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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.7 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:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
617 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of starting point: 


Inhalation NOAEC from oral NOAEL  


NOAELsubchronic oral = 250 mg/kg/day rat: A conservative assumption. The NOAEL of 13 week study was considered to be 500 mg/kg bw/d. However, 250 mg/kg was selected as starting point based on the finding of a lower relative and absolute spleen weight in males as only finding at 500 mg/kg, of which biological relevance is questionable.


NOAELoral -> ratNOAECinhalation: Available data on absorption kinetics after oral dosing indicates rapid hydrolysation with complete absorption. Higher absorption via airways is therefore not possible. Additionally, vp is low and exposures via aerosols are expected to deposit in higher airways and via mucociliary transport to pharynx and subsequently swallowed, again indicating no differences between oral and inhalation. 


adjusted ratNOAECinhalation =   ratNOAELoral / 0.38m3/kg bw X (100%/100%) = 657.9 mg/m3 (8 hours)  


ratNOAECinhalation -> humanNOAECinhalation   = (ratNOAECinhalation X 6.7m3)/10m3  = 440.8 mg/m3  


Correction for exposure conditions for daily oral dosing 7/wk to occupational exposures 5/wk: 7/5 x 440.8 = 617.1 mg/m3


humanNOAECinhalation = 617.1 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:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
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:
17.5 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:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 750 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.  Studies on dermal absorption in rat indicated that 16% of the dos was observed via the skin. For the DNEl setting  this has been conservatively rounded up to 20%.


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%”. Basically studies indicate a complete absorption following oral dosing.  


NOAELsubchronic oral = 250 mg/kg/day: A conservative assumption. The NOAEL of 13 week study was considered to be 500 mg/kg bw/d. However, 250 mg/kg was selected as starting point based on the finding of a lower relative and absolute spleen weight in males as only finding at 500 mg/kg, of which biological relevance is questionable. 


Correction for exposure conditions for daily oral dosing 7/wk to occupational exposures 5/wk: NOAELdermal = 7/5 x NOAEL subchronic oral / 20%  = 1750 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:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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 relative spleen weights in males receiving the high dose of 500 mg/kg/day.


(At CoRAP evaluation 125 mg/kg was selected at point of departure based on higher kidney weight in females observed only at 250 mg dose group but not at 500 mg/kg.)

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

There are no consumer uses of this substance. Human exposure, via the environment, is unlikely considering the hydrolysis of the peroxide into ter.butyl alcohol and benzoic acid.