Synthetic resin, a reaction product of 4,4'-bis(N-maleimido)diphenylmethane with 3-aminobenzoic acid hydrazide

Endpoint summary

Description of key information

- study conducted according to OECD guideline 203 (1983), 50 carp were exposed to nominal 0.19, 0.34, 0.62, 1.11 and 2 mg/L of 1,1'-(methylenedi-p-phenylene)bismaleimide for 96 h under semi static conditions, LC50 = 0.91 mg/L, read-across

- Short-term toxicity to aquatic invertebrates: QSAR estimation for the pentamers and dimers (most occurring oligomers) of Compimide 183 using ECOSAR v2.0, short-term toxicity to aquatic invertebrates lowest estimated 48 h - LC50 value: 9.5 mg/L;lowest 48h - LC50 value for pentamers = 63.68 mg/L

- toxicity to aquatic algae and cyanobacteria: QSAR estimation for the pentamers and dimers (most occurring oligomers) of Compimide 183 using ECOSAR v2.0, Toxicity to aquatic algae and cyanobacteria lowest 96 h - EC50 value for dimers: EC50 = 3.58 mg/L; lowest 96 h EC50 value for pentamers: EC50 = 22.17 mg/L

Additional information

There are no experimental data for ecotoxicological effects of Compimide 183, however, a short-term toxicity to fish study according to OECD guideline 203 is available for the structurally similar substance 1,1'-(methylenedi-p-phenylene)bismaleimide. Furthermore, QSAR estimations were performed for short-term toxicity to aquatic invertebrates and for toxicity to aquatic algae and cyanobacteria for the dimers and pentamers present in the oligomer-mixture of Compimide 183. Dimers and pentamers are considered to be the main oligomers present in Compimide 183. These information are assumed to be reliable and sufficient to characterize the ecotoxicological profile of Compimide 183, a justification is given below.

Short-term toxicity to fish:

In a study conducted according to OECD guideline 203 (adopted 1983) 10 fish each were exposed to nominal concentrations of 0.19, 0.34, 0.62, 1.11 and 2.0 mg/L of 1,1'-(methylenedi-p-phenylene)bismaleimide for 96 h under semi-static conditions. The analysis of the nominal concentrations by HPLC in samples of the nominal concentrations 0.19 and 0.62 no test item was detected (concentration below the limit of quantification). At higher nominal concentrations, i.e. 2.0 mg/L only 29.0 to 38.4 % of the test item were detected by HPLC, thus the test item is considered to be unstable in aqueous solutions. However, the following LC50 (96 hours) was obtained: 0.91 mg/L (nominal).

During synthesis of Compimide 183 both reactants 3-aminobenzohydrazide (ABH) and 1,1'-(methylenedi-p-phenylene)bismaleimide (MDAB) are used as follows: ABH is completely consumed and MDAB constitutes approximately 50% of the final composition of Compimide 183.

At reaction start, the mol ratio of MDAB to ABH is 1:0.195, i.e. roughly 5.13 mole MDAB per mole ABH. The underlying mechanism of the reaction is the Aza-Michael addition of ABH to MDAB. It is therefore anticipated that, in a first step, practically all ABH molecules will readily react with the excess of MDAB molecules to build dimers (1MDAB:1ABH) and trimers (2MDAB:1ABH and 1MDAB:2ABH), followed by the generation of tetramers (2MDAB :2ABH) and pentamers (3MDAB:2ABH). Higher oligomers are possible, but given the low amount of ABH present, the reaction is anticipated to end once all ABH molecules are bond to 2 molecules of MDAB, and thus saturated, as in the case of the trimers 2MDAB:1ABH and pentamers 3MDAB:2ABH. For the same reason, the content of oligomeric products containing one or two ABH molecules at the end(s) of an oligomer chain (such as trimers 1MDAB:2ABH and tetramers 2MDAB:2ABH) is expected to be low. Except for the dimeric products, due to the mol ratio of the starting materials all other constituents are anticipated to be oligomeric products, in which an MDAB monomeric unit is always present at both ends of each oligomer chain. Therefore, all constituents of the target substance and the source substance MDAB share structural similarities with common functional groups, in particular the N-phenylmaleimide moiety.

Furthermore, the main reactive group of Compimide 183 and MDAB is theN-phenylmaleimide-moiety. Especially the susceptibility of fish to this reactive group is well-known and the toxicity was shown for Bismaleimides where the N-phenylmaleimide groups are connected by the nitrogen atoms via alkyl- or aryl-group linker. In the final composition of Compimide 183 (oligomers) this group exhibits a reduced reactivity due to their participation in the polymerization and the reduced availability of reactive groups due to steric congestion of the long polymer chains, thus, the use of the results obtained from the monomer MDAB can be considered as a worst case approach to conservatively characterize the ecotoxicological hazard of Compimide 183.Moreover, the functional groups resulting from the covalent bonding of the source substances MDAB and ABH, e.g. alkylaniline and (mono- and dialkyl)hydrazine do not provide structural alerts for an increased toxicity in comparison to those already exhibited by the parent compounds.Thus, fish toxicity data for MDAB is the most relevant data for risk assessment as well as classification and labeling of Compimide 183.

In order to evaluate the short-term toxicity to aquatic invertebrates and to algae and cyanobacteria a QSAR prediction was performed using ECOSAR v2.0 software. The program uses a linear mathematical relationship between the predicted log Kow values and the corresponding log of the measured toxicity values (mmol/L) for a suite of training set chemicals within each class of interest to predict the toxicity to aquatic invertebrates and algae and cyanobacteria. The substance, in this case the mainly occurring dimers and pentamers of Compimide 183, is screened for known structural features with a known reactivity. For the exact algorithm please refer to the 'attached justification' section.

However, Compimide 183 contains several structural fragments which are known to mediate toxicity by other modes than narcosis, i.e. structures similar to the anilines (unhindered), hydrazines, imides and amides class of substances and also the maleimide moieties mentioned above. The majority of these structures are assumed to exhibit a reduced reactivity within the respective oligomer due to their participation in the polymerization and formation of functional groups with no toxicological alert. Thus, only the terminal groups are considered to be sufficiently reactive. Based on the hypothesis mentioned above the oligomers are most likely less toxic than the monomers.

However, due to lack of experimental data and for precautionary reasons, the substance is classified into Category Acute 1 according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) based on the short-term toxicity to fish study conducted with MDAB.