Bis(2,6-diisopropylphenyl)carbodiimide

Endpoint summary

Additional information

Stability

According to REACH Regulation (EC) 1907/2006 information about the phototransformation in air, water and soil is not mandatory for a registration of a chemical at a tonnage band of 100 - 1000 tons/year. However, the phototransformation in air was predicted by the computer program AOPWIN v1.92, resulting in an atmospheric half-life of 0.322 days (3.87 minutes; Chemservice S.A., 2011).

Bis(2,6-diisopropylphenyl)carbodiimide is considered as hydrolytically unstable at pH 4, 7 and 9 and temperatures up to 50 °C. (Holzaht-Grimme, 2020). The major degradation rate products is DIPA (2,6 -diisopropylaniline; CAS 24544 -04 -5). This result of the key study is in line with the provided supporting information (Cizek, 2012 and EFSA 2010) regarding hydrolysis.The rate of hydrolysis increases with decreasing pH and temperature. 2,6 -Diiospropyleaniline is the hydrolyisis product.

A Scientific Opinion of the European Food Safety Agency (EFSA) deals with the risk assessment of bis(2,6-diisopropylphenyl)carbodiimide, (CAS No. 2162 -74 -5 (EFSA, 2010). The EFSA Panel considered that the substance hydrolyses first into the corresponding diisopropylphenyl isocyanate (DIPI; CAS No. 28178 -42 -9) which is chemically unstable and readily hydrolyses into the 2,6-diisopropylaniline (DIPA; CAS-No. 24544 -04 -5) which is the final and chemically stable and quantifiable decomposition product. CDI is also chemically reactive during the manufacturing process and forms DIPI in the polymer.

Biodegradation

The biodegradation potential of bis(2,6-diisopropylphenyl)carbodiimide was investigated in experiments conducted according to OECD Guideline 301 F (Weyers, 2009) and OECD Guideline 301 B (Mead, 2001). In both studies, the substance was found to be "not readily biodegradable", which is confirmed by a QSAR prediction with BIOWIN v4.10 (Chemservice S.A., 2011) and an evaluation with the Start plug-in in Toxtree v2.5.0. (Chemservice S.A., 2011).

The prediction for biodegradability of main hydrolytical degradation product DIPA was also done with BIOWIN v4.10 (Chemservice S. A., 2016). A probability greater than or equal to 0.5 indicates "Biodegrades fast". A probability less than 0.5 indicates "Does NOT biodegrade fast". The Expert Survey Biodegradation Results (Biowin model 3 & 4) are clearly above the 0.5 threshold indicating a potential biodegradation. However, as the other Biowin models show, it is assumed that DIPA is not readily biodegradable.

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 bis(2,6-diisopropylphenyl)carbodiimide 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 test item concentration on feed, k₂and a test item concentration of c_0,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. With that a substance specific half-life (t_1/2) of 8.52 days could be determined. Based on the assimilation efficiency and the feed ingestion rate of 0.02 a kinetic BMF_Kof 0.0391, a growth-corrected BMF_Kgof 0.0634 and a growth- and lipid-corrected BMF_KgLof 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 c_14d,ERR = 0.378 ±0.079 mg/kg and c_14d,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(t_1/2) 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-correctedBMF_KgLof 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 1456.0 - 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 (Chemservice S.A., 2011). 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 (Chemservice S.A., 2016). 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

An investigation of the terrestrial bioaccumulation potential is no mandatory endpoint in accordance with REACH Regulation (EC) 1907/2006 for a registration of a substance in a tonnage band of 100 - 1000 tons/year.

Transport and distribution

The adsorption coefficient (Koc) of bis(2,6-diisopropylphenyl)carbodiimide was determined using the HPLC screening method in accordance with OECD Guideline 121 (Garcia-Sanchez, 2011). As result a logKoc greater than 5 is reported, the extrapolated value is 6.4 at 40 °C and 25 °C.

Additionally, the Koc was predicted by the computer program KOCWIN v2.00, resulting in a value of 17,320,000 L/kg using the MCI method (Chemservice S.A., 2011). The traditional method gives a value of 36,960,000 L/kg.

Henry´s law states that the solubility of a gas in a liquid solution at a constant temperature will be proportional to the partial pressure of the gas which is above the solution (Henry, 1803). This information is not mandatory for a registration under REACH Regulation (EC) 1907/2006 in a tonnage band of 100 - 1000 tons/year. However, the Henry´s Law Constant can be predicted with the help of HENRYWIN v3.20 (Chemservice S.A., 2011). A constant of 2.93 E+001 Pa*m³/mol was estimated at 25 °C for the substance bis(2,6-diisopropylphenyl)carbodiimide.

Monitoring data

In accordance to REACH Regulation (EC) 1907/2006 this information is not mandatory for a registration of a chemical at a tonnage band of 100 - 1000 tons/year.