Phenothiazine

PBT assessment

PBT assessment: overall result

PBT status:

the substance is not PBT / vPvB

Justification:

The substance phenothiazine is considered to be persistent, as no sufficient data exist, which could demonstrate a degradation of the substance in the environment. The screening test for ready biodegradation revealed neither microbial break down of the substance by STP (sewage treatment plant) microorganisms nor does it show toxic effects to microorganisms. The conducted test for respiration inhibition of STP microorganisms confirms these data.

No long term studies on ecotoxicity are available. Nevertheless the substance is showing a high toxicity in short term studies and evidence for chronic toxicity in animal studies, resulting in a classification as STOT Rep. Exp. 2 according to Directive 1272/2008. Therefore the “T”-criterion according to Annex XIII of REACH is fulfilled.

For the assessment of the bioaccumulation potential of phenothiazine four arguments were considered.

1. No bioaccumulation is expected as the log Kow is 3.78. The actual ECHA Guidance (Guidance on information requirements and chemical safety assessment, Chapter R.11: PBT Assessment (Last release version 1.1, Dec. 2011, Last draft version 2.0 February 2014)) as well as the most recent ECETOC-Report (ECETOC Special Report No. 18: Information to be considered in a weight-of-evidence-based PBT/vPvB assessment of chemicals (Annex XIII of REACH), July 2014) state, that a Log Kow < 4.5 is a definitive indicator for non B/vB properties in aquatic systems. According to the ECHA Guidance the uptake of an organic substance is driven by its hydrophobicity. For organic substances with a log Kow value below 4.5 it is assumed that the affinity for the lipids of an organism is insufficient to exceed the B criterion, i.e. a BCF value of 2000 L/kg.

2. A Japanese study supported these arguments as it reported BCF-values in fish between 127 and 660 L/kg. Taking the threshold criteria of 2000 respectively 5000 according Annex XIII REACH into account, it is concluded that phenothiazine is not a “B” or a “vB” substance .

3. Calculations with the EPI-Suite 4.11 (BCFBAF 3.01) software result in BCF-values, which are significantly lower than 500.

4. According to ECHA Guidance all available relevant information (testing data and non-testing information) should be taken into account, incl. toxicokinetic studies with mammalians.

There are several studies on the metabolism and the toxicokinetics of phenothiazine in mammals and man, e.g. the study cited in section 7.1.1. According to this study, in man phenothiazine and/or its metabolites are excreted totally via faeces and urine within 5 days. This is supported by an older review of the same author (Mitchell et. al., Drug Metabolism Reviews, 13(2), 319-343 (1982)). In this review it is shown, that phenothiazine and/or its metabolites are excreted via the urine and faeces, even so, depending on the species, it may take days or week for nearly total elimination. From this studies it can be concluded, that bioaccumulation in terrestrial animals can be considered to be not relevant.

In general, phenothiazine is fulfilling the criteria of persistence and toxicity. The criterion to classify the substance as bioaccumulative is not fulfilled. Further testing therefore appears scientifically not justified.