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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.4 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):
75
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following corrections are made to the LOAEL (oral): Respiratory volume rat = 0.38 m3/kg bw/8 hr day. Respiratory volume human = 6.7 m3. Respiratory volume worker = 10 m3. Bioavailability in the rat and human is assumed equal. Oral absorption in the rat and inhalation absorption in the human are assumed equal. Therefore, the corrected worker LOAEC for repeat-dose systemic effects via the inhalation route is: 100 mg/kg bw/day x (1/0.38) x (6.7) / (10) = 176 mg/m3.

AF for dose response relationship:
3
Justification:
ECHA REACH default, LOAEL starting point
AF for differences in duration of exposure:
2
Justification:
ECHA REACH default, extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Per ECHA REACH, not required for inhalation exposure
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default, rat to human
AF for intraspecies differences:
5
Justification:
ECHA REACH default, worker
AF for the quality of the whole database:
1
Justification:
Based on the availability of the OECD Test Guideline 408 study conducted in compliance with GLP
AF for remaining uncertainties:
1
Justification:
No further uncertainties identified
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:
0.33 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
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No corrections are made to the LOAEL (oral). Bioavailability in the rat and human is assumed equal. Oral absorption in the rat and dermal absorption in the human are assumed equal. Therefore, the corrected worker LOAEL for repeat-dose systemic effects via the dermal route is: 100 mg/kg bw/day.

AF for dose response relationship:
3
Justification:
ECHA REACH default, LOAEL starting point
AF for differences in duration of exposure:
2
Justification:
ECHA REACH default, extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH default, extrapolation from oral rat to dermal human
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default, rat to human
AF for intraspecies differences:
5
Justification:
ECHA REACH default, worker
AF for the quality of the whole database:
1
Justification:
Based on the availability of the OECD Test Guideline 408 study conducted in compliance with GLP
AF for remaining uncertainties:
1
Justification:
No further uncertainties identified
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The systemic oral LOAEL of 100 mg/kg bw/day identified in the OECD Test Guideline 408 and GLP compliant study with 3-(triethoxysilyl)propanethiol is primarily based on renal effects in female rats starting at 100 mg/kg bw/day (and starting at 300 mg/kg bw/day in male rats). The effects on the kidneys were degenerative in nature (tubular degeneration, papillary necrosis and granular casts). It is therefore appropriate to use the oral LOAEL as the starting point to derive the inhalation and dermal DNELs for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 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
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following corrections are made to the LOAEL (oral): Respiratory volume rat = 1.15 m3/kg bw/24 hr day. Bioavailability in the rat and human is assumed equal. Oral absorption in the rat and inhalation absorption in the human are assumed equal. Therefore, the corrected general population LOAEC for repeat-dose systemic effects via the inhalation route is: 100 mg/kg bw/day x (1/1.15) = 87.0 mg/m3.

AF for dose response relationship:
3
Justification:
ECHA REACH default, LOAEL starting point
AF for differences in duration of exposure:
2
Justification:
ECHA REACH default, extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Per ECHA REACH, not required for inhalation exposure
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default, rat to human
AF for intraspecies differences:
10
Justification:
ECHA REACH default, general population
AF for the quality of the whole database:
1
Justification:
Based on the availability of the OECD Test Guideline 408 study conducted in compliance with GLP
AF for remaining uncertainties:
1
Justification:
No further uncertainties identified
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:
no hazard identified
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

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
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No corrections are made to the LOAEL (oral). Bioavailability in the rat and human is assumed equal. Oral absorption in the rat and human is assumed equal. Therefore, the corrected general population LOAEL for repeat-dose systemic effects via the oral route is: 100 mg/kg bw/day.

AF for dose response relationship:
3
Justification:
ECHA REACH default, LOAEL starting point
AF for differences in duration of exposure:
2
Justification:
ECHA REACH default, extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH default, extrapolation from oral rat to oral human
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default, rat to human
AF for intraspecies differences:
10
Justification:
ECHA REACH default, general population
AF for the quality of the whole database:
1
Justification:
Based on the availability of the OECD Test Guideline 408 study conducted in compliance with GLP
AF for remaining uncertainties:
1
Justification:
No further uncertainties identified
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

The systemic oral LOAEL of 100 mg/kg bw/day identified in the OECD Test Guideline 408 and GLP compliant study with 3-(triethoxysilyl)propanethiol is primarily based on renal effects in female rats starting at 100 mg/kg bw/day (and starting at 300 mg/kg bw/day in male rats). The effects on the kidneys were degenerative in nature (tubular degeneration, papillary necrosis and granular casts). It is therefore appropriate to use the oral LOAEL as the starting point to derive the inhalation and oral DNELs for the general population (man via the environment).