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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:
1.4 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
20 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 20 mg/kg/day from a 52-week repeat dose oral study with rats was used.  

Corrected inhal N(L)OAEC = oral N(L)OAELrat * 1/0.38  * 6.7/10

Corrected inhal N(L)OAEC = 20 * 1/0.38  * 6.7/10 = 35.26

Assuming an oral/inhalation absorption of 0.5, a dose descriptor of 17.42 mg/m3 was derived as the starting point.

For further informatio see: additional information - workers

AF for dose response relationship:
1
Justification:
REACH guidance
AF for differences in duration of exposure:
1
Justification:
REACH guidance Chronic study
AF for interspecies differences (allometric scaling):
1
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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):
50
Dose descriptor starting point:
NOAEL
Value:
20 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 dose descriptor of 20 mg/kg/day was selected from a 52-week repeat dose oral study with rats.  Oral absorption rat - oral/dermal absorption human: Assume 20% absorption based on the physical-chemical properties in accordance with Endpoint Specific Guidance Chapter 8 and 7c(R.7.12). The modified dose descriptor starting point is 100 mg/kg bw/d.

For further informatio see: additional information - workers

AF for dose response relationship:
1
Justification:
REACH Guidance
AF for differences in duration of exposure:
1
Justification:
REACH Guidance 52-week study
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

Preliminary DNEL Discussion

 

CAS# 6731-36-8

 

Name: di-tert-butyl 3,3,5-trimethylcyclohexylidene diperoxide

 

Study: 52 week oral gavage study in rats with dose groups of 4, 20 and 100 mg/kg/day. The NOEL for males was considered to be 4 mg/kg/day and < 4 mg/kg/day for females. However, after evaluating the data in terms of biological significance, degree and severity of the effect as well as considering the data as a whole for a specific parameter, the effects observed at 4 and 20 mg/kg/day were considered to be non-adverse in this 52-week study. These effects included reduced hemoglobin level, hepatic hypertrophy, and presence of foam cells in liver.

  

NOAEL:         males:            20 mg/kg/day

                       females:         20 mg/kg/day

 

Molecular Weight: 302.46

 

Water solubility = 0.4 mg/L (NITE study)

 

Kow = 6.53 (NITE study)

 

Vapor Pressure = 0.02 hPa (AN data) at 20 degrees C by Antoine equation

 

Dermal Absorption: no direct information

 

Other Information: OPPSD trout preliminary hydrolysis study at pH 2.6

 

Expect oral absorption to be greater than dermal. Absorption predictor parameter values do not consistently favor oral route, but toxicity was observed by the oral route.

 

Approximate saturated vapor concentration is ~ 247 mm/m3. Exposure to vapor is possible.

Worker Dermal Systemic DNEL

 

Modification of starting point

 

Oral -> dermal when dermal uptake is 20% of oral (Based on molecular weight, water solubility Kow and no acute dermal tox at 1 g/kg 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.

 

Corrected Dermal NOAEL 20 mg/kg/day/0.20 = 100 mg/kg/day

 

Assessment Factors:

 

Allometric                                          4         rat -> human

Other                                                  2.5

Intraspecies                                      5         Worker

Duration                                             1         chronic study

Dose Response                              1      

Quality of Database                         1

 

Product of assessment factors:      50

Long-term systemic DNELdermal

 = humanNOAELdermal / Product of Assessment Factors

 

Long-term worker systemic DNELdermal =2.0 mg/kg/day

Worker Inhalation Systemic DNEL           

 

Modification of starting point

 

Inhalation NOAEC from oral NOAEL of 20 mg/kg/day from a 52 -week study

 

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)

 

Corrected inhalatoary NOAEC from oral NOAEL

Oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinh-human) x (sRVhuman/wRV)

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

Corrected NOAEC = 20 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3 = 17.42mg/m3

 

Assessment Factors:

 

Allometric                                          1         route-to-route extrapolation used

Other                                                  2.5

Intraspecies                                     5         Worker

Duration                                            1         chronic study

Dose Response                              1

Quality of Database                         1

 

Product of assessment factors:  12.5

 

Long-term systemic DNELinhalation

 = humanNOAECinhalation / Product of Assessment Factors

 

Long-term worker systemic DNELinhalation = 1.4 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