Undecanal

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23.5 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):

75

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

1 763 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg bw and day (rat, oral, subacute) may be used to calculate, according to the guidance document R8, a corrected inhalation NOAEC of 1763 mg/m³ for workers.

AF for dose response relationship:

1

Justification:

Starting point NOAEL

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable for inhalative DNEL

AF for other interspecies differences:

2.5

Justification:

default value for remaining differences

AF for intraspecies differences:

5

Justification:

worker

AF for the quality of the whole database:

1

Justification:

database sufficient for assessment

AF for remaining uncertainties:

1

Justification:

no assessment factor for route-to-route extrapolation was applied as 100% bioavailability is assumed for both routes

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:

DNEL (Derived No Effect Level)

Value:

10 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

other: generic cut-off limit for skin irritating substances

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

other: generic cut-off limit for skin irritating substances

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.3 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):

300

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

In accordance with guidance R.8 no default factor is used for oral-to-dermal extrapolation as in general dermal absorption will not be higher than oral absorption.

AF for dose response relationship:

1

Justification:

Starting point NOAEL

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat

AF for other interspecies differences:

2.5

Justification:

default value for remaining differences.

AF for intraspecies differences:

5

Justification:

worker

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Justification:

no assessment factor for route-to-route extrapolation was applied as dermal bioavailability usually is not higher than oral bioavailability

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low 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

Toxicology profile

N-undecanal (CAS 112-44-7) is a long chain, saturated straight chain aliphatic aldehyde. Water solubility and vapour pressure are both low. The substance may be rapidly absorbed following oral intake or inhalation exposure. The inhalation exposure is not considered to represent a relevant exposure pathway, based on the low vapour pressure, and based on the results of recent indoor air monitoring measurements (n ~ 3000) conducted in Germany during 2002-2006. The mean undecanal concentration was 3 µg/m³, calculated for those samples where the substance was found. Following absorption, undecanal is expected to be predominantly oxidised to undecanoic acid, a linear, saturated fatty acid which is expected to be degraded and utilized via fatty acid oxidation and intermediary metabolism. However, undecanoic acid and derivatives may also appear in the urine.

The acute toxicity was found to be low in rats (oral LD₅₀>5000 mg/kg bw) and rabbits (dermal LD₅₀>5000 mg/kg bw). Undecanal was irritating to the rabbit’s skin (at a level that requires classification), whereas eye irritation was mild and did not gain a level that requires classification. The substance showed no skin sensitising properties in humans who underwent a maximisation test.

 

Undecanal (100, 300, 1000 mg/kg bw and day) was tested in a combined OECD TG 422 study for repeated dose/reproduction toxicity in male and female rats (10 rats/sex and dose). There was no systemic toxicity up to and including the top dose, whereas local irritation was seen in the stomachs of animals from all dose levels. Likewise, there were no adverse effects on fertility and development noted. Therefore, the NOAEL was 1000 mg/kg bw and day for systemic toxicity, toxicity to reproduction and development under the conditions of this study.

 

Regarding genetic toxicity, undecanal was not mutagenic in bacterial (Salmonella typhimurium) or mammalian cells (HGPRT assay) in vitro. Undecanal was not clastogenic in-vitro (human leucocytes). All assays were conducted with and without metabolic activation.

  

Overall, undecanal is of low acute and subacute toxicity and no target tissue was identified.

DNELs may be derived from the NOAEL (rat, oral, subacute) of 1000 mg/kg bw and day. Undecanal is irritating to skin (Skin Irrit. 2).      

DNEL derivation  

Long term exposure, systemic effects: Inhalation: The NOAEL of 1000 mg/kg bw and day (rat, oral, subacute) may be used to calculate a corrected inhalation NOAEC of 1763 mg/m³ for workers ccording to guidance document R8. Assessment factors for intraspecies differences (5; workers), remaining interspecies differences (2.5) and for the duration of treatment (subacute > chronic; 6) may be used and result in a DNEL of 23.5 mg/m³.

Dermal: The NOAEL of 1000 mg/kg bw and day (rat, oral, subacute) may be used to calculate a DNEL of 3.3 mg/kg bw and day, using an overall assessment factor of 300 (allometric factor = 4; remaining interspecies differences = 2.5; intraspecies differences = 5; duration of experiment (subacute > chronic =6)).

