tert-butyl peracetate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.4 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

75

Dose descriptor starting point:

NOAEC

Value:

560 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

328.3 mg/m³

Explanation for the modification of the dose descriptor starting point:

For the given human exposure route there is a dose descriptor for the same route in experimental animals but there are differences in respiratory volumes between experimental animals (at rest) and humans (light activity).

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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (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:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.2 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

0.33

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.7 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:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

140 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Therefore, route-to-route extrapolation was performed. Please refer to discussion for details.

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:

4

Justification:

The exposure duration of the OECD TG 422 study performed with the test item was 54 days for females and 42 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and reproduction of the parental generation and furthermore information on developmental toxicity of the offspring. Together with the longer exposure duration (57 days) for females an Assessment factor of 4 is justified.

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

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:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012). 

 

Acute, systemic, DNEL

Tert-butyl peracetate is not classified and labelled for acute systemic dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP).

However, the test substance is classified and labelled for acute inhalation toxicity cat. 3 (H331: toxic if inhaled) according to Regulation (EC) No 1272/2008 (CLP). Hence, the DNEL for acute, short term exposure is derived from the long-term, inhalation DNEL.

 

DNEL (long-term, systemic, inhalation) x 3 = 4.4 mg/m³ x 3 = 13.2 mg/m³= DNEL (acute, short term)

 

Acute/long term DNEL for local effects

Inhalation DNEL for short term as well as long term local effects does not need to derived as no adverse local effects were observed in the subacute inhalation study.

However, the test item is classified as a skin sensitizer cat. 1 B according Regulation (EC) No 1272/2008 (CLP) and associated to the medium hazard band.

The test item is classified for eye irritation cat. 2 according to Regulation (EC) No 1272/2008 (CLP) and associated to the low hazard band.

 

Long term, systemic DNEL

Occupational exposure to TBPA occurs by dermal route and also 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 uncertainties” 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 sub-acute (four-week) inhalation toxicity study is selected for DNEL derivation as it is the relevant repeated dose study which is equivalent to the OECD guideline 412. In this study, the NOAEC in rats is 560 mg/ m³, the highest dose tested.

 

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 (NOAEC): 560 mg/ m³

Duration of exposure used in study: 7 h (5 days/week)

Duration of exposure of the worker: 8 h (5 days/week)

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

 

Corrected inhalatory NOAEC for workers:

= 560 mg/ m³x 7 h/8 h x 6.7 m³/10 m³= 328.3 mg/ m³

 

Step 3: Use of assessment factors: 75

AF for differences in duration of exposure: 6

AF for interspecies differences (allometric scaling): 1

AF for other interspecies differences: 2.5

AF for intraspecies differences: 5

 

In conclusion, long term systemic inhalation DNEL, workers = 4.4 mg/m³

 

Dermal exposure

 

Step 1: Selection of the relevant dose descriptor (starting point):

The OECD TG 422 study (2007) 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 100 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 physico-chemical properties of TBPA (log Kow: 1.6 and water solubility: calculated to be 5000 mg/L) the substance favour dermal absorption. Since the substance has been identified as a skin sensitizer, some uptake must have occurred although it may only have been a small fraction of the applied dose. However, TBPA is not a skin irritant or corrosive and no signs of acute dermal toxicity indicate that absorption has occurred.

 

Oral absorption of the rat/ dermal absorption of humans (ABS oral-rat / ABS derm-human): 100%/100 % (default)

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

= 100 mg/kg bw/day x 1.4

= 140 mg/kg bw/day

 

Step 3: Use of assessment factors: 200

AF for differences in duration of exposure: 4

The exposure duration of the OECD TG 422 study performed with the test item was 54 days for females and 42 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and reproduction of the parental generation and furthermore information on developmental toxicity of the offspring. Together with the longer exposure duration (57 days) for females an Assessment factor of 4 is justified.

AF for interspecies differences (allometric scaling): 4

AF for other interspecies differences: 2.5

AF for intraspecies differences: 5

 

In conclusion, long term systemic dermal DNEL, workers = 0.7 mg/kg bw/day

 

 References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:

Characterization of dose [concentration]-response for human health. Version 2.1, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterization, Version 3.0, May 2016

 

General Population - Hazard via inhalation 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

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

General 

General population is not intended to be exposed to tert-butyl peracetate (TBPA) via inhalation or dermal route. Therefore, no DNEL (long-term, inhalation and dermal exposure) is derived for general population. As TBPA has no bioaccumulation potential no risk assessment for secondary poisoning is required for the general population.