PRODUCTS

GLUTARALDEHYDE

CAS No. : 111-30-8
EC No. : 203-856-5

Synonyms:
glutaraldehyde; Pentanedial; Glutaral; 111-30-8; Glutaric dialdehyde; Cidex; Glutardialdehyde; 1,5-Pentanedial; Sonacide; Pentane-1,5-dial; Glutaric aldehyde; Glutaraldehyd; Glutaralum; Glutarol; Ucarcide; Aldesan; Alhydex; Hospex; Glutaric acid dialdehyde; 1,3-Diformylpropane; Gluteraldehyde; 1,5-Pentanedione; Aldesen; Novaruca; Sporicidin; Aldehyd glutarowy; Polyglutaraldehyde; Poly(glutaraldehyde); NCI-C55425; Caswell No. 468; Glutaraldehyd [Czech]; Glutaraldehyde solution; Glutaclean; Sterihyde; Aqucar; glutaraldehyde; Pentanedial; Glutaral; 111-30-8; Glutaric dialdehyde; Cidex; Glutardialdehyde; 1,5-Pentanedial; Sonacide; Pentane-1,5-dial; Glutaric aldehyde; Glutaraldehyd; Glutaralum; Glutarol; Ucarcide; Aldesan; Alhydex; Hospex; Glutaric acid dialdehyde; 1,3-Diformylpropane; Gluteraldehyde; 1,5-Pentanedione; Aldesen; Novaruca; Sporicidin; GLUTARALDEHYDE (GLUTARALDEHİT); Aldehyd glutarowy; Polyglutaraldehyde; Poly(glutaraldehyde); NCI-C55425; Caswell No. 468; Glutaraldehyd [Czech]; Glutaraldehyde solution; Glutaclean; Sterihyde; Aqucar; Glutaralum [INN-Latin]; Veruca-sep; Relugan GT; Relugan GTW; Aldehyd glutarowy [Polish]; component of Cidex; Glutarex 28; NSC 13392; Glutaral [USAN:INN:JAN]; Sonacide (TN); Cidex 7; Ucarcide 250; UNII-T3C89M417N; Relugan GT 50; Sterihyde L (TN); CCRIS 3800; HSDB 949; Pentanedial, homopolymer; Coldcide-25 microbiocide; EINECS 203-856-5; EPA Pesticide Chemical Code 043901; Glutaral (JAN/USP/INN); BRN 0605390; Potentiated acid glutaraldehyde; CHEBI:64276; T3C89M417N; 1, 5-Pentanedial; MFCD00007025; Glutaraldehyde solution (50% or less); Glutaraldehyde solution, 25% in water; NCGC00091110-01; DSSTox_CID_5355; DSSTox_RID_77761; DSSTox_GSID_25355; Glutaraldehyde Solution, 25%; 1,3-Diformyl propane; Diswart; Gludesin; Glutarol-1,5-pentanedial; CAS-111-30-8; Glutaric dialdehyde, 25 wt.% solution in water; Glutaric dialdehyde, 50 wt.% solution in water; pentandial; Dioxopentane; Glutural; Ucarset; Verucasep; Glutaraldehyde solution, for electron microscopy, ~25% in H2O; Virsal; Glutaral(usan); Sterihyde L; glutaric dihydride; Glutaral [USAN:USP:INN:JAN]; Glutaric dialdehyde, electron microscopy grade, 25% solution in water, purified; GLUTARALDEHYDE (GLUTARALDEHİT); GLUTARALDEHYDE, 25% SOLN; Bactron K31; Ucarcide 225; Glutaraldehyde,solution; ACMC-1BGTC; pentane-1,5-dialdehyde; Glutaral, INN, USAN; EC 203-856-5; Glutaric dialdehyde, 25%sol. In water; Glutaric dialdehyde, 25% sol. in water; 29257-65-6; I856; SC-22641; Glutaric dialdehyde, 8% solution in water; Glutaraldehyde solution, 25 wt. % in H2O; Glutaraldehyde solution, 50 wt. % in H2O; FT-0626730; G0067; G0068; NS00004136; EN300-18037; C12518; D01120; glutaral;glutaraldehyde;Glutaraldehyde;GLUTARAL; Glutaraldehyde solution, for synthesis, 25.0%; Glutaraldehyde solution, Grade II, 25% in H2O; Glutaric dialdehyde solution, 50 wt. % in H2O; A802339; Q416475; Glutaraldehyde solution, for in vitro diagnostic use; Q-201162; Glutaric dialdehyde solution, 50 wt. % in H2O, FCC; F2191-0161; Glutaraldehyde solution, SAJ first grade, 20.0-26.0%; Glutaraldehyde solution, technical, ~25% in H2O (2.6 M); Glutaraldehyde solution, technical, ~50% in H2O (5.6 M); Glutaraldehyde solution, 1.2 % (w/v) glutaraldehyde in H2O; Glutaraldehyde solution, for electron microscopy, ~50% in H2O; Glutaraldehyde solution, for electron microscopy, ~8% in H2O; Glutaraldehyde solution, 50% in H2O, suitable for photographic applications; Glutaraldehyde solution, Grade I, 25% in H2O, specially purified for use as an electron microscopy fixative; Glutaraldehyde solution, Grade I, 50% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use; Glutaralum [INN-Latin]; Veruca-sep; Relugan GT; Relugan GTW; Aldehyd glutarowy [Polish]; component of Cidex; Glutarex 28; GLUTARALDEHYDE (GLUTARALDEHİT); NSC 13392; Glutaral [USAN:INN:JAN]; Sonacide (TN); Cidex 7; Ucarcide 250; UNII-T3C89M417N; Relugan GT 50; Sterihyde L (TN); Pentanedial, homopolymer; Coldcide-25 microbiocide; EINECS 203-856-5; Glutaral (JAN/USP/INN); BRN 0605390; Potentiated acid glutaraldehyde; 1, 5-Pentanedial; Glutaraldehyde Solution, 25%; 1,3-Diformyl propane; Diswart; Gludesin; Glutarol-1,5-pentanedial; CAS-111-30-8; Glutaric dialdehyde; pentandial; Dioxopentane; Glutural; Ucarset; Cidex; Diswart; Gludesin; Glutaral; Glutaraldehyde; Glutardialdehyde; Glutarol; Korsolex; Novaruca; Sekumatic; Sonacide; Sporicidin; 111-30-8 [RN]; 203-856-5 [EINECS]; glutaral [Wiki]; Glutaraldehyd [German] [ACD/IUPAC Name]; Glutaraldehyde [ACD/IUPAC Name]; Glutaraldéhyde [French] [ACD/IUPAC Name]; glutaralum; Glutardialdehyde; Glutaric acid dialdehyde; Glutaric aldehyde; glutaric dialdehyde; Gluteraldehyde; MFCD00007025 [MDL number]; PENTANE-1,5-DIAL; Pentanedial [ACD/Index Name]; [111-30-8]; 1,3-Diformyl propane; 1,3-Diformylpropane; 1,5-Pentanedial; 5-Pentanedial; Aldehyd glutarowy [Polish]; Aldesan; Alhydex; Aqucar; Bactron K31; Cidex; Cidex 7; Coldcide-25 microbiocide; Dioxopentane; Diswart; GINKGO BILOBA EXTRACT; Gludesin; Glutaclean; Glutaral [USAN:INN:JAN] [INN] [JAN] [USAN]; Glutaraldehyd [Czech]; Glutaraldehyde (50per cent in water); Glutaraldehyde solution, 50% in water; GLUTARALDEHYDE[3H(G)]; Glutaralum [Latin]; Glutaralum [INN-Latin]; Glutarex 28; Glutaricdialdehyde; Glutarol; Glutarol-1,5-pentanedial; Glutural; Hospex; Novaruca; GLUTARALDEHYDE (GLUTARALDEHİT); PTD; Relugan GT; Relugan GT 50; Relugan GTW; Sonacide; Sporicidin; Sterihyde; Sterihyde L; STR01121; Ucarcide; Ucarcide 225; Ucarcide 250; Ucarset; 1,3-Diformylpropane; Aldehyd glutarowy; Aldesan; Aldesen; Alhydex; Cidex; glutaral; glutaraldehyde; 1,5-pentanedial; Glutaraldehyde; Glutaralum; Glutardialdehyde; Glutaric acid dialdehyde; Glutaric aldehyde; Glutaric dialdehyde; Glutarol; Hospex; Pentane-1,5-dial; Sonacide

