Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.18 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
88.16 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects in workers after long-term inhalation exposure to decan-1,2-diol was derived via route-to-route extrapolation from the most sensitive endpoints observed in the 28-day repeated dose toxicity screening study in Wistar rats. The lowest NOAEL (100 mg/kg bw/day) was based upon effects observed in the stomach and central nervous system, the NOAEL for reproductive parameters was in excess of 1000 mg/kg bw/day. To convert the oral NOAEL in rats to an inhalation NOAEC in humans, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38m3/kg bw/8h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8h exposure period); extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Therefore, inhalatory NOAEC = oral NOAEL (100 mg/kg bw/day)*(1/sRVrat 8h)*(ABSoral/ABSinh)*(sRVhuman/wRV) OR 105*(1/0.38)*(50/100)*(6.7/10) = 88.16. DNEL = Corrected inhalation NOAEC (88.16 mg/m3)*(1/75{Overall AF}) = 1.18 mg/m3.
AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for concentrations
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
5
Justification:
Default for Workers
AF for the quality of the whole database:
1
Justification:
Not required
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects in workers after long-term dermal exposure to Decan-1,2-diol was derived via route-to-route extrapolation from the NOAEL of 100 mg/kg bw/d obtained in the sub acute (28-day) oral repeated dose toxicity study in rats. Therefore, DNEL = 100 mg/kg bw/day*(1/6{exposure duration sub acute to chronic}*4{allometric scaling rat-human}*2.5{interspecies differences}*5{intraspecies differences-worker population}) = 0.33 mg/kg bw/day. This is considered to be the worst-case scenario assuming 100% dermal absorption hence 100% bioavailability and systemic exposure at this level.
AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat-human
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
5
Justification:
Default for Workers
AF for the quality of the whole database:
1
Justification:
Not required
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The basis for the inhalation and dermal DNEL for worker exposure is an oral 28-day toxicity study with decan-1,2-diol, from which a NOAEL of 100 mg/kg bw/day was identified. There were also no adverse effects observed at 1000 mg/kg bw/day in a reproductive toxicity study of a similar duration. Sub-chronic oral administration of decan-1,2-diol (100, 300 and 1000 mg/kg/day) did not affect mortality, body weight, haematology, clinical biochemistry or urinalysis parameters. However, some mild and transient effects were observed at the highest dose of 1000 mg/kg bw/day, such as reduced mean locomotor activity and food consumption in females and squamous epithelial hyperplasia of the forestomach. Effects on the gastrointestinal system were also observed in the reproductive toxicity test; females administered ≥ 300 mg/kg bw/day and males receiving 1000 mg/kg bw/day of decan-1,2-diol presented test item-related thickening of the non-glandular stomach.

The NOAEL (No Observed Adverse Effect Level) of 100 mg/kg bw/day was used as the basis of the DNEL calculations using appropriate assessment factors for relevant indicators including route to route extrapolation, allometric scaling, exposure duration and study length. The worker DNELs for inhalation and dermal exposure, of 1.18 mg/m3 and 0.33 mg/kg bw/day respectively, assumed 100% bioavailability and may be considered to be the worst-case scenario. 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
43.48 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects in general population after long-term inhalation exposure to Decan-1,2-diol was derived via route-to-route extrapolation from the NOAEL obtained in the sub acute (28-day) oral repeated dose toxicity study in rats (100 mg/kg bw/day). To convert oral rat NOAEL into inhalatory NOAEC in humans, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24h); extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Therefore, the corrected inhalation NOAEC for general population is oral NOAEL*(1/sRVrat 24h)*(ABSoral/ABSinh) or 100*(1/1.15)*(50/100) = 43.48 mg/m3. Therefore, DNEL = Corrected inhalation NOAEC (43.48 mg/m3)*(1/150{Overall AF}) = 0.29 mg/m3.
AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for concentrations
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
10
Justification:
Default for General Population
AF for the quality of the whole database:
1
Justification:
Not required
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects in the general population after long-term dermal exposure to decan-1,2-diol was derived via route-to-route extrapolation from the NOAEL of100 mg/kg bw/day obtained in the sub-acute (28-day) oral repeated dose toxicity study in rats. Therefore, the dermal DNEL = 100 mg/kg bw/day*(1/6{exposure duration sub-acute to chronic}*4{allometric scaling rat-human}*2.5{interspecies differences}*10{intraspecies differences-general population}) = 0.17 mg/kg bw/day. This is considered to be the worst-case scenario assuming 100% dermal absorption hence 100% bioavailability and systemic exposure at this level.
AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat-human
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
10
Justification:
Default for General Population
AF for the quality of the whole database:
1
Justification:
Not required
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic effects in the general population after long-term oral exposure to decan-1,2-diol was derived via from the NOAEL of100 mg/kg bw/day obtained in the sub-acute (28-day) oral repeated dose toxicity study in rats. Therefore, the dermal DNEL = 100 mg/kg bw/day*(1/6{exposure duration sub-acute to chronic}*4{allometric scaling rat-human}*2.5{interspecies differences}*10{intraspecies differences-general population}) = 0.17 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat-human
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
10
Justification:
Default for General Population
AF for the quality of the whole database:
1
Justification:
Not required
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

The basis for the inhalation, dermal and oral DNEL for general population exposure is an oral 28-day toxicity study with decan-1,2 -diol, from which a NOAEL of 100 mg/kg bw/day were identified. There were also no adverse effects observed at 1000 mg/kg bw/day in a reproductive toxicity study of a similar duration. Sub-chronic oral administration of decan-1,2-diol (100, 300 and 1000 mg/kg/day) did not affect mortality, body weight, haematology, clinical biochemistry or urinalysis parameters. However, some mild and transient effects were observed at the highest dose of 1000 mg/kg bw/day, such as reduced mean locomotor activity and food consumption in females and squamous epithelial hyperplasia of the forestomach. Effects on the gastrointestinal system were also observed in the reproductive toxicity test; females administered ≥ 300 mg/kg bw/day and males receiving 1000 mg/kg bw/day of decan-1,2-diol presented test item-related thickening of the non-glandular stomach.

The NOAEL (No Observed Adverse Effect Level) of 100 mg/kg bw/day was used as the basis of the DNEL calculations using appropriate assessment factors for relevant indicators including route to route extrapolation, allometric scaling, exposure duration and study length. The general population DNELs for inhalation, dermal and oral exposure were 0.29 mg/m3, 0.17 mg/kg bw/day and 0.17 mg/kg bw/day, respectively.