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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:
0.23 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
Value:
33.6 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
16.88 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified in accordance with 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. Correction of the inhalatory NOAEC from rat to human (worker) was conducted using the following equation:

Inhalatory NOAEC = (6 h/d / 8 h/d) x ((6.7 m3 (8h) / 10 m3 (8h))

AF for dose response relationship:
1
Justification:
ECHA Default
AF for differences in duration of exposure:
6
Justification:
ECHA Default: sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Default: Allometric scaling already considered when correcting dose descriptor.
AF for other interspecies differences:
2.5
Justification:
ECHA Default
AF for intraspecies differences:
5
Justification:
ECHA Default
AF for the quality of the whole database:
1
Justification:
ECHA Default
AF for remaining uncertainties:
1
Justification:
ECHA Default
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high 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:
0.09 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
Value:
33.6 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
6.42 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified in accordance with 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. Correction of the inhalatory NOAEC from rat to a dermal NOAEL was conducted using the following equation:

Corrected NOAEL = inhalatory NOAEC (8h) x sRVratx (ABSinh-rat/ ABSoral-human)

AF for dose response relationship:
1
Justification:
ECHA Default
AF for differences in duration of exposure:
6
Justification:
ECHA Default: Sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Default: Allometric scaling already considered in correction of dose descriptor
AF for other interspecies differences:
2.5
Justification:
ECHA Default
AF for intraspecies differences:
5
Justification:
ECHA Default
AF for the quality of the whole database:
1
Justification:
ECHA Default
AF for remaining uncertainties:
1
Justification:
ECHA Default
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Correction of Dose Descriptors

Although the main focus of the hazard assessment was the Category 1A corrosivity of the substance, long-term DNELs were derived for systemic inhalation and dermal exposure, to ensure that the prescribed operational conditions and risk management measures were suitable protective against the hazards identified for effects on fertility (sub-acute NOAEC = 33.6 mg/m3)

Correction of the starting dose descriptors, to allow derivation of DNELs, was conducted in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8.

Inhalatory NOAEC

The corrected inhalatory NOAEC was calculated as follows:

 Corrected NOAEC

= inhalatory NOAEC x (exp.cond.rat/exp.cond.human

  = 33.6 mg/m3 x ((6 h/d) / (8 h/d)) x (6.7 m3 (8h) / 10 m3 (8h))
  = 16.88 mg/m3

Dermal NOAEL

The dermal NOAEL was calculated, using route-to-route extrapolation, as follows:

 Corrected NOAEL  = inhalatory NOAEC (8h) x sRVrat x (ABSinh-rat / ABSoral-human)
 

= 16.88 x 0.38 x (1/1)

   = 6.415 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.056 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEC
Value:
33.6 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
8.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified in accordance with 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. Correction of the inhalatory NOAEC from rat to human (general public) was conducted using the following equation:

Inhalatory NOAEC = (6 h/d / 24h/d)

AF for dose response relationship:
1
Justification:
ECHA Default
AF for differences in duration of exposure:
6
Justification:
ECHA Default: sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Default: Allometric scaling already considered when correcting dose descriptor.
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
ECHA Default
AF for remaining uncertainties:
1
Justification:
ECHA Default
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high 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:
0.064 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEC
Value:
33.6 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
9.66 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified in accordance with 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. Correction of the inhalatory NOAEC from rat to a dermal NOAEL was conducted using the following equation:

Corrected NOAEL = inhalatory NOAEC (24h) x sRVratx (ABSinh-rat/ ABSoral-human)

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default. Allometric scaling already considered in correction of dose descriptor
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default (general public)
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECHA default
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high 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:
0.064 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEC
Value:
33.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
9.66 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified in accordance with 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. Correction of the inhalatory NOAEC from rat to a dermal NOAEL was conducted using the following equation:

Corrected NOAEL = inhalatory NOAEC (24h) x sRVratx (ABSinh-rat/ ABSoral-human)

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default. Allometric scaling already considered in correction of dose descriptor
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
ECHA default
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Correction of Dose Descriptors

Long-term DNELs for the general public were derived for systemic inhalation, dermal and oral exposure. The starting point for hazard assessment was effects on fertility observed in the OECD 421 study (Brooker, 2013; sub-acute NOAEC = 33.6 mg/m3).

Correction of the starting dose descriptors, to allow derivation of DNELs, was conducted in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8.

Inhalatory NOAEC

The corrected inhalatory NOAEC was calculated as follows:

 Corrected NOAEC

= inhalatory NOAEC x (exp.cond.rat/exp.cond.human

  = 33.6 mg/m3x (6 h/d / 24 h/d)
  = 16.88 mg/m3

Oral & Dermal NOAEL

The oral dermal NOAEL was calculated, using route-to-route extrapolation, as follows:

 Corrected NOAEL  = inhalatory NOAEC (24h) x sRVratx (ABSinh-rat/ ABSoral-human)
 

= 8.4 x 1.15 x (1/1)

   = 9.66 mg/kg bw/day