Glutaraldehyde

Glutaraldehyde, sold under the brandname Cidex and Glutaral among others, is a disinfectant, medication, preservative, and fixative. As a disinfectant, it is used to sterilize surgical instruments and other areas of hospitals.[3] As a medication, it is used to treat warts on the bottom of the feet.[4] Glutaraldehyde is applied as a liquid.
Side effects include skin irritation. If exposed to large amounts, nausea, headache, and shortness of breath may occur.[3] Protective equipment is recommended when used, especially in high concentrations.[3] Glutaraldehyde is effective against a range of microorganisms including spores. Glutaraldehyde is a dialdehyde.[8] Glutaraldehyde works by a number of mechanisms.[7]
Glutaraldehyde came into medical use in the 1960s. Glutaraldehyde is on the World Health Organization's List of Essential Medicines. There are a number of other commercial uses such as leather tanning.
Contents
1 Uses of glutaraldehyde
1.1 Disinfection of glutaraldehyde
1.2 Fixative of glutaraldehyde
1.3 Wart treatment of glutaraldehyde
2 Safety of glutaraldehyde
3 Mechanism of action of glutaraldehyde
4 Production and reactions of glutaraldehyde
5 History and culture of glutaraldehyde
Uses of glutaraldehyde
Disinfection of glutaraldehyde
Glutaraldehyde is used as a disinfectant and medication.
Usually applied as a solution, it is used to sterilize surgical instruments and other areas.

Fixative of glutaraldehyde
Glutaraldehyde is used in biochemistry applications as an amine-reactive homobifunctional crosslinker and fixative prior to SDS-PAGE, staining, or electron microscopy. It kills cells quickly by crosslinking their proteins. It is usually employed alone or mixed with formaldehyde[13] as the first of two fixative processes to stabilize specimens such as bacteria, plant material, and human cells. A second fixative procedure uses osmium tetroxide to crosslink and stabilize cell and organelle membrane lipids. Fixation is usually followed by dehydration of the tissue in ethanol or acetone, followed by embedding in an epoxy resin or acrylic resin.[citation needed]
Another application for treatment of proteins with glutaraldehyde is the inactivation of bacterial toxins to generate toxoid vaccines, e.g., the pertussis (whooping cough) toxoid component in the Boostrix Tdap vaccine produced by GlaxoSmithKline.[14]
In a related application, glutaraldehyde is sometimes employed in the tanning of leather and in embalming.
Wart treatment of glutaraldehyde
As a medication it is used to treat plantar warts.[4] For this purpose, a 10% w/v solution is used. It dries the skin, facilitating physical removal of the wart.[15] Trade names include Diswart Solution and Glutarol.

Safety of glutaraldehyde
Side effects include skin irritation.[4] If exposed to large amounts, nausea, headache, and shortness of breath may occur.[3] Protective equipment is recommended when used, especially in high concentrations.[3] Glutaraldehyde is effective against a range of microorganisms including spores.[3][7]
As a strong sterilant, glutaraldehyde is toxic and a strong irritant.[16] There is no strong evidence of carcinogenic activity.[17] Some occupations that work with this chemical have an increased risk of some cancers.[17]
Mechanism of action of glutaraldehyde
A number of mechanisms have been invoked to explain the biocidal properties of glutaraldehyde.[7] Like many other aldehydes, it reacts with amines and thiol groups, which are common functional groups in proteins. Being bi-function, it is also a potential crosslinker.[18]
Production and reactions of glutaraldehyde
Synthesis of glutaraldehyde via the Diels-Alder reaction.
Glutaraldehyde is produced industrially by the oxidation of cyclopentene. Alternatively it can be made by the Diels-Alder reaction of acrolein and vinyl ethers followed by hydrolysis.[19]
Like many other dialdehydes, (e.g., glyoxal) and simple aldehydes (e.g., formaldehyde), glutaraldehyde converts in aqueous solution to various hydrates that in turn convert to other equilibrating species.
Monomeric glutaraldehyde polymerizes by aldol condensation reaction yielding alpha, beta-unsaturated poly-glutaraldehyde. This reaction usually occurs at alkaline pH values.[medical citation needed]
History and culture of glutaraldehyde
Glutaraldehyde came into medical use in the 1960s.[9] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[10] There are a number of other commercial uses such as leather tanning.[11]
A glutaraldehyde solution of 0.1% to 1.0% concentration may be used as a biocide for system disinfection and as a preservative for long-term storage. It is a sterilant, killing endospores in addition to many microorganisms and viruses.
As a biocide, glutaraldehyde is a component of hydraulic fracturing ("fracking") fluid. It is included in the additive called Alpha 1427.[22] Bacterial growth impairs extraction of oil and gas from these wells. Glutaraldehyde is pumped as a component of the fracturing fluid to inhibit microbial growth.

