A species specific metabolism leading to male rat reprotoxicity of Cyclamen aldehyde: in vivo and in vitro evaluation
Autor: | Gregory M. Adamson, Adrian Nordone, Heike Laue, Andreas Natsch |
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Rok vydání: | 2020 |
Předmět: |
Male
Metabolite Coenzyme A Toxicology 03 medical and health sciences chemistry.chemical_compound 0404 agricultural biotechnology Species Specificity In vivo Animals Spermatogenesis Infertility Male 030304 developmental biology 0303 health sciences Chemistry 04 agricultural and veterinary sciences General Medicine Metabolism 040401 food science In vitro Rats Biochemistry Cinnamates Toxicity Reproductive toxicity Food Science |
Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 153 |
ISSN: | 1873-6351 |
Popis: | Cyclamen aldehyde (CA; 3-(4-isopropylphenyl)-2-methylpropanal) is a widely used fragrance material. Repeated dose studies in rats revealed adverse effects on sperm maturation. Here we review all the mechanistic and in vivo evidence, to determine relevancy to human health. The effect on spermatogenesis appears to be linked to the metabolite p-isopropyl-benzoic acid (p-iPBA). Studies in rat, rabbit and human suspended hepatocytes indicated species differences with p-iPBA detected in rat hepatocytes only. In plated rat hepatocytes, p-iPBA is conjugated to Coenzyme A (CoA) and p-iPBA-CoA accumulates to stable levels over 22 h. In vitro accumulation of CoA conjugates is a metabolic hallmark correlated to male rat reproductive toxicity for related compounds. p-iPBA-CoA is formed in vivo in liver and testes of rats dosed with CA. In plated rabbit and human hepatocytes p-iPBA-CoA doesn't accumulate. Correlating to this lack of metabolite accumulation, no effects of CA on spermatogenesis were observed in a rabbit in vivo study. A species specific metabolic fate linked to CA toxicity in male rats is postulated which appears not relevant to the rabbit as non-responder species. Lack of accumulation of p-iPBA-CoA in human hepatocytes indicates that like rabbits, humans are unlikely to be vulnerable to p-iPBA hepatic and testicular toxicity. |
Databáze: | OpenAIRE |
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