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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.8 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:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
141.1 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:
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:
2
Justification:
Adequate AF for uncertainties from read-across approach.
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:
8 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:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. 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):
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:
2
Justification:
Adequate AF for uncertainties from read-across approach.
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:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (2010).

 

Acute, systemic DNEL

Tert-butyl peroxyneodecanoate (TBPND) is not classified and labelled for acute systemic toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP), based on the test data for acute oral, dermal and inhalation toxicity.

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 irritation: 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 irritation/corrosion: TBPND has skin irritation potential and is classified as skin irritant, cat. 2 according to Regulation (EC) No 1272/2008 (CLP) and associated to the low Hazard Band. A qualitative risk assessment is conducted for acute/long-term local toxicity (dermal) in order to ensure an appropriate level of protection regarding skin irritation.

 

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

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

The NOAEL of 160 mg/kg bw/day, assessed in the key 90-day repeated dose oral toxicity study with a structural analogue (TBPIN) of TBPND (2013) 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): 160 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

 

Corrected inhalatory NOAEC for workers

= 160 mg/kg bw/day× 0.5 × (1 / 0.38 m³/kg bw/day) × (6.7 m³/10 m³)

= 141.1 mg/m³

 

Step 3: Use of assessment factors: 50

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 (read-across): 2

 

In conclusion, long-term systemic inhalation DNEL, workers = 2.8 mg/m3

 

Note: If the 28d repeated dose inhalation toxicity study with TBPND (Toxi-coop, 2012) would be used for hazard assessment a comparable DNEL would be achieved considering the reliability of the read across approach.

 

Dermal exposure

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

The 90-day repeated dose toxicity study with a structural analogue (TBPIN) of TBPND (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 is 160 mg/kg bw/day the highest dose tested.

 

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%.

In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat /ABS dermal human] =
160 x (100/10) = 1600 mg/kg bw/d.

 

Step 3: Use of assessment factors: 200

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 (read-across): 2

 

In conclusion, long term systemic dermal DNEL, workers = 8.0 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 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 (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 (2011) Guidance on information requirements and chemical safety assessment. Part B: Hazard assessment. Version 2