RESULTS: An outbreak of six patients occurred in April 2002 and one cirrhotic patient was admitted in July 2008. All patients developed a self-limited syndrome of abdominal pain and bloody diarrhea within 48 h of uncomplicated endoscopy. One severely ill patient required hospitalization to receive intravenous fluid and antibiotics. After the investigation in April 2002, glutaraldehyde-induced colitis was diagnosed due to a defect in the endoscope-cleansing procedure. There were no deficiencies in the cleansing procedure in July 2008. Considering the patient's concomitant disease, we postulated that ischemic colitis with cirrhosis-related intestinal inflammation and endotoxemia was the possible diagnosis in this sporadic case. CONCLUSIONS: Endoscopists should be aware of this iatrogenic complication in patients presenting with acute rectocolitis, especially in those who have undergone recent endoscopic examination. An outbreak of acute rectocolitis following endoscopy should be considered glutaraldehyde-induced and should lead to an investigation of cleansing and equipment-disinfection procedures. In the absence of strong evidence of an outbreak, an infectious disease, or contamination of glutaraldehyde, a sporadic case should be considered ischemic colitis especially in patients with relevant concomitant diseases or predisposing factors.

Dermal and intravenous studies in the rat with dilute aqueous glutaraldehyde solutions (0.075-7.5%) showed that, in dermal tests, approx 5% was absorbed in the rat, and 30-50% in the rabbit. In the intravenous injection tests, approx 12% was absorbed in the rat and approx 33% in the rabbit. There were no significant differences between males and females in the study. The dermal absorption rate constant was low (0.2-2 hr) in each species. The elimination times were long for both intravenous injection (t0.5 for the rat 10 hr, rabbit 15-30 hr) and dermal application (t0.5 for the rat 40-110 hr, rabbit 20-100 hr), possibly due to the binding of glutaraldehyde to protein and the slow excretion of metabolites. The principal metabolite in both species was CO2 with other metabolites not identified. /It was/ proposed that the metabolism probably involved initial oxidation to corresponding carboxylic acids by aldehyde dehydrogenase, and then further oxidation to CO2.
IDENTIFICATION: Glutaraldehyde is a colorless oily liquid with a strong, rotten apple odor. It is very soluble in water. USE: Glutaraldehyde is an antimicrobial chemical commonly used as a disinfectant in hospitals, agriculture and aquaculture, food handling and food storage establishments, and water treatment plants. It is used as a preservative in the manufacture of several consumer products, including cosmetics, cleaners, adhesives, paper, textiles and leathers, paints and coatings, and inks and dyes. Glutaraldehyde is also used as a tissue fixative in laboratories and embalming fluid and in photographic and X-ray development fluids. Glutaraldehyde is used in hydraulic fracturing and off-shore oil operations. EXPOSURE: Workers in hospitals, janitorial services, nursing homes, veterinary hospitals, and commercial and industrial businesses may be exposed to glutaraldehyde by breathing vapors in air or skin contact. General population exposure may occur by breathing in air and skin contact with consumer products containing glutaraldehyde. Glutaraldehyde is also present in gasoline and diesel engine exhaust. If glutaraldehyde is released to air, it will be degraded by reaction with other chemicals and light. If released to water or soil, it is expected to bind to soil particles or suspended particles. Glutaraldehyde is not expected to move into air from wet soils or water surfaces, but may move to air from dry soils. Glutaraldehyde is expected to be degraded by microorganisms and not build up in aquatic organisms.

RISK: Runny nose, headache, facial and eye irritation, respiratory problems, skin irritation, and allergic skin reactions have been reported in medical and agricultural workers exposed to glutaraldehyde liquid or vapor during disinfection and sanitization activities. Asthma has been found in workers repeatedly exposed to glutaraldehyde vapors. Swelling, burning pain, and sensitivity to light can occur with direct eye contact. The risk of death from cancer was not increased with a history of occupational glutaraldehyde exposure. Eye irritation and skin irritation/sensitization occur with direct skin contact with diluted glutaraldehyde in laboratory animals. Severe irritation and burns occur with contact to undiluted gluraraldehyde. Stomach lesions, liver damage, and decreased body weight occurred in laboratory animals given repeated moderate doses of glutaraldehyde in water. Death occurred at high oral doses. Nasal, throat, and lung lesions and decreased body weights were found in laboratory animals repeatedly exposed to low air concentrations of glutaraldehyde. Birth defects and abortions were observed in laboratory animals at high oral doses that were also toxic to the mothers. Fertility was not affected in laboratory animals given high oral doses prior to mating. Tumors were not induced in laboratory animals given high oral doses in water or exposed to moderate air concentrations for their lifetime. The American Conference of Governmental Industrial Hygienists determined that glutaraldehyde is not classifiable as a human carcinogen. The US EPA Carcinogenicity Assessment Review Committee classified glutaraldehyde as 'Not Likely to be Carcinogenetic to Humans" by any route of exposure, based on the lack tumor induction in several 2-year laboratory animal studies. The potential for glutaraldehyde to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, or the U.S. National Toxicology Program 13th Report on Carcinogens.

