diethyl pyridine-2,4-dicarboxylate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.29 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEC

Value:

429.77 mg/m³

Explanation for the modification of the dose descriptor starting point:

No data are available to evaluate the long term inhalation toxicity.

No data are available to evaluate the long term inhalation toxicity.

According to column 2 part 8.5.2 "testing by the inhalation route is appropriate if exposure of humans via inhalation is likely, taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

The test substance at room temperature can have different aspects: amorphous solid with better crystallized parts (brown to yellow staining), yellow liquid if it remained supercooled appearance. The melting point is 29.5 °C. No particle size could be evaluated because of the liquid supercooled form. No aerosol are expected. The calculation of the vapor pressure of MEXORYL SBU at 25 °C by interpolation based upon the simplified Clausius-Clapeyron equation resulted in a vapor pressure of 2.2 x 10-2 Pa at 25 °C. Based on ECHA's "Guidance on information requirements and chemical safety assessment - Chapter R.14: Occupational exposure estimation", Table R.14-4, the "low vapour pressure " regarding fugacity and dustiness is being defined as the vapour pressure range upper or equal to 0.00001 and lower than 0.5 kPa. So MEXORYL SBU has a low fugacity. A low exposure by inhalation is expected furthermore, according to long term dermal toxicity data available no toxic effects are expected, a route to route extrapolation could be done for DNEL calculation.

According to column 2 part 8.5.2 "testing by the inhalation route is appropriate if exposure of humans via inhalation is likely, taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. The test substance at room temperature can have different aspects: amorphous solid with better crystallized parts (brown to yellow staining), yellow liquid if it remained supercooled appearance. The melting point is 29.5 °C. No particle size could be evaluated because of the liquid supercooled form. No aerosol are expected. The calculation of the vapor pressure of MEXORYL SBU at 25 °C by interpolation based upon the simplified Clausius-Clapeyron equation resulted in a vapor pressure of 2.2 x 10-2 Pa at 25 °C. Based on ECHA's "Guidance on information requirements and chemical safety assessment - Chapter R.14: Occupational exposure estimation", Table R.14-4, the "low vapour pressure " regarding fugacity and dustiness is being defined as the vapour pressure range >=0.00001- <0.5 kPa. So MEXORYL SBU has a low fugacity. A low exposure by inhalation is expected furthermore, according to long term dermal toxicity data available no toxic effects are expected, a route to route extrapolation could be done for DNEL calculation.

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

2

Justification:

for extrapolation subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

allometric value

AF for other interspecies differences:

2.5

Justification:

R8 ECHA guidance

AF for intraspecies differences:

5

Justification:

default value for workers

AF for the quality of the whole database:

1

Justification:

reliability 1

AF for remaining uncertainties:

1

Justification:

not concerned

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Value:

750 mg/kg bw/day

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

2

Justification:

for extrapolation subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

allometric value (rat)

AF for other interspecies differences:

2.5

Justification:

default value systemic effect or for effects on skin, eye and GI tract via local metabolism, for effects on respiratory tract

AF for intraspecies differences:

5

Justification:

default value worker

AF for the quality of the whole database:

1

Justification:

reliability 1

AF for remaining uncertainties:

1

Justification:

not concerned

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

The potential of the undiluted test item Mexoryl SBU to induce ocular irritation was evaluated in three rabbits according OECD and EC guidelines. Mean scores calculated for each animal over 24, 48 and 72 hours were 3.0, 1.3 and 2.0 for chemosis, 3.0, 2.0 and 2.0 for redness of the conjunctivae, 1.0, 0.0 and 1.0 for iris lesions and 1.7, 1.7 and 2.0 for corneal opacity.

Under applied experimental conditions, the test item Mexoryl SBU is irritant when administered by ocular route to rabbits.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown (no further information necessary)