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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.46 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
Modified dose descriptor starting point:
NOAEC
Value:
334.7 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:
13.4 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):
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:
1 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
Modified dose descriptor starting point:
NOAEL
Value:
200 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 and toxic properties of the substance, dermal absorption is anticipated to be 50 % of oral absorption.

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:
As the NOAEL of a repeated dose toxicity study (OECD422) with an exposure time of 45 days (males and females) was used as point of depature an AF of 4 is considered as adequate for the exposure duration extrapolation.
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:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high 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.

 

Acute, systemic, DNEL

Tert-butyl peracetate is not classified and labelled for acute systemic dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).

However, the test substance is classified and labelled for acute inhalation toxicity cat. 3 (H331: toxic if inhaled) and R20 (harmful by inhalation) according to Regulation (EC) No 1272/2008 (CLP) and to Directive 67/548/EEC (DSD), respectively. Hence, the DNEL for acute, short term exposure is derived from the chronic, inhalativ DNEL.

 

DNEL (chronic, inhalativ) x 3 = 4.46 mg/m3 x 3 = 13.4 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 according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP) and associated to the high hazard band.

The test item is classified for eye irritation cat. 2 according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD) 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 euqivalent to the OECD guideline 412. In this study, the NOAEC in rats is 571 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): 571 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 (sRVhumane) for 8 hours: 6.7 m3

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

 

Corrected inhalatory NOAEC for workers:

= 571 mg/ m3x 7 h/8 h x 6.7 m3/10 m3= 334.7 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 = 4.46 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 occured. Thus, a dermal absorption of 50% of oral absorption is assumed as worst case.

In conclusion, the dermal NOAEL = 2 x oral NOAEL = 200 mg/kg bw/day

 

Step 3: Use of assessment factors: 200

AF for differences in duration of exposure: 4

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 = 1.0 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:
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.

References

(not included as endpoint study record)

 

- ECHA (2014) Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1 ECHA-2010 -G-19 –EN.