No assessment factor for route-to-route extrapolation was applied as 100% bioavailability is assumed for inhalation and oral exposure; additionally, dermal bioavailability is usually not higher than oral bioavailability

There are no inhalation studies available for undecanal and no information exists if the substance causes local effects in the respiratory tract after inahalation exposure. As undecanal is not hydrolytically unstable and does not form strong acids or bases nor is a strong acid that vigorously reacts with water (exclusion criteria) the generic cut-off limit of 10 mg/m³for skin irritating subsances as suggested by Messinger (Regulatory Toxicology and Pharmacology 2014, 68: 317 -324) is applicable and suggested as DNEL for local effects after long-term inhalation exposure.   In accordance with the procedure described by the German MAK Commission (Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area), applying an exceedance factor 1 for substances with local effects and in a conservative manner in the absence of data the same DNEL is derived for local effects after long-term and acute exposure.  

The following DNELS were not derived:

- DNELs for systemic effects following short-term dermal exposure, as the substance is not classified for acute toxicity

- DNELs for acute systemic effects following inhalative exposure since the substance is not classified for acute toxicity.

- DNEL for local dermal effects could not be derived from the available data, therefore a qualitative assessment as described in guidance on information requirements – part E has been conducted (leading to an allocation to the “low hazard band” for skin irritation)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.8 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):

150

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

other: NOAEL

Value:

870 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg bw and day (rat, oral, subacute) may be used to calculate a corrected inhalation NOAEC of 870 mg/m³ for the general population according to the guidance document R.8.

.

AF for dose response relationship:

1

Justification:

Starting point NOAEL

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable for inhalative DNEL

AF for other interspecies differences:

2.5

Justification:

default value for remaining differences

AF for intraspecies differences:

10

Justification:

default value for consumer

AF for the quality of the whole database:

1

Justification:

database sufficient for assessment

AF for remaining uncertainties:

1

Justification:

no assessment factor for route-to-route extrapolation was applied as 100% bioavailability is assumed for both routes

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:

DNEL (Derived No Effect Level)

Value:

5 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

other: generic cut-off limit for skin irritating substances

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

other: generic cut-off limit for skin irritating substances

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.7 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):

600

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

In accordance with guidance R.8 no default factor is used for oral-to-dermal extrapolation as in general dermal absorption will not be higher than oral absorption.

AF for dose response relationship:

1

Justification:

Starting point NOAEL

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat

AF for other interspecies differences:

2.5

Justification:

default value for remaining differences

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

sufficiently qualified database

AF for remaining uncertainties:

1

Justification:

no assessment factor for route-to-route extrapolation was applied as dermal bioavailability usually is not higher than oral bioavailability

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:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.7 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):

600

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No modification required as an oral study is available.

AF for dose response relationship:

1

Justification:

Starting point NOAEL

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat

AF for other interspecies differences:

2.5

Justification:

default value for remaining differences

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

sufficiently qualified database

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

DNELs may be derived from the NOAEL (rat, oral, subacute) of 1000 mg/kg bw and day. Undecanal is irritating to skin (Skin Irrit. 2).

 

 

 

DNEL derivation

 

Long term exposure, systemic effects:

Inhalation: The NOAEL of 1000 mg/kg bw and day (rat, oral, subacute) may be used to calculate, according to guidance document R8, a corrected inhalation NOAEC of 870 mg/m³ for workers. Assessment factors for

intraspecies differences (10; general population), remaining interspecies differences (2.5) and for the duration of treatment (subacute > chronic; 6) may be used and result in a DNEL of 5.8 mg/m³.

Dermal and oral: The NOAEL of 1000 mg/kg bw and day (rat, oral, subacute) may be used to calculate a DNEL of 1.7

mg/kg bw and day, using an overall assessment factor of 600 (allometric factor = 4; remaining interspecies differences = 2.5; intraspecies differences = 10; duration of experiment (subacute > chronic =6)).

No assessment factor for route-to-route extrapolation was applied as 100% bioavailability is assumed for inhalation and oral exposure; additionally, dermal bioavailability is usually not higher than oral bioavailability.

There are no inhalation studies available for undecanal and no information exists if the substance causes local effects in the respiratory tract after inahalation exposure. As undecanal is not hydrolytically unstable and does not form strong acids or bases nor is a strong acid that vigorously reacts with water (exclusion criteria) based on the the generic cut-off limit for workers of 10 mg/m3 for skin irritating substances as suggested by Messinger (Regulatory Toxicology and Pharmacology 2014, 68: 317 -324) a DNEL of 5 mg/m3 for local effects after long-term inhalation exposure is suggested for the general population assuming a twofold higher factor for intraspecies variability.

In a conservative manner in the absence of data the same DNEL value has been derived for local effects after long-term and acute exposure.  

The following DNELS were not derived:

-   DNELs for systemic acute effects after inhalation, dermal and oral exposure, as the substance is not classified for acute toxicity.

-    DNEL for local dermal effects could not be derived from the available data, therefore a qualitative assessment as described in guidance on information requirements – part E will be conducted in the CSR (allocation of “low hazard band” for skin irritation)