Repeated-dose toxicity testing under REACH uses large numbers of animals, and no new approach methods (NAMs) have yet achieved regulatory acceptance to replace it. This study tested a “smart” approach: a short-term animal study combined with modern metabolomics, designed to provide more information from fewer animals.
Dicyclopentadiene (DCPD, CAS 77-73-6) is an olefinic hydrocarbon used to make resins, adhesives, coatings and elastomers. It already has a rich toxicity dataset, including 90-day studies, so it made a good test case. Wistar rats received DCPD daily for 14 days at 0, 50 and 150 mg/kg bw. Classical OECD 407 endpoints were assessed, and blood samples were profiled using GC-MS and LC-MS/MS. The results were compared against more than 110 known toxicity patterns in the MetaMap®Tox database.
The metabolomics pointed to liver enzyme induction leading to increased breakdown of thyroid hormones, possible liver effects in males, and adrenal effects consistent with stress. All of these matched the known findings from DCPD’s existing studies, and no new organ toxicity or hormone disruption was identified. The study shows that short-term studies combining classical toxicology with metabolomics can accurately reflect repeat-dose organ toxicity data, support integrated assessments, and reduce the number of animals needed under REACH.
Authors
C. Haines, B. van Ravenzwaay, N. Aygun Kocabas, F. Faulhammer, B. Flick, V. Giri, S. Sperber, M. Penman, L. G. Higgins, H. Kamp, M. Rooseboom
EUROTOX 2024, Poster P06-08 (Session PV01, Omics in Toxicology), Abstract ID 479.