Microscopy/histology. Glutaraldehyde is used as a tissue fixative in histology and electron and light microscopy, generally as a 1.5-6% aqueous solution. Aquaculture. Glutaraldehyde is used, generally in conjunction with wetting agents, to control viruses and other micro-organisms in fish farming. Cosmetics. Glutaraldehyde is allowed as a preservative in cosmetics in Europe at concentrations up to 0.1%. It is not allowed in aerosols and sprays.
The National Pesticide Information Retrieval System (NPIRS) identifies 24 companies with active labels for products containing the chemical glutaraldehyde. To view the complete list of companies, product names and percent glutaraldehyde in formulated products click the following url and enter the CAS Registry number in the Active Ingredient field.
In Australia, it is estimated that glutaraldehyde is distributed in end-use as follows: 55% as a cold disinfectant in the health care industry, 20% in x-ray film processing, 10% in water treatment, 5% in animal housing, 5% in tanning and 5% in other uses such as toilet disinfection, microscopy, aquaculture and air duct disinfection. In France, 50% is used in disinfection/control, 40% in the photographic industry, 5% in the leather industry and 5% in the paper industry. In Norway, 80% is used in industrial cleaning agents and 14% in photocopying developers. In the UK, glutaraldehyde is used mainly as a cold disinfectant and as a biocide in off-shore oil operations.
Glutaraldehyde is a colorless, oily liquid with a sharp, pungent odor. Glutaraldehyde is used for industrial, laboratory, agricultural, medical, and some household purposes, primarily for disinfecting and sterilization of surfaces and equipment. For example, it is used in oil and gas recovery operations and pipelines, waste water treatment, x-ray processing, embalming fluid, leather tanning, paper industry, in fogging and cleaning of poultry houses, and as a chemical intermediate in the production of various materials. It may be used in select goods, such as paint and laundry detergent.

The critical effects /of glutaraldehyde exposure/ are eye, skin, and respiratory irritation, skin sensitization and occupational asthma. Nose and throat irritation has been observed in humans at vapor concentrations below 0.2 ppm. Occupational asthma has also been reported in workers exposed to dilute solutions of glutaraldehyde ... Contact dermatitis and eye irritation have been reported in workers using glutaraldehyde solutions, usually 2% or higher. Skin sensitization has been confirmed in workers using dilute solutions.
Application restrictions. Use: paint preservative. Maximum application rate of 100 ppm. Use: medical premises disinfection. Maximum application rate of 0.1% of the active ingredient by weight of material being treated. All glutaraldehyde once-through cooling tower uses, glutaraldehyde macrofoulant control uses and all critical medical equipment/instrument uses are cancelled. Critical medical equipment use is defined as use of a pesticide in or on any equipment that comes into contact with bodily fluids. Examples of critical medical equipment/instruments include, but are not limited to hemodyalysis tubing, dental instruments.

GLUTARALDEHYDE may discolor on exposure to air. It polymerizes on heating. This chemical is incompatible with strong oxidizing agents. It polymerizes in the presence of water.
Strong oxidizers, strong bases [Note: Alkaline solutions of glutaraldehyde (i.e., activated glutaraldehyde) react with alcohol, ketones, amines, hydrazines and proteins].
The Agency has completed its assessment of the dietary, occupational, drinking water, and ecological risks associated with the use of pesticide products containing the active ingredient glutaraldehyde. Based on a review of these data and on public comments on the Agency's assessments for the active ingredient glutaraldehyde, the Agency has sufficient information on the human health and ecological effects of glutaraldehyde to make decisions as part of the tolerance reassessment process under FFDCA and reregistration process under FIFRA, as amended by FQPA. The Agency has determined that glutaraldehyde-containing products are eligible for reregistration provided that: (i) confirmatory data needs are addressed; (ii) the risk mitigation measures outlined in this document are adopted; and (iii) label amendments are made to reflect these measures. ... Based on its evaluation of glutaraldehyde, the Agency has determined that glutaraldehyde products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement the risk mitigation measures identified in this document, the Agency may take regulatory action to address the risk concerns from the use of glutaraldehyde. If all changes outlined in this document are incorporated into the product labels, then all current risks for glutaraldehyde will be substantially mitigated for the purposes of this determination. Once an Endangered Species assessment is completed, further changes to these registrations may be necessary as explained in Section III of this document.

IDENTIFICATION AND USE: Glutaraldehyde is a colorless liquid. It is registered for pesticide use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. It is used as algaecide, bacteriocide and fungicide. Glutaraldehyde is used as a tissue fixative in histology and electron and light microscopy, generally as a 1.5-6% aqueous solution. Glutaraldehyde is used, generally in conjunction with wetting agents, to control viruses and other micro-organisms in fish farming. Glutaraldehyde is allowed as a preservative in cosmetics in Europe at concentrations up to 0.1%. It is not allowed in aerosols and sprays. Glutaraldehyde is a biocide commonly used in a 2% concentration for cold sterilization of surgical and dental equipment. Biocides, such as glutaraldehyde, are added to eliminate bacterial growth in fracturing fluids. HUMAN EXPOSURE AND TOXICITY: Exposure to concentrations < 1 ppm by inhalation or skin contact may cause irritation of the skin and/or mucous membranes. The critical effects of glutaraldehyde exposure are eye, skin, and respiratory irritation, skin sensitization and occupational asthma. Nose and throat irritation has been observed in humans at vapor concentrations below 0.2 ppm. Occupational asthma has also been reported in workers exposed to dilute solutions of glutaraldehyde. Contact dermatitis and eye irritation have been reported in workers using glutaraldehyde solutions, usually 2% or higher. Skin sensitization has been confirmed in workers using dilute solutions. Other symptoms that may be brought on by glutaraldehyde exposure include heart palpitations and tachycardia. The incidence of death and incidence of cancer deaths in 186 male employees at a glutaraldehyde production unit were compared to those of US white males and to 29,000 other chemical workers during the period 1959 - 1978. All subjects were observed for 10 yr. The number of deaths was less than expected, as was the incidence of cancer deaths.

