tert-pentyl 2-ethylperoxyhexanoate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15.87 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

Modified dose descriptor starting point:

NOAEC

Value:

396.71 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. For details on calculations please refer to discussion.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

default AF

AF for intraspecies differences:

5

Justification:

default AF

AF for the quality of the whole database:

1

Justification:

not needed

AF for remaining uncertainties:

1

Justification:

default AF

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

The substance is not classified for acute toxicity and therefore no short term systemic DNEL is derived. Acute toxcity is low and due to the physico-chemical properties of the substance (especially the low volatility), inhalation exposure was considered less likely than dermal exposure. Moreover, the LD0 in rats by oral route and by dermal route were more than 2000 mg/kg bw and therefore acute toxicity is of a low concern.

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:

9 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

Modified dose descriptor starting point:

NOAEL

Value:

900 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Taken into account the physico-chemical properties of the substance, dermal absoption is anticipated to be 50 % of oral absorption. For details refer to discussion.

AF for dose response relationship:

1

Justification:

Not needed

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

Default AF

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

5

Justification:

Default AF

AF for the quality of the whole database:

1

Justification:

Not needed

AF for remaining uncertainties:

1

Justification:

default AF

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

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

DNELs have been calculated based on the NOAEL from the OECD 408 repeat dose 90 -day study conducted on the read-across substance CAS# 3006 -82 -4. The DNELs calcuated using this study were the most conservative of studies available when considering the repeat dose study on the read-across substance CAS# 3006-82-4 and OECD 421 available on CAS# 686-31-7.

Long term, systemic DNEL Occupational exposure to TBPEH occurs mainly by dermal route, and may also occur by inhalation exposure. Therefore two long-term DNELs are calculated for workers. In view of the data used for evaluation, the "quality of whole database factor", “remaining interspecies differences” and "dose-response factor" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

Exposure by inhalation

Step 1: Selection of the relevant dose descriptor (starting point): The OECD TG 408 study (2013) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL in rats is 450 mg/kg bw/day.

Step 2: Modification into a correct starting point: Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived. This worker DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

Relevant dose descriptor (NOAEL): 450 mg/kg bw/day Body weight of worker: 70 kg AF for allometric scaling: 4 Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 0.5 Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Corrected inhalatory NOAEC for workers = 450 mg/kg bw/d × 0.5 × (1 / 0.38 m³/kg bw/d) × (6.7 m³/10 m³) = 396.71 mg/m³

Step 3: Use of assessment factors: 25 Interspecies: Respiratory interspecies differences are fully covered by the modification of the NOAEC Interspecies AF, remaining differences: 2.5 Intraspecies AF (worker): 5 Exposure duration AF: 2 Remaining uncertainties: 1

In conclusion, long term systemic inhalation DNEL, workers = 15.87 mg/m3

Dermal exposure

Step 1: Selection of the relevant dose descriptor (starting point): The OECD TG 408 study (2013) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL in rats is 450 mg/kg bw/day.

Step 2: Modification of the starting point: Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. Based on the physicochemical properties of TBPEH (log Kow: 4.79 and water solubility: 46.3 mg/L) a dermal absorption of 50% of oral absorption is assumed as a worst case. In conclusion, dermal NOAEL = 2 x oral NOAEL = 900 mg/kg bw/day.

Step 3: Use of assessment factors: 100 Interspecies AF, allometric scaling (rat to human): 4 Interspecies AF, remaining differences: 2.5 Endpoint summary: Toxicological information file:///C|/Temp/index.html[6/3/2016 1:23:02 PM] Intraspecies AF (worker): 5 Exposure duration AF: 2 Remaining uncertainties: 1

In conclusion, long term systemic dermal DNEL, workers = 9 mg/kg bw/day

References (not included as endpoint study record)

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. May 2008

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

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