Genetic toxicology studies with glutaraldehyde

Abstract

Glutaraldehyde (GA; CAS no. 111-30-8) has a wide spectrum of industrial, scientific and biomedical applications, with a potential for human exposure particularly in its biocidal applications. The likelihood for genotoxic effects was investigated in vitro and in vivo. A Salmonella typhimurium reverse mutation assay showed no evidence for mutagenic activity with strains TA98, TA1535, TA1537 and TA1538, with or without metabolic activation. However, there was a weak mutagenic response (1.9-2.3-fold at the highest non-toxic concentration) with TA100 in the presence of metabolic activation. In a Chinese hamster ovary (CHO) forward gene mutation assay (HGPRT locus) there were no consistent, statistically significant, reproducible or dosage-related increases in the frequency of 6-thioguanine resistant cells. There were no reproducible or dosage-related increases in sister chromatid exchanges in an in vitro test in CHO cells. An in vitro cytogenetics study in CHO cells showed no evidence for an increase in chromosomal aberrations on treatment with GA, either in the presence or absence of metabolic activation. In vivo, a mouse peripheral blood micronucleus test showed no increase in micronucleated polychromatophils at sampling times of 30, 48 and 72 h after acute gavage dosing with GA at 40, 80 and 125 mg kg(-1) (corresponding to 25, 50 and 85% of the LD(50)). The absence of an in vivo clastogenic potential was confirmed by no increase in chromosomal aberrations in a rat bone marrow cytogenetics study with sampling at 12, 24 and 48 h after acute gavage dosing with GA (12.5, 30 or 60 mg kg(-1) with males, and 7.5, 20 or 40 mg kg(-1) with females). Thus, in this series of tests, GA produced genotoxic effects in vitro only in a bacterial reverse mutation assay with no evidence for in vivo genotoxicity.

Effects of Glutaraldehyde Exposure on Human Health

“…GA exhibited mild to strong mutagenic effects with and without S9 metabolic activation in S. typhimurium strain TA102 [77][78][79] . In TA100, negative results were reported both with and without S9 81) , while weakly positive results were reported with S9 76) . GA was mutagenic without S9 in TA104, which exhibited higher sensitivity to carbonyl mutagenesis than TA100 did 82) .…”

“…Although there has been no report on genetic toxicity of GA to humans, it has been investigated extensively in animals 75,76) . Both positive and negative results have been reported in in vitro mutagenicity studies [76][77][78][79][80][81][82][83][84][85][86] , while almost all in vivo tests have yielded negative results 75,76,87,88) .…”

“…Both positive and negative results have been reported in in vitro mutagenicity studies [76][77][78][79][80][81][82][83][84][85][86] , while almost all in vivo tests have yielded negative results 75,76,87,88) . GA exhibited mild to strong mutagenic effects with and without S9 metabolic activation in S. typhimurium strain TA102 [77][78][79] .…”

Laryngeal edema and metabolic acidosis after Omnicide® ingestion

“…Sensory irritant effects and sensitization of respiratory mucous membranes following chronic inhalation due to GA vapors has been reported [7][8][9][10]. Although exposure and consequential human health effects of skin, eye, and respiratory tract exposure to GA have been well documented [2,[11][12][13], data on its acute oral toxicity is limited to animal studies. In acute oral toxicity testing in the rat, solutions less than 5% GA were of slight toxicity (LD 50 range 3.34 to 12.30 ml/kg for 1 and 2% solutions) [13].…”

“…It is also used as an embalming fluid, a chemical intermediate, a fixative for tissues, for cross-linking protein and polyhydroxy materials, and tanning of soft leathers [1]. It is also used as a disinfectant and in sterilization of endoscopic and surgical instruments [2]. There are no published reports of oral GA poisoning.…”