Toxicity studies on alkyldimethylbenzylammonium chloride in rats and in dogs * *Michigan State College, East Lansing, Mich.

Kinetic characteristics and toxic effects of benzalkonium chloride following intravascular and oral administration in rats

“…The LD 50 of BZK in rats was reported as 234-525 and 14 mg/kg when administered orally and intravenously, respectively [6,26,29,30]. In humans, an oral dose of 100-400 mg/kg [13] or a parenteral dose of 5-15 mg/kg [9,31] is thought to be fatal.…”

“…A dose of 250 mg/kg BZK [=2.5 ml/kg of Osvan ® (100 mg/ml of BZK solution)] was given by stomach tube. This dose was based on the smallest LD 50 (234 mg/kg PO in rats) reported by Alfredson et al [26]. Blood samples were collected by cardiac puncture at 1, 2, 4, 8 and 24 h (six rats of each sampling point and 30 rats in total) and the rats were then sacrificed by injecting the anesthetic (0.2 ml) into the heart.…”

Safety Studies Conducted on a Sanitizing Agent Containing Benzalkonium Chloride

“…Previous oral subchronic or chronic toxicity studies that have been conducted with higher doses and concentrations of BAC indicate variable NOAELs for BAC, depending on concentration, method of administration, and/or vehicle. One 2 y dietary study in rats showed no adverse effects at up to approximately 125 mg BAC/kg bw/day (0.25% or 2500 ppm in the diet) (Alfredson and others 1951), and another showed decreased growth at approximately 31.5 mg/kg bw/day (0.063% or 630 ppm in the diet) (Fitzhugh and Nelson 1948). In both studies, increased mortality, decreased weight gain, diarrhea, gastritis, and gross and microscopic changes in the stomach and small intestine were noted in rats administered approximately 250 mg/kg bw/day (0.5% in the diet).…”

“…BAC that does not conform to the USP specification may contain entirely different amounts of C 12 and C 14 homologs than USP‐BAC and/or may be composed of higher or lower molecular weight homologues that are not present in USP‐BAC. Although the toxicity of BAC has been previously examined in rodents (Harshbarger 1942; Fitzhugh and Nelson 1948; Shelanski 1949; Alfredson and others 1951; Coulston and others 1961), nonrodents (Coulston and others 1961), and in vitro (Elder 1989), results of these studies may not be predictive of the toxicity of USP‐BAC. Furthermore, the combination of acetic acid, methylparaben, and BAC in Free N Clear may affect the ability of the BAC component to produce toxicity.…”

Evaluation of pulmonary toxicity of benzalkonium chloride and triethylene glycol mixtures using in vitro and in vivo systems

“…Highly toxic effects of BAC have also been found in animal studies. BAC orally administered to rats causes significant lethality, and the lethal dose 50 (LD 50 ) has been reported to be 234‐525 mg/kg . Pulmonary effects of BAC have particularly been investigated since this preservative has been used in inhalable medications.…”