ANIMAL STUDIES: Glutaraldehyde was corrosive to the skin and eyes of rabbits at high concentrations, with signs of skin irritation evident at 2%, and eye irritation at 0.2%. In an inhalation study where mice were exposed to glutaraldehyde at concentrations of 33 or 133 ppb for 24 hours, the animals exhibited panting and increased grooming, mice that inhaled the highest concentration developed toxic hepatitis. Following a single whole-body inhalation exposure at 1 ppm for 1 day, rats and mice developed coagulation pathology of the upper respiratory tract squamous epithelium. After 4 days of such exposures, inflammatory granulocytic infiltrate into the squamous epithelium and lamina propria with thickened epithelium of the nasal lumen ensued. In those animals inhaling 0.5 or 1 ppm glutaraldehyde for four days, the nasal passages became obstructed with intraluminal debris; degenerative/hyperplastic erosions with epithelial abscesses extended as far as the nasopharyngeal meatus in the 1-ppm exposure group. A study of male and female rats given glutaraldehyde in drinking water at concentrations of 0, 50, 250, or 100 ppm through two generations indicated a dose-related decrease in parental water consumption and body weight (attributed to adverse taste) and decrease in offspring (1000-ppm group) body weights. No adverse reproductive effects were observed. In other study there was a significant dose-dependent reduction in the average of maternal body weight gain and a significant increase in the number of stunted (body weight) and malformed fetuses at the 5 mL/mg/day dose level. Early mutagenicity studies were negative, but more recent studies have indicated that glutaraldehyde is mutagenic in vitro in bacterial assays and tests in mammalian cells. In vivo genotoxicity tests to date have proven negative. Groups of 50 male and 50 female rats and mice were exposed to glutaraldehyde vapor at concentrations of 0, 0.25, 0.50, or 0.75 (rats) and 0, 0.062, 0.12, or 0.25 ppm (mice) 6 hr/day, 5 days /week. The incidences of non-neoplastic lesions of the nose were reported to be significantly increased in the 0.50 and 0.75-ppm exposed rats and in the 0.12 and 0.25-ppm exposed male and female mice. ECOTOXICITY STUDIES: Available chronic toxicity data for glutaraldehyde indicate that continuous exposure results in measurable effects on coldwater fish at a concentration of 5.1 mg a.i./L. A second study on coldwater fish resulted in measurable effects at 2.5 mg a.i./L. Measurable effects on freshwater invertebrates were noted at concentrations of 8.5 mg/L product and 4.9 mg a.i./L.

/LABORATORY ANIMALS: Acute Exposure/ Occluded contact /in rabbit/ with 50% glutaraldehyde solutions in water. Two products tested: Ucarcide 250 and BASF 50% Glutaraldehyde. Severity of irritation was dependent on the duration of contact. Application of 50% glutaraldehyde for 60 min caused severe irritation and necrosis; 3 min produced transient minor irritation and some discoloration of the skin.
In genetic toxicity studies, glutaraldehyde was mutagenic with and without S9 metabolic activation in S. typhimurium strains TA100, TA102, and TA104. Glutaraldehyde was mutagenic in mouse L5178Y lymphoma cells in the absence of S9 and induced sister chromatid exchanges in cultured Chinese hamster ovary cells with and without S9. No increase in chromosomal aberrations was induced by glutaraldehyde in cultured Chinese hamster ovary cells with or without S9 at one laboratory; at another laboratory, chromosomal aberrations were induced in the absence of S9 only. Glutaraldehyde did not induce sex-linked recessive lethal mutations in germ cells of male /Drosophila/ melanogaster treated as adults by feeding or injection or treated as larvae by feeding. In vivo, glutaraldehyde induced a significant increase in chromosomal aberrations in mouse bone marrow cells 36 hr after a single intraperitoneal injection. In a subset of the 36 hr chromosomal aberrations test, there was a small increase in the number of micronucleated bone marrow polychromatic erythrocytes, which was judged to be equivocal. Additional short-term (3 day) and subchronic (13 week) micronucleus tests in mice, using the intraperitoneal or inhalation routes, respectively, yielded negative results.

Glutaraldehyde's production and use as a disinfectant, as a cross-linking agent, as a tanning agent for leather and use in the paper and textile industries to improve wet strength and dimensional stability of fibers may result in its release to the environment through various waste streams. Its use as a biocide in water treatment, hydraulic fracturing fluids and oil-field applications and as a preservative in cosmetics and personal-care products will result in its direct release to the environment. Glutaraldehyde has been detected in gasoline and diesel engine emissions. If released to air, a vapor pressure of 0.6 mm Hg at 30 °C indicates glutaraldehyde will exist solely as a vapor in the atmosphere. Vapor-phase glutaraldehyde will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 16 hours. Glutaraldehyde may be susceptible to direct photolysis in the atmosphere based upon aqueous photolysis studies. If released to soil, glutaraldehyde is expected to have very high to moderate mobility based upon measured Koc values ranging from 5.1 to 500. Volatilization from moist soil surfaces is not expected to be an important fate process based upon a Henry's Law constant of 3.3X10-8 atm-cu m/mole. Glutaraldehyde is expected to volatilize from dry soil surfaces based upon its vapor pressure and it has been reported that small amounts of glutaraldehyde will volatilize to the atmosphere. Results of biodegradation screening tests indicate that glutaraldehyde is readily biodegradable. A soil degradation study using a loamy sand soil observed a pseudo-first order dissipation half-life of 1.7 days due primarily to soil microorganisms. If released into water, glutaraldehyde is not expected to adsorb to suspended solids and sediment based upon the Koc. In a closed bottle test using seawater as inoculum, glutaraldehyde showed 73% degradation in 28 days indicating that biodegradation is expected to be an important fate process in water. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. At 25 °C, glutaraldehyde has measured hydrolysis half-lives of 508-628, 102-394 and 46-63.8 days at pH 5, pH 7 and pH 9 respectively. The measured half-life for the photolysis of aqueous solutions of glutaraldehyde exposed to natural sunlight was 196 days. Occupational exposure to glutaraldehyde may occur through inhalation and dermal contact with this compound at workplaces where glutaraldehyde is produced or used. Use and limited monitoring data indicate that the general population may be exposed to glutaraldehyde via inhalation of ambient air and dermal contact with consumer products containing glutaraldehyde.

TERRESTRIAL FATE: Based on a classification scheme(1), measured Koc values ranging from 5.1 to 500(2,3) indicate that glutaraldehyde is expected to have very high to moderate mobility in soil(SRC). Volatilization of glutaraldehyde from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 3.3X10-8 atm-cu m/mole(2). Glutaraldehyde is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.6 mm Hg at 30 °C(4), and it has been reported that small amounts of glutaraldehyde will volatilize to the atmosphere(4). Results of biodegradation screening tests indicate that glutaraldehyde is readily biodegradable(2,3,5). A soil degradation study using a loamy sand soil and and initial glutaraldehyde concentration of 10 ppm observed a pseudo-first order dissipation half-life of 1.7 days due primarily to soil microorganisms(3).

