Toxicological, medical and industrial hygiene aspects of glutaraldehyde with particular reference to its biocidal use in cold sterilization procedures

Aqueous solutions of greater than or equal to5% glutaraldehyde (GA) are of moderate acute peroral toxicity and those of less than or equal to2% are of slight toxicity. By single sustained skin contact, aqueous GA solutions of greater than or equal to 45% are of moderate acute percutaneous toxicity, those of 25% are of slight toxicity and those of less than or equal to 15% do not present an acute percutaneous hazard. Vapor generated at ambient tem perature may cause sensory irritant effects to the eye and respiratory trac t, but not acute respiratory tract injury. The 50% decrease in respiratory rate (RD50) is 13.86 ppm. A 0.1% solution of GA is not irritating to the ey e; the threshold for conjunctival irritation is 0.2% and for corneal injury it is 1.0%. Eye injury is moderate at 2% and severe at greater than or equ al to5%. Primary skin irritation depends on the duration and contact site, occlusion and solvent. By sustained contact, the threshold for skin irritat ion is 1%, above which erythema and edema are dose related. With 45% and hi gher, skin corrosion may occur. There is a low incidence of skin sensitizin g reactions, with an eliciting threshold of 0.58 aqueous GA. However, GA is neither phototoxic nor photosensitizing. Subchronic repeated exposure stud ies by the peroral route show only renal physiological compensatory effects , secondary to reduced water consumption. Repeated skin contact shows only minor skin irritant effects without systemic toxicity. By subchronic vapor exposure, effects are limited to the nasal mucosa at 1.0 ppm, with a no-eff ect concentration generally at 0.1 ppm. There is no evidence for systemic t arget organ or tissue toxicity by subchronic repeated exposure by any route . A chronic drinking water study showed an apparent increase, in females on ly, of large granular cell lymphocytic leukemia but this was not dosage rel ated. This is most likely the result of a modifying effect on the factor(s) responsible for the expression of this commonly occurring rat neoplasm. A chronic (2-year) inhalation toxicity/oncogenicity study showed inflammatory changes In the anterior nasal cavity but no neoplasms or systemic toxicity . In vitro genotoxicity studies- bacterial mutagenicity, forward gene mutat ion (HGPRT and TK loci), sister chromatid exchange, chromosome aberration, UDS and DNA repair tests-have given variable results, ranging from no effec t through to weak positive. In vivo genotoxicity studies-micronucleus, chro mosome aberration, dominant lethal and Drosophila tests-generally have show n no activity but one mouse intraperitoneal study showed bone marrow cell c hromosome aberrations. Developmental toxicity studies show GA not to be ter atogenic, and a two-generation study showed no adverse reproductive effects . Percutaneous pharmacokinetic studies showed low skin penetration, with lo west values measured in vitro in rats and human skin. Overexposure of human s produces typical sensory irritant effects on the eye, skin and respirator y tract. Some reports have described an asthmatic-like reaction by overexpo sure to GA vapor. In most cases this resembles reactive airways dysfunction syndrome, and the role of immune mechanisms is uncertain. Local mucosal ef fects may occur if medical instruments or endoscopes are not adequately dec ontaminated. Protection of individuals from the potential adverse effects of GA exposure requires that there be adequate protection of the skin, eyes and respirato ry tract. The airborne concentration of GA vapor should be kept below the r ecommended safe exposure level (e.g. the threshold limit value) by the use of engineering controls. Those who work with GA should, through a training program, be aware of the properties of GA, its potential adverse effects, h ow to handle the material safely and how to deal with accidental situations involving GA. If effects develop in exposed workers, the reasons should be determined immediately and corrective methods initiated. Copyright (C) 200 1 John Wiley & Sons, Ltd.