Smithers will exhibit at stand A1-07 during the SETAC Europe 32^nd Annual Meeting, May 15-19, 2022, in Denmark. Meet with our team to discuss testing needs or hear about the latest developments in REACh requirements and SANTE guidance.

Several experts from our Harrogate, UK lab will be available for discussions during the conference. Stop by the booth to speak with Dr. Sharon Swales, Managing Director. Meet Sara Penketh, who was recently appointed as Director of Fate & Metabolism, UK and and Dr. Kalumbu Malekani, Technical Director, North America, and Director of Environmental Fate & Metabolism, US.

Talk to Rory Mumford, Senior Manager Accurate Mass, to learn about in vitro techniques for plant and animal metabolism and practical approaches to separation of stereoisomers.

Speak with Tracey Goodband, Senior Manager, Aquatic Ecotoxicology, about MEOGRT and recent Endocrine Testing updates.

Meet Joseph Marini, Senior Research Biologist, who has co-authored the poster “Comparison of Xenopus laevis NF developmental stage-matched control data in Amphibian Metamorphosis Assay continuous quantitative endpoints.”

Discuss Environmental Risk Assessment and pharmaceutical regulatory updates with Dr. Erick Nfon, Regulatory Affairs Scientist, who will present the poster “Environmental Fate of Estetrol (E4), a native estrogen used in oral contraception.”

Learn more about the presentation topics below. We look forward to seeing you in Denmark. Contact us to schedule a time to meet.

Poster presentations:

Title: Environmental Fate of Estetrol (E4), a native estrogen used in oral contraception
Session: Pharmaceuticals in the environment – New insights, regulatory needs, and knowledge gap

Authors: Erick Nfon¹, Patrick Kestemont², Glwadys Rausin³, Céline Gérard³, Jean-Michel Foidart^3
1Smithers, North Yorkshire, United Kingdom; ²Institute of Life, Earth & Environment, University of Namur, Belgium; ³Mithra Pharmaceuticals, Liege, Belgium

Estetrol (E4) is a unique native estrogen produced by the human fetus during pregnancy. E4 formulated as the monohydrate is a new active substance that received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for use in a combined oral contraceptive. E4 is projected to enter the aquatic environment through effluents discharged by sewage treatment plants. The environmental fate of E4 was investigated using a battery of studies designed to describe its physical/chemical characteristics and potential for persistence and bioaccumulation in the environment. The mean measured octanol/water partition coefficient (log K_OW) of E4 was determined to be 1.65. In a ready biodegradability study, the mean biodegradation was 3% after 28 days incubation. E4 is not significantly sorbed to soils and sewage treatment solids with Freundlich isotherm adsorption coefficients K_f between 88 and 147 in soils and 35 and 36 in sludges, respectively. In a 100-d aerobic–aquatic biodegradation study into two systems, E4 biodegradation rates in water were 0.182/d and 0.057/d (half-life 3.81 and 12.08 d, respectively) and in sediment were 0.103/d and 0.169/d (half-life 6.71 and 4.09 d, respectively). The results presented illustrate the transient nature of E4 in the aquatic environment and indicate that bioaccumulation of E4 would not be expected.

Title: Comparison of Xenopus laevis NF developmental stage-matched control data in Amphibian Metamorphosis Assay continuous quantitative endpoints (HLL, SVL, wet weight).
Session: Investigating endocrine-disrupting properties of chemicals: developments and challenges towards new approach methodologies (NAMs)

Authors: Maria Estebaranz-Yubero¹, Apostolos Koutsaftis¹, Oliver Koerner², Sonja Haaf², Joseph Marini³, Lee Sayers^3
 1ERM, UK, ²ADAMA, Cologne Germany, ³Smithers, Wareham, MA

The analysis of continuous quantitative Xenopus laevis endpoints such as snout-to-vent length (SVL), hind limb length (HLL), nHLL (normalized by SVL) and wet weight is performed to assess statistically significant differences between the negative control and active substance treatments in the Amphibian Metamorphosis Assay (AMA) for the detection of potential thyroid modes of action according to Guidelines OECD 231 and OPPTS 890.1100. However, the current statistical analysis of these parameters at Day 7 and 21 is routinely performed by using the replicate means or medians of the recorded HLL, nHLL, SVL and wet weight individual values without taking into consideration the different stages of development within each control or treatment replicate. Furthermore, these endpoints are well known to be directly impacted by developmental stage in tadpoles and so using stage-matched data may have an impact in the interpretation of the biological results. This is also the case for tadpole thyroid gland histopathological findings, where it is already recognised in both Guidelines that the most appropriate approach is to use NF developmental stage-matched tadpoles for evaluation. Consequently, individual control HLL, nHLL, SVL and wet weight values on Day 7 and 21 from the available data set have been extracted and evaluated according to NF developmental stage. The analysis presented here aims to develop a NF developmental stage-matched Historical Control Database (HCD) that allows the assessment of potential impact in the outcome of statistically significant results of these thyroid screening parameters, as well as the variability of NF developmental stage-matched control data across different GLP AMA-performing laboratories.