AQUATIC FATE: Based on a classification scheme(1), measured Koc values ranging from 5.1 to 500(2,3) indicate that glutaraldehyde is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon a Henry's Law constant of 3.3X10-8 atm-cu m/mole(2). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -0.33(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Results of biodegradation screening tests indicate that glutaraldehyde is readily biodegradable(2,3,7). In a closed bottle test using seawater as inoculum, glutaraldehyde showed 73% degradation in 28 days(2). At 25 °C, glutaraldehyde has measured hydrolysis half-lives of 508-628, 102-394 and 46-63.8 days at pH 5, pH 7 and pH 9 respectively(2,3). The measured half-life for the photolysis of sterile aqueous solutions of glutaraldehyde exposed to natural sunlight was 196 days(2).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), glutaraldehyde, which has a vapor pressure of 0.6 mm Hg at 30 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase glutaraldehyde is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 15 hours(SRC), calculated from its rate constant of 2.52X10-11 cu cm/molecule-sec at 25 °C(3). Aqueous solutions of glutaraldehyde have an observed photolysis half-life of 196 days when exposed to sunlight(4) suggesting that direct photolysis may occur in the ambient atmosphere(SRC).

AEROBIC: Glutaraldehyde, present at 100 mg/L, reached 59% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1). Using OECD Guideline 301C (Ready biodegradability: Modified MITI Test (I)), glutaraldehyde reached 74% of its theoretical BOD in 28 days and 80% DOC in 15 days with classified the compound as readily biodegradable(2). Glutaraldehyde was found to be readily biodegradable using OECD Guideline 301D (Closed Bottle Test)(2). In a DOC die-away test, glutaradehyde, present at 25 mg/L, showed 83% degradation in 5 days using a sewage inoculum(3). Glutaraldehyde, present at 8.3 mg/L, degraded 60% in 28 days using sewage inoculum in a CO2 evolution test(3). In a closed bottle test, glutaraldehyde present at 2.0 mg/L, degraded 64% in 28 days using a Polyseed inoculum(3). A higher biodegradability with a short lag time was observed when the glutaraldehyde concentrations in the test systems were low (<2 mg/L) than when the concentrations were high (>8 mg/L). Since bacterial inhibition for glutaraldehyde occurs at about 5 mg/L, the lower biodegradation rates observed in studies where high concentrations of glutaraldehyde were used were likely due to inhibition of the inoculum(3). In a closed bottle test using seawater as inoculum, glutaraldehyde showed 73% degradation in 28 days(3). The major metabolite of glutaraldehyde produced by microbes in an aerobic sediment-river water system was carbon dioxide, with glutaric acid formed as an intermediate in the water phase(3). The calculated pseudo-first-order half-life of glutaraldehyde catabolism in water (based on the loss of the parent compound) under aerobic conditions was 10.6 hours(3). A soil degradation study using a loamy sand soil and initial glutaraldehyde concentration of 10 ppm observed a pseudo-first order biodegradation half-life of 1.7 days due primarily to soil microorganisms(4).

ANAEROBIC: The major metabolites of glutaraldehyde produced by microbes in an anaerobic sediment-river water system were 1,5-pentanediol with 5-hydroxypentanal formed as an intermediate, and 3-formyl-6-hydroxy-2-cyclohexene-1-propanal, a cyclicized dimer of glutaraldehyde. The calculated pseudo-first-order half-life of glutaraldehyde catabolism in water (based on the loss of the parent compound) under anaerobic conditions was 7.7 hours(1).
The rate constant for the vapor-phase reaction of glutaraldehyde with photochemically-produced hydroxyl radicals has been measured as 2.52X10-11 cu cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of about 15 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(2). The measured first-order rate constants of the hydrolysis of glutaraldehyde at pH 5 and 7 were 0.0014 and 0.0068 per day (at 25 °C), which corresponds to half-lives of 508 and 102 days, respectively(3). At pH 9, the first-order rate constant was measured to be 0.015 per day, corresponding to a half-life of 46 days(4). The only major degradate observed and identified was a cyclized dimer of glutaraldehyde, 3-formyl-6-hydroxy-2-cyclohexene-1-propanal(3). Hydrolysis tests conducted at 40 and 50 °C and pH 9 for 165 hours determined the hydrolysis half-life is >24 hours at 50 °C and >59 hours at 40 °C(4). An hydrolysis test according to OECD Guideline 111 (Hydrolysis as a Function of pH) reported glutaraldehyde to be hydrolytically stable at pH 4 and pH 7 with decomposition at pH 9(4). At 25 °C, hydrolysis half-lives were 628, 394 and 63.8 days respectively at pH 5, pH 7 and pH 9(4). The measured first-order rate constant for the photolysis of sterile aqueous solutions of glutaraldehyde exposed to natural sunlight was 0.0035 per day with a corresponding half life was 196 days(3).

The Henry's Law constant for glutaraldehyde has been experimentally determined to be 3.30X10-8 atm-cu m/mole(1). This Henry's Law constant indicates that glutaraldehyde is expected to be essentially nonvolatile from water surfaces(2). Glutaraldehyde's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Glutaraldehyde is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.6 mm Hg(3), and it has been reported that small amounts of glutaraldehyde will volatilize to the atmosphere(4).
Glutaraldehyde was detected at mean emission factors of 0.13 and 0.06 mg/kg fuel burned in the emissions from light-duty vehicles measured in a San Francisco Bay area highway tunnel bore during the summers of 2001 and 2006, respectively(1). Glutaraldehyde was not detected in samples taken in 1999. The mean glutaraldehyde emission factor for medium- and heavy-duty diesel trucks measured in 2006 in a separate mixed-traffic bore of the tunnel was 0.55 mg/kg fuel burned(1). Glutaraldehyde concentrations of 170-3700 ug/L were detected in pharmaceutical wastewater effluents from Rouen, France(2).
NIOSH (NOES Survey 1981-1983) has statistically estimated that 367,330 workers (265,564 of these were female) were potentially exposed to glutaraldehyde in the US(1). The NOES Survey does not include farm workers. Occupational exposure to glutaraldehyde may occur through inhalation and dermal contact with this compound at workplaces where glutaraldehyde is produced or used. Use and limited monitoring data indicate that the general population may be exposed to glutaraldehyde via inhalation of ambient air and dermal contact with consumer products containing glutaraldehyde(SRC).

