Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35 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
Modified dose descriptor starting point:
NOAEC
Value:
881 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL of 1000 mg/kg from a repeat dose oral study was used as the starting dose.

AF for dose response relationship:
1
Justification:
REACH Guidance
AF for differences in duration of exposure:
2
Justification:
REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable per REACH Guidance
AF for other interspecies differences:
2.5
Justification:
REACH Guidance
AF for intraspecies differences:
5
Justification:
REACH Guidance
AF for the quality of the whole database:
1
Justification:
REACH Guidance
AF for remaining uncertainties:
1
Justification:
REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
10 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: Occupational Exposure Limit for dust.
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
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL of 1000 mg/kg from a repeat dose oral study was used as the starting dose.

AF for dose response relationship:
1
Justification:
REACH Guidance
AF for differences in duration of exposure:
2
Justification:
REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
REACH Guidance
AF for other interspecies differences:
2.5
Justification:
REACH Guidance
AF for intraspecies differences:
5
Justification:
REACH Guidance
AF for the quality of the whole database:
1
Justification:
REACH Guidance
AF for remaining uncertainties:
1
Justification:
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

Under CLP dilauroyl peroxide is not classified as acutely hazardous based on a series of acute toxicity studies. Therefore acute DNELS were not derived for systemic or local effects. A DNEL for acute toxicity should only be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposure (Guidance on information requirements and chemical safety assessments Chapter 8.1.2.5).

Long term systemic DNELs were derived using the NOAEL from a repeat dose 90 -day study and applying the appropriate assessment factors in accordance with Guidance on information requirements and chemical safety assessments Chapter 8.

Long term local DNELs were not derived as no local effects were reported in a series of acute studies as well as in the 90 -day repeat dose study.

Systemic Long Term Dermal DNEL Worker

NOAEL from a 90-day oral rat gavage study was 1000 mg/kg. Which was the highest dose tested.

 

Oral absorption rat — oral/dermal absorption human: Assume 10% dermal absorption based on molecular weight of 399, Log Pow of > 11.8, water solubility of < 0.1 mg/l and vapor pressure 0.000266 Pa (EPIWEB).

 

                                  = 1000 mg/kg bw/day/0.1

                                  = 10000 mg/kg bw/day dermal dose descriptor

 

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

                                 = 10000 mg/kg bw/day/10

                                 = 1000 mg/kg bw/day

Correction for intraspecies differences: 5

                                 = 1000 mg/kg bw/day/5

                                  = 200 mg/kg bw/day

Correction for duration between sub-chronic to chronic: 2

                                 = 200 mg/kg bw/day/2

                                  = 100 mg/kg bw/day

Correction for dose-response: 1 due to NOEL

                                  = 100 mg/kg bw/day/1

                                  = 100 mg/kg bw/day

Correction of whole database: 1 due to quality of study

                               = 100 mg/kg bw/day/1

                               =100 mg/kg bw/day (DNELdermal-worker-systemic)

                                 based on overall AF of 100

  

 

Systemic Inhalatory DNEL Workers

 

Corrected inhalatory NOAEC from oral NOAEL

 

oral NOAEL x (1/sRVrat)x(ABSoral-rat/ABSinh-human)xs(RVhuman/wRV)

ABSoral-rat/ABSinh-human is 50/100 = 0.5

 

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

 

                = 881 mg/m3inhalation dose descriptor

 

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

 

Correction for interspecies differences: 2.5

 

                 = 881 mg/m3/ 2.5

 

                 = 352 mg/m3

 

Correction for intraspecies differences: 5

 

                 = 352 mg/m3/ 5

 

                 = 70 mg/m3

 

 

Correction for duration between sub-chronic to chronic: 2

 

                = 70 rng/m3/2

 

                = 35 mg/m3

 

Correction for dose-response: 1 due to NOEL

               = 35 mg/m3/1

               = 35 mg/m3

Correction of whole database: 1 due to quality of study

               = 35 mg/m3/1

               = 35 mg/m3(DNELinhalation-worker-systemic)

              based on overall AF of 25

 

 While the long-term systemic DNEL was calculated to be 35 mg/m3, the lower Occupational Exposure Limit for dust, 10 mg/m3, was used for the exposure assessment.

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
Most sensitive endpoint:
repeated dose toxicity
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