Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.6 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):
20
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
352.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Long-term inhalatory DNELbased on NOAEL (90 d, oral) in rats:
a) NOAEL(inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.3 (p. 68).
corrected NOAEL(inhalation)
 = NOAEL(oral, rat) x 1/sRVratxABS(oral-rat)/ABS(inh-human)  x sRVhuman/wRV
           = 200 mg/kg x 1/0.38 m3/kg/d x 100%/100% x 6.7 m3/10 m3
            = 352.6 mg/m3
with sRV: standard respiratory volume (8h); ABS: Absorption; wRV: worker respiratory volume
b) DNEL(inhalation) derived from corrected NOAEL(inhalation) applying the assessment factor 20 (5(intraspecies) x 2(subchronic-chronic)x 2 (remaining uncertainties)
=> = 17.6 mg/m3

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for intraspecies differences:
5
AF for remaining uncertainties:
2
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:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
80
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long-term dermal systemic DNELbased on NOAEL (90 d, oral) in rats:
a) NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected NOAEL(dermal)         = NOAEL(oral, rat) x Absorption(oral-rat)/Absorption(dermal-human)
                                                  = 200 mg/kg bw x 100%/100%
                                                  = 200 mg/kg bw
b) DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 80 (4(interspecies rat-human) x 5(intraspecies worker) x 2(subchronic-chronic)x 2 (remaining uncertaintoes)
=>= 2.5 mg/kg bw/d

AF for differences in duration of exposure:
2
AF for other interspecies differences:
4
AF for intraspecies differences:
5
AF for remaining uncertainties:
2
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

Acute DNELs

According to RIP 3.2.2, Chapter R8, R8.1.2.5, p. 16 no acute DNELs were derived since no acute toxicity hazard has been identified.

Long-term dermal systemic DNEL based on NOAEL (90 d, oral) in rats:
a) NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected NOAEL(dermal)         = NOAEL(oral, rat) x Absorption(oral-rat)/Absorption(dermal-human)
                                                  = 200 mg/kg bw x 100%/100%
                                                  = 200 mg/kg bw
b) DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 40 (4(interspecies rat-human) x 5(intraspecies worker) x 2(subchronic-chronic)x 2 (remaining uncertainties)
=> = 2.5 mg/kg bw/d

Long-term inhalatory DNEL based on NOAEL (90 d, oral) in rats:
a) NOAEL(inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.3 (p. 68).
corrected NOAEL(inhalation)
 = NOAEL(oral, rat) x 1/sRVratxABS(oral-rat)/ABS(inh-human)  x sRVhuman/wRV
            = 200 mg/kg x 1/0.38 m3/kg/d x 100%/100% x 6.7 m3/10 m3
            = 352.6 mg/m3
with sRV: standard respiratory volume (8h); ABS: Absorption; wRV: worker respiratory volume
b) DNEL(inhalation) derived from corrected NOAEL(inhalation) applying the assessment factor 20 (5(intraspecies) x 2(subchronic-chronic) x 2 (remaining uncertainties))
=> = 17.6 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.4 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):
40
Dose descriptor starting point:
NOAEL
Value:
200 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
173.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

corrected NOAEL(inhalation)     = NOAEL(oral, rat) x 1/sRVratxABS(oral-rat)/ABS(inh-human)
                                                  = 200 mg/kg x 1/1.15 m3/kg/d x 100%/100%
                                                  = 173.9 mg/m3
with sRV: standard respiratory volume; ABS: Absorption

DNEL(inhalation) derived from corrected NOAEL(inhalation) applying the assessment factor 40 (10(intraspecies) x 2(subchronic-chronic) 2x /remaining uncertainties)
=>= 4.4 mg/m3

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for intraspecies differences:
10
AF for remaining uncertainties:
2
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:
DNEL (Derived No Effect Level)
Value:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

a) NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected NOAEL(dermal)         = NOAEL(oral, rat) x Absorption(oral-rat)/Absorption(dermal-human)
                                                  = 200 mg/kg bw x 100%/100%
                                                  = 200 mg/kg bw
b) DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 80 (4(interspecies rat-human) x 10(intraspecies general population) x 2(subchronic-chronic))
=>= 2.5 mg/kg bw/d

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for intraspecies differences:
10
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:
1.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
160
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long-term oral systemic DNELbased on NOAEL (90d, oral) in rats: 200 mg/kg bw
applying assessment factor 160 (4(interspecies rat-human) x 10 (intraspecies general population) x 2(subchronic-chronic)x 2 (remaining uncertainties)
=>= 1.25 mg/kg bw/d

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Sub chronic to chronic
AF for interspecies differences (allometric scaling):
4
AF for intraspecies differences:
10
AF for remaining uncertainties:
2
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

Acute DNELs

According to RIP 3.2.2, Chapter R8, R8.1.2.5, p. 16 no acute DNELs were derived since no acute toxicity hazard has been identified.

Long-term oral systemic DNEL based on NOAEL (90d, oral) in rats: 200 mg/kg bw
applying assessment factor 160 (4(interspecies rat-human) x 10 (intraspecies general population) x 2(subchronic-chronic)x 2
=> = 1.25 mg/kg bw/d

Long-term dermal systemic DNEL based on NOAEL (90 d, oral) in rats:
a) NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected NOAEL(dermal)         = NOAEL(oral, rat) x Absorption(oral-rat)/Absorption(dermal-human)
                                                  = 200 mg/kg bw x 100%/100%
                                                  = 200 mg/kg bw
b) DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 80 (4(interspecies rat-human) x 10(intraspecies general population) x 2(subchronic-chronic))
=> = 2.5 mg/kg bw/d

Long-term inhalatory DNEL based on NOAEL (90 d, oral) in rats:
a) NOAEL(inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.3 (p. 68).
corrected NOAEL(inhalation)     = NOAEL(oral, rat) x 1/sRVratxABS(oral-rat)/ABS(inh-human)
                                                  = 200 mg/kg x 1/1.15 m3/kg/d x 100%/100%
                                                  = 173.9 mg/m3
with sRV: standard respiratory volume; ABS: Absorption

b) DNEL(inhalation) derived from corrected NOAEL(inhalation) applying the assessment factor 20 (10(intraspecies) x 2(subchronic-chronic))
=> = 4.4 mg/m3