Propionamide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.96 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:

120 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

148.11 mg/m³

Explanation for the modification of the dose descriptor starting point:

No data on systemic toxicity after inhalation is available. Derivation of the long term inhalation DNEL is done on the basis of the corresponding NOAEL from the combined oral repeated dose toxicity study with the reproduction/developmental toxicity screening test.

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:

The exposure duration of the OECD TG 422 study performed with the test item was 56 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and reproduction of the parental generation and furthermore information on developmental toxicity of the offspring. Together with the longer exposure duration (57 days) for females an Assessment factor of 4 is justified.

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

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:

1.68 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:

120 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

336 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No data on systemic toxicity after dermal exposure is available. Derivation of the long term dermal DNEL is done on the basis of the corresponding NOAEL from the combined oral repeated dose toxicity study with the reproduction/developmental toxicity screening test with oral application.

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:

The exposure duration of the OECD TG 422 study performed with the test item was 56 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and reproduction of the parental generation and furthermore information on developmental toxicity of the offspring. Together with the longer exposure duration (57 days) for females an Assessment factor of 4 is justified.

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

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Workers – Hazard via inhalation route

 

Long term systemic inhalation DNEL, worker

The DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with oral application.

 

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

The combined repeated dose oral toxicity study 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 120 mg/kg bw/day.

 

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 (100 %) than oral (50 %) absorption.

 

Relevant dose descriptor (NOAEL): 120 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 50 % / ABSinh-human 100 %): 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

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

 

Corrected inhalatory NOAEC for workers

= 120 mg/kg bw/day * 0.5 * (1 / 0.38 m³/kg bw/day) * (6.7 m³/10 m³) * (7/5)

= 148.11 mg/m³

 

Step 3: Use of assessment factors: 50

Interspecies: Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation. 

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 4

The exposure duration of the OECD TG 422 study performed with the test item was 56 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and reproduction of the parental generation and furthermore information on developmental toxicity of the offspring. Together with the longer exposure duration (57 days) for females an Assessment factor of 4 is justified.

Remaining uncertainties AF: 1

 

In conclusion, long term systemic inhalation DNEL, workers = 2.96 mg/m3

 

Short term systemic inhalation DNEL, worker

No experimental data on acute systemic toxicity (inhalation) of the test substance is available. The substance is not classified for acute oral toxicity and acute dermal toxicity, therefore no adverse result for inhalation toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.

 

Short and long term local inhalation DNEL, worker

No data on long-term local toxicity after inhalation is available. Data on acute local toxicity after oral application and dermal exposure is available and showed no specific local effects. Therefore, no adverse effects on the respiratory system are expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL local, long-term and acute (inhalation) is required.

 

Workers – Hazard via dermal route

Long term systemic dermal DNEL, worker

The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with oral application.

 

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

The combined repeated dose toxicity study 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 120 mg/kg bw/day.

 

Step 2: Modification of the starting point:

The logPow of the test substance was determined to be -0.7 and the water solubility was determined to be 720 g/L. Therefore, the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum and dermal uptake for the substances will be low. Thus, the dermal uptake is considered to be 50 % of the oral uptake in the worst case

 

Factor for dermal NOAEL= 100 % oral / 50 % dermal= 2

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

 

oral NOAEL 120 mg/kg bw/day * 2 * (7/5) = 336 mg/kg bw/day dermal NOAEL

 

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: 4

The exposure duration of the OECD TG 422 study performed with the test item was 56 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and reproduction of the parental generation and furthermore information on developmental toxicity of the offspring. Together with the longer exposure duration (57 days) for females an Assessment factor of 4 is justified.

Remaining uncertainties AF: 1

 

In conclusion, long term systemic dermal DNEL, workers = 1.68 mg/kg bw/day

 

Short term systemic dermal DNEL, worker

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

 

Short term and long term local dermal DNEL, worker

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Worker – Hazard for the eyes

For exposure to the eyes a low hazard was identified, as the test substance is classified for causing eye irritation Cat.2 according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E). Therefore goggles and further appropriate RMMs are carried into execution.

 

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 (2017). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. June 2017.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, 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:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected