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Description of key information

The results of basic toxicity testing give no reason to anticipate unusual characteristics with regards to the toxicokinetics of Reactive Orange 107. The data indicate that there is little or no dermal or oral absorption. No signs of a significant systemic toxicity associated with absorption potential have been observed. Bioaccumulation of Reactive Orange 107 can most probably be excluded due to the available data. Based on the results of genotoxicity assays, a metabolisation towards genotoxic metabolites can also be excluded.
On the basis of the results, it is anticipated that the substance does not undergo significant metabolic activity; rather it is metabolized for excretion with little subsequent toxicity. The substance is therefore not considered to be of concern for ADME related effects.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Introduction

Toxicokinetic parameters such as uptake, distribution, metabolism and excretion form the essential toxicological profile of a substance. An approximate indication of the toxicokinetic pattern can be gained from the physico-chemical properties taking into account the molecular weight, the number of atoms (hydrogen bond donors and acceptors), the solubility in solvents, log KOW, etc. and the results of basic toxicity testing of the test article. The assessment of the toxicokinetic properties of given below is based on the results obtained for, the following toxicological endpoints:

 

·        Acute oral toxicity in rats

·        In vivo skin irritation in rabbits

·        In vivo eye irritation in rabbits

·        Skin sensitization

·        Bacterial reverse mutation test

All studies were carried out according to the principles of Good Laboratory Practice and met the requirements of the OECD and EU-Guideline for the Testing of Chemicals.

Physico-chemical properties

Name:                                    Reactive Orange 107

CAS number:                         94158-82-4

CAS name:                              Benzenesulfonic acid, 4-(acetylamino)-2-amino-5-[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, sodium salt

Physical state:                         solid, orange odourless powder

Empirical formula:              C16H16N4Na2O10S3

Molecular weight:                522.5 to 566.5g/mol                 (>500 daltons = bad absorption)

Water solubility:                   > 500 g/L                                       (= very soluble in water)

Partition coefficient:            log Kow:-4.52                            (<-0.4 or >5.6 = bad absorption)

Melting point:                        > 450°C                                         (not volatile)

Atom count (natoms):       33                                                     (<70 = good bioavailability)

H-bond acceptor (nON):  14                                                     (>10 = bad bioavailability)

H-bond donor (nOHNH):    3                                                   (<5 = good bioavailability)

Evaluation and Assessment

Reactive Orange 107 is an orange powdered solid at room temperature conditions; it is commercialized as granules with a particle size > 10 µm or as dedusted powder. The melting point of the substance is >450°C therefore a significant inhalation exposure to vapours or particles is not expected. In view of the very high solubility in water (> 500 mg/L), the low n‑octanol/water partition coefficient (log Kow – 4.52 at 20°C), and the high molecular weight, systemic bioavailability after dermal or oral exposure is not anticipated.

Reactive107 has a very low acute toxicity potential. The data of the acute dermal irritation test and skin sensitization testing indicate low dermal permeability, owing to the fact that no systemic effects were observed. This is in accordance with the extremely good solubility of the test substance in water, the resulting low log Kow and with the molecular weight and number of H-bond acceptors, giving evidence of a poor systemic bioavailability. However, the number of atoms and of H-bond donors indicate that the test substance is at least partially absorbed, what is confirmed by the results of the acute oral toxicity study, where hyperreflexia and discolored urine was observed after test substance administration.

According to the molecular weight, excretion of Reactive Orange 107 is most likely predominantly eliminated via intestine, as substances with a molecular weight above 300 g/mol are preferentially excreted via the feces in rats. However, at least a part of Reactive Orange 107 or its metabolites are excreted via the kidneys, as indicated by the discoloration of the urine in the acute oral toxicity study. Due to its high water solubility and low log Kow, Reactive Orange 107 shows no potential for bioaccumulation. This is confirmed by the results of the bioaccumulation modeling, excluding a significant bioaccumulation potential of Reactive Orange 107.

Reactive Orange 107 was not genotoxic in an in-vitro cell mutagenicity test. Therefore, a metabolisation towards genotoxic structures can most probably be excluded.

Summary

The results of basic toxicity testing give no reason to anticipate unusual characteristics with regards to the toxicokinetics of Reactive Orange 107. The data indicate that there is little or no dermal or oral absorption. No signs of a significant systemic toxicity associated with absorption potential have been observed. Bioaccumulation of Reactive Orange 107 can most probably be excluded due to the available data. Based on the results of genotoxicity assays, a metabolisation towards genotoxic metabolites can also be excluded.

On the basis of the results, it is anticipated that the substance does not undergo significant metabolic activity; rather it is metabolized for excretion with little subsequent toxicity. The substance is therefore not considered to be of concern for ADME related effects.

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