QSARs and Read-Across for Thiochemicals: A Case Study of Using Alternative Information for REACH Registrations

  • Monika NendzaEmail author
  • Jan Ahlers
  • Dirk Schwartz
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


A case study on acute aquatic toxicity of thiochemicals shows the possibilities and limitations of filling data gaps with alternative information in accordance with the requirements of REACH. It is the objective of this study to extract as much information as possible from available experimental studies with fish, daphnia, and algae to estimate required data by QSARs and read-across.

Thiochemicals are considered to be toxic with an unspecific reactive mode of action (MoA) causing so-called excess toxicity, i.e., the effects are much higher than estimated from log KOW-dependent baseline QSARs. Differences in toxicity between groups of thiochemicals, for example, thioglycolates or mercaptopropionates, are thought to be due to differences in reactivity of the respective sulfur moiety, i.e., toxicodynamic differences. Thiochemicals within each group are different with regard to partitioning between biophases related to, e.g., increasing aliphatic chain length, i.e., toxicokinetic differences.

Due to the toxicodynamic and toxicokinetic differences, QSARs and read-across are limited to thiochemicals within the same group. Since the database per group of thiochemicals is too small to derive scientifically valid QSARs, most of the 36 data gaps for 16 thiochemicals to be registered by 2018 were closed by read-across. Testing strategies to fill remaining data gaps include tests with algae (six substances) and daphnia (six substances). Only for two substances, experimental (limit) fish studies are recommended. Overall, a substantial (>60%) reduction of tests by predictive in silico methods is possible.

Key words

REACH QSARs Read-across Category approaches Acute aquatic toxicity Unspecific reactive mode of action (MoA) Excess toxicity Integrated testing strategies (ITS) 3Rs 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Analytical LaboratoryLuhnstedtGermany
  2. 2.ConsultantBerlinGermany
  3. 3.Bruno Bock ThiochemicalsMarschachtGermany

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