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Glutaraldehyde  (1,5-pentanedial  OCH(CH2)CHO   ) - GA was synthesised about 1908.  Health concerns about formaldehyde in the 1970s led to increasing GA usage.  It is widely used as a ; hardener in X-ray developer solution, (acts on the gelatine in the film); cold sterilant for endoscopes in hospital theatres; in dentistry and by vets; for farm housing at a 50% solution, eg chicken sheds; biocide in cooling towers and for inhibition of corrosion-causing bacteria in off-shore oil operations, and  in water reservoirs.  In mines.  It controls bacterial growth in metal working equipment.fixative for tissue in electron microscopy because of its preservation of fine structural detail  and localisation of  enzymatic activity.  Glutaraldehyde inhibits enzyme activity more than formaldehyde, the inhibition increasing with time in the fixative.

[1] A fixative also in the tanning industry from the '60s. 

From the early 1970s, glutaraldehyde has been used to treat skin disorders eg (warts, herpes simplex, and  hyperhidrosis - excessive sweating of the hands and feet), and used as an adhesive in dentistry.  It was also used as a fixative component in the manufacture of tissue transplants (from the late '80s),  in  washable wallpaper, sausage casings, cork gaskets, wet strength paper/cardboard (including food packaging) and paper towels, and in textile sizing mixtures made from PVA to waterproof materials; 

preservative in pigments and fillers, and even in cosmetics and toiletries  (between 1973 and 1984,  74 cosmetics were registered containing  GA - hand cream, toner, cleanser, powder, conditioner etc).

2]inert  (unspecified) ingredient of sprays.  Also a chemical intermediate in the synthesis of pesticides and pharmaceuticals eg in the development of vaccines for certain allergens.

c leaner/reodorant  on some aeroplanes 

Commercial names include:  Actisan, Aidal (sterilant), Aldecyde 28, Aldesan, Aldespray, Aldetex, Alhydex, Aqucar, Asep, Biomate, Cidex, Coldcide-25 micrpbiocide, Cronex, Derugan, Dioxopentane, DSD,  Duraflo, Formula 936N, Gibson's Formula (aircraft), Gibson's Actisan (aircraft), Glutaral, Glutaralum, Glutarol, Glutasept, Glutex, Hospex, Ilfotec RT Developer, Industrex, Keymix Glutacide, Microcide, Nalco, Neoquat LA, Parvocide, Pentanedione, Performax, Piror Slimicide, Protectol GDA, Protosan, Relugan GT (tanning), RDIII Developer, RP X-Omat Developer, Safeguard, Sepacid GA 50, Sporicidin, Sonacide, Sterilite, Surflo, Technicide, Tegodor, Totacide 28, Ucarcide, Ucarsan, Uconex, Ultrasan, Veruