A toxicological evaluation of a fulvic and humic acids preparation

Timothy S Murbach; Róbert Glávits; John R Endres; Amy E Clewell; Gábor Hirka; Adél Vértesi; Erzsébet Béres; Ilona Pasics Szakonyiné

doi:10.1016/j.toxrep.2020.08.030

A toxicological evaluation of a fulvic and humic acids preparation

Toxicol Rep. 2020 Sep 14:7:1242-1254. doi: 10.1016/j.toxrep.2020.08.030. eCollection 2020.

Authors

Timothy S Murbach¹, Róbert Glávits², John R Endres¹, Amy E Clewell¹, Gábor Hirka^{2

3}, Adél Vértesi³, Erzsébet Béres³, Ilona Pasics Szakonyiné²

Affiliations

¹ AIBMR Life Sciences, Inc., 1425 Broadway, Suite 458, Seattle, WA 98122, USA.
² Toxi-Coop Zrt., Berlini utca 47-49, H-1045 Budapest, Hungary.
³ Toxi-Coop Zrt., Arácsi út 97, 8230 Balatonfüred, Hungary.

Abstract

Humic substances are ubiquitous in soils and waters. These complex superstructures are derived from the decomposition of dead plant and animal matter and are vital to soil health. Their heterogenous composition is specific to their site of origin and is comprised of weakly bound aggregates of small organic compounds that can sequester minerals and make them available to plants. As such, they may possess potential nutritional value for humans, and extractions of fulvic and humic acids can be produced that could be suitable for such purposes. For this reason, we evaluated the toxicological profile of a specific preparation (blk. 333) of fulvic and humic acids derived from a lignite deposit in Alberta, Canada and found it to lack genotoxic potential in a bacterial reverse mutation test, in vitro mammalian chromosomal aberration test, and in vivo mammalian micronucleus test. No general or organ toxicity was observed in Wistar rats following 90 days of continuous exposure, and a no observed adverse effect level (NOEAL) was determined at 2000 mg/kg bw/day, the highest tested dose. Our results suggest the feasibility of further evaluation for development of the preparation as a nutritional supplement in food.

Keywords: ANOVA, analysis of variance; CDFA, California Department of Food and Agricultural; Cl-HA, chlorinated humic acid; DME, Dulbecco’s modified Eagle’s; EFSA, European Food Safety Authority; FA, fulvic acid; FOB, functional observation battery; Fulvic acid; GLP, good laboratory practice; HA, humic acid; Humic acid; MPCE, micronucleated polychromatic erythrocytes; NOAEL; NOAEL, no observed adverse effect level; O3-HA, ozonated humic acid; O3/Cl2-HA, ozonated and chlorinated humic acid; OECD, Organisation for Economic Co-operation and Development; S9, post mitochondrial supernatant S9-mix Phenobarbital/β-naphthoflavone-induced rat liver S9 metabolic activation system; SCE, sister chromatid exchange; SD, Sprague-Dawley; SOP, standard operating procedure; SPF, specific pathogen-free; Safety; TG, test guideline; TSH, thyroid stimulating hormone; Toxicity; blk. 333; fT4, free thyroxine.