Uses
Disinfection
Glutaraldehyde is used as a disinfectant and medication.
Usually applied as a solution, it is used to sterilize surgical instruments and other areas.[3]

Fixative
Glutaraldehyde is used in biochemistry applications as an amine-reactive homobifunctional crosslinker and fixative prior to SDS-PAGE, staining, or electron microscopy. It kills cells quickly by crosslinking their proteins. It is usually employed alone or mixed with formaldehyde[13] as the first of two fixative processes to stabilize specimens such as bacteria, plant material, and human cells. A second fixative procedure uses osmium tetroxide to crosslink and stabilize cell and organelle membrane lipids. Fixation is usually followed by dehydration of the tissue in ethanol or acetone, followed by embedding in an epoxy resin or acrylic resin.[citation needed]
Another application for treatment of proteins with glutaraldehyde is the inactivation of bacterial toxins to generate toxoid vaccines, e.g., the pertussis (whooping cough) toxoid component in the Boostrix Tdap vaccine produced by GlaxoSmithKline.[14]
In a related application, glutaraldehyde is sometimes employed in the tanning of leather and in embalming.[citation needed]

Wart treatment
As a medication it is used to treat plantar warts.[4] For this purpose, a 10% w/v solution is used. It dries the skin, facilitating physical removal of the wart. Trade names include Diswart Solution and Glutarol.[citation needed]

Safety
Side effects include skin irritation.[4] If exposed to large amounts, nausea, headache, and shortness of breath may occur.[3] Protective equipment is recommended when used, especially in high concentrations.[3] Glutaraldehyde is effective against a range of microorganisms including spores.
As a strong sterilant, glutaraldehyde is toxic and a strong irritant.[16] There is no strong evidence of carcinogenic activity.[17] Some occupations that work with this chemical have an increased risk of some cancers.[17]

Mechanism of action
A number of mechanisms have been invoked to explain the biocidal properties of glutaraldehyde.[7] Like many other aldehydes, it reacts with amines and thiol groups, which are common functional groups in proteins. Being bi-function, it is also a potential crosslinker.[18]

Production and reactions
Synthesis of glutaraldehyde via the Diels-Alder reaction.
Glutaraldehyde is produced industrially by the oxidation of cyclopentene. Alternatively it can be made by the Diels-Alder reaction of acrolein and vinyl ethers followed by hydrolysis.[19]
Like many other dialdehydes, (e.g., glyoxal) and simple aldehydes (e.g., formaldehyde), glutaraldehyde converts in aqueous solution to various hydrates that in turn convert to other equilibrating species.

History and culture
Glutaraldehyde came into medical use in the 1960s.[9] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[10] There are a number of other commercial uses such as leather tanning.
A glutaraldehyde solution of 0.1% to 1.0% concentration may be used as a biocide for system disinfection and as a preservative for long-term storage. It is a sterilant, killing endospores in addition to many microorganisms and viruses.[21]
As a biocide, glutaraldehyde is a component of hydraulic fracturing ("fracking") fluid. It is included in the additive called Alpha 1427.[22] Bacterial growth impairs extraction of oil and gas from these wells. Glutaraldehyde is pumped as a component of the fracturing fluid to inhibit microbial growth.
Glutaraldehyde cross-linked gelatin was used to form a seamless coating over all the blood-contacting surfaces of the left and right pumps, with the intention of forming a biolized layer that would eliminate the need for systemic anticoagulation.

Glutaraldehyde Pulpotomy
Glutaraldehyde has been a suggested alternative to formocresol as a tissue fixative for vital pulpotomy. Histologic studies showed that it produced rapid surface fixation of pulp tissue but with limited depth of penetration, so a larger amount of radicular pulp tissue remained vital.290,322 Fixed pulp tissue may be replaced with dense collagenous tissue over time.150 Studies have also demonstrated less systemic distribution than was thought to occur with formocresol.

Glutaraldehyde has been shown to be rapidly metabolized with little toxic effect.118,137,143,196,240 It has also been demonstrated that although glutaraldehyde has antigenic action similar to formocresol, it is of a lower potential.237,239 However, there are perceived problems with the use of glutaraldehyde as a pulpotomy agent:
•Glutaraldehyde solutions are reported to be unstable.235
•Neither the optimum concentration nor time of application of glutaraldehyde solution has been established conclusively.97,162,238
•Clinical studies reported increasing failure rates with increasing time post pulpotomy,89 with lower levels of clinical success than formocresol.
Despite the perceived enhanced safety of glutaraldehyde with respect to formocresol, it did not gain favor over formocresol for pulpotomy in the primary dentition.

Glutaraldehyde has been investigated as an alternative fixative to formocresol because of its lower toxicity.50 Glutaraldehyde is a larger molecule than formaldehyde, and as a result diffusion through the tissues is reduced. When 2% unbuffered glutaraldehyde was used, over 96% clinical success was reported after 42 months.51,52 A 90% clinical success rate was reported after 1 year, where 2% buffered glutaraldehyde was applied for 5 minutes in pulpotomies.53 At follow-up after 2 years there was a failure rate of 18% as a result of internal resorption;54 the authors concluded that the relatively high failure rate reported in this study does not justify recommending a 2% buffered glutaraldehyde solution as a substitute to formocresol. Although glutaraldehyde was proposed as a replacement for formocresol, questions remain about its safety.36 On a weight-for-weight basis there is little difference in toxicity between formocresol and glutaraldehyde.

Glutaraldehyde is a saturated dialdehyde that has gained wide acceptance as a high-level disinfectant and chemical sterilant.101 Aqueous solutions of glutaraldehyde are acidic and generally in this state are not sporicidal. Only when the solution is “activated” (made alkaline) by use of alkalinizing agents to pH 7.5 to 8.5 does the solution become sporicidal. Once “activated” these solutions have a shelf life of minimally 14 days because of the polymerization of the glutaraldehyde molecules at alkaline pH levels. This polymerization blocks the active sites (aldehyde groups) of the glutaraldehyde molecules that are responsible for its biocidal activity.

