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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.1 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following corrections are made to the NOAEL (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 NOAEC 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:
1
Justification:
Based on the availability of a study conducted according to OECD Test Guideline 408 and in compliance with GLP
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 applicable for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default
AF for intraspecies differences:
5
Justification:
ECHA REACH default for workers
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:
1 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):
100
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No corrections are made to the NOAEL (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 NOAEL for repeat-dose systemic effects via the dermal route is also: 100 mg/kg bw/day. 

AF for dose response relationship:
1
Justification:
Based on the availability of a study conducted according to OECD Test Guideline 408 and in compliance with GLP
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
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default
AF for intraspecies differences:
5
Justification:
ECHA REACH default for workers
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 NOAEL of 100 mg/kg bw/day identified in the OECD Test Guideline 408 study with triethoxy(3-thiocyanatopropyl)silane (conducted according to GLP) is based on effects in male (decreased body weight, body weight gain and food consumption) and female (increased renal organ weight and histopathological alterations) rats at 300 mg/kg bw/day. It is therefore appropriate to use the oral NOAEL as the starting point to derive the inhalation and dermal systemic long term DNELs for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

The following corrections are made to the NOAEL (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 NOAEC for repeat-dose systemic effects via the inhalation route is: 100 mg/kg bw/day*(1/1.15) = 87.0 mg/m3.

AF for dose response relationship:
1
Justification:
Default ECHA assessment factor
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 applicable for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default
AF for intraspecies differences:
10
Justification:
ECHA REACH default for the 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:
0.5 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No corrections are made to the NOAEL (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 NOAEL for repeat-dose systemic effects via the oral route is also: 100 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Based on the availability of a study conducted according to OECD Test Guideline 408 and in compliance with GLP
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
AF for other interspecies differences:
2.5
Justification:
ECHA REACH default
AF for intraspecies differences:
10
Justification:
ECHA REACH default for 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:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The systemic oral NOAEL of 100 mg/kg bw/day identified in the OECD Test Guideline 408 study with triethoxy(3-thiocyanatopropyl)silane (conducted according to GLP) is based on effects in male (decreased body weight, body weight gain and food consumption) and female (increased renal organ weight and histopathological alterations) rats at 300 mg/kg bw/day. It is therefore appropriate to use the oral NOAEL as the starting point to derive the inhalation and oral systemic long-term DNELs for the general population.

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