Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Explanation for the modification of the dose descriptor starting point:

Since the registered substance is solid at room temperature and the DNEL derived from the oral repeated dose toxicity study (OECD 408) with the read-across substance was 35.2 mg/m3 the general dust limit of 10 mg/m3 for the respirable airborne fraction was used for setting an occupational exposure limit. For more information please refer to discussion below.

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:
100 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):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg/day from an OECD 408 oral repeated dose study with the read-across substance in rats was used as point of departure.

Oral/dermal absorption was assumed to be 10%. The modified dose descriptor was therefore 10000 mg/kg/day.

AF for dose response relationship:
1
Justification:
based on REACH guidance
AF for differences in duration of exposure:
2
Justification:
based on REACH guidance for subchronic to chronic
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
Justification:
Even though the Point of departure for DNEL Derivation is based on results obtained from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered sufficiently conservative. Therefore, there are no remaining uncertainties with this approach.
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

Initial Dose Descriptor

In an OECD 408 oral gavage study with the read-across substance in rats a No Observed Adverse Effect Level (NOAEL) of 1000 mg/kg was established, since no adverse effects were observed at the highest dose tested.

Therefore, the NOAEL of 1000 mg/kg bw/day was used for DNEL derivation.

DNEL dermal-systemic-worker

Endpoint

dihexadecyl peroxodicarbonate

MW

570.88

WS

Insoluble in water

MP

49.0°C to 57.0°C

Log Pow

15.5 (calculated)

VP

<< 0.01 Pa at 20°C(calculated)

Skin irritation

not irritating 

 

Oral absorption rat – oral/dermal absorption human: Assume 10% absorption based on the data above in accordance with Endpoint Specific Guidance Chapter 8 and 7c (R.7.12).

 

1000 mg/kg bw/day * 0.1 = 10000 mg/kg bw/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

Correction for intraspecies difference: 5

Correction for duration between sub-chronic to chronic: 2

Correction for dose-response: 1 due to NOAEL

Correction for whole database: 1 due to quality of study

Total AF = 100

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

 

DNEL inhalation-systemic-worker

The measured vapor pressure of the registered substance was << 0.01 Pa. The substance is available as flakes and in powder form. For the flakes less than 1% w/w is <100 µm. For the powder 3.6% of the particles is < 100 µm of that fraction only 0.036% is <10 µm and no particles are <5 µm.

Based on the low vapor pressure and particle size inhalation is not expected to be a major route of exposure.

 

Corrected inhalatory NOAEC from oral NOAEL

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

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)

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

Corrected NOAEC = 1000 mg/kg bw/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3

                               = 882 mg/m3

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

Correction for interspecies differences: 2.5

Correction for intraspecies differences: 5

Correction for duration between sub-chronic to chronic: 2

Correction for dose-response: 1

Correction for whole database: 1 due to quality of study

Total AF =25

A DNEL was calculated based on route-to-route extrapolation.

ECHA guidance R8 (p.48) states that

“For exposure to dust, it should be considered whether a derived DNEL for inhalation may have to be lowered. The general dust limits of 10 mg/m3 for the inhalable airborne fraction and 3 mg/m3 for the respirable airborne fraction used in setting Occupational Exposure Limits in many countries should be considered in combination with nature of the dust. The following should be considered:

• For non-soluble inert dusts if the derived DNEL for inhalation is above these dust limits, the general dust limits should apply for exposure scenarios with exposure to dust

• For significantly soluble dusts, if the derived DNEL for inhalation is above, the general dust limit might apply. Where it is not to be used, the rationale for any deviation from the general dust limits should be justified.

Note that DNELs derived based on substance specific data can never be adjusted upwards based on the general dust limits and that the dust limits can not be used as a surrogate DNEL when there is no data to set a substance-specific DNEL.”

For the registered substance the particle size does not indicate that inhalation is a major route of exposure and the substance is not soluble in water. However the DNEL is above the general dust limit of 10 mg/m3 for inhalable dust and 3 mg/m3 for respirable dust, therefore in the hazard and exposure assessment these general dust limits will be applied.

10 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