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

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Assessment based on available physico-chemical data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Assessment based on available physico-chemical data

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Assessment based on available physico-chemical data

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

224-583-8

EC Name:

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

Cas Number:

4419-11-8

Molecular formula:

C14H24N4

IUPAC Name:

2-[(E)-2-(1-cyano-1,3-dimethylbutyl)diazen-1-yl]-2,4-dimethylpentanenitrile

Details on test material:

CC(C)CC(C)(N=NC(C)(CC(C)C)C#N)C#N

Specific details on test material used for the study:

no actual test material used

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

see "any other information on results incl. tables" section

Main ADME results 2

Type:

distribution

Results:

see "any other information on results incl. tables" section

Main ADME results 3

Type:

metabolism

Results:

see "any other information on results incl. tables" section

Main ADME results 4

Type:

excretion

Results:

see "any other information on results incl. tables" section

Any other information on results incl. tables

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	248.4 g/mol
Melting point	52.1 °C
Boiling point	Decomposition/Self-Reactive
Density	0.9691
Vapour pressure	0.812 Pa (25 °C), calculated
Partition coefficient n-octanol/water (log POW)	3.37 (25 °C)
Calculated log POW(EPIWin)
Water solubility	9.37 mg/L (20 °C)
pH	Not relevant
pKa	Not relevant
Particle size	MMAD 157 µm

 

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 by more than 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 absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

 

Distribution:

The substance is lipophilic and Protein binding is of relevance, resulting in a high distribution volume. Crossing of membrane barriers like the Blood/Brain barrier seems unlikely.

The LogPow indicates a low potential for bioaccumulation. Giving the low half life of the substance, the potential is rated as not present.

 

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 of 1‐cyano‐1,3‐dimethylbutyl.

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 Phase-II-conjugation Enzymes can be the formed Aminogroups in metabolites. 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.

Applicant's summary and conclusion

Conclusions:

An assessment based on available physico-chemical data is performed.
The relevant results are taken for risk assessment purposes:
dermal absorption: 100%
inhalative absorption: 10%
oral absorption: 100 %
Bioaccumulation: unlikely