Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Environmental fate & pathways

Endpoint summary

Administrative data

Description of key information

Key_Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) conducted a guideline study (OECD 305 -III) by exposing rainbow trout (Oncorhynchus mykiss) via diet over a 14-Day uptake period followed by a 21-Day depuration period in a flow-through limit test with the nominal concentration of 10 mg test substance/kg feed.

As radioactive material was used in this study, it was possible to evaluate the obtained results based on the analytically determined concentrations of the parent compound, the complete extractable fraction (ERR) and, as an absolute worst case scenario, the total radioactive residues (TRR), resulting from the sum of the ERR and NER. Following the worst case assumption on TRR, a BMFKGLof 0.479 and an estimated BCF of 14631.8 resulted as key values.

Supporting_As supporting information the BCF was calculated by the QSAR model BCFBAFWIN v3.01 implemented in EPIWIN v4.1. Using the regression-based estimate (traditional method) a BCF of 1912 L/kg wet-wt was calculated. Using the Arnot-Gobas method, which is based on the mechanistic first principles, the BCF results in a value of 1209 L/kg wet-wt.

Supporting_As second supporting information the BCF was calculated for DIPA as relevant hydrolytical degradation product of the registered substance by the QSAR model BCFBAFWIN v3.01 implemented in EPIWIN v4.1. Using the regression-based estimate (traditional method) a BCF of 58.23 L/kg wet-wt was calculated. Using the Arnot-Gobas method, the BCF results in a value of 69.94 L/kg wet-wt.

Additional information

Bioaccumulation: aquatic / sediment

A GLP study was performed at the Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) to determine the biomagnification factor of the registered substance in the fish speciesOncorhynchus mykiss.

 

The registered substance was administered to a test population of fish via feed in accordance to the conditions of the OECD TG 305 for BMF studies.

The suitability of aqueous exposure of the test item to be applied in a BCF study according to OECD TG 305 was tested and evaluated in the test facility of Fraunhofer IME (see statement ‘Suitability of an aqueous exposure for a BCF study with Bis(2,6-diisopropylphenyl)carbodiimide (non-GLP pre-test)’dated on March 27, 2019 as attached background material). The results on the low stability of the test item in the aqueous phase provided clear indications that an aqueous exposure is not practicable.

According to OECD TG 305, a dietary exposure test can alternatively be used for substances with high hydrophobicity (test item log KOW= 6.2) and low water solubilities (test item solubility < 0.53 µg/L). Thus, the dietary approach, generating a biomagnification factor (BMF) was further investigated to evaluate of the bioaccumulation potential of carbodiimide.

 

A test concentration of 8.02 ± 1.13 mg/kg CDI was achieved by applying solvent-mediated spiking on commercially available feed pellets. The feed pellets were pretreated by methylation of external carboxylic acid functionalities.

 

In addition, a control population of fish was fed with similar prepared feed (solvent-spiked) without the test substance to monitor potential mortalities or other adverse effects over time. Both feed types were administered with a rate of 2 % mean body weight per day.

 

The test duration was 14 days for the uptake and another 21 days for the depuration phase. No adverse effects were observed during the time course of the study.

 

Repeated samplings were done for both fish populations and five individuals were picked at each time point for chemical analyses. During the uptake phase, fish were sampled twice, at days 12 and 14 and the highest mean CDI concentration in fish was 0.322 ± 0.073 mg/kg at day 14.

 

During depuration the fish were sampled six times, at day 1, 3, 7, 10, 14 and 21 day of depuration. The test item concentration at the sampling points was used to assess the elimination kinetics of CDI in fish matrix. Based on that, a depuration rate constant of k2 = 0.0814 was calculated.

 

With that a substance specific half-life (t1/2) of 8.52 days could be determined.

 

The test item concentration on feed, k2and a test item concentration of c0,d = 0.213 mg/kg in fish at the beginning of the depuration phase was used to determine an assimilation efficiency (α) of 0.159.

 

Based on the assimilation efficiency and the feed ingestion rate of 0.02 a kinetic BMFKof 0.0391, a growth-corrected BMFKgof 0.0634 and a growth- and lipid-corrected BMFKgLof 0.194 was specified for the registered substance.

As radioactive material was used in this study, it was possible to gain a broader insight into the bioaccumulating potential of test item related residues. Thus, two additional perspectives were evaluated. Notably, those evaluations constitute worst case considerations and could only be made due to the usage of radiolabeled material.The first consideration is based on the complete extractable fraction (ERR, no parent specific analysis) and the second, as an absolute worst case scenario, is based on total radioactive residues (TRR), resulting from the sum of the ERR and NER.

For ERR and TRRmean tissue concentrations of c14d,ERR = 0.378 ±0.079 mg/kg and c14d,TRR = 0.378 mg/kg were determined in fish matrix, respectively at the end of the uptake phase. Based on the analytical measurements during the depuration phase and the assessment of the elimination kinetics, the depuration rate constant (k2) was determined to be0.0774 for ERR and 0.0663 for TRR with substance specific half-lifes(t1/2) of 8.96 and 10.5 days, respectively.

Accordingly, the assimilation efficiency was determined to be 0.159 for ERR and 0.274 for TRR, resulting in final growth - and lipid-correctedBMFKgLof 0.251 for ERR and 0.479 for TRR.

By the use of the spreadsheet provided in conjunction with the Guidance Document to OECD TG 305, a BCF was estimated for the registered substance as well as for the TRR as worst-case assumption. Taking into account that the registered substance is not molecularly large containing two not halogenated aromatic rings only, the logKow was experimentally determined to be 6.2 and the assimilation efficiency within the experimental bioaccumulation study was determined to be 0.159 for the parent compound, the test substance falls within the applicability domain of the first and second BCF estimation method as outlined in the respective guidance document to OECD TG 305 (Table 4 -14). The result obtained by estimation method 3 is considered to be not reliable accordingly, as the test substance is not within its indicative applicability domains.

 

Hence, the results obtained by estimation method 1 and 2 are considered most meaningful with a worst-case BCF of 10251.0 for the parent compound (range 1020.1 - 10251.0) and 14631.8 for TRR (range 1456.8 - 14631.8). Thus, it can finally be concluded that the registered substance has a very bioaccumulative potential in the aquatic environment.

Modelling of the BCF was performed for the registered substance and also for the relevant hydrolytical degradation product 2,6 -diisopropylaniline (DIPA):

The prediction for the bioconcentration factor (BCF) of the registered substance was determined by the computer program BCFBAFWIN v3.01 (EPIWIN software) of US-EPA. Furthermore the whole body primary biotransformation rate estimation for fish was calculated with the notation that the bio half-life normalized to 10 g fish at 15 °C. It is possible to predict the apparent metabolism half-life in fish for three different trophic levels (lower, mid and upper). Using the regression-based estimate (traditional method) a BCF of 1912 L/kg wet-wt was calculated. Using the Arnot-Gobas method, which is based on the mechanistic first principles, the BCF results in a value of 1209 L/kg wet-wt. The whole body primary biotransformation rate estimate for fish gives a half-life of 59.9 days, whereby the rate constant (kM) for 10 g fish is designated as 0.01158/day. This is taken into account to predict the apparent metabolism half-life in fish for the substance. For the lower trophic level a BCF of 295.80 L/kg wet-wt is calculated, whereas for the mid trophic level the BCF will result in 267.00 L/kg wet-wt and the higher trophic level gives a value of 190.90 L/kg wet-wt.

No GLP criteria are applicable for the usage of this tool, but due to the fact that it is a scientifically accepted calculation method, the estimations performed are reliable with restrictions and can be used for the chemical safety assessment.

DIPA is the relevant hydrolytical degradation product of the registered substance. The prediction for the bioconcentration factor (BCF) of the substance 2,6-diisopropylaniline (DIPA) was determined also by BCFBAFWIN v3.01. Using the regression-based estimate (traditional method) a BCF of 58.23 L/kg wet-wt was calculated. Using the Arnot-Gobas method, the BCF results in a value of 69.94 L/kg wet-wt. The whole body primary biotransformation rate estimate for fish gives a half-life of 0.301 days, whereby the rate constant (kM) for 10 g fish is designated as 0.4093/day. For the lower trophic level a BCF of 61.51 L/kg wet-wt is calculated, whereas for the mid trophic level the BCF will result in 64.68 L/kg wet-wt and the higher trophic level gives a value of 69.94 L/kg wet-wt.

Conclusion:

It can be concluded that relevant bioaccumulation of the hydrolysis product DIPA is not to be expected with regard to the results of the QSAR analysis but a very bioaccumulative potential has to be considered for the registered substance following the results of the experimental study according to OECD 305.

Bioaccumulation: terrestrial

This is no mandatory endpoint to be fulfilled for a registration of a tonnage band of 100 - 1000 tons/year according to REACH Regulation (EC) 1907/2006.