Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The UVCB substance caused effects on the liver upon subchronic gavage application of high doses.

It is therefore absorbed to some extent after ingestion. The effects on the liver indicate induction of xenobiotic metabolizing enzymes, but no proof such as enzyme activity measurements are available. No information is yet available regarding the reversibility of the effects.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

The UVCB substance causes liver effects, but is tolerated up to 1000 mg/kg bw in the 90-day study (OECD 408, GLP). No information is yet available on the reversibility of these effects.

The absence of any effects observed in the 90day-study (OECD 408, GLP) with bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine (CAS 15721-78-5) is indicative of lack of systemic uptake of the di-isoC9 -substituted components (421 g/mol) and shows that systemic toxicity is likely to be caused by the mono-isoC9-substituted components (295 g/mol). The di-isoC9-substituted components are expected to be too bulky and too poorly soluble for systemic uptake. The same applies to trisubstituted components.

Water solubility:

Measured value for UVCB: <5 µg/L at 20°C at pH 6.1

The estimated values of the individual components are as follows:

Structure A (dialkylated) = 1.62E-4 µg/L at 25°C

Structure B (monoalkylated) = 4.36 µg/L at 25°C

For the water solubility of a homologue dialkylated substance with CAS number 15721 -78 -5 (Di-octylphenyl, C8) has been reported a value of 0.0523 mg/L at 28°C (ECHA-dissiminated dossier, accessed 2015)

LogPOW:

The estimated values of the individual components are as follows:

Log Pow of structure A (dialkylated) = 11.9 at 25°C

Log Pow of structure B (monoalkylated) = 7.6 at 25°C

The components contain branched side chains that may undergo oxidation of an hydroxy group. The corresponding alcohols could be conjugated via phase II enzymes. N-hydroylation and consequent phase-II conjugation is also possible unless steric hindrance by the branched alkyl chains interferes. As the analytical information shows that substitution is predominantly at the para-position, steric hindrance is however not likely. Reversible oxidation at the nitrogen is part of the technical function as an antioxidant in engine oils.

Extra investigations regarding potential methaemoglobin formation were included in the 90-day study. Since the rate of Heinz bodies was not increased up to the limit dose (1000 mg/kg bw), the alkylated diphenylamines are considered to be inactive regarding methaemoglobin formation. Extra investigations on the influence on endogenous plasma constituents showed dose-dependent effects on lipid metabolism and liver parameters but no pattern that could be matched to any known mode of action.

Based on the possibility of metabolic transformation to species of higher water solubility, the substance is considered to have a low potential for bioaccumulation. Overall, there is no potential for bioaccumulation as long as there is no overload of xenobiotic metabolism.

Absorption via skin of the high molecular weight fraction is expected to be very low, since molecular weight and its high log POWimpede skin permeability [Guidance Document on Dermal Absorption, European Commission; Health and Consumer Protection, DGSanco /222/2000 rev. 7, March 19, 2004].

Inhalative exposure is of no relevance due to the low vapour pressure.