In vitro assessment of skin sensitization, photosensitization and phototoxicity potential of commercial glyphosate-containing formulations

Toxicol In Vitro. 2017 Dec;45(Pt 3):386-392. doi: 10.1016/j.tiv.2017.04.001. Epub 2017 Apr 4.

Abstract

This study evaluated the applicability of a modified Direct Peptide Reactivity Assay (DPRA) (OECD N° 442C, 2015) through the 10-fold reduction of reaction volume (micro-DPRA, mDPRA) for skin sensitization evaluation of six commercial glyphosate-containing formulations. In addition, another modification of DPRA was proposed by adding a UVA (5J/cm2) irradiation step, namely photo-mDPRA, to better characterize (photo)sensitizer materials. The phototoxicity profile of pesticides was also evaluated using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU-PT) (OECD N° 432, 2004). The mDPRA could represent an environmentally acceptable test approach, since it reduces costs and organic waste. Peptide depletion was greater in photo-mDPRA and changed the reactivity class of each test material, in comparison to mDPRA. Thus, the association of mDPRA with photo-mDPRA was better for correctly characterizing human (photo)sensitizer substances and pesticides. In general, cysteine depletion was greater than that of lysine for all materials tested in both mDPRA and photo-mDPRA. Furthermore, while 3T3-NRU-PT is unable to predict (photo)sensitizers, it was capable of correctly identifying the phototoxic potential of the tested agrochemical formulations. In conclusion, mDPRA plus photo-mDPRA and 3T3-NRU-PT seem to be preliminary non-animal test batteries for skin (photo)sensitization/phototoxicity assessment of chemicals, agrochemical formulations and their ingredients.

Keywords: Agrochemical mixtures; Glyphosate; Non-animal testing; Phototoxicity; Skin photosensitization; Skin sensitization.

MeSH terms

  • Animal Testing Alternatives
  • Animals
  • BALB 3T3 Cells
  • Cysteine / metabolism
  • Dermatitis, Phototoxic / pathology*
  • Drug Compounding
  • Glycine / analogs & derivatives*
  • Glycine / toxicity
  • Glyphosate
  • Herbicides / toxicity*
  • Humans
  • Lysine / metabolism
  • Mice
  • Neutral Red
  • Photosensitivity Disorders / chemically induced*
  • Photosensitivity Disorders / pathology
  • Skin / drug effects*
  • Skin / pathology
  • Ultraviolet Rays

Substances

  • Herbicides
  • Neutral Red
  • Lysine
  • Cysteine
  • Glycine