Unraveling How Membrane Nanostructure Changes Impact the Eye Irritation of Nonionic Alkyl Ethoxylate Surfactants.

Nonionic surfactants used in agri-spraying processes may cause varying degrees of corneal irritation when they come in direct contact with farmers' eyes, and the exact irritations are thought to be determined by how surfactants interact with corneal cell membranes. However, how nonionic surfactants interact with cell membranes at the molecular and nano levels remains largely unexplored. In this study, the interactions between nonionic surfactants (alkyl ethoxylate, C12Em) and lipid membranes were examined by membrane permeability measurement, quartz crystal microbalance with dissipation, dual polarization interferometry, confocal laser scanning microscopy, and neutron reflection, aiming to reveal complementary structural features at the molecular and nano levels. Apart from the extremely hydrophobic surfactant C12E2, all nonionic surfactants studied could penetrate the model cell membrane composed of a phosphocholine lipid bilayer. Nonionic surfactants with intermediate amphiphilicity (C12E6) rapidly fused into the lipid membrane and stimulated the formation of pores across the lipid bilayer, consistent with the cytoplasm leakage and fast cell necrosis observed from the cytotoxicity study of corneal cells. In comparison, while hydrophobic and hydrophilic surfactants [those with long and short ethoxylates (C12E4,12,23)] could cause mild structural alteration to the outer lipid layer of the membrane, these structural changes were insufficient to elicit large cytoplasmic leakage rapidly and instead cell death occurred over longer periods of time due to changes in the membrane permeability. These results reveal the strong link of surfactant-lipid membrane interactions to surfactant cytotoxicity and the association with amphiphilicity of nonionic surfactants.

Increasing confidence in waiving dermal toxicity studies: A comparison of oral and dermal acute data with alternative approaches for agrochemicals and products.

The refinement of OECD 402 study design and criteria under which the study can be waived has been welcomed in some regulatory regions but met with uncertainty in others. To address these human safety concerns, previously available in vivo acute oral and acute dermal toxicity data was evaluated from a total of 597 agrochemical active ingredients and products. It was identified that all active ingredients and 99.6% of products had an acute dermal classification equal to or less toxic than their acute oral classification, confirming that waiving the acute dermal study and basing the outcome on the acute oral toxicity result has no impact on human health assessment. Additionally, automated Acute Toxicity Estimate (ATE) calculations were conducted on 440 products to evaluate if the predicted dermal toxicity resulted in the same in vivo classification. 93% of ATE predictions provided excellent correlation to the in vivo result and 6.4% resulted in a more conservative prediction. It is therefore clear that the results of this investigation, should remove any regulatory concerns and that OECD 402 can be confidently eliminated in its entirety from testing requirements globally.