1-amino-4-hydroxy-2-phenoxyanthraquinone

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics

Type of information:

other: expert judgement

Justification for type of information:

There is no specific requirement to generate toxicokinetic information in the REACH Regulation (EC 1907/2006). As reported in the Annex VIII, it is required to perform an assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information.

Objective of study:

other: Assessment

Principles of method if other than guideline:

Assessment

Preliminary studies:

Assessment

Details on absorption:

Assessment

Details on distribution in tissues:

Assessment

Details on excretion:

Assessment

Details on metabolites:

Assessment

Bioaccessibility (or Bioavailability) testing results:

Assessment

Assessment

Conclusions:

Assessment

Description of key information

Low bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

According to the Annex VIII of the REACH Regulation (EC 1907/2006), the assessment of the toxicokinetics behaviour of the substance should be done to the extent that can be derived from the relevant available information.

Based on the physicochemical properties of the substance (mainly physical state and particle size, chemical structure and functional groups, molecular weight, water solubility, octanol/water partition coefficient), absorption is expected to some extent, depending on tested species, exposure route, exposure duration...

In particular, absorption, distribution and excretion of test substance are controlled by:

1. molecular weight below 500 a.u,

2. higher affinity to organic phase than to water with log P_ow of 1.776 at 20 °C,

3. particle size distribution with only 7 % in volume of particles below 4 µm size,

4. low water solubility, i.e. less than 20 mg/l at 20 °C and pH ca. 7.

As for the potential of bioaccumulation, it is expected to be low, based on log P_ow below the threshold value of 4.

Once entered the body, molecules may undergo oxidative and reductive processes as well as as functionalisation and bond cleavage. The last two process are expected to enhance water solubility and, consequently, rate of excretion of test substance.

In available toxicological studies by oral route, i.e. acute toxicity, combined repeated dose toxicity and reproductive/developmental toxicity and micronucleus assay, systemic effects were evident, with different severity, depending on tested animals, doses and duration of exposure. These findings proved absorption of test substance and toxicity of the substance itself and/or of its metabolites.

Low absorption rate by dermal route was demonstrated in an in vitro experiment using human epidermis. No systemic effects were noted in the available skin irritation studies.

However, the substance proved to be sensitising in a skin sensitisation study (GPMT), thus indicating systemic bioavailability upon induction phase.

No studies via inhalation route were conducted. However, absorption by this exposure route is expected to be negligible based on the particle size distribution of test substance. Indeed, only 7 % in volume of particles may reach the alveolar region and be absorbed. As for particles in the upper respiratory tract, mainly deposited in mucus, either clearance from the body or swallowing may occur.