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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:
5.8 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:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
440.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL for repeated oral dose was determined at at500 mg/kg bw/d.  

Derivation of DNELs - Chronic Systemic effects from Inhalation Exposure:

NOEC derivation from Route-Route extrapolation:

An extrapolation is needed to convert oral exposures in the 28 day study (NOAEC: expressed as mg/kg/bw) to a dose descriptor relevant for inhalation exposures (NOAEC expressed as mg/m3). 

 

This is calculated based on the methods described in the ECAH guidance document: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14

https://echa.europa.eu/documents/10162/13655/pg_14_on_hazard_endpoint_en.pdf

 

 

Workers:

Inhalatory N(L)OAEC= oral N(L)OAEL*(1/0.38m3/kg/d)*0.67*(ABSoral/ABSinhuman)

 

This yields a NOECcorr of 500mg/kg/d*(1/0.38 m3/kg/d)*0.67*(0.5*1)

= 500 * 2.63 * 0.67 * 0.5

 

= 440.525 mg/m3= NOECcorr Workers

Based on theNOAEL NOECcorr of 440.5 mg/m3, and divided by the Overall AF of 75, the Long-termSystemic Inhalation DNEL (Workers)is calculated as

 

440.5 mg /m3/ 75

= 5.8 mg/m3

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.4 mg/m³
DNEL related information
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:

According to the ECHA Guidance, Appendix R 8.8, there is “no accepted methodology for determining acute dermal exposures, and protection is generally accommodated by more conservative long-term systemic DNELs” (p. 106).

 

One well-established method used to estimate an acute threshold limit value (TLV) is the multiplication of the long-term DNEL by a factor of 3 (Guidance R.8, Appendix R.8.8, p. 110, 2008, equivalent to dividing by 0.33 as required in the IUCLID5 format). 

 

Therefore the following Acute Systemic DNELs are derived:

 

Worker:

Acute Systemic Oral/Dermal: 1.6 x 3 =4.8 mg/kg bw/d

Acute Systemic Inhalation:5.8 x 3 =17.4 mg/m3

 

It should be noted that, at exposures to these levels, a local irritant effect may already be obvious to the user. The amelioration of local skin/eye risks should provide an adequate degree of safety from systemic effects.

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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:
2.33 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:
NOAEL
Value:
500 mg/kg bw/day
Value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.8 mg/kg bw/day
DNEL related information
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

According to the ECHA Guidance, Appendix R 8.8, there is “no accepted methodology for determining acute dermal exposures, and protection is generally accommodated by more conservative long-term systemic DNELs” (p. 106).

 

One well-established method used to estimate an acute threshold limit value (TLV) is the multiplication of the long-term DNEL by a factor of 3 (Guidance R.8, Appendix R.8.8, p. 110, 2008, equivalent to dividing by 0.33 as required in the IUCLID5 format). 

 

Therefore the following Acute Systemic DNELs are derived:

 

Worker:

Acute Systemic Oral/Dermal: 1.6 x 3 =4.8 mg/kg bw/d

Acute Systemic Inhalation:5.8 x 3 =17.4 mg/m3

 

It should be noted that, at exposures to these levels, a local irritant effect may already be obvious to the user. The amelioration of local skin/eye risks should provide an adequate degree of safety from systemic effects.

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

As there are no consumer uses of the substance, and it is matrix-bound after use, there is no potential for exposure of the general population by inhalation.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

As there are no consumer uses of the substance, and it is matrix-bound after use, there is no potential for exposure of the general population by inhalation.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

As there are no consumer uses of the substance, and it is matrix-bound after use, there is no potential for exposure of the general population by the dermal route.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

As there are no consumer uses of the substance, and it is matrix-bound after use, there is no potential for exposure of the general population by the dermal route.

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:
0.833 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:
NOAEL
Value:
500 mg/kg bw/day
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

As there are no consumer uses of the substance, and it is matrix-bound after use, there is no potential for exposure of the general population by the dermal route.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population