The use of adverse outcome pathways in the safety evaluation of food additives
Vinken, Mathieu ; Kramer, Nynke ; Allen, Timothy E.H. ; Hoffmans, Yvette ; Thatcher, Natalie ; Levorato, Sara ; Traussnig, Heinz ; Schulte, Stefan ; Boobis, Alan ; Thiel, Anette ; Rietjens, Ivonne M.C.M. - \ 2020
Archives of Toxicology 94 (2020). - ISSN 0340-5761
Adverse outcome pathway - Food additive - Safety evaluation
In the last decade, adverse outcome pathways have been introduced in the fields of toxicology and risk assessment of chemicals as pragmatic tools with broad application potential. While their use in the pharmaceutical and cosmetics sectors has been well documented, their application in the food area remains largely unexplored. In this respect, an expert group of the International Life Sciences Institute Europe has recently explored the use of adverse outcome pathways in the safety evaluation of food additives. A key activity was the organization of a workshop, gathering delegates from the regulatory, industrial and academic areas, to discuss the potentials and challenges related to the application of adverse outcome pathways in the safety assessment of food additives. The present paper describes the outcome of this workshop followed by a number of critical considerations and perspectives defined by the International Life Sciences Institute Europe expert group.
Characterizing the coverage of critical effects relevant in the safety evaluation of food additives by AOPs
Kramer, Nynke I. ; Hoffmans, Yvette ; Wu, Siyao ; Thiel, Anette ; Thatcher, Natalie ; Allen, Timothy E.H. ; Levorato, Sara ; Traussnig, Heinz ; Schulte, Stefan ; Boobis, Alan ; Rietjens, Ivonne M.C.M. ; Vinken, Mathieu - \ 2019
Archives of Toxicology 93 (2019)8. - ISSN 0340-5761 - p. 2115 - 2125.
3Rs - Acceptable daily intake - Adverse outcome pathway - Critical adverse effect - Food additives
There is considerable interest in adverse outcome pathways (AOPs) as a means of organizing biological and toxicological information to assist in data interpretation and method development. While several chemical sectors have shown considerable progress in applying this approach, this has not been the case in the food sector. In the present study, safety evaluation reports of food additives listed in Annex II of Regulation (EC) No 1333/2008 of the European Union were screened to qualitatively and quantitatively characterize toxicity induced in laboratory animals. The resulting database was used to identify the critical adverse effects used for risk assessment and to investigate whether food additives share common AOPs. Analysis of the database revealed that often such scrutiny of AOPs was not possible or necessary. For 69% of the food additives, the report did not document any adverse effects in studies based on which the safety evaluation was performed. For the remaining 31% of the 326 investigated food additives, critical adverse effects and related points of departure for establishing health-based guidance values could be identified. These mainly involved effects on the liver, kidney, cardiovascular system, lymphatic system, central nervous system and reproductive system. AOPs are available for many of these apical endpoints, albeit to different degrees of maturity. For other adverse outcomes pertinent to food additives, including gastrointestinal irritation and corrosion, AOPs are lacking. Efforts should focus on developing AOPs for these particular endpoints.
Synchronization and resynchronization of inseminations in lactating dairy cows with the CIDR insert and the Ovsynch protocol
Bartolome, J.A. ; Leeuwen, J.J.J. van; Thieme, M. ; Sa'filho, O.G. ; Melendez, P. ; Archbald, L.F. ; Thatcher, W.W. - \ 2009
Theriogenology 72 (2009)6. - ISSN 0093-691X - p. 869 - 878.
timed artificial-insemination - unknown pregnancy status - estrous-cycle - nonpregnancy diagnosis - bovine somatotropin - progesterone insert - holstein cows - ovulation - ultrasonography - presynchronization
Pregnancy per artificial insemination (AI) was evaluated in dairy cows (Bos taurus) subjected to synchronization and resynchronization for timed AI (TAI). Cows (n = 718) received prostaglandin F2a (PGF) on Days –38 and –24 (Days 39 and 53 postpartum), gonadotropin-releasing hormone (GnRH) on Day –10, PGF on Day –3, and GnRH and TAI on Day 0. Between Days –10 and –3, cows received a progesterone intravaginal insert (CIDR group) or no CIDR (Control group). Between Days 14 and 23, cows received a CIDR (Resynch CIDR group) or no CIDR (Resynch control group), GnRH on Day 23, with pregnancy diagnosis on Day 30. Cows in estrus (between Days 0 and 30) were re-inseminated at detected estrus (RIDE). Nonpregnant cows received PGF on Day 30 and GnRH and TAI on Day 33. Plasma progesterone was determined to be low or high on Days –24 and –10. Pregnancy rates were evaluated 30 and 55 d after AI. The CIDR insert included in the Presynch-Ovsynch protocol did not increase overall pregnancy per AI for first service (36.1% and 33.6% for CIDR; 34.1% and 28.8% for Control) but did decrease pregnancy loss (7.0% for CIDR and 15.6% for Control). The CIDR insert increased pregnancy per AI in cows with high progesterone at the time the CIDR insert was applied. Administration of a CIDR insert between Days 14 and 23 of the estrous cycle after first service did not increase overall pregnancy per AI to second service (24.7% and 22.7% for Resynch CIDR; 28.6% and 25.3% for Resynch control). For second service, RIDE cows had lower pregnancy rates in the Resynch CIDR group than in the Resynch control group. Cows with a CL (corpus luteum) at Day 30 had higher pregnancy rates in the Resynch CIDR group than those in the Resynch control group
The degree of phenotypic resemblance of the near-isogenic lines of the wheat cultivar Thatcher with their recurrent parent.
Zeven, A.C. ; Waninge, J. - \ 1986
Euphytica 35 (1986). - ISSN 0014-2336 - p. 665 - 676.