Reaction mixture of hydrogenated tallow alkyl amines with sebacic acid and lithium hydroxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.93 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:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

396.71 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 OECD 422 repeated dose oral toxicity study.

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:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 42 days (males) and 51-71 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

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:

4.5 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:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

900 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 inhalation DNEL is done on the basis of the OECD 422 repeated dose oral toxicity study.

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:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 42 days (males) and 51-71 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

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:

no hazard identified

Additional information - workers

WORKER

 

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 repeated dose oral toxicity study.

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

The OECD 422 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 450 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 than oral absorption.

Relevant dose descriptor (NOAEL): 450 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

= 450 mg/kg bw/day× 0.5 × (1 / 0.38 m³/kg bw/day) × (6.7 m³/10 m³)

= 396.71 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: 4

Remaining uncertainties AF: 1

In conclusion, long-term systemic inhalation DNEL, workers = 7.93 mg/m3

 

Short term systemic inhalation DNEL, worker

No data for the classification and labelling of the test substance for acute systemic toxicity (inhalation) is available. The substance is not classified for acute oral toxicity and in vivo skin sensitization and skin irritation studies showed no systemic effects, 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.

 

Acute/longterm, local effects, inhalation worker

No data on long-term local toxicity after inhalation is available. Data on acute local toxicity after oral application is available and showed no specific local effects. Studies on skin and eye irritation showed no adverse effects and 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. In addition DNEL for local effects does also not need to be derived as no eye irritation (leading to classification) and in conclusion no indication of local mucosal membrane damages has been identified (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8).

 

 

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 repeated dose oral toxicity study.

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

TheOECD 422 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 450 mg/kg bw/day.

Step 2: Modification of the starting point:

The logPow of the test substance was determined to have a broad range from -3.1 to 18, due to the different constituents. Therefore the dermal uptake is considered to be 50 % of the oral uptake as a worst case assumption.

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

oral NOAEL 450 mg/kg bw/day * 2 = 900 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

Remaining uncertainties AF: 1

In conclusion, long term systemic dermal DNEL, workers = 4.5 mg/kg bw/day

 

Short-term systemic dermal DNEL, worker

No data for the classification and labelling of the test substance for acute dermal toxicity is available. The substance is not classified for acute oral toxicity and in vivo skin sensitization and skin irritation studies showed no systemic effects. Therefore no adverse result for dermal toxicity is expected for the test substance (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.

 

Local effects, long and short term dermal exposure, worker

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

 

 

Worker – Hazard for the eyes

The test item is not classified for eye irritation or severe eye damage according to Regulation (EC) No 1272/2008 (CLP). Thus, no qualitative risk assessment is required. 

 

 

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:

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 Population

 

Since no exposure of the general population is intended or anticipated as the substance is not present in consumer–available products and is not released to the environment and therefore is not present as an environmental contaminant, no DNELs for general population have been derived (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).