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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
61.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

No studies have been undertaken by the inhalatory route to characterize the dose-response relationship for systemic effects. Therefore, it will be necessary to obtain a long-term inhalatory DNEL by route-to route extrapolation. 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:
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:
No remaining uncertainties.
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:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
100
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No repeated dose dermal toxicity study with the substance is available. Therefore, it will be necessary to obtain a long-term dermal DNEL by route-to-route extrapolation.

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):
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:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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:
no hazard identified

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


Based on the test data for acute oral, dermal and inhalation toxicity, Tert-butyl peroxyneodecanoate (TBPND) is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP). However, TBPND was shown to be a skin sensitiser in a GPMT. The substance is therefore classified as skin sensitiser, cat. 1 according to Regulation (EC) No 1272/2008 (CLP) and associated to the high Hazard Band. A qualitative risk assessment is conducted for acute dermal toxicity in order to ensure an appropriate level of protection regarding sensitisation.


 


Acute/ long term, local effects


Respiratory: Local effects on respiratory system were observed in an acute inhalation study, which is in line with the irritation properties of TBPND. Therefore, the test substance is associated to the low Hazard Band and a qualitative risk assessment is conducted.


 


Skin: The test item is classified and labelled for skin sensitisation, cat.1, according to Regulation 1272/2008 (CLP) and associated to the high Hazard Band. A qualitative risk assessment is conducted.


 


Eye irritation: TBPND is not irritating in conducted eye irritation tests and it is not classified for eye irritation. Therefore, no qualitative assessment is conducted.


 


Long term, systemic DNEL


Occupational exposure to TBPND 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" 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


No studies have been undertaken by the inhalatory route to characterize the dose-response relationship for systemic effects. Therefore, it will be necessary to obtain a long-term inhalatory DNEL by route-to route extrapolation.


 


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


The systemic NOAEL of 50 mg/kg bw/day, assessed in the OECD 443 study in male rats, is identified as the relevant dose descriptor and starting point.


 


Step 2: Modification into a correct starting point:


Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.


 


Relevant dose descriptor (NOAEL): 50 mg/kg bw/day


Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d


Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 0.5


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


Correction for difference between human and experimental exposure conditions: 1.4 (7 d rat/5 d worker)


 


Corrected inhalatory NOAEC for workers


= 50 mg/kg bw/day× 0.5 × (1 / 0.38 m³/kg bw/day) × (6.7 m³/10 m³) × 1.4


= 61.7 mg/m³


 


Step 3: Use of assessment factors: 25


Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.


Interspecies AF, remaining differences: 2.5


Intraspecies AF (worker): 5


Exposure duration AF: 2


Remaining uncertainties AF: 1


 


In conclusion, long-term systemic inhalation DNEL, workers = 2.5 mg/m3


  


Dermal exposure


 


No repeated dose dermal toxicity study with the substance is available. Therefore, it will be necessary to obtain a long-term dermal DNEL by route-to-route extrapolation.


 


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


The systemic NOAEL of 50 mg/kg bw/day, assessed in the OECD 443 study in male rats, is identified as the relevant dose descriptor and starting point.


 


Step 2: Modification of the starting point:


Correction for dermal absorption rates of TBPND (based on Guidance on information requirements and chemical safety assessment, Chapter R 7.12): Dermal absorption is supposed low for several reasons: 1. Low water solubility (0.9 mg/L). 2. High log Kow of 5.0.


Taken together with the molecular weight of 244.38 g/mol dermal uptake is anticipated to be low. In addition, the results of the acute dermal toxicity support a low absorption via dermal route. Therefore, dermal absorption can be reasonably estimated to be lower than 10% as compared to the oral absorption.


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


In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat /ABS dermal human] =
50 x (100/10) x 1.4 = 700 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


Intraspecies AF (worker): 5


Exposure duration AF: 2


Remaining uncertainties AF: 1


 


In conclusion, long term systemic dermal DNEL, workers = 7.0 mg/kg bw/day


 


References


(not included as endpoint study record)


 


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


Characterisation 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 Characterisation, 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 peroxyneodecanoate (TBPND) via inhalation or dermal route. Therefore, no DNEL (long-term, inhalation and dermal exposure) is derived for general population. As TBPND has no bioaccumulation potential no risk assessment for secondary poisoning is required for the general population.


References


(not included as endpoint study record)


ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012