2,2'-azobis[2-methylbutyronitrile]

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.99 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):

25

Dose descriptor starting point:

NOAEL

Modified dose descriptor starting point:

NOAEC

Value:

24.68 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 10 mg/kg/day from an OECD 408 oral study with rats on a read-across substance was used as the starting point.

Indication is that the substance is well absorbed following oral route. Further the substance is a crystalline solid with a relatively large mean particle size of  43.5 microns. Therefore, it can be expected that after inhalation exposure, particles will mainly be deposited high in bronchial tract, and removed from the upper respiratory tract by the mucociliary elevator. With subsequent swallowing, this results to no principal difference in absorption compared to oral route.

An additional correction from 7d/w dosing to 5d/w occupational exposures has been subsequently applied.

The corrected 8 hr inhalation NOAEC for workers is NOAEL(10 mg/kg) * 1/0.38 * 6.7/10(light exercise) * 7/5(correction dosing 7days/wk)  = 24.68 mg/m3.

AF for dose response relationship:

1

Justification:

In accordance with ECHA guidance

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA guidance

AF for interspecies differences (allometric scaling):

1

Justification:

In accordance with ECHA guidance

AF for other interspecies differences:

2.5

Justification:

In accordance with ECHA guidance

AF for intraspecies differences:

5

Justification:

In accordance with ECHA guidance

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA guidance

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA guidance

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

By inhalation

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:

467 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

Modified dose descriptor starting point:

NOAEL

Value:

46 667 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 10 mg/kg/day from an OECD 408 oral study with rats on a read-across substance  (AIBN)was used.  A dermal penetration study is available on the read-across substance (AIBN). This resulted to a penetrated amount of 0.01% of applied dose on human skin. QSARs indicate that the dermal absorption rate of the target substance AMBN is 3 times higher than that of AIBN. A dermal absorption of 3*0.01% = 0.03% was taken to correct the starting point of 10 mg/kg/day.
An additional correction from 7d/w dosing to 5d/w occupational exposures has been subsequently applied.

The corrected 8 hr dermal NOAEL for workers is NOAEL(10 mg/kg/0.03%) * 7/5 (correction dosing 7days/wk) = 46667 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

In accordance with ECHA guidance

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA guidance

AF for interspecies differences (allometric scaling):

4

Justification:

In accordance with ECHA guidance

AF for other interspecies differences:

2.5

Justification:

In accordance with ECHA guidance

AF for intraspecies differences:

5

Justification:

In accordance with ECHA guidance

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA guidance

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA guidance

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

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