Reaction mass of Amines, C10-14-branched and linear alkyl, [1-[(2-hydroxy-4-nitrophenyl)azo]-2-naphthalenolato(2-)][1-[(2-hydroxy-5-nitrophenyl)azo]-2-naphthalenolato(2-)]chromate(1-) and Amines, C10-14-branched and linear alkyl, bis[1-[(2-hydroxy-4-nitrophenyl)azo]-2-naphthalenolato(2-)]chromate(1-) and Amines, C10-14-branched and linear alkyl, bis[1-[(2-hydroxy-5-nitrophenyl)azo]-2-naphthalenolato(2-)]chromate(1-)

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

There are no studies available that investigate the toxicokinetic behaviour of the substance. However, based on the molecular structure and physicochemical properties a toxicokinetic assessment can be performed.

 

Absorption

Uptake of the substance in the intestines is, based on the low water solubility and relatively large molecular weight of the undissociated complex, expected to be limited (ECHA guidance R7c Table R.7.12-1). The calculated log Kow is moderate and is within the favourable range for passive diffusion. Altogether, the ingested fraction is likely to partially pass the intestine unchanged and to be excreted directly via faeces. The chromium complexes present in source and target substances are anticipated to (at least partly) dissociate in the gastric environment, leading to the release of chromium (III) and the corresponding ligands, which are also strongly coloured. The dissociation of the complex is expected to be identical for all constituents, due to the common molecular structures. This direct excretion of the unchanged substance or ligandsis potentially experimentally supported by the observed dark coloration of the faeces in the acute oral toxicity study with the source substance CAS 85186-64-7 (BASF 1972) and OECD 422 study with the target substance. In the OECD 422 (oral gavage) study with the target substance additionally, black discoloration of all organs and systemic effects were observed, which indicates that the substance is at least partially bioavailable (Charles River Laboratories 2018a). Most likely the substances are taken up after dissociation of the complex in the intestine.

Even though the log Kow is within the optimal domain for dermal absorption, absorption via the skin of neat substance is unlikely due to the physical state, estimated molecular weight, and the low water solubility (ECHA guidance R7c Table R.7.12-3). Nevertheless, based on the LLNA study, in which solubilized substance was dermally administered, absorption is suggested due to the observed black discoloration of faeces in all dose groups (BASF 2017a). Exposure via the inhalation route is expected to be limited since the substance decomposes before melting, indicating that evaporation will not occur. Based on the particle size, only a small fraction of substance has the potential to be inhaled (D10= 62 µm). However, most of the particles are too big to reach the thoracic region (particle size > 50 µm) (ECHA guidance R7c Table R.7.12-2). Based on these consideration, exposure to the substances via the inhalation route is unlikely. 

 

Distribution

The (dissociated) substances are expected to be widely distributed through the body based on the observed staining of all organs and the eyes in the oral OECD 422 study (Charles River Laboratories 2018).Since the calculated log Kow is below 4 bioaccumulation is not expected (ECHA guidance R7c).

 

Metabolism

As mentioned above, the chromium complexes in the substances may dissociate in the gastrointestinal tract, releasing the ligands and chromium (III).Upon absorption, oxidation reactions on the phenyl groups and alkyl chain might be expected by Cytochrome P450 enzymes. Resulting hydroxy or epoxide groups are potential substrates for phase II conjugation reactions such as glucuronidation of glutathione conjugation. Reduction of azo bonds might also be catalysed by enzymatic processes, for example in the liver or by the microflora in the intestine.

 

Excretion

The observed coloration of faeces indicate that the substance(or at least the ligands of the chromium complexes) are excreted in the faeces. The excretion in the faeces might be direct (e.g. without intestinal absorption) or via biliary excretion which might occur after metabolic conversion of the substance. There are no indications for excretion via the urinary tract (e.g. no discoloration of urine or effects on the kidneys).