Reaction products of furan-2,5-dione and octadec-1-ene

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21.16 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:

528.95 mg/m³

Explanation for the modification of the dose descriptor starting point:

Theoretical inhalation DNEL only. Route-to-route extrapolation is not technically valid due to rapid hydrolysis of the anhydride moiety in aqueous body fluids, and a low vapour pressure suggesting that inhalation is not a realistic route of exposure.

AF for dose response relationship:

1

Justification:

Dose-response is exhibited in repeated dose toxicity testing

AF for differences in duration of exposure:

2

Justification:

subchronic (90-day) to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

accounted for in modification of starting dose descriptor

AF for other interspecies differences:

2.5

Justification:

pharmacodynamic (remainder)

AF for intraspecies differences:

5

Justification:

individual variability among workers

AF for the quality of the whole database:

1

Justification:

adequate data on analogues

AF for remaining uncertainties:

1

Justification:

Uncertainty accounted for by other assessment factors

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:

3 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:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Dermal DNEL is considered equivalent to an oral DNEL, assuming skin absorption is 100% of oral absorption

AF for dose response relationship:

1

Justification:

A dose response is demonstrated in repeated dose toxicity testing

AF for differences in duration of exposure:

2

Justification:

subchronic (90-day) to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to human

AF for other interspecies differences:

2.5

Justification:

pharmacodynamic (remainder)

AF for intraspecies differences:

5

Justification:

individual variability among workers

AF for the quality of the whole database:

1

Justification:

adequate for analogues

AF for remaining uncertainties:

1

Justification:

Uncertainty is accommodated by other AF

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)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Information on repeated dose toxicity testing is from the substance 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivatives, CAS 68784-12-3, a mixture of a hexadecenyl- and octadecenyl succinic anhydride, as part of an analogue approach. The data is informative for evaluation of the toxicity of n-ODSA EC 701-338-8, and is adequate for filling the data requirement for the registration of this substance. It is valid for hazard classification and risk assessment.

The DNELs were calculated with a starting 90-day repeated oral dose NOAEL in rats of 300 mg/kg bw/d (Harlan, 2014). Assessment factors were applied as per ECHA, 2015.

Regarding local inhalation effects, respiratory irritation or sensitisation is a theoretical risk, but there is no known evidence from human workplaces for local respiratory effects. Low vapour pressure of C15-20 ASAs makes a respiratory toxicity a negligible risk.

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:

1.5 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

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no route-to-route extrapolation done

AF for dose response relationship:

1

Justification:

displays dose-response in repeated dose studies

AF for differences in duration of exposure:

2

Justification:

subchronic (90-day) to chronice

AF for interspecies differences (allometric scaling):

4

Justification:

rat to human

AF for other interspecies differences:

2.5

Justification:

pharmacodynamic

AF for intraspecies differences:

10

Justification:

individual variability

AF for the quality of the whole database:

1

Justification:

adequate data for category

AF for remaining uncertainties:

1

Justification:

Uncertainty accommodated by other AF

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

An oral DNEL for consumers is calculated for exposure of man via the environment. Information on repeated dose toxicity testing is from the substance 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivatives, CAS 68784-12-3, a mixture of a hexadecenyl- and octadecenyl succinic anhydride, as part of an analogue approach. The data is informative for evaluation of the toxicity of n-ODSA EC 701-338-8, and is adequate for filling the data requirement for the registration of this substance. It is valid for hazard classification and risk assessment.

The DNEL was calculated with a starting 90-day repeated oral dose NOAEL in rats of 300 mg/kg bw/d (Harlan, 2014). Assessment factors were applied as per ECHA, 2015.

There are no known consumer exposures. Exposure of the general population via the environment includes large dilution factors for the inhalation and dermal routes of exposure. There is a low probability of exposure and hazard.