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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.65 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):
50
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
132.237 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 150 mg/kg bw/d from an OECD 422 repeat dose oral gavage study in rats was used (males 42 days and females 56 days). assuming an oral/inhalation absorption of 0.5, a dose descriptor of 132.2368 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:
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:
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:
1.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 150 mg/kg bw/d from an OECD 422 repeat dose oral gavage study in rats was used (males 42 days and females 56 days). Assuming an oral/dermal absorption of 50%, a dose descriptor of 300 mg/kg bw/d was derived as the starting point. A 50% dermal absorption was based on the molecular weight of 234.3 g/mol, log Pow of 5.4 at 300C, water solubility of 8.3 mg/L at 200C.

AF for dose response relationship:
1
Justification:
Based on REACH guidance
AF for differences in duration of exposure:
4
Justification:
Correction for the duration of subchronic (6 weeks) to chronic (13 weeks); Based on REACH guidance
AF for interspecies differences (allometric scaling):
4
Justification:
Based on REACH guidance
AF for other interspecies differences:
2.5
Justification:
Additional factors (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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Correction of dose descriptors for route-to-route extrapolation, application of assessment factors and derivation of the endpoint specific DNEL

Phys-Chem data considered for the calculation of DNEL for CAS 2167-23-9 were:

Endpoint                   CAS Number 2167-23-9:

MW                            234.3 g/mol,

Appearance                Liquid

Water solubility           8.3 mg/L at 200C (measured)

Log Pow                     5.4 (measured)

VP                              15 Pa at 25oC (measured)

Skin irritation               Mild irritant, but not classifiable

Skin Sensitization        No

 

Initial Dose Descriptor

In a OECD 422 oral gavage reproductive toxicity screening study with rats, a no-observed-adverse-effect-level (NOAEL) of 150 mg/kg/day was established for the systemic toxic effects of 2,2-di(ter-butylperoxy) butane (CAS # 2167-23-9) in males and females. Treatment-related microscopic findings noted in the liver, and thyroid in females were noted at 500 mg/kg/d but were considered to be adaptive changes. Therefore, 150 mg/kg/d was considered to be the no-observed-adverse-effect-level (NOAEL) in females. The microscopic findings in the male kidney (tubular basophilia and proteinaceous casts) were considered to be associated with alpha 2u-globulin and formation of hyaline droplets, an effect recognized as being both species specific and sex specific and not relevant for humans. (Alden, CL and Frith CH. Urinary System, Ch. 15, pp 315-387. In: Handbook of Toxicologic Pathology Eds. Haschek WM and Rousseaux CG. Academic Press, San Diego. 1991). A range of chemicals are known to increase hyaline droplet formation beyond the physiological capacity of the tubular epithelium which may then result in tubular epithelial cell damage (hyaline droplet nephropathy) which was evident in this study. The NOAEL for males was therefore considered to be 150 mg/kg/day. The no-observed-effect-level (NOEL) was 50 mg/kg/d for either sex and the NOEL for reproductive toxicity was considered to be 500 mg/kg/d.

In summary, based on the entire study findings, the systemic NOAEL for DNEL calculations was set a 150 mg/kg/day.

Due to low vapor pressure, inhalation is not expected to be a major route of exposure. For the DNEL covering local effects of inhalation or dermal routes of exposure, route-specific data need to be available (Guidance on information requirements and chemical safety assessment R 8.1.2.6). Exposure to a repeated oral high dose is not expected under normal occupational settings and there are no consumer uses of this substance. Human exposure, via the environment, is unlikely due to the instability of the peroxide. DNELs were derived for systemic long term effects for inhalation and dermal routes.

 

DNEL dermal-systemic-worker

The NOAEL of 150 mg/kg/day was selected from an OECD 422 repeat dose oral study in rats. Oral absorption rat – oral/dermal absorption human: Assume 50% absorption based on the physical-chemical properties (low water solubility, higher log Kow, low molecular weight) in accordance with Endpoint Specific Guidance Chapter 8 and 7c (R.7.12). Therefore, a dose descriptor of 300 mg/kg/day was derived as the starting point. See discussion for route to route extrapolation calculations.

DNEL dermal-systemic-worker:

150 mg/kg/day / 0.5 = 300 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.  Therefore, 300 mg/kg/day/10 = 30 mg/kg/day

Correction for intraspecies difference: 5

30 mg/kg/day/5 = 6 mg/kg/day

 

Correction for duration between sub-chronic (6 weeks) to chronic: 4

6 mg/kg/day/4 = 1.5 mg/kg/day

 

Correction for dose-response: 1 due to NOAEL

1.5 mg/kg/day/1 = 1.5 mg/kg/day

 

Correction for whole database: 1 due to quality of study

1.5 mg/kg/day/1 = 1.5 mg/kg/day

 

Total AF = 200

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

 

DNEL inhalation-systemic-worker:

The dose descriptor of 150 mg/kg/day was selected from an OECD 422 repeat dose oral study in rats.

Assume ABSoral-rat/ABSinh-human is 50/100 = 0.5 based on physical-chemical properties and Endpoint Specific Guidance chapters 8 and 7c (R.7.12)

Corrected inhalatory 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 = 150 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7m3/10m3   =132.2368 mg/m3 = inhalation dose descriptor.

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

Correction for interspecies differences: 2.5

132.2368 mg/m3/2.5 = 52.89474 mg/m3

 

Correction for intraspecies difference: 5

52.89474 mg/m3/5 = 10.57895 mg/m3

 

Correction for duration between sub-chronic to chronic: 4

10.57895 mg/m3/4 = 2.644737 mg/m3

 

Correction for dose-response: 1

2.644737 mg/m3/1 = 2.644737 mg/m3

 

Correction for whole database: 1 due to quality of study

2.644737 mg/m3/1 = 2.644737 mg/m3

 

Total AF = 50

2.65 mg/m3DNEL inhalation-systemic-worker

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No exposure to the general population is anticipated for this route of exposure.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No exposure to the general population is anticipated for this route of exposure.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population