title: Pre-clinical safety evaluation of soluble glucan.
abstract: Soluble glucan, a beta-1,3-linked glucopyranose biological response modifier, is effective in the therapy of experimental neoplasia, infectious diseases and immune suppression. Currently, soluble glucan is undergoing phase I clinical trials. The present study describes the pre-clinical safety evaluation of soluble glucan in mice, rats, guinea pigs and rabbits. ICR/HSD mice and Harlan Sprague-Dawley rats received a single i.v. injection of soluble glucan in doses ranging from 40 to 1000 mg/kg. Soluble glucan administration did not induce mortality, appearance or behavioral changes in mice or rats. In subsequent studies, mice and guinea pigs were injected i.p. with glucan (250 mg/kg) for 7 consecutive days. ICR/HSD mice gained weight at the same rate as the saline-treated controls. In contrast, guinea pigs receiving i.p. injections of soluble glucan showed a significant (P less than 0.05) 10-13% decrease in weight gain over the 7 day period. No other toxicologic, behavioral or appearance changes were noted. To examine chronic toxicity, soluble glucan was administered twice weekly for a period of 30 or 60 days to ICR/HSD mice in the dose of 40, 200 or 1000 mg/kg. No deaths were observed in any group. Chronic glucan administration did not alter body weight, liver, lung or kidney weight. However, a significant splenomegaly was observed in both the 30 and 60 day study. Histopathologic examination showed no tissue alterations at 40 or 200 mg/kg. However, at 1000 mg/kg a mononuclear infiltrate was observed in the liver. Pyrogenicity testing, employing New Zealand white rabbits, revealed that parenteral glucan administration (5 mg/kg) did not significantly alter body temperature. These data indicate that the systemic administration of soluble glucan, over a wide dose range, does not induce mortality or significant toxicity, an important consideration in preparing soluble glucan for parenteral administration to human populations.
authors.affiliation: Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112.
authors.forename: D L
authors.initials: DL
authors.lastname: Williams
authors.forename: E R
authors.initials: ER
authors.lastname: Sherwood
authors.forename: I W
authors.initials: IW
authors.lastname: Browder
authors.forename: R B
authors.initials: RB
authors.lastname: McNamee
authors.forename: E L
authors.initials: EL
authors.lastname: Jones
authors.forename: N R
authors.initials: NR
authors.lastname: Di Luzio
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D005334:Fever / Q000139:chemically induced; D005936:Glucans / Q000633:toxicity*; D006168:Guinea Pigs; D007375:Interleukin-1 / Q000096:biosynthesis; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013045:Species Specificity
chemical_list: D005936:Glucans; D007375:Interleukin-1