2-(dimethylamino)ethyl acrylate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.5 mg/m³

Most sensitive endpoint:

acute toxicity

DNEL related information

Overall assessment factor (AF):

50

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

10

Dose descriptor:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.5 mg/m³

Most sensitive endpoint:

acute toxicity

DNEL related information

Overall assessment factor (AF):

50

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - workers

The acute as well as the repeated inhalation toxicity is based on the corrosive properties of the substance.

The acute inhalation DNEL for local effects is therefore based on the acute inhalation toxicity study showing a LC0 = 0.09 mg/l analytically measured (BASF 1979) . The dose-response curve in the acute inhalation toxicity studies is very steep, therefore an assessment factor of 50 seems to be appropriate, resulting in an acute inhalation DNEL of 4.5 mg/m3.

For workers the inhalative and dermal routes are the most likely for exposure. On account of the corrosive effect of ADAME and of the highly accepted use of suitable protective equipment it can be assumed that, as a rule, daily repeated immediate skin or eye contact is avoided to a large extent by using suitable personal protective equipment. Therefore, the DNELs derived for local and systemic effects from long-term exposure by inhalation are considered sufficient to ensure the safety of human workers.

Long-term exposure - local & systemic effects:

The NOAEL value from a subchronic oral repeated dose study with rats (Atochem, 1999) was identified to be the most appropriate starting point for DNEL derivation for long-term exposure following inhalation. The respective NOAEL for local and systemic effects was 10 mg/kg bw/day, based on histopathological findings in the forestomach due to direct irritation of the test substance. At the next dose level of 50 mg/kg bw/day lethality occured in 22 out of 40 animals due to direct irritant effects in the lungs of regurgitated stomach contents. Further findings were ptyalism, loud breathing, increase in neutrophil counts, and direct irritant effects in the forestomach (gross pathological findings with histopathological correlates).

The starting point was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, for differences between oral absorption in rats and inhalative absorption in humans (50% and 100%, respectively), and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg/d x 50%/100% x 6.7 m³/10 m³). The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 8.8 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the correct starting point:

- Interspecies factor: 1

Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and human have to be taken into account.

- Intraspecies factor: 2

Systemic effects in the repeated dose study with rats were minimal and restricted to an increase in neutrophil counts probably as a secondary effect following local irritation in the forestomach of rats. Furthermore, since the test substance is considered to be a local irritant without much specific systemic toxicity, not much variation of the irritant effect of the test substance in human workers is expected. Therefore an intraspecies factor of 2 is considered to be sufficient.

- Exposure duration: 2 (default)

From subchronic to chronic an assessment factor of 2 was taken by default.

- Dose-response: 1 (default)

- Uncertainty factor: 2.5 (default)

Total AF = 2 x 2 x 2.5 = 10

Based on this calculation the resulting DNEL is 0.9 mg/m³ ( 0.15 ppm)

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General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.09 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.09 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

50

Dose descriptor:

NOAEC

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

Consumer exposure to 2-(dimethylamino) ethyl acrylate is very unlikely. Only a DNEL for local and systemic effects from long-term exposure by inhalation are determined for the safety of the general population.

Long-term exposure - local & systemic effects:

The NOAEL value from a subchronic oral repeated dose study with rats (Atochem, 1999) was identified to be the most appropriate starting point for DNEL derivation for long-term exposure following inhalation. The respective NOAEL for local and systemic effects was 10 mg/kg bw/day, based on histopathological findings in the forestomach due to direct irritance of the test substance. At the next dose level of 50 mg/kg bw/day lethality occured in 22 out of 40 animals due to direct irritant effects in the lungs of regurgitated stomach contents. Further findings were ptyalism, loud breathing, increase in neutrophil counts, and direct irritant effects in the forestomach (gross pathological findings with histopathological correlates).

The starting point was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24-hour standard inhalation volume of rats versus humans and for differences between oral absorption in rats and inhalative abosrption in humans (50% and 100%, respectively), by multiplying with the corresponding factors (x 1/1.15 m³/kg/d x 50%/100%). The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 4.3 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the correct starting point:

- Interspecies factor: 1

Besides the applied allometric scaling factors no interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and human have to be taken into account.

- Intraspecies factor: 10 (default)

The intraspecies variations were recognised by an assessment factor of 10 by default.

- Exposure duration: 2 (default)

From subchronic to chronic an assessment factor of 2 was taken by default.

- Dose-response: 1 (default)

- Uncertainty factor: 2.5 (default)

Total AF = 50

Based on this calculation the resulting DNEL is 0.09 mg/m³ ( 0.015 ppm).