2,2'-azobis[4-methoxy-2,4-dimethylvaleronitrile]

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Assessment based on physico-chemical data

Type of information:

other: Assessment based on physico-chemical data

Adequacy of study:

key study

Study period:

April 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Assessment in accordance with (EC) No 1907/2006, Annex VIII, 8.8.1.

Objective of study:

absorption

bioaccessibility (or bioavailability)

distribution

excretion

metabolism

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

In Accordance with (EC) No 1907/2006, Annex VIII, 8.8.1, the toxicokinetic behaviour is assessed based on available physico-chemical information.

GLP compliance:

no

Specific details on test material used for the study:

no physical representative sample used

Details on absorption:

Based on above data the substance may be absorbed through the skin in relevant amounts (molecular weight < 500 g/Mol, -1 < log POW < 4, see EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRETORATE-GENERAL: Guidance Document on Dermal Absorpiton Sanco/222/2000 rev. 7 19 March 2004).
The log POW is within the thresholds for dermal absorption and the molecular weight indicates a “small molecule”. Therefore relevant amounts of the substance may to be absorbed via the skin.
For exposure assessments a default value of 100 % of absorption after dermal exposure may be appropriate.
The uptake after direct inhalation of the substance may be of medium relevance due to the mean diameter of particles, which exceeds the maximum inhalable particle diameter of 10 µm by 5 times. Uptake by inhalation after evaporation is unlikely. The substance is a solid at room temperature and decomposes upon heating.
For exposure assessments a default value of 10 % of absorption via inhalation may be appropriate.
The absorption after oral ingestion cannot be calculated due to lack of data; by default an absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

Details on distribution in tissues:

The substance is hydrophilic and Protein binding should be quite low, resulting in a low distribution volume. Therefore distribution to specific organs should only depend on the blood flow rate of the organs with lung, kidney and liver as potentially primary targets. Crossing of membrane barriers like the Blood/Brain barrier seems unlikely.

Details on excretion:

Metabolic reactions will further increase the water solubility of the substance and improve urinary excretion, which may be the most relevant way of excretion for this substance.
Another relevant pathway for excretion may be by feces, especially for the fraction, which has not been absorbed in the gastrointestinal tract after oral uptake.
Excretion by exhalation does not seem to be relevant.
For the decomposition products similar excretion seems feasible. In the case of N2 the major excretion way will be by exhalation.

Metabolites identified:

no

Details on metabolites:

The half life of the substance lies within hours depending on the pH value and the temperature in aqueous medium. Without metabolic activity, the substance undergoes decomposition to N2 and two radical molecules of 1‐cyano‐3‐methoxy‐1,3‐dimethylbutyl.
The azo group in the unchanged molecule can be reduced by Phase-I-reductases like Cytochromes P450 leading to amino groups in the resulting fragments.

Targets for Phase-II-conjugation Enzymes can be the Hydroxy-functionalities in the substance as well as the formed amino groups in metabolites. These groups are targets for Glutathione, Glucuronosyl-transferases and in the case of Amino-groups sulfotransferases and N-Acetyltransferases as well.

Bioaccessibility (or Bioavailability) testing results:

see absorption

Conclusions:

Absorption: 100 % for the routes oral, dermal and 10 % for the route inhalative.
no bioaccumulation potential

Executive summary:

The toxicokinetic properties of the substance are assessed based on physico-chemical properties

and conclusions on ADME are drawn.

Absorption: 100 % for the routes oral, dermal and 10 % for inhalative route.

low bioaccumulation potential.

Description of key information

Assessment of the toxicokinetic properties performed based on available physicochemical properties

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

10