Ditetradecyl peroxydicarbonate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

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:

no hazard identified

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:

100 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:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

10 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Due to the physico-chemical properties (logPow >6.5; water solubility < 1 mg/L) dermal absorption (end route) is assumed to be 10 % of oral absorption (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:

A standard assessment factor of 2 was used from subchronic to chronic exposure.

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:

sensitisation (skin)

DNEL related information

Explanation for the modification of the dose descriptor starting point:

The test material is not classified and labelled for acute dermal systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL acute dermal is required.

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 ditetradecyl peroxydicarbonate is performed under consideration of the recommendations of ECHA (2010).

 

Acute/short-term systemic DNEL

Ditetradecyl peroxydicarbonate 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.

 

Skin sensitisation potential was observed in the available LLNA with ditetradecyl peroxydicarbonate. 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 local dermal toxicity in order to ensure an appropriate level of protection regarding sensitisation.

 

Acute/longterm, local effects

Respiratory irritation: No study for respiratory effects of the test material is available. However, since the test material showed no eye irritation potential and the volatility is low exposure via inhalation route is not likely to occur. Therefore, no adverse effects on respiratory system are expected and no local DNEL (long-term-inhalation) was derived.

 

Skin: 

Skin sensitisation potential was observed in the available LLNA with ditetradecyl peroxydicarbonate. 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 local dermal toxicity in order to ensure an appropriate level of protection regarding sensitisation.

 

Eye irritation: Ditetradecyl peroxydicarbonate is not classified for eye irritation based on the results of the acute eye irritation study available. Therefore, no qualitative risk assessment is required.

 

Long term, systemic effects

Occupational exposure to ditetradecyl peroxydicarbonate 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 1000 mg/kg bw/d, assessed in the key repeated dose oral toxicity study (OECD 408, 2020) 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. 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): 1000 mg/kg bw/d

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

= 1000 mg/kg bw/d × 0.5 × (1 / 0.38 m³/kg bw/d) × (6.7 m³/10 m³)

= 881.6 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 (OECD 408): 2

 

Long-term inhalation DNEL, worker = 35.2 mg/m³

 

Since the test material is solid at room temperature and the long-term inhalation DNEL derived from the oral repeated dose toxicity study (OECD 408, 2020) was 35.2 mg/m³ the general dust limit of 10 mg/m³ for the respirable airborne fraction was used for setting an occupational exposure limit.

 

In conclusion, long term systemic inhalation DNEL, workers = 10 mg/m³

Dermal exposure

 

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

The NOAEL of 1000 mg/kg bw/d, assessed in the key repeated dose oral toxicity study (OECD 408, 2020) is identified as the relevant dose descriptor and starting point.

 

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 ditetradecyl peroxydicarbonate (log Kow: > 6.5 and water solubility: 1 mg/L) a dermal absorption of 10 % is assumed as a worst case scenario.

In conclusion, dermal NOAEL = oral NOAEL × 10 = 10000 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 (OECD 408): 2

 

In conclusion, long term systemic dermal DNEL, workers = 100 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 ditetradecyl peroxydicarbonate via inhalation or dermal route. Therefore, no DNEL (long-term, inhalation and dermal exposure) is derived for general population.

Ditetradecyl peroxydicarbonate has a low bioaccumulation potential and a low degradability. However, the substance is not associated with any of the following R-phrases R48, R60, R61, R62, R63, R64, thus there is no identified potential to cause toxic effects if accumulated in the higher food chain. Therefore, no DNEL (long-term, oral exposure) is derived 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.