1,3-bis[12-hydroxy-octadecamide-N-methylene]-benzene

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.41 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

Modified dose descriptor starting point:

NOAEC

Value:

220.26 mg/m³

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation required for oral to inhalation as no long-term inhalation study available.

AF for dose response relationship:

1

Justification:

When the starting point for DNEL calculation is a NOAEL the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

Default AF for subchronic (90 day study) to chronic studies.

AF for interspecies differences (allometric scaling):

1

Justification:

AF for allometric scaling not required as the differences in allometry (respiration rate and rat to human body sizes) were considered in the conversion from oral to inhalation starting point.

AF for other interspecies differences:

2.5

Justification:

Default AF for remaining interspecies differences.

AF for intraspecies differences:

5

Justification:

Default AF for worker population

AF for the quality of the whole database:

1

Justification:

Relevant studies conducted to GLP and to standard scientific methods/guidelines.

AF for remaining uncertainties:

2

Justification:

An additional AF of 2 is applied as the 90 day repeat dose toxicity study result has been read-across from a comparable supporting substance (structural analogue). Therefore an additional AF has been considered appropriate based on minor potential differences between the substances.

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:

1.25 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

Modified dose descriptor starting point:

NOAEL

Value:

250 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation required for oral to dermal as no long-term inhalation study available.

AF for dose response relationship:

1

Justification:

When the starting point for DNEL calculation is a NOAEL the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

Default AF for subchronic (90 day study) to chronic studies.

AF for interspecies differences (allometric scaling):

4

Justification:

Default AF for allometric scaling based on rats

AF for other interspecies differences:

2.5

Justification:

Default AF for remaining interspecies differences.

AF for intraspecies differences:

5

Justification:

Default AF for worker population

AF for the quality of the whole database:

1

Justification:

Relevant studies conducted to GLP and to standard scientific methods/guidelines.

AF for remaining uncertainties:

2

Justification:

An additional AF of 2 is applied as the 90 day repeat dose toxicity study result has been read-across from a comparable supporting substance (structural analogue). Therefore an additional AF has been considered appropriate based on minor potential differences between the substances.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

The substance is classified for human health as a skin sensitiser.

Inhalation:

A long-term DNEL for systemic effects have been derived, based on the results obtained from the 90-day oral repeat dose toxicity study.

Long-term systemic effects:

A modification of the dose descriptor starting point (oral to inhalation) was conducted. It is assumed as a worst case assumption that the oral absorption rate is 50% of that of the inhalation absorption.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (in the case of 8 hour exposure/day).

Default parameters for rats and humans (for 8 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

Conversion of an oral rate N(L) OAEL into a correct inhalatory N(L) OAEC to assess human inhalatory exposure:

For workers (in case of 8h exposure/day):

Corrected inhalatory N(L) OAEC = oral N(L) OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human) x (sRVhuman / wRV)

Corrected inhalatory N(L) OAEC= 250 mg/kg bw/day x (1 / 0.38 m³/kg/d) x (0.5) x (6.7 m³(8h) / 10 m³(8h))= 220.26 mg/m³

^Where:

^{ABS: Absorption}

^{sRV: standard Respiratory Volume}

^{wRV: worker Respiratory Volume (light activity)}

^{Default parametrs:}

sRVrat (8 h) : 0.38m³/kg bw

sRVhuman (8 h) : 6.7 m³/ person

wRV (8 h): 10 m³/ person

The appropriate assessment factors were then applied to give an overall assessment factor of 50

Long-term systemic DNEL (inhalation)= 4.41 mg/m³

This long-term inhalation systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the inhalation route.

This long term DNEL is also used to cover acute/short-term inhalation exposure.

Local inhalation effects are not considered to be of concern due to inhalation not being a significant route of exposure and the lack of significant local effects seen in acute inhalation study.

Dermal:

A DNEL has been derived for long-term systemic effects by the dermal route, based on the results obtained from the 90-day oral repeat dose toxicity study.

Long-term systemic DNEL (dermal) = 1.25 mg/kg bw/day

This long-term dermal systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the dermal route.

DNELs for local effects have not been derived. Although the substance is classified as a skin sensitiser, insufficient data is available from the study to allow a reasonable DNEL to be calculated. No skin irritation was observed in skin irritation or acute dermal toxicity studies. Therefore, local effects will be assessed qualitatively.

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:

DNEL (Derived No Effect Level)

Value:

0.625 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):

400

Modified dose descriptor starting point:

NOAEL

Value:

250 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not required.

AF for dose response relationship:

1

Justification:

When the starting point for DNEL calculation is a NOAEL the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

Default AF for subchronic (90 day study) to chronic studies.

AF for interspecies differences (allometric scaling):

4

Justification:

Default AF for allometric scaling based on rats

AF for other interspecies differences:

2.5

Justification:

Default AF for remaining interspecies differences.

AF for intraspecies differences:

10

Justification:

Default AF for general population.

AF for the quality of the whole database:

1

Justification:

Relevant studies conducted to GLP and to standard scientific methods/guidelines.

AF for remaining uncertainties:

2

Justification:

An additional AF of 2 is applied as the 90 day repeat dose toxicity study result has been read-across from a comparable supporting substance (structural analogue). Therefore an additional AF has been considered appropriate based on minor potential differences between the substances.

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

DNELs have not been derived for the general public (apart from via the oral route for systemic effects) as there is no anticipated exposure to the general public/consumers, as there are no consumer uses of the substance. The only uses are industrial and heavy professional use. As a worst case, minute amounts of substance may potentially end up in consumer products, through cross contamination etc. However, it is considered that the freqency of this occuring and the minute amounts involved do not present a significant level of potential exposure to the general public.

A DNEL for long-term systemic effects via the oral route has been derived, in order to assess indirect exposure of humans via the environment.