Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
10 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg/day from an OECD422 repeat dose oral study with rats was used (males 42 days, females 56 days exposure).  Assuming an oral /inhalation absorption of 0.5 a dose descriptor of 882 mg/m3 was derived as the starting point. This would result in a DNEL of 11.7 mg/m3 based on route-to-route extrapolation, for further justification on why an other toxicological threshold is used in the hazard assessment see "justifcation and comments" below.

AF for dose response relationship:
1
Justification:
based on REACH guidance
AF for differences in duration of exposure:
6
Justification:
based on REACH guidance for subacute to chronic
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:
33.33 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):
300
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 OECD422 repeat dose oral study with rats was used (males 42 days, females 56 days exposure).  Oral/dermal absorption was assumed to be 10%.  The 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:
6
Justification:
based on REACH guidance for subacute 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
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 OECD422 oral gavage study with rats a No Observed Adverse Effect Level (NOAEL) of

1000 mg/kg was established. The only effect observed was a slight body weight gain reduction in males in week 6.

Therefore, the NOAEL, for DNEL calculation, was set a 1000 mg/kg/day.

DNEL dermal-systemic-worker

n.

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 at20°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/day/0.1 = 10000 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

10000 mg/kg/day/10 = 1000 mg/kg/day

Correction for intraspecies difference: 5

1000 mg/kg/day/5 = 200 mg/kg/day

Correction for duration between sub-acute to chronic: 6

200 mg/kg/day/6 = 33.33 mg/kg/day

Correction for dose-response: 1 due to NOAEL

33.33 mg/kg/day/1 = 33.33

Correction for whole database: 1 due to quality of study

33.33 mg/kg/day/1 = 33.33 mg/kg/day

Total AF = 300

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

 

DNEL inhalation-systemic-worker

The measured vapor pressure of the peroxide 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/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

882 mg/m3/2.5 = 352.6 mg/m3

Correction for intraspecies differences: 5

352.6 mg/m3/5 = 70.5 mg/m3

Correction for duration between sub-acute to chronic: 6

70.5 mg/m3/6 = 11.7 mg/m3

Correction for dose-response: 1

11.7 mg/m3/1 = 11.7 mg/m3

Correction for whole database: 1 due to quality of study

11.7 mg/m3/1 = 11.7 mg/m3

Total AF =75

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

In guidance R8 (p.48) is says: “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 this 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
DNEL derivation method:
ECHA REACH Guidance

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