Himematsutake (Iwade Strain 101) extract (ABM-FD): Genetic toxicology and a 3-month dietary toxicity study in rats

Abstract

Agaricus blazei Murrill, an edible mushroom, is used as a functional food due to medicinal effects of (1→6)-β-D-glucan protein complex which has been shown to have anti tumour activity in mice. A 13week oral subchronic study in rats performed at 500, 1000 or 2000mg/kg/day caused, at the highest dose, reduced erythrocyte numbers and high mean cell volume in males, high creatinine and urea concentrations in both sexes and low spleen weights in females, but no histopathological change. The findings suggested low level chronic toxicity at 2000mg/kg/day and a no observed adverse effect level (NOAEL) of 1000mg/kg/day. Genotoxicity tests on the aqueous extract were negative in the bacterial reverse mutation test, either with or without S9 mix, up to 5000μg/plate and in a rat bone marrow micronucleus test up to 2g/kg bodyweight. The extract was positive at acceptable levels of toxicity in an L5178Y mouse lymphoma assay following 24h exposure in the absence of S9 and this was associated with an increase in the number of small colonies, suggesting possible clastogenic activity or aneuploidy, rather than point mutation. The aqueous extract of A. blazei is therefore of low subchronic toxicity and did not cause any direct effect upon the DNA molecule and the weak positive in the L5178 mouse lymphoma test was likely due to large deletions or the loss of the whole chromosomes rather than to direct damage to the DNA.