Docosyl acrylate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

97.9 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):

18

Modified dose descriptor starting point:

NOAEC

Value:

1 763 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:

3

Justification:

Considering that the entire family of long-chain Behenylacrylates did not pose any severe risk for human helath, an intraspecies difference factor of 3 for workers is considered to be sufficient (ECETOC Technical Report No. 110)

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:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

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:

138.9 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):

72

Modified dose descriptor starting point:

NOAEL

Value:

10 000 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:

3

Justification:

Considering that the entire family of long-chain acrylates did not pose any severe risk for human helath, an intraspecies difference factor of 3 for workers is considered to be sufficient (ECETOC Technical Report No. 110)

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:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

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

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) and ECETOC (2003). 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 toxicity of the long-chain Acrylates (C18 -C22) is considered low. Acute dermal toxicity was assessed in a read-across approach. The read-across test items (mixture of octadecyl acrylate, docosyl acrylate and icosyl acrylate with C18 –C 22 alkyl chains) were not classified and labelled for acute systemic toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Due to the extremely low vapour pressure of the long-chain Acrylates (C18 – C22), 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 the test item was assessed in several studies by using a read across approach. The long chain Acrylates (C18 – C22) did not show skin irritation or skin sensitization potential.

 

Eye irritation:

The eye irritation was assessed by using read across approach. No irritation potential was observed for the long chain Acrylates (C18 – C22).

 

Thus, no hazard has been identified in toxicity studies.

However, the monoalkyl or monoaryl or monoalkylaryl esters of acrylic acid are classified as irritating to eyes, respiratory tract and skin with R36/37/38 according to Directive 67/548/EEC (DSD) and with H315, H319 and H335 according to Regulation (EC) No 1272/2008 (CLP).

A local quantitative risk assessment is however not required as no local hazard was shown in the respective toxicity studies with the read across substance Behenyl Acrylate 22 45 %. Thus, no DNEL for local effects is required.

 

Long-term exposure-systemic effects

Inhalation exposure

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the combined repeated dose oral toxicity study with reproduction/developmental toxicity screening test (BASF SE, 2013) is identified as the relevant dose descriptor (NOAEL = 1000 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: 1000 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 1000 mg/kg bw/day is converted in an inhalation NOAEC of 1763 mg/m3.

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

Worker DNEL (inhalation exposure) = 1763 mg/m3 / (1 x 6 x 1 x 3 x 1 x 1) = 1763 mg/m3 / 18 = 97.9 mg/m3

 

Dermal exposure

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the combined repeated dose oral toxicity study with reproduction/developmental toxicity screening test (BASF SE, 2013) is identified as the relevant dose descriptor (NOAEL = 1000 mg/kg bw). A low dermal absorption was shown for the structural analogous substance dodecyl methacrylate (0.26 %, Jones, O., 2002). As docosyl 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: 1000 mg/kg bw/d (NOAEL)

Dermal absorption: 10 %

= NOAEL x 10 = 10000 mg/kg bw/d

 

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

 

Worker DNEL (dermal exposure) = 10000 mg/kg bw/d / (1 x 6 x 4 x 1 x 3 x 1 x 1) = 10000 mg/kg bw/d / 72 = 138.9 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.

- ECETOC (2010). Technical Report 110.Guidance on assessment factors to derive a DNEL.

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 docosyl acrylate.