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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:
8.82 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA guidance combined with ECETOC
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Value:
158.68 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of repeated dose inhalation toxicity data, the NOAEL from the 28 day repeated dose oral toxicity study in rat (30 mg/kg bw/day) can be taken as a starting point for deriving a DNELlong-term, workers, inhalation. The value must first be corrected for route differences as described in REACH guidance document R.8 version 2.1, November 2012 (‘Characterisation of dose (concentration)-response for human health’) to obtain a corrected inhalation NOAEC: Inhalation NOAEC corr = (NOAEL oral/vSRrat) X (vSR human / vWSRhuman) x ABSoral/ABSinh = (30 / 0.38) x (6.7/10) x (90/30) = 158.6842 mg/m3 Based on the toxicokinetics assessment ABSoral=90% and ABSinhalation=30%.
AF for dose response relationship:
1
Justification:
NOAEL is starting point
AF for differences in duration of exposure:
6
Justification:
base-study 28 days (subacute)
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
1
Justification:
ECETOC (not considered)
AF for intraspecies differences:
3
Justification:
workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.82 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:
In the absence of repeated dose inhalation toxicity data, the NOAEL from the 28 day repeated dose oral toxicity study in rat (30 mg/kg bw/day) can be taken as a starting point for deriving a DNELlong-term, workers, inhalation. The value must first be corrected for route differences as described in REACH guidance document R.8 version 2.1, November 2012 (‘Characterisation of dose (concentration)-response for human health’) to obtain a corrected inhalation NOAEC: Inhalation NOAEC corr = (NOAEL oral/vSRrat) X (vSR human / vWSRhuman) x ABSoral/ABSinh = (30 / 0.38) x (6.7/10) x (90/30) = 158.6842 mg/m3 Based on the toxicokinetics assessment ABSoral=90% and ABSinhalation=30%.

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA guidance combined with ECETOC
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Value:
270 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of repeated dose dermal toxicity data, the NOAEL from the 28 day repeated dose oral toxicity study in rat (30 mg/kg bw/day) can be taken as a starting point for deriving a DNELlong-term, workers, dermal. In a first step, the oral value should be corrected for route-to-route extrapolation. In accordance with REACH Guidance document R8 (v2.1, November 2012) the dermal NOAEL is calculated according to: Dermal N(L)OAEL=oral (N(L)OAEL x ( ABSoral/ABSdermal). Based on the toxicokinetics assessment ABSoral=90% and ABSdermal=10%. The Dermal Corrected NOAEL=270 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL is starting point
AF for differences in duration of exposure:
6
Justification:
base-study 28 days (subacute)
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
1
Justification:
ECETOC (not considered)
AF for intraspecies differences:
3
Justification:
workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

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

The derivation of DNELS for workers has taken into consideration how the substance is used and the toxicological properties available for the substance.

The substance is used as such. The substance is manufactured in closed system and connected to exhaustion systems. The registrant doesn't manufacture the substance in EU. The substance is used in EU in industrial sites as auxiliary and/or as an intermediate. Exhaustion systems are also considered to be in place not allowing the substance to reach workers.

 

No non-threshold effects for this substance were identified.

The substance causes local effects: skin and eye irritation.

The substance doesn't cause acute toxic effects.

The starting point for DNEL calculations is the NOAEL (oral route - rat) from a <90-day study = 30 mg/kg bw/day. Following the Practical Guide 14 and the ECHA Guidance R.8, the NOAEL oral is corrected to a NOAEC, which is used afterwards to derive the DNELs.

The Assessment Factors taken are the ones as described in ECETOC Technical Reports No 86 and 110.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.61 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance combined with ECETOC
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Value:
78.26 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELoral * (1 / 1.15 m3/kg/d) * (ABSoral-rat/ABSinh-human) NOAECcorr = 30 * (1/1.15) * (90/30) = 78.26 mg/m3
AF for dose response relationship:
1
Justification:
NOAEL starting point
AF for differences in duration of exposure:
6
Justification:
base study duration <90 days
AF for interspecies differences (allometric scaling):
1
Justification:
not for inhalation
AF for other interspecies differences:
1
Justification:
ECETOC (not considered)
AF for intraspecies differences:
5
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.61 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELoral * (1 / 1.15 m3/kg/d) * (ABSoral-rat/ABSinh-human) NOAECcorr = 30 * (1/1.15) * (90/30) = 78.26 mg/m3

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance combined with ECETOC
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
270 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is considered that the oral and dermal absorption rates are 90% and 10% respectively, and the following equation has been applied: NOAECcorr = NOAELoral * (ABSoral-rat/ABSdermal-human), NOAECcorr = 30 * (0.9/0.1) = 270 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL as starting point
AF for differences in duration of exposure:
6
Justification:
base study <90 days
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
1
Justification:
ECETOC (not considered)
AF for intraspecies differences:
5
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.25 mg/kg bw/day
DNEL related information
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance combined with ECETOC
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is not route-to-route extrapolation
AF for dose response relationship:
1
Justification:
NOAEL is starting point
AF for differences in duration of exposure:
6
Justification:
study base <90 days
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
1
Justification:
ECETOC (not considered)
AF for intraspecies differences:
5
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The derivation of DNELS for general population has taken into consideration how the substance reaches the targets.

The substance is only used in an industrial site. In case of an accidental release it is possible that the substance gets out of the site.

 

No non-threshold effects for this substance were identified.

The substance causes local effects: skin and eye irritation.

The substance doesn't cause acute toxic effects.

The starting point for DNEL calculations is the NOAEL (oral route - rat) from a <90-day study = 30 mg/kg bw/day. Following the Practical Guide 14 and the ECHA Guidance R.8, the NOAEL oral is corrected to a NOAEC.