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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:
58.76 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):
30
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:

The original study is reliable without restrictions.

The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "explanation for hazard conclusion")
AF for other interspecies differences:
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "explanation for hazard conclusion")
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
No further AF applied
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:
9.8 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):
120
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Since at this step a dermal absorption of 100% was assumed the orally derived dose descriptor starting point does not need to be modified.

AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
No further AF applied, since no effects were observed at NOAEL
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 (28 d,OECD 442 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)
                                                  = 1000 mg/kg bw/d x 100%/85%
                                                  = 1176,5 mg/kg bw/d

(ca. 85% dermal absorption in human based on a dermal absorption study of Methylparaben)

b. DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 120 (4(interspecies rat-human) x 5(intraspecies worker) x 6(subacute-chronic))

=> =9.8 mg/kg bw/d

Long-term inhalatory DNEL based on NOAEL (28 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
                                                  = 1000 mg/kg/d x 1/0.38 m3/kg/d x 100%/100% x 6.7 m3/10 m3
                                                  = 1763,1 mg/m3
with sRV: standard respiratory volume; ABS: Absorption; wRV: worker respiratory volume
b. DNEL(inhalation) derived from corrected NOAEL(inhalation) applying the assessment factor 30 (5(intraspecies) x 6(subacute-chronic))
=>= 58,76 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.49 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):
60
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
869.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "explanation for hazard conclusion")
AF for other interspecies differences:
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "explanation for hazard conclusion")
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
No further AF applied.
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:
4.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Since at this step a dermal absoprtion of 100% was assumed the orally derived dose descriptor starting point does not need to be modified.

AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
No further AF applied, since no severe effects were observed at NOAEL
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:
4.16 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):
240
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of dose descriptor starting point needed since original study used oral route.

AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
No further AF applied
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 (28d, oral) in rats: 1000 mg/kg bw
applying assessment factor 240 (4(interspecies rat-human) x 10 (intraspecies general population) x 6(subacute-chronic))

=> =4,16 mg/kg bw/d

Long-term dermal systemic DNEL based on NOAEL (28 d, oral) in rats:
- 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)
                                                  = 1000 mg/kg bw x 100%/85%
                                                  = 1176 mg/kg bw

ca. 85% dermal absorption in human based on a dermal absorption study of Methylparaben


- DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 240 (4(interspecies rat-human) x 10(intraspecies general population) x 6(subacute-chronic))
=> =4,9 mg/kg bw/d

Long-term inhalatory DNEL based on NOAEL (28 d, oral) in rats:
- 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)
                                                  = 1000 mg/kg x 1/1.15 m3/kg/d x 100%/100%
                                                  = 869,5 mg/m3
with sRV: standard respiratory volume; ABS: Absorption
- DNEL(inhalation) derived from corrected NOAEL(inhalation) applying the assessment factor 60 (10(intraspecies) x 6(subacute-chronic))
=> =14,49 mg/m3