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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29.6 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:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
741 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic inhalative effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to "ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health" (Version 2.1, November 2012), and "ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14" (Version 1, July 2012).


The calculation of the DNEL is based on an oral NOAEL observed in a subchronic toxicity study in rats (OECD 408). To convert the rat oral NOAEL into an inhalation NOAEC to assess human exposure via the inhalation route, the NOAEL has to be corrected as follows:


Corrected inhal NOAEC = NOAEL(oral) × (1 / sRVrat) × (ABSoral-rat / ABSinh-human) × (sRVhuman / wRV) × (Fstudy / Fworker)


= 600 mg/kg bw/day × (1 / 0.38 m³/kg bw/day) × (1 / 2) × (6.7 m³ / 10 m³) × (7 / 5) = 741  mg/m³


sRV = standard respiratory volume; wRV = respiratory volume light activity for worker (8 h); ABS = absorption; Fstudy = frequency of exposure in study (days per week); Fworker = frequency of exposure worker (days per week)


The NOAEL was corrected for interspecies difference between rat and human as well as for the differences in the experimental and human exposure conditions. The animals (rats) were exposed to the test substance 7 days/week; whereas workers are in general exposed 5 days/week (factor 7 days/5 days), this correction factor is included according to IUCLID 6.4 DNEL calculator. 


As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption.


Thus, the corrected starting point for workers is 741 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study (subchronic to chronic).
AF for interspecies differences (allometric scaling):
1
Justification:
AF not applicable for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences according to ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
Default AF for Worker according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL based on reliable study.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.4 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:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
840 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for dermal effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to "ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health" (Version 2.1, November 2012), and "ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14" (Version 1, July 2012).


The calculation of the DNEL is based on an oral NOAEL observed in a subchronic toxicity study in rats (OECD 408). To convert the rat oral NOAEL into a dermal NOAEL to assess human exposure via the dermal route, the NOAEL has to be corrected as follows:


Corrected dermal NOAEL = NOAEL(oral) × (ABSoral-rat / ABSdermal-human) × (Fstudy / Fworker)


= 600 mg/kg bw/day ×  (1 / 1) × (7 / 5)= 840 mg/kg bw/day


ABS = absorption; Fstudy = frequency of exposure in study (days per week); Fworker = frequency of exposure worker (days per week).


The animals (rats) were exposed to the test substance 7 days/week; whereas workers are in general exposed 5 days/week (factor 7 days/5 days), this correction factor is included according to IUCLID 6.4 DNEL calculator. 


On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor is introduced.


Thus, the corrected starting point for workers is 840 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study (subchronic to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rat to human according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default AF for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on reliable study.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.22 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:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
261 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic inhalative effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to "ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health" (Version 2.1, November 2012), and "ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14" (Version 1, July 2012).


The calculation of the DNEL is based on an oral NOAEL observed in a subchronic toxicity study in rats (OECD 408). To convert the rat oral NOAEL into an inhalation NOAEC to assess human exposure via the inhalation route, the NOAEL has to be corrected as follows:


Corrected inhal NOAEC = NOAEL(oral) × (1 / sRVrat) × (ABSoral-rat / ABSinh-human)


= 600 mg/kg bw/day × (1 / 1.15 m³/kg bw/day) × (1 / 2) = 261  mg/m³


sRV = standard respiratory volume;  ABS = absorption


The NOAEL was corrected for interspecies difference between rat and human. As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption.


Thus, the corrected starting point for the general population is 261 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study (subchronic to chronic).
AF for interspecies differences (allometric scaling):
1
Justification:
AF not applicable for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for General population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on reliable study.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 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:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for dermal effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to "ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health" (Version 2.1, November 2012), and "ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14" (Version 1, July 2012).


The calculation of the DNEL is based on an oral NOAEL observed in a subchronic toxicity study in rats (OECD 408). To convert the rat oral NOAEL into a dermal NOAEL to assess human exposure via the dermal route, the NOAEL has to be corrected as follows:


Corrected dermal NOAEL = NOAEL(oral) × (ABSoral-rat / ABSdermal-human)


= 600 mg/kg bw/day ×  (1 / 1) =600 mg/kg bw/day


ABS = absorption;


On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor is introduced.


Thus, the corrected starting point for the general population is 600 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on subchronic study (subchronic to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rat to human according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on reliable study.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 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:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is needed.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study (subchronic to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for Rat to human
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on reliable study.
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:
medium hazard (no threshold derived)

Additional information - General Population