2-ethylhexanal

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.53 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

150

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.62 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

75

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

Because of the wide use of the substance as an intermediate, long-term oral, dermal and inhalation intakes are the possible exposure routes of 2-ethylhexanal.

 

The DNELs for long-term exposure are derived from the no observed effect level obtained in a 28 day sub-acute repeated inhalation study, where a NOAEC (systemic effects) of 540 mg/m3/d was estimated (BIBRA 1554/1/3/97). In general, the calculation of DNEL is based on the observed effect level which has to be modified as described in R8 (ECHA, May 2008). For derivation of the inhalative DNEL, the experimental NOAEC had to be corrected for interspecies difference between rat and human by the risk assessors 6h/8h and 6.7 m3/10 m3 regarding exposure time and breathing volume. A corrected inhalation NOAEC of 271.4 mg/m3/d according to the procedure, recommended in the current guidance document was obtained (R8, ECHA 2008).

 

Additionally an assessment factor (AF) of 75 (interspecies: allometric scaling = 1; remaining differences = 2.5; intraspezies = 5; exposure duration = 6 (subacute to chronic); dose-response = 1; quality of whole database = 1: AF = 1 x 2.5 x 5 x 6 x 1 x 1 = 75) was calculated. Consequently, the inhalative long-term systemic DNEL derived was 3.62 mg/m3/d for the worker.

 

For derivation of the systemic dermal DNEL, the same NOAEC from the subacute repeated dose study (540 mg/m3/d) was chosen as the point of departure. The inhalative NOAEL was converted into a corrected starting point of 154 mg/m3/d according to the procedure, recommended in the current guidance document (R8, ECHA 2008). It is assumed that there is an adsorption difference of the test material when administered by the dermal and not by the oral route (only 50 % of the doses are adsorbed dermally). Consequently, the assessment factor was multiplied with a factor of 0.5 to obtain an overall assessment factor for the dermal DNEL. As a result an assessment factor (AF) of 150 (interspezies: allometric scaling = 4; remaining differences = 2.5; intraspezies = 5; exposure duration = 6 (subacute to chronic); dose-response = 1; quality of whole database = 1; adsorbtion difference = 0.5: AF = 4 x 2.5 x 5 x 6 x 1 x 1 x 0.5 = 150) was calculated. The dermal long-term systemic DNEL derived was 1.53 mg/kg bw/d for the worker.

2-Ethylhexanal is in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 classified as eye and skin irritant (Cat. 2). Furthermore, from the read across to 2-ethylhex-2-enal (CAS 645-62-5) a skin sensitising potential is assumed. The performed guideline tests are not providing dose-response data that could be used for the derivation of a DNEL.

According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoints. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent eye and skin exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.64 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

600

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.37 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

300

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.18 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

150

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

For the consumer, the same general considerations for the calculation of DNELs were taken into account as already mentioned above for the worker. Therefore, also here the subacute repeated inhalation study was taken for derivation of the inhalation long term systemic DNEL.

 

The derivation of the inhalative DNEL requires the conversion of the experimental NOAEC into a corrected inhalative NOAEC of 96.4 mg/m3/d according to the procedure, recommended in the current guidance document (R8, ECHA 2008). Additionally an assessment factor (AF) of 150 (interspezies: allometric scaling = 1; remaining differences = 2.5; intraspezies = 10; exposure duration = 6 (subacute to chronic); dose-response = 1; quality of whole database = 1: AF = 1 x 2.5 x 10 x 6 x 1 x 1 = 150) was calculated. Consequently, the inhalative long-term systemic DNEL derived was 0.64 mg/m3/d for the consumer.

 

For derivation of the systemic dermal and oral DNEL for the general population, the same NOAEC from a the 28 day subacute repeated dose study (540 mg/m3/d) was chosen as the point of departure and a corrected starting point of 110.9 mg/kg bw/d according to the procedure, recommended in the current guidance document (R8, ECHA 2008) was calculated. The following assessment factor (AF) for the oral DNEL were applied: Interspezies: allometric scaling = 4; remaining differences = 2.5; intraspezies = 10; exposure duration = 6 (subacute to chronic); dose-response = 1; quality of whole database = 1: AF = 4 x 2.5 x 10 x 6 x 1 x 1 = 600.

 

The resulting DNEL for long-term oral systemic effects of 2-ethylhexanal was 0.18 mg/kg bw/d for the general population. Additionally, it is assumed that there is an adsorption difference of the test material when administered by the dermal and not by the oral route (only 50 % of the doses are adsorbed dermally). Consequently, the assessment factor was multiplied with a factor of 0.5 to obtain an overall assessment factor of 300. The dermal long-term systemic DNEL derived was 0.37 mg/kg bw/d for the consumer.

 

The observed skin irritation effects are caused by a threshold mode of action, but the available data do not allow identifying the threshold. Due to the design of the study these tests only provide potency data (scores for skin are reported for one tested concentration), but do not provide dose-response data which would support determination of a DNEL. Therefore, a qualitative assessment of the available data is conducted in terms of irritant/corrosive properties: Based on the available results on skin and eye irritation 2-diethylaminoethanol has to be considered as irritating (EU R36/38; GHS Cat. 2).