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Classification & Labelling & PBT assessment

PBT assessment

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PBT assessment: overall result

Reference
Name:
Reaction mass of (2R*,4R*,4aR*,9bS*)-2,4-dimethyl-4,4a,5,9b-tetrahydroindeno[1,2-d][1,3]dioxine and (2R*,4R*,4aS*,9bR*)-2,4-dimethyl-4,4a,5,9b-tetrahydroindeno[1,2-d][1,3]dioxine
Type of composition:
legal entity composition of the substance
State / form:
liquid
Reference substance:
Composition 1
Reference substance:
Composition 1
PBT status:
the substance is not PBT / vPvB
Justification:

The PBT Assessment for the substance is based on the criteria set out in the “Guidance on information requirements and chemical safety assessment, Chapter R.11: PBT Assessment” (ECHA, 2014).

 

Persistence

The substance is not readily biodegradable in view of the results of one study conducted according to OECD 301D (0% biodegradation after 28 d). Thus, the substance meets the screening criterion for persistency and it is considered to be persistent (P) or very persistent (vP).

 

Bioaccumulation

In accordance with ECHA Guidance R.11 (ECHA, 2017) the substance is not considered to meet the screening criterion for bioaccumulation in aquatic species since the log Kow of 2.43- 2.9 is below the trigger value of 4.5.

However, according to ECHA Guidance R.11 (ECHA, 2017) there is indication that accumulation in air breathing organisms might occur based on the calculated log Koa of 6.51-6.98 (calculated with KOAWIN v.1.1 using the Henry's law constant of 0.208 Pa m³/mol (2.0528e-6 atm) and the Log Pow of 2.43-2.9 as input parameters) in combination with the log Kow > 2. These screening values (Kow and Koa) referred to in the ECHA Guidance R.11 are a function of the modelled organisms, food webs and environments used to obtain these values. To develop this partition coefficient combination it was clearly indicated in the guidance that biomagnification potential is only assumed for substances with high chemical absorption efficiency from the diet, no biotransformation after absorption and negligible active transport (in or out).  

The evaluation of the toxicokinetic behavior indicates a high absorption potential of the substance via the lung, skin and gastrointestinal tract. The relatively low molecular weight of 204.29 g/mol, moderate log Pow of 2.43-2.9 and relatively high water solubility of the substance (1.6 g/L) favour oral and skin absorption. However, there is evidence for biotransformation and active transport of the substance after uptake. The molecular weight (< 300 g/mol) and the water solubility of the molecule (1.6 g/L) are properties favouring excretion via urine. The potential metabolites following enzymatic metabolism were predicted using the QSAR OECD toolbox (v3.3, OECD, 2014). This QSAR tool predicts which metabolites may result from enzymatic activity in the liver and in the skin, and by intestinal bacteria in the gastrointestinal tract. 12 hepatic and 12 dermal metabolites were predicted for the test substance, respectively. Primarily, hydroxylation of the substance occurs in the liver and skin. In general, the hydroxyl groups make the substances more water-soluble and susceptible to metabolism by phase II-enzymes. Up to 63 metabolites were predicted to result from all kinds of microbiological metabolism for the test substance. Most of the metabolites were found to be a consequence of the degradation of the molecule. There was no evidence for differences in genotoxic potencies due to metabolic changes in in vitro genotoxicity tests. The studies performed on genotoxicity (Ames test and HPRT test and micronucleus test in mammalian cells in vitro) were negative, with and without metabolic activation (2001, 2015, 2014). For further details on the toxicokinetic behavior please refer to the toxicokinetic statement in IUCLID section 7.1.

Reliable QSAR models (BCFBAF Program v3.01) incorporated in the EPI Suite v4.1 interphase, were additional used to calculate the bioconcentration factors (BCF) of the substance. A BCF value of 38.1 L/Kg was predicted by the regression based model (Meylan, 1997) while a BCF of 64.5 L/Kg was estimated by the Arnot & Gobas model (2003) taking biotransformation into account (biotransformation rate kM = 1.035/d, 10 gram fish). These results show a low bioaccumulation potential of the substance and support the toxicocinetics outcome concerning the biotransformation of the substance after uptake.    

In conclusion, the trigger values for biomagnification in air-breathing (terrestrial) organisms as stipulated in the ECHA Guidance R.11 are likely to overestimate the potential for biomagnification in the food chain. Even though absorption via oral exposure has been evident the described metabolic and excretion pathways are likely to minimize biomagnification in the food chain.

Thus, the substance does not meet the screening criterion for bioaccumulation and it is not considered to be bioaccumulative (B) or very bioaccumulative (vB) in the environment.

 

Toxicity

A long-term toxicity result for Pseudokirchneriella subcapitata is available with an ErC10 (72 h) of  61.4 mg/L (nominal). Moreover, the test substance is not classified for toxicity according to the criteria in Annex XIII of Regulation (EC) No 1907/2006 based on Regulation (EC) No 1272/2008 (6th ATP). Thus, the criteria set out in Annex XIII of Regulation (EC) No 1907/2006 are not met and the test substance is not considered to meet the T criterion.

 

In conclusion, the test substance is not considered to be PBT or vPvB.