Heinz Walter Thielmann

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substances potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen . The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ‘glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential’. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected. EFSA concluded ‘that there is very limited evidence for an association between glyphosate-based formulations …

Struktur-Wirkungsbeziehungen polyfunktioneller Diterpene des Tigliantyps, IV [1-3]. Derivate des Tiglians mit fehlendem oder geöffnetem Cyclopropanring und ihre irritierende und tumorpromovierende Wirkung / Structure-Activity Relationships of Polyfunctional Diterpenes of the Tigliane Type, IV [1-3]. Derivatives of Tigliane without or with Opened Cyclopropane Ring and their Irritant and Promoting Activity

Abstract The synthesis of the esters 6d-8d, 9 c and 10 c is described. These compounds are closely structurally related to the irritant and tumorpromoting 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 a) and to phorbol-12,13-didecanoate (PDD, 2 c) except that they possess no cyclopropane ring. Biological tests show that opening or complete removal of the cyclopropane ring leads to nearly total loss of irritant or tumorpromoting (tested in the case of 9 c and 10 c) activity.

[On the chemistry of phorbol. IV. Polybenzoate and acetate of phorbol and phorbol-3-ol and functional derivatives of the allyl grouping of phorbol].

Base catalysed transesterification of phorbol-12,13,20-tribenzoate yields phorbol-12,13-dibenzoate. By base catalysed transesterification of phorbol-pentaacetate phorbol-9,12,13-triacetate is obtained. This can be re-acetylated to give phorbol-9,12,13,20-tetraacetate which is also obtained by treatment of phorbol-12,13,20-triacetate with acetic anhydride/p-toluene-sulfonic acid. Reduction of phorbol-12,13,20-triacetate with LiAlH4 yields phorbol-3-ol which reduces Fehlings and Tollens reagent. Reduction of the 3-keto group alone can be accomplished with sodium borohydride. From all phorbol-esters investigated only in phorbol-pentaacetate an acetyl migration is observed during the sodium borohydride reduction leading to phorbol-3-ol-3,9,12,13,20-pentaacetate. By these findings those two tertiary hydroxyl groups of phorbol which are not acetylated with acetic anhydride/pyridine at room temperature were further characterized. Oxidation of phorbol-12,13-diacetate with activated manganese dioxide yields phorbol-20-al-12,13-diacetate. By evaluation of nmr-spectra of this aldehyde and of some of its derivatives as well as of the epoxide of phorbol-12,13-diacetate and of 6-oxo-7-hydroxy- and 6,7-diacetoxy-20-nor-phorbol-12,13-diacetate the sequence of C-atoms around the allylic alcohol group of phorbol is further characterized.