 6.7/10).


corrected NOAEC = 145 mg/kg bw/d / 0.38 m³/kg bw * (6.7 / 10) m³/d * 1/2 * 7d/5d = 178.96 mg/m³.


 


A corrected NOAEC of 178.96 mg/m³ is derived.

AF for dose response relationship:
1
Justification:
Default, as the PoD is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default as allometric scaling is already included in corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The database is of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.656 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
87.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
65.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The long-term systemic DNEL for dermal route has been derived from the NOAEL of 87.5 mg/kg bw established in the dermal 3-month study in rats (NTP, 2012). The substance is systemically available by the oral and dermal route and caused decreased body weights and body weight gains and dermal irritation in the treated animals in the two highest dose groups (175 and 350 mg/kg bw). The starting point for the DNEL derivation is the dermal NOAEL.


This NOAEL is corrected for the duration of exposure (6 h in animal test vs. 8 h exposure for workers):


87.5 mg/kg bw/day * 6 h/8 h = 65.63 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default, as the PoD is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The database is of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.26 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
Value:
145 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
63.04 mg/m³
Explanation for the modification of the dose descriptor starting point:

The test substance is a waxy solid with a low vapor pressure (1.34 Pa at 25°C), therefore the exposure hazard via inhalation is unlikely for humans. As no route-specific data are available, a route-to-route extrapolation from an oral repeated dose study in rats (90 days, NTP, 2012) as a worst-case is justified. The oral NOAEL of 145 mg/kg bw/day was corrected for absorption (assumption according to ECHA Guidance R.8: 50% absorbed oral, 100 % absorbed via inhalation; factor: 1/2), and respiratory volume within 24 h (factor * 1/1.15).


corrected NOAEC = 145 mg/kg bw/d / 1.15 m³/kg bw * 1/2 = 63.04 mg/m³.


 


A corrected NOAEC of 63.04 mg/m³ is derived.

AF for dose response relationship:
1
Justification:
Default, as the PoD is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default as allometric scaling is already included in corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
The database is of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
78.1 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
87.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
15.63 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The long-term systemic DNEL for dermal route has been derived from the NOAEL of 87.5 mg/kg bw established in the dermal 3-month study in rats (NTP, 2012). The starting point for the DNEL derivation is the dermal NOAEL.


This NOAEL is corrected for the duration of exposure (6 h in animal test vs. 24 h exposure for workers; 5 d/week in animal test and 7 days/week for general population):


Corrected NOAEL is 87.5 mg/kg bw/day * 6 h/24 h * 5 d/7 d= 15.63 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default, as the PoD is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
The database is of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.725 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
Value:
145 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
145 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral rat NOAEL of 145 mg/kg bw derived in a subchronic study (NTP, 2012) served as the starting point for the DNEL derivation. The NOAEL was not modified (oral absorption rat = oral absorption human), since no substance- and route specific information on absorption is available.

AF for dose response relationship:
1
Justification:
Default, as the PoD is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
The database is of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population