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Administrative data

Link to relevant study record(s)

Description of key information

Based on in vitro and in vivo data from studies performed with 1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione] (EC 264-637-8, CAS 64051-50-9), oral absorption is assumed to be 50 %, dermal absorption 25 % and inhalation absorption 100 %. Furthermore, the potential for distribution and bioaccumulation is low and the substance is expected to be completely metabolised to water and CO2, through beta-oxidation producing energy, or endogenous metabolites.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
25
Absorption rate - inhalation (%):
100

Additional information

Introduction

The substance is 1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione] (EC 264-637-8, CAS 64051-50-9) which also goes under the code names EXP1507738 and EXP1505454.

Physico-chemical properties and the results of in vitro and in vivo studies with 1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione] have been used to determine a toxicokinetic profile as detailed below.

 

Physico-Chemical Properties

The substance is a brown viscous liquid. The molecular weight (MW) is 853 g/mol and its water solubility is < 0.05 µg/mL (poorly water soluble) with a calculated log Pow value of 13.9396. The vapour pressure was determined to be 1.471 × 10^-7 Pa at 20 °C and 2.036 × 10^-7 Pa at 25 °C.

Adsorption

Oral Adsorption

The high molecular weight in combination with the poor water-solubility and high octanol/water partition coefficient may limit the rate absorption from the gut.

Repeated dose oral and reproduction/developmental toxicitystudies conducted up to and including the limit dose of 1000 mg/kg bw/day were well tolerated, without any mortality and no evidence of any target organ of toxicity. In addition, an acute oral toxicity study at 2000 mg/kg bw showed no mortality, no clinical signs and no findings during necropsy. This would infer that 1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione] has either a very favourable toxicological profile following oral administration, or limited to no oral absorption. The latter is however considered highly unlikely given the lipophilic nature of the substance and by the increased body weights observed in females during pregnancy and lactation, and in their offspring, in the OECD 421 study. 

Therefore, in the absence of any quantitative data, the default value of 50 % is assumed for oral absorption in accordance with the ECHA guidance.

Dermal Adsorption

A substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis, and since the water solubility of 1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione] is very low it is expected that dermal penetration will also be very limited to extremely limited. This is further supported by the estimated Log Pow values which also suggest limited dermal absorption.

In conclusion, in the absence of any quantitative data and in line with latest EC guidance on dermal absorption (EFSA Panel on Plant Protection Products and their Residues (PPR); Guidance on Dermal Absorption. EFSA Journal 2017;15(6):4873), the default value of 25 % is assumed for dermal absorption.

Inhalation Adsorption

With respect to inhalation absorption, in the absence of any quantitative data and as a worst-case assumption for human health risk assessment purposes absorption by inhalation of 1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione] is assumed to be 100 %.

Distribution

Repeat-dose oral toxicity studies did not identify any target organ. The high molecular weight and low water solubility suggest poor distribution. Moreover, the high estimated Log Pow value suggests that the intracellular concentration of components may be higher than extracellular concentration, and preferential partition to fatty tissues. However, there was no evidence of bioaccumulation from the available repeat-dose toxicity studies and based on this the potential for bioaccumulation is considered low.

Metabolism and Elimination

Nothing could be inferred from the results of the Ames test or in vitro genotoxicity studies (chromosome aberration and gene mutations in mammalian cells), because1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione]was not genotoxic, mutagenic or clastogenic in either the presence or absence of S9 metabolising system. The nature of the components suggests that most components may be metabolised to water and CO2, through beta-oxidation, producing energy, or transformed into endogenous metabolites.


Conclusion

Based on in vitro and in vivo data from studies performed with 1,1'-[iminobis(ethyleneiminoethylene)]bis[3-(octadecenyl)pyrrolidine-2,5-dione] (EC 264-637-8, CAS 64051-50-9), oral absorption is assumed to be 50 %, dermal absorption 25 % and inhalation absorption 100 %. Furthermore, the potential for distribution and bioaccumulation is low, and the substance is expected to be completely metabolised to water and CO2, through beta-oxidation producing energy, or endogenous metabolites.