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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:
4.41 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
220.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 250 mg/kg/day from a 90-day repeat dose oral study with rats was used.

Assuming an oral/inhalation rate of absorption of 0.5, a dose descriptor of 220.4 mg/m3 was derived as the starting point.

AF for dose response relationship:
1
Justification:
based on REACH guidance
AF for differences in duration of exposure:
4
Justification:
based on REACH guidance for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable when setting an inhalation DNEL based on REACH guidance
AF for other interspecies differences:
2.5
Justification:
based on REACH guidance
AF for intraspecies differences:
5
Justification:
based on REACH guidance
AF for the quality of the whole database:
1
Justification:
based on REACH guidance
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:
5 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A NOAEL of 250 mg/kg/day was selected from a 90-day repeat dose oral study with rats. 

Oral absorption rat – oral/dermal absorption human: Assume 25% absorption based on the physical-chemical properties (water solubility, liquid nature, low molecular weight) in accordance with Endpoint Specific Guidance Chapter 8 and 7c (R.7.12).

Therefore, a dose descriptor of 1000 mg/kg/day was derived as the starting point. See discussion for route to route extrapolation caluculations.

AF for dose response relationship:
1
Justification:
Based on REACH guidance.
AF for differences in duration of exposure:
4
Justification:
Based on REACH guidance.
AF for interspecies differences (allometric scaling):
4
Justification:
Based on REACH guidance.
AF for other interspecies differences:
2.5
Justification:
Based on REACH guidance.
AF for intraspecies differences:
5
Justification:
Based on REACH guidance.
AF for the quality of the whole database:
1
Justification:
Based on REACH guidance.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
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:
low hazard (no threshold derived)

Additional information - workers

Endpoint

Peroxide

MW

134.1 g/mol, liquid

WS

Freely soluble (>500 g/L) (measured, OECD 105)

Log Pow

1.1 (measured, OECD 117)

VP

6.28 Pa at 20oC (measured, OECD 104)

Skin irritation

Non irritant

Initial Dose Descriptor

In a 90-day oral gavage study with rats a No-Observed-Adverse-Effect-Level (NOAEL) of 250 mg/kg bw/d was set.

Due to low vapor pressure, inhalation is not expected to be a major route of exposure. For the DNEL covering local effects of inhalation, route-specific data need to be available (Guidance on information requirements and chemical safety assessment R 8.1.2.6). Exposure to a repeated oral high dose is not expected under normal occupational settings and there are no consumer uses of this substance. Human exposure, via the environment, is unlikely due to the instability of the peroxide.

 

The test substance is a skin sensitizer, which is considered a systemic effect. Therefore, a qualitative risk assessment, for dermal systemic effects will be conducted based on its classification as a Category 1 sensitizer which is considered as a high hazard (ECHA Guidance on information requirements and chemical safety assessment Part E, Table E.3 -1). However, DNELs were derived for non-sensitizing systemic effects.

DNEL dermal-systemic-worker for CAS 37187 -22 -7

A NOAEL of 250 mg/kg/day was selected from a 90-day repeat dose oral study with rats. 

Oral absorption rat – oral/dermal absorption human: Assume 25% absorption based on the physical-chemical properties (water solubility, liquid nature, low Log Pow value) in accordance with Endpoint Specific Guidance Chapter 8 and 7c (R.7.12).

DNEL dermal-systemic-worker

250 mg/kg/day / 0.25 = 1000 mg/kg/day = dermal dose descriptor

Applying assessment factors in accordance with Endpoint Specific Guidance Chapter 8:

Correction for interspecies differences (apply factor for allometric scaling 4 for rat x 2.5 for additional factors): 10

=  1000 mg/kg/day/10 = 100 mg/kg/day

Correction for intraspecies difference: 5

100 mg/kg/day/5 = 25 mg/kg/day

Correction for duration between sub-acute to chronic: 4

100 mg/kg/day/4 = 5 mg/kg/day

Correction for dose-response: 1 due to NOAEL

5 mg/kg/day/1 = 5 mg/kg/day

Correction for whole database: 1 due to quality of study

5 mg/kg/day/1 = 5 mg/kg/day

Total AF = 200

5 mg/kg/day DNEL dermal-systemic-worker

DNEL inhalation-systemic-worker

The dose descriptor of 250 mg/kg/day was selected from a 90-day repeat dose oral study in rats.

Assume ABSoral-rat/ABSinh-human is 50/100 = 0.5 based on phys-chem properties and Endpoint Specific Guidance chapters 8 and 7c (R.7.12)

Corrected inhalatory NOAEC from oral NOAEL:

Oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinh-human) x (sRVhuman/wRV)

[ABS: absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume]

Corrected NOAEC = 250 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7m3/10m3

= 220.4 mg/m3 = inhalation dose descriptor

Applying remaining assessment factors in accordance with Endpoint Specific Guidance Chapter 8:

Correction for interspecies differences: 2.5

220.4 mg/m3/2.5 = 88.16 mg/m3

Correction for intraspecies difference: 5

88.16 mg/m3/5 = 17.63 mg/m3

Correction for duration between sub-acute to chronic: 4

17.63 mg/m3/4 = 4.41 mg/m3

Correction for dose-response: 1

4.41 mg/m3/1 = 4.41 mg/m3

Correction for whole database: 1 due to quality of study

4.41 mg/m3/1 = 4.41 mg/m3

Total AF = 50

4.41 mg/m3 DNEL inhalation-systemic-worker

General Population - Hazard via inhalation route

Systemic effects

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

Local effects

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

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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 for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population