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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 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
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
110 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of starting point  

Inhalation NOAEC from oral NOAEL  

NOAELsubchronic oral = 125 mg/kg/day   rat

NOAELoral -> ratNOAECinhalation   (adjusted per R.8.4 based on lack of information to assume worst-case of 50% oral and 100% inhalation absorbtion)  

adjusted ratNOAECinhalation =   ratNOAELoral / 0.38m3/kg bw X (50%/100%) = 164 mg/m3 (8 hours)  

ratNOAECinhalation -> humanNOAECinhalation   = (ratNOAECinhalation X 6.7m3)/10m3  = 110 mg/m3  

humanNOAECinhalation = 110 mg/m3  

AF for dose response relationship:
1
Justification:
Based on REACH Guidance
AF for differences in duration of exposure:
2
Justification:
Based on REACH Guidance sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Based on REACH Guidance not applicable when setting an inhalation DNEL
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)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
125 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
625 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Worker Dermal Systemic DNEL  

Modification of starting point  

Oral -> dermal when dermal uptake is 20% of oral.  

Per R.7.C (p 179), it does not appear that a “scientifically defensible database demonstrates that the GI absorption of the chemical in question, from a medium (e.g. water, feed) similar to the one employed in the critical study is significantly less than 100%”, therefore a 50% correction for the oral absorption is not used.  

NOAELsubchronic oral = 125 mg/kg/day  

NOAELdermal = NOAEL subchronic oral X  5 = 625 mg/kg/day  

Long-term worker systemic DNELdermal =6.25 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 sub-chronic 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:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Preliminary DNEL Discussion

 

CAS# 614-45-9

 

Name:           tert-Butylperoxybenzoate

 

Study: 13 week oral gavage described in NTP Report 15

 

NOAEL: 125 mg/kg/day

 

Critical endpoints: Hyperplasia of the forestomach mucosa was observed in most groups of dosed rats and increased in severity with dose. Female rats receiving the lowest dose, 30 mg/kg bw/day did not show evidence of forestomach hyperplasia. Forestomach weights were increased in male rats receiving the 250 and 500 mg/kg doses and in female rats receiving 60 mg/kg and higher doses. Weights of the glandular stomachs also were increased in both males and females, but the increases were largely restricted to high dose animals (250 and 500 mg/kg/day) and the percent increase was smaller than observed in the forestomach. Other changes in organ weights included slightly decreased spleen weights in males and females receiving the high dose, and increased kidney weights in female rats receiving 250 mg/kg.

Therefore as forestomach effects are not relevant for humans and based on slight spleen and kidney weight changes in the higher dose groups, 125 mg/kg/day was selected as the NOAEL.

 Molecular Weight: 194.23

 

Water solubility = 159.2 mg/L (EpiWeb 4 calculation)

 

Kow = 3 (OPPSD study)

 

Vapor Pressure = 0.00003 hPa at 20 degrees C by Antoine equation

 

Dermal Absorption: NTP Report 15 indicates ~ 16%

 

Other Information: NTP report 15 indicates that the test article at a concentration of 1.1 mg/mL in simulated stomach contents  did not have a reduced concentration after 15 minutes

 

Expect oral absorption to be greater than dermal. The molecular weight less than 200, Kow of 3, and water solubility of 150 mg/L, and the use of aqueous vehicle in study in NTP Report 15 are all consistent with oral route uptake. In addition, the reported 16% dermal uptake suggests that dermal uptake is about 20% of oral uptake.

 

Approximate saturated vapor concentration ~ 0.24 mg/m3.

Worker Dermal Systemic DNEL

 

Modification of starting point

 

Oral -> dermal when dermal uptake is 20% of oral.

 Per R.7.C (p 179), it does not appear that a “scientifically defensible database demonstrates that the GI absorption of the chemical in question, from a medium (e.g. water, feed) similar to the one employed in the critical study is significantly less than 100%”, therefore a 50% correction for the oral absorption is not used.

 

 

NOAELsubchronic oral = 125 mg/kg/day

 

NOAELdermal = NOAEL subchronic oral X 5 = 625 mg/kg/day

 

Assessment Factors:

 

Allometric                                          4         rat -> human

Other                                                  2.5

Intraspecies                                        5         Worker

Duration                                             2         sub-chronic -> chronic

Dose Response                                   1

Quality of Database                           1

 

Product of assessment factors:         100

 

Long-term systemic DNELdermal = NOAELsubchronic dermal / Product of Assessment Factors

 

Long-term worker systemic DNELdermal =6.25 mg/kg/day

Worker Inhalation Systemic DNEL           

 

 

Modification of starting point

 

Inhalation NOAEC from oral NOAEL

 

NOAELsubchronic oral = 125 mg/kg/day

 

ratNOAELoral -> ratNOAECinhalation 

(adjusted per R.8.4 based on lack of information to assume worst-case of 50% oral and 100% inhalation absorbtion)

 adjusted ratNOAECinhalation =

 

 ratNOAELoral / 0.38m3/kg bw X (50%/100%) = 164 mg/m3(8 hours)

 

ratNOAECinhalation -> humanNOAECinhalation

 

 = (ratNOAECinhalation X 6.7m3)/10m3 = 110 mg/m3

 

humanNOAECinhalation = 110 mg/m3

 

Assessment Factors:

 

Allometric                                          1         route-to-route extrapolation used

Other                                                  2.5

Intraspecies                                        5         Worker

Duration                                             2         sub-chronic -> chronic

Dose Response                                   1

Quality of Database                           1

 

Product of assessment factors:         25

 

Long-term systemic DNELinhalation

 = humanNOAEHCinhalation / Product of Assessment Factors

 

Long-term worker systemic DNELinhalation = 4 mg/m3/day

 

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