title: Using in vitro/in silico data for consumer safety assessment of feed flavoring additives--A feasibility study using piperine.
abstract: Consumer health risk assessment for feed additives is based on the estimated human exposure to the additive that may occur in livestock edible tissues compared to its hazard. We present an approach using alternative methods for consumer health risk assessment. The aim was to use the fewest possible number of animals to estimate its hazard and human exposure without jeopardizing the safety upon use. As an example we selected the feed flavoring substance piperine and applied in silico modeling for residue estimation, results from literature surveys, and Read-Across to assess metabolism in different species. Results were compared to experimental in vitro metabolism data in rat and chicken, and to quantitative analysis of residues' levels from the in vivo situation in livestock. In silico residue modeling showed to be a worst case: the modeled residual levels were considerably higher than the measured residual levels. The in vitro evaluation of livestock versus rodent metabolism revealed no major differences in metabolism between the species. We successfully performed a consumer health risk assessment without performing additional animal experiments. As shown, the use and combination of different alternative methods supports animal welfare consideration and provides future perspective to reducing the number of animals.
authors.affiliation: DSM Nutritional Products AG, Wurmisweg 576, 4303 Kaiseraugst, Switzerland. Electronic address: anette.thiel@dsm.com.
authors.forename: A
authors.initials: A
authors.lastname: Thiel
authors.affiliation: DSM Nutritional Products AG, Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Etheve
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Fabian
authors.affiliation: TNO, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
authors.forename: W R
authors.initials: WR
authors.lastname: Leeman
authors.affiliation: DSM Nutritional Products AG, Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
authors.forename: J R
authors.initials: JR
authors.lastname: Plautz
mesh_terms: D000470:Alkaloids / Q000009:adverse effects*; D000821:Animal Feed / Q000009:adverse effects*; D000818:Animals; D052117:Benzodioxoles / Q000009:adverse effects*; D002645:Chickens; D003198:Computer Simulation; D003257:Consumer Product Safety; D005240:Feasibility Studies; D005260:Female; D005421:Flavoring Agents / Q000009:adverse effects*; D008297:Male; D010880:Piperidines / Q000009:adverse effects*; D053284:Polyunsaturated Alkamides / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment / Q000379:methods; D012449:Safety
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D005421:Flavoring Agents; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C008922:piperine
keywords: Metabolism; Piperine; Residue estimation; Risk assessment; Transfer database