O,O-tert-butyl isopropyl monoperoxycarbonate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15.868 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:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

793.421 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation study data are available. The NOAEL of 450 mg/kg bw/day from an OECD 422 repeat dose oral gavage study in rats was used (males 42 days and females 56 days) as the starting point to calculate the DNEL. Assuming an oral/inhalation rate of absorption of 1.0, a dose descriptor of 15.868 mg/m3 was derived as the starting point. See discussion under "Additional information - Workers" for route to route extrapolation calculations.

AF for dose response relationship:

1

Justification:

In accordance with REACH guidance 8.4.3.1

AF for differences in duration of exposure:

4

Justification:

Sub-chronic to chronic; in accordance with Endpoint Specific Guidance Chapter 8

AF for interspecies differences (allometric scaling):

1

Justification:

REACH guidance 8.4.3.1. AF included in route-to-route conversion

AF for other interspecies differences:

2.5

Justification:

REACH guidance 8.4.3.1

AF for intraspecies differences:

5

Justification:

REACH guidance 8.4.3.1

AF for the quality of the whole database:

1

Justification:

Quality of study -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:

4.5 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:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

900 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 450 mg/kg/day from an OECD 422 repeat dose oral gavage study in rats was used (dosing: males 42 days and females 56 days) as the starting point to calculate the DNEL. Assumed 50% dermal absorption based on the physical-chemical properties (low molecular weight, Pow, and vapor pressure, and the water solubility of of 2.2 g/L) and in accordance with Endpoint Specific Guidance Chapters 8 and 7c (R.7.12). Therefore, a dose descriptor of 900 mg/kg bw/day was derived as the starting point. See discussion under "Additional information - Workers" for route to route extrapolation calculations.

AF for dose response relationship:

1

Justification:

Based on reach guidance

AF for differences in duration of exposure:

4

Justification:

Based on Reach guidance; sub-chronic to chronic exposure study

AF for interspecies differences (allometric scaling):

10

Justification:

applying for allometric scaling 4 for rat x 2.5 for 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

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

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:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

O,O-tert-butyl isopropylmonoperoxycarbonate with a molecular weight of 176.21, has a low vapor pressure of 60 Pa at 22 degrees C, water solubility of 2.2 g/L at 20 degrees C, and log Kow of 2.5 at 30 degress C. It is a skin sensitizer (Cat 1b), and skin irritant (Cat 2).

 

DNEL dermal-systemic-worker;

The NOAEL of 450 mg/kg bw/day was selected from the OECD 422 repeat dose oral study in rats used for DNEL calculations on systemic effects of the substance. In that study, the substance was administered to rats at 50, 150, and 450 mg/kg bw/d by oral gavage.

Oral absorption rat – oral/dermal absorption human: Assume 50% dermal absorption based on the physical-chemical properties and in accordance with Endpoint Specific Guidance Chapter 8 and 7c (R.7.12). The substance being classified for skin irritation Cat. 2. The substance is a skin sensitizer, which is considered a systemic effect. Therefore, a qualitative risk assessment was done for acute dermal effects. However, DNELs were calculated for non-sensitizing systemic long term effects. For the DNEL covering local effects of inhalation and dermal routes of exposure, route-specific data need to be available (Guidance on information requirements and chemical safety assessment R 8.1.2.6). No such information is available.

Due to the low volatility and high water solubility, the respiratory absorption and oral absorption were considered equal. Guidance on requirements and chemical safety assessment Ch. R7c (page 159) states that "Vapors of very hydrophilic substances may be retained within the mucus. For absorption of deposited material similar criteria as for GI absorption apply."

There are no consumer uses of this substance. Human exposure, via the environment, is unlikely due to the instability of the peroxide.

DNEL inhalation-systemic-worker         

Corrected inhalatoary NOAEC from oral NOAEL

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

Assume ABSoral-rat/ABSinh-human is 100/100 = 1.0, based on phys-chem properties and Endpoint Specific Guidance chapters 8 and 7c (R.7.12)

 

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

Corrected NOAEC= 450 mg/kg/day x (1/0.38 m3/kg/day) x (1.0) x 6.7m3/10m3 = 793.421 mg/m3

 

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

Correction for interspecies differences: 2.5       

793.421 mg/m3/2.5 = 317.368 mg/m3     

Correction for intraspecies differences: 5         

317.368 mg/m3/5 = 63.474 mg/m3                       

Correction for duration between subacute (6-8 weeks) to chronic: 4

63.474 mg/m3/4 = 15.868 mg/m3             

Correction for dose-response: 1                       

15.868 mg/m3/1 = 15.868 mg/m3             

Correction for whole database: 1 due to quality of study

15.868 mg/m3/1 = 15.868 mg/m3             

Total AF = 50                                  

15.868 mg/m3, DNEL inhalation-systemic-worker

 

 

DNEL dermal-systemic-worker 

Assume 50% dermal absorption based on the physical-chemical properties.

450 mg/kg/day/0.5 = 900 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

900 mg/kg/day/10 = 90 mg/kg/day       

Correction for intraspecies difference: 5           

90 mg/kg/day/5 = 18 mg/kg/day          

Correction for duration between sub-chronic (6-8 weeks) to chronic: 4

18 mg/kg/day/4 = 4.5 mg/kg/day         

Correction for dose-response: 1 due to NOAEL

4.5mg/kg/day/1 = 4.5              

Correction for whole database: 1 due to quality of study

4.5 mg/kg/day/1 = 4.5 mg/kg/day        

Total AF = 200                         

4.5mg/kg/day, DNEL dermal-worker-systemic

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