2-Propenoic acid, heptadecyl ester, branched

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.8 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):

30

Modified dose descriptor starting point:

NOAEC

Value:

264.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. The recommended approach using oral data and assuming the same absorption for inhalation and oral route is used.

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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

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:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics.

AF for intraspecies differences:

5

Justification:

The ECHA 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:

No remaining uncertainties.

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:

12.5 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):

120

Modified dose descriptor starting point:

NOAEL

Value:

1 500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Since dermal absoption was shown to be 0.26 % for analogous substances DNEL is derived assuming 10 % of oral absorption for dermal absorption as a worst case scenario.

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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

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:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics.

AF for intraspecies differences:

5

Justification:

The ECHA 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:

No remaining uncertainties.

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:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

General

DNEL derivation for the substance is performed under consideration of the recommendations of ECHA REACH Guidance (2010). In view of the data used for evaluation, the "quality of whole database factors" is considered to amount to a value of 1, and is thus not shown in the calculations presented below.  

Acute- systemic effects

A short-term DNEL oral is not required as the acute oral and dermal toxicity of the test item is low. The test item was not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP). Due to the very low vapour pressure of 2-Propenoic acid, heptadecyl ester, inhalation exposure is not considered as relevant.  

Acute/short-term and long-term exposure - local effects  

Skin irritation/corrosion and sensitization:

The skin irritation and sensitization potential for read across substances 2-Propenoic acid, heptadecyl ester was assessed in several studies.

The substances has been demonstrated to be no skin irritant, but a skin sensitizer. Therefore 2-Propenoic acid, heptadecyl ester is also considered as no skin irritant, but a skin sensitizer.

Eye irritation:

No irritation potential was observed for 2 -Propenoic acid, heptadecyl esters.  

Therefore 2-Propenoic acid, heptadecyl ester is also considered as no eye irritant.

However, the monoalkyl or monoaryl or monoalkylaryl esters of acrylic acid are classified as irritating to eyes, respiratory tract and skin with H315, H319 and H335 according to Regulation (EC) No 1272/2008 (CLP).

Thus, a qualitative risk assessment is conducted.   

Long-term exposure-systemic effects  

Inhalation exposure

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the 28 -day repeated dose toxicity study are identified as the relevant dose descriptor (NOAEL = 150 mg/kg bw).The oral NOAEL was converted to an inhalation NOAEC, assuming 100 % absorption via the lung and 100 % absorption via the oral route.   Inhalation NOAEC = oral NOAEL x 1/sRV(rat) x ABSoral(rat)/ABSinhalation(human) x sRV(human)/wRV(human)   With Oral NOAEL: 150 mg/kg bw/day sRV(rat): 0.38 m3/kg bw (8 hours) [standard respiratory volume of the rat] ABSoral(rat)/ABSinhalation(human): 1 [ratio of oral absorption in the rat to inhalative absorption in the human] sRV(human)/wRV(human): 6.7 m3/10 m3 [ratio of human standard respiratory volume to worker respiratory volume]  

Accordingly, the oral NOAEL of 150 mg/kg bw/day is converted in an inhalation NOAEC of 264.5 mg/m3.

Taking the above mentioned assessment factors into account, the following worker DNEL is:

Worker DNEL (inhalation exposure) = 264.5 mg/m3 / (1 x 6 x 1 x 5 x 1 x 1) = 264.5 mg/m3 / 30 = 8.8 mg/m3    

Dermal exposure

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the 28 -day repeated dose toxicity study are identified as the relevant dose descriptor (NOAEL = 150 mg/kg bw). A low dermal absorption was shown for the structural analogous substance dodecyl methacrylate (0.26 %, Jones, O., 2002). As icosyl acrylate has a longer carbon chain, lower water solubility and a higher log Pow it can be assumed that the substance will not penetrate the stratum corneum. However, the NOAEL, taken from the oral repeated dose study, is modified assuming 10 % absorption through the skin as a worst case approach. Considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:   - Modification of the dose descriptor:

Dose descriptor of relevant study: 150 mg/kg bw/d (NOAEL) Dermal absorption: 10 % = NOAEL x 10 = 1500 mg/kg bw/d  

Taking the above mentioned assessment factors into account, the following worker DNEL is:  

Worker DNEL (dermal exposure) = 1500 mg/kg bw/d / (1 x 6 x 4 x 1 x 5 x 1 x 1) = 1500 mg/kg bw/d / 120 = 12.5 mg/kg bw/d    

References   - ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version 2. ECHA-2010 -G-19 –EN.

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

The test item was not classified and labelled regarding oral, dermal and inhalative toxicity.

Further no consumer use is intended.

Therefore no DNEL`s were derived for the general population risk assessment of 2-Propenoic acid, heptadecyl ester.