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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.6 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:
141.05 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).

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:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
3.2 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:
320 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.

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:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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 3,5,5-trimethylperoxyhexanoate (TBPIN) is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP), based on the test data for acute oral, dermal and inhalation toxicity.

 

However, TBPIN was shown to be a skin sensitiser in a GPMT (CIT, 1998). 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 DNEL for local effects

Skin irritation/corrosion: TBPIN is not classified for skin irritation/corrosion according to Regulation (EC) No 1272/2008 (CLP) based on the available experimental data. Therefore, no qualitative assessment is conducted.

 

Eye irritation: TBPIN is not classified for eye irritation based on the results of the eye irritation studies available. Therefore, no qualitative assessment is conducted.

 

Respiratory irritation: No signs of local irritation were observed in animals exposed to TBPIN via inhalation for 4 hours. Although no pathological examinations of the respiratory tract were conducted it is considered that no irritating effect occurred. This assumption is also based on the results of the skin and eye irritation tests where no irritating effects were observed.

 

Long term, systemic DNEL

Occupational exposure to TBPIN 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 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 160 mg/kg bw/day, 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 (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/d × 0.5 × (1 / 0.38 m³/kg bw/d) × (6.7 m³/10 m³)

= 141.05 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

 

In conclusion, long term systemic inhalation DNEL, workers = 5.6 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 160 mg/kg bw/day, the highest dose tested.

 

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 TBPIN (log Kow: 5.16 and water solubility: 14 mg/L) a dermal absorption of 50% of oral absorption is assumed as a worst case.

In conclusion, dermal NOAEL = 2 x oral NOAEL = 320 mg/kg bw/d.

 

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

 

In conclusion, long term systemic dermal DNEL, workers = 3.2 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 3,5,5 trimethylperoxyhexanoate (TBPIN) via inhalation or dermal route. Therefore, no DNEL (long-term, inhalation and dermal exposure) is derived for general population. As TBPIN 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.