Dimethyl 2,2'-azobis(2-methylpropionate)

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information

Type of information:

other: Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information

Adequacy of study:

key study

Study period:

March 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Objective of study:

absorption

bioaccessibility (or bioavailability)

distribution

excretion

metabolism

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information

GLP compliance:

no

Specific details on test material used for the study:

no physical test material used

Data from in vivo studies, which were designed to identify the toxicokinetic properties of the substance, are not available.

This means, that absorption, distribution, metabolism and excretion (ADME) can only be derived from available physical-chemical data.

To estimate the toxicokinetic properties of the substance the following information was considered (cited from IUCLID6 data file, section 4):

Parameter	Value used for CSR
Molecular weight	230.26 g/mol
Melting point	26.2 °C
Boiling point	Decomposition/Self-Reactive
Density	1.0875
Vapour pressure	2.85 Pa (20 °C)
Partition coefficient n-octanol/water (log POW)	2.47 (25 °C)
Calculated log POW(EPIWin)	2.50
Water solubility	3251 mg/L (20 °C)
pH	Not relevant
pKa	Not relevant
Particle size	D50 = 697 µm (median diameter)

 

Absorption:

Based on above data the substance may be absorbed through the skin in relevant amounts (molecular weight < 500 g/Mol, -1 < log P_OW< 4, see EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRETORATE-GENERAL: Guidance Document on Dermal Absorption Sanco/222/2000 rev. 7 19 March 2004).

The log P_OWis 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. 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 absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

 

Distribution:

The substance is neither very lipophilic nor very hydrophilic. Water solubility and Log Pow indicate that Protein binding may be of relevance. Crossing of biological membrane barriers like the Blood/Brain barrier seems unlikely.

The LogPow indicates a low potential for bioaccumulation. In addition the low half life of the substance indicates no potential for bioaccumulation.

 

Metabolism and Excretion:

 

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 N₂and two radical molecules.

The Azogroup in the unchanged molecule can be reduced by Phase-I-reductases like Cytochromes P450 leading to Aminogroups in the resulting fragments. Targets for Esterases are the Methyl esters of the substance.

 

Targets for Phase-II-conjugation Enzymes can be the formed Aminogroups in metabolites or the COOH from hydrolysed Ester functionalities . These groups are targets for Glutathione, Glucuronosyl-transferases and in the case of Amino-groups sulfotransferases and N-Acetyltransferases as well.

 

All of these reactions will 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 N₂the major excretion way will be by exhalation.

Description of key information

Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

10