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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:
0.7 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):
25
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
17.42 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 10 mg/kg/day from an OECD408 repeat dose oral study with rats was used. Assuming an oral /inhalation absorption of 1.0 a dose descriptor of 17.42 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:
2
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
AF for remaining uncertainties:
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:
1 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:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 10 mg/kg/day from an OECD408 repeat dose oral study with rats was used. Oral/dermal absorption was assumed to be 10%. The dose descriptor was therefore 100 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 sub-acute 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:
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:
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:
no hazard identified

Additional information - workers

Initial Dose Descriptor

The test item was administered by gavage to three groups, each of ten male and ten female Wistar Han™:RccHan™:WIST strain rats, for ninety consecutive days, at dose levels of 10, 100 or 300 mg/kg bw/day. A control group of ten males and ten females were dosed with vehicle alone (Arachis oil BP). Two recovery groups, each of ten males and ten females, were treated with the high dose (300 mg/kg bw/day) or the vehicle alone for ninety consecutive days and then maintained without treatment for a further twenty-eight days.

 

The oral (gavage) administration of 1,1,3,3-tetramethylbutyl peroxyneodecanoate (CAS#51240-95-0) to male and female Wistar Han™:RccHan™:WIST strain rats at a dose level of 100 or 300 mg/kg bw/day resulted in toxicologically significant changes in sperm

concentration and motility and an associated increase in sperm abnormalities. These were not reversible in males previously treated with 300 mg/kg bw/day after a twenty-eight day treatment-free period. It is therefore considered that a dose level of 10 mg/kg bw/day could be established as a No Observed Adverse Effect Level (NOAEL) for systemic toxicity in the male within the confines of this type of study. In contrast, there were no changes of toxicological significance in the females up to a dose level of 300 mg/kg bw/day, which

could therefore be established as a NOAEL in the female within the confines of this type of study.

 

The NOAEL used to calculate DNELs is 10 mg/kg/day

DNEL dermal-systemic-worker

Based on the log Pow of 6.9, the peroxide is expected to stay partitioned in the phlegmatizer. Based on the log kow of 6.96, vapor pressure and water solubility, the phlegmatizer is not expected to penetrate the skin to a significant degree. Therefore, the peroxide will not be significantly absorbed via the skin.

Endpoint

dihexadecyl peroxodicarbonate

MW

300.48

WS

33.6 µg/L

MP

< -28.0°C

Log Pow

> 6.5 (6.9 extrapolated)

VP

Peroxide in solvent < 0.24 Pa at25°C

Pure peroxide: 0.0001 -0.01 Pa at25°C

Skin irritation

Mild irritant (Cat 3)

 

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).

 

NOAEL 10 mg/kg/day/0.1 = 100 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

100 mg/kg/day/10 = 10 mg/kg/day

Correction for intraspecies difference: 5

10 mg/kg/day/5 = 2 mg/kg/day

Correction for duration between sub-acute to chronic: 2

2 mg/kg/day/2 = 1 mg/kg/day

Correction for dose-response: 1 due to NOAEL

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

Correction for whole database: 1 due to quality of study

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

Total AF = 100

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

 

DNEL inhalation-systemic-worker

The vapor pressure of the pure peroxide was pure peroxide: 0.0001 -0.01 Pa at 25°C. The vapor pressure of the solvent peroxide mixture is < 0.24 Pa at 25°C

Based on the low vapor pressure, 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 1.0 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 = 10 mg/kg/day x (1/0.38 m3/kg/day) x (1.0) x 6.7 m3/10m3 = 17.42 mg/m3

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

Correction for interspecies differences: 2.5

17.42 mg/m3/2.5 = 6.97 mg/m3

Correction for intraspecies differences: 5

6.97 mg/m3/5 = 1.39 mg/m3

Correction for duration between subacute to chronic: 2

1.39 mg/m3/2 =0.7 mg/m3

Correction for dose-response: 1

0.7 mg/m3/1 = 0.7 mg/m3

Correction for whole database: 1 due to quality of study

0.7 mg/m3/1 = 0.7 mg/m3

Total AF = 25

0.7mg/m3 DNEL inhalation-systemic-worker

 

General Population - Hazard via inhalation route

Systemic 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

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

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:
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 for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - General Population