Registration Dossier

Diss Factsheets

Classification & Labelling & PBT assessment

PBT assessment

Currently viewing:

Administrative data

PBT assessment: overall result

PBT status:
the substance is not PBT / vPvB

P assessment:

A single study analysing the persistent nature of TBMD in soil by Ritchie et al. (2013) shows that 85 ± 2.5% of the test substance was recovered on day 63. This means the substance should be considered as persistent. Additionally, the substance was not readily biodegradable in two studies for ready biodegradability. This is also the expected outcome of model calculations. However in an activated sludge die-away test using both adapted and non-adapted microorganisms rapid primary degradation of the substance was observed, both in the abiotic control, the non-adapted and adapted sludge. No original substance was present anymore after 1 hour and four metabolites were observed, but not further characterised. This result conflicts with the initial study findings.


A paper by Liu et al (2015) looks at developing an analytical method for determining the level of specific synthetic phenolic antioxidants and their metabolites in sewage sludge, effluent and river water. This study includes data on 2,2’,6,6’-tetra-tert-butyl-4,4’-methylenediphenol levels in all three matrices. The results show that the test substance is not present in any of the three matrices, therefore indicating that it is readily biodegradable and not persistent. The method is validated within the paper and determined to be a reliable method for the determination of substances within these matrices.


In a study assessing the aerobic transformation in soil. Transformation of the test item [rings-U-14C]TBMD was rapid in all four soils. Even directly after application several metabolites were detected in the soil extracts. Within the study duration up to 32 metabolites (> 0.2 % AR) were detected. Based on the available data; the test substance and its metabolites are not anticipated to persist in the environment. 


B assessment:

For aquatic bioaccumulation, several studies are available for the substance. The key study, a flow through study in rainbow trout conducted at the saturation concentration yielded a steady state BCF of 600 for the test substance and 1146 based on total radioactivity. However, other studies report BCFs of 4000 to 9000 - but these are noted as being wholely unreliable studies with a Klimisch score of 4 in each case. As only one reliable study is available, the results of it should be taken as the key value for the chemical safety assessment for the the assessment of the aquatic bioaccumulation. Therefore, it can be concluded that, based on the reliable evidence presented, the BCF of the test substance is 600, and it does not meet the requirements for being considered as bioaccumulative in the aquatic compartment.


For terrestrial bioaccumulation, a number of literature sources are available. The key study is a paper by Princz et al (2014) which includes reliable test data on the substance and shows that it does not bioaccumulate in the terrestrial speciesEisenia Andrei. A number of other papers offer conflicting results on the BCF of the substance, all of which are based on theoretical modelling and not considered as reliable as validated study data. It is therefore concluded that the Princz study provides the most useful results, with a BSAF of 0.13 – 0.32 g organic carbon/g lipid in a clay soil and 0.067 – 3.5 g organic carbon/g lipid in a sandy soil. Based on these results, the test substance is not expected to bioaccumulate in terrestrial species.


T assessment:

The available ecotoxicological data suggest that the substance is not acutely and chronically toxic to aquatic organisms at its solubility limit. Based on the available mammalian toxicological data the substance is not classified as carcinogenic, mutagenic or toxic to reproduction and these endpoints have been addressed with respective studies. The repeated dose toxicity profile also suggest that no classification for repeated dose specific organ toxicity is warranted.


Additionally, two literature sources are available. A paper by Miller et al (2001) looks at the estrogenic activity of a number of phenolic additives using an in vitro yeast assay. The target substance is included within the study, and is marked as having no detected estrogenic activity. The study concludes that the strongest estrogen activity is observed in those substances that have a para-orientated phenolic group to some other substituents and a molecular weight in the range of 200-250. 2,2’,6,6’-tetra-tert-butyl-4,4’-methylenediphenol does have a para-orientated phenol group, however it has a molecular weight well outside of that quoted in the paper and therefore any estrogenic activity would be predicted to be low.


A further paper by Blair et al (1999) uses a validated assay to assess the estrogen receptor affinity for a large, structurally diverse group of chemicals, and determines that certain structural features are important for binding. This paper establishes that the target substance has a mean IC50value of >1.00 x 10-4and that it has no relative binding affinity, therefore meaning it will not bind to the estrogen receptor. This would therefore suggest that it was not an endocrine disruptor via this route.


Based on the available data, the T criterion is not fulfilled.


Reference list:


Blair, R. et al (2000), The Estrogen Receptor Relative Binding Affinities of 188 Natural and Xenochemicals: Structural Diversity of Ligands,Toxicol. Sci. 54, 138-153


Liu, R. et al (2015), Determination of synthetic phenolic antioxidants and relative metabolites in sewage treatment plant and recipient river by high performance liquid chromatography–electrospray tandem mass spectrometry,Journal of Chromatography A: 1381, 13-21


Miller, D. et al (2001), Estrogenic Activity of Phenolic Additives Determined by an in Vitro Yeast Bioassay,Environmental Health Perspectives, Vol. 109. Number 2. February 2001