Docosyl methacrylate

Toxicological Summary

Workers - 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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

46.7 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):

100

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

4 666.7 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Please refer to "Additional information"

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:

2

Justification:

The default extrapolation factor for exposure duration from subchronic to chronic is used.

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:

2.5

Justification:

The default value for interspecies differences is used.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported.

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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

Inhalation

Long term and acute, systemic DNEL – exposure via inhalation (workers)

Due to the extremely low vapour pressure of the solid waxen substance Docosyl methacrylate (1.96E-5 Pa), inhalation exposure is not considered as relevant. Docosyl methacrylate is unlikely to be available for inhalation exposure. Therefore, no DNEL was derived.

Long term & acute, local DNEL- exposure via inhalation (workers)

Due to the extremely low vapour pressure of the solid waxen substance Docosyl methacrylate (1.96E-5 Pa), inhalation exposure is not considered as relevant. Docosyl methacrylate is unlikely to be available for inhalation exposure. Therefore, no DNEL was derived.

Dermal

Long term, systemic DNEL- exposure via dermal route (workers)

No repeated dose dermal toxicity study with the target substance is available. Therefore, it will be necessary to obtain a long-term dermal DNEL by route-to-route extrapolation.

Step 1:PoD and most sensitive endpoint: repeated dose toxicity (oral)

The NOAEL of 1000 mg/kg bw/day derived from an OECD TG 422 study performed with the structural analogue substance Dodecyl methacrylate was used as the PoD.

Step 2:Modification into a correct starting point:

Relevant dose descriptor (NOAEL): 1000 mg/kg bw/day

In ECHA guidance R.8 it is stated that “substance specific data on absorption via the different routes are to be preferred.” Therefore, in the present situation experimental data from a dermal toxicokinetic study was used showing up to 0.3 % absorption by rat skin. This is a worst case situation as rat skin is much more permeable than human skin.

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

= 1000 mg/kg bw/day/ 0.3 ×1.4

= 4666.7 mg/kg bw/day

Step 3:Overall AF= 100

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Dose-response relationship AF: 1

Exposure duration AF: 2

In conclusion,long term systemic dermal DNEL, workers = 46.7 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (workers)

As there is no evidence for critical effects from acute oral and inhalative toxicity studies, the long-term dermal DNEL will be protective also for acute dermal exposure.

Long term & acute, local DNEL- dermal exposure (workers)

The substance causes skin sensitization in experimental animals.

For these effects, a qualitative assessment was conducted: Therefore the use of gloves and the use of stringent risk management measures as outlined in ECHA guidance document Part E: Risk Characterization (Table E. 3-1) is required in order to prevent any skin contact with the test substance and thus the occurrence of skin sensitization.

Hazard to the eye-local effects (worker)

The test item is not classified for eye damage according to Regulation (EC) No 1272/2008 (CLP).

 

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:

Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016

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:

DNEL (Derived No Effect Level)

Value:

15 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

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

3 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Please refer to "Additional information"

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is use

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration from subchronic to chronic is used.

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:

2.5

Justification:

The default value for interspecies differences is used.

AF for intraspecies differences:

10

Justification:

The default value for the relatively homogenous group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported.

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

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

1. Inhalation

Long termand acute, systemic DNEL – exposure by inhalation (general population)

Docosyl methacrylate is not intended for consumer use.

Due to the extremely low vapour pressure of the solid waxen substance Docosyl methacrylate (1.96E-5 Pa), inhalation exposure is not considered as relevant. Docosyl methacrylate is unlikely to be available for inhalation exposure. Therefore, no DNEL was derived.

Long term, local DNEL- exposure via inhalation (general population)

Docosyl methacrylate is not intended for consumer use.

Due to the extremely low vapour pressure of the solid waxen substance Docosyl methacrylate (1.96E-5 Pa), inhalation exposure is not considered as relevant. Docosyl methacrylate is unlikely to be available for inhalation exposure. Therefore, no DNEL was derived.

2.    Dermal

Docosyl methacrylate is not intended for consumer use.

No repeated dose dermal toxicity study with the target substance is available. Therefore, it will be necessary to obtain a long-term dermal DNEL by route-to-route extrapolation.

Long term, systemic DNEL- exposure via dermal route (general population)

Step 1:PoD and most sensitive endpoint: repeated dose toxicity (oral)

The NOAEL of 1000 mg/kg bw/day derived from an OECD TG 422 study performed with the structural analogue substance Dodecyl methacrylate was used as the PoD.

Step 2:Modification into a correct starting point:

Relevant dose descriptor (NOAEL): 1000 mg/kg bw/day

In ECHA guidance R.8 it is stated that “substance specific data on absorption via the different routes are to be preferred.” Therefore, in the present situation experimental data from a dermal toxicokinetic study was used showing up to 0.3 % absorption by rat skin.

Correction for difference between human and experimental exposure conditions: 7 d rat/7 d general population

Corrected NOAEL (dermal) for workers:

= 1000 mg/kg bw/day/ 0.3 ×1

= 3000 mg/kg bw/day

Step 3:Overall AF= 200

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 10

Dose-response relationship AF: 1

Exposure duration AF: 2

In conclusion,long term systemic dermal DNEL, workers = 15 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (general population)

Docosyl methacrylate is not intended for consumer use.

As there is no evidence for critical effects from acute oral and inhalative toxicity studies, the long-term dermal DNEL will be protective also for acute dermal exposure.

Long term & acute, local DNEL- dermal exposure (general population)

A DNEL long term/acute - local effects is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation (EC) No 1272/2008.

Long term & acute, systemic DNEL- exposure by oral route (general population)

Since the substance is readily biodegradable and expected to be rapidly metabolized in rodents and humans, secondary poisoning is unlikely to be a relevant route of exposure. Additionally, acute oral toxicity is low.