Novel glutaraldehyde formulations (e.g., glutaraldehyde-phenol-sodium phenate, potentiated acid glutaraldehyde, stabilized alkaline glutaraldehyde) produced in the past 40 years have overcome the problem of rapid loss of activity (e.g., now use life of 28 to 30 days) while generally maintaining excellent microbicidal activity.74,75,102,103 However, it should be recognized that antimicrobial activity is dependent not only on age but also on use conditions such as dilution and organic stress. The use of glutaraldehyde-based solutions in health care facilities is common because of their advantages, which include excellent biocidal properties; activity in the presence of organic matter (20% bovine serum); and noncorrosive action to endoscopic equipment, thermometers, rubber, or plastic equipment. The advantages, disadvantages, and characteristics of glutaraldehyde are listed in Table 301-2.

The in vitro inactivation of microorganisms by glutaraldehydes has been extensively investigated and reviewed.104 Several investigators showed that 2% or greater aqueous solutions of glutaraldehyde, buffered to pH 7.5 to 8.5 with sodium bicarbonate, were effective in killing vegetative bacteria in less than 2 minutes; M. tuberculosis, fungi, and viruses in less than 10 minutes; and spores of Bacillus and Clostridium species in 3 hours.104 Spores of C. difficile are more rapidly killed by 2% glutaraldehyde than are spores of other species of Clostridium and Bacillus,105,106 and this includes the hypervirulent binary toxin strains of C. difficile spores (W.A. Rutala, unpublished data, December 2012). There have been reports of microorganisms with relative resistance to glutaraldehyde, including some mycobacteria (M. chelonae, Mycobacterium avium-intracellulare, Mycobacterium xenopi),107-109 Methylobacterium mesophilicum,110 Trichosporon, fungal ascospores (e.g., Microascus cinereus, Chaetomium globosum), and Cryptosporidium.111 M. chelonae persisted in a 0.2% glutaraldehyde solution used to store porcine prosthetic heart valves,112 and a large outbreak of Mycobacterium massiliense infections in Brazil after videolaparoscopy equipment used for different elective cosmetic procedures (e.g., liposuction) was highly tolerant to 2% glutaraldehyde.113 Porins may have a role in the resistance of mycobacteria to glutaraldehyde and ortho-phthalaldehyde.114

Dilution of glutaraldehyde during use commonly occurs, and studies show a glutaraldehyde concentration decline after a few days of use in an automatic endoscope washer.115 This decline occurs because instruments are not thoroughly dried and water is carried in with the instrument, which increases the solution's volume and dilutes its effective concentration. This emphasizes the need to ensure that semicritical equipment is disinfected with an acceptable concentration of glutaraldehyde. Data suggest that 1.0% to 1.5% glutaraldehyde is the minimal effective concentration (MEC) for 2% or greater glutaraldehyde solutions when used as a high-level disinfectant.115-117 Chemical test strips or liquid chemical monitors are available for determining whether an effective concentration of glutaraldehyde is present despite repeated use and dilution. The frequency of testing should be based on how frequently the solutions are used (e.g., used daily, test daily; used weekly, test before use), but the strips should not be used to extend the use life beyond the expiration date. Data suggest the chemicals in the test strip deteriorate with time,118 and a manufacturer's expiration date should be placed on the bottles. The bottle of test strips should be dated when opened and used for the period of time indicated on the bottle (e.g., 120 days). The results of test strip monitoring should be documented. The glutaraldehyde test kits have been preliminarily evaluated for accuracy and range,118 but their reliability has been questioned.119 The concentration should be considered unacceptable or unsafe when the test indicates a dilution below the product's MEC (generally to 1.0% to 1.5% glutaraldehyde or lower) by the indicator not changing color.

Glutaraldehyde is used most commonly as a high-level disinfectant for medical equipment such as endoscopes,93 endocavitary probes, spirometry tubing, dialyzers, transducers, anesthesia and respiratory therapy equipment, hemodialysis proportioning and dialysate delivery systems, and reuse of laparoscopic disposable plastic trocars.75 Glutaraldehyde is noncorrosive to metal and does not damage lensed instruments, rubber, or plastics. The FDA-cleared labels for high-level disinfection with 2% or greater glutaraldehyde at 25° C range from 20 to 90 minutes depending on the product. However, multiple scientific studies and professional organizations support the efficacy of 2% or greater glutaraldehyde for 20 minutes at 20° C.9,18,37 Minimally, this latter recommendation should be followed. Glutaraldehyde should not be used for cleaning noncritical surfaces because it is too toxic and expensive.

Colitis believed to be due to glutaraldehyde exposure from residual disinfecting solution in the endoscope solution channels has been reported and is preventable by careful endoscope rinsing.69 One study found that residual glutaraldehyde levels were higher and more variable after manual disinfection (<0.2 to 159.5 mg/L) than after automatic disinfection (0.2 to 6.3 mg/L).120 Similarly, keratopathy and corneal damage were caused by ophthalmic instruments that were inadequately rinsed after soaking in 2% glutaraldehyde.121
Glutaraldehyde exposure should be monitored to ensure a safe work environment. In the absence of an OSHA permissible exposure limit, if the glutaraldehyde level is higher than the American Conference of Industrial Hygienists ceiling limit of 0.05 ppm, it would be prudent to take corrective action and repeat monitoring.

Glutaraldehyde is the agent most commonly used to disinfect endoscopic equipment. Outbreaks of hemorrhagic colitis in patients who underwent colonoscopy have been attributed to inadequate cleaning and rinsing of the endoscopic equipment with subsequent exposure of the colonic mucosa to residual glutaraldehyde.141 A study on laboratory rats showed that glutaraldehyde also has a toxic effect on the esophagus, causing inflammation and segmental vasculitis.142 Rarely, esophageal strictures may develop in humans within several weeks of endoscopy, presumably because of exposure to glutaraldehyde-contaminated endoscopic equipment (Fig. 25-26).142 Exposure to glutaraldehyde should therefore be considered as a possible cause of esophagitis and rapidly progressive esophageal strictures in these patients.