4,4'-[1,3-phenylenebis(azo)]bisbenzene-1,3-diamine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2022

Reliability:

2 (reliable with restrictions)

Justification for type of information:

In order to evaluate the possible absorption and distribution of the Solvent Brown 41 within the
body, an overall assessment of key physicochemical properties was performed, then the possible
pathways were listed and discussed.
● The substance shows experimental water solubility < 10 mg/l, that is typical for water
insoluble substances. Based on information and protocols summarised in an internal
document [1], the water solubility value of the target was evaluated with a Klimisch score of
2 (reliable with restrictions).
● According to the REACH Regulation, Annex VII, Column 2 if a test cannot be performed
(e.g. the substance does not dissolve in water or in octanol), a calculated value for
octanol/water partition coefficient as well as details of the calculation method shall be
provided. Based on these considerations, the logP was equal to 3.58 [2]. The predicted
logP value results from the application of the VEGA AlogP model v. 1.0.1, implementing a
regression equation to calculate the Ghose-Crippen-Viswanadhan LogP (ALogP) and
consists of a regression equation based on the hydrophobicity contribution of 120 atom
types. Additional details on the model were reported in the reference QMRF [3]. The
prediction was evaluated with a Klimisch score of 2 (reliable with restrictions).

1) Inhalation: Solvent Brown 41 is a high melting point (MP) and boiling point (BP) solid (MP
and BP > 200 °C, the substance decomposes before this temperature) [1]. According to
Table R.7.12-2 of the Guidance on Information Requirements and Chemical Safety
Assessment Chapter R.7c, substances with BP >150 °C are characterised by low volatility
and may be not available for inhalation as vapours. Exposure of Solvent Brown 41 is also
limited to trained operating personnel and the substance is only supplied to the market as a
dust-free powder formulation. In relation to the possible occupational exposure, the contact
with the potential dust is limited by the treatment in fabrication with anti-dusting compound
(vaseline oil) and the use of individual protection devices (DPI) by operators.

2) Dermal absorption. Absorption of azo dyes through the skin is doubtful, as intact azo dyes
may not penetrate the skin [4]. Table R.7.12-3 of the Guidance on Information
Requirements and Chemical Safety Assessment Chapter R.7c reports that the
substance must be sufficiently soluble in water to partition from the stratum corneum into the
epidermis. In the specific case, the low water solubility (WS) of the target (<10 mg/L)
suggests that dermal uptake is likely to be low. In addition, Solvent Brown 41 was evaluated
for its acute dermal toxicity (endpoint 7.2.3) and LD50 >2000 mg/kg bw was suggested
[5], reinforcing the hypothesis of a limited dermal absorption of this chemical.

3) Oral and GI absorption: The only expected absorption of the substance is supposed to
happen through the GI tract. The target has an estimated logP = 3.58 that is close to the
range suggested by Table R.7.12-1 of the Guidance on Information Requirements and
Chemical Safety Assessment Chapter R.7c, that indicates a logP between 2.0 and 3.00
for optimal absorption. The oral absorption is confirmed by the estimation of oral acute
toxicity for the target that returns a LD50 in a range of 50-75 mg/kg bw (endpoint 7.2.1) [6].

4) Distribution and accumulation potential: with an estimated logP = 3.58 the substance is
not expected to accumulate in the lipophilic district of the body (e.g. adipose tissue and
stratum corneum) as a logP value higher than 4 is usually required to a chemical to
accumulate (Table R.7.12-5 of the Guidance on Information Requirements and
Chemical Safety Assessment Chapter R.7c).
5) Excretion: The substance is not soluble in water and therefore it is likely to be rapidly
excreted in the faeces without participating in the enterohepatic circulation.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2020

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-[1,3-phenylenebis(azo)]bisbenzene-1,3-diamine

EC Number:

213-888-1

EC Name:

4,4'-[1,3-phenylenebis(azo)]bisbenzene-1,3-diamine

Cas Number:

1052-38-6

Molecular formula:

C18H18N8

IUPAC Name:

4,4'-(1E,1'E)-1,3-phenylenebis(diazene-2,1-diyl)dibenzene-1,3-diamine

Applicant's summary and conclusion

Conclusions:

Based on the information available it is possible to infer that the only possible route of absorption for
Solvent Brown 41 is through the GI tract. Conversely, dermal absorption or absorption through
inhalation are unlikely due to the unfavourable physico-chemical properties of the target.

Executive summary:

The information presented here suggested that the only expected absorption of Solvent Brown 41 is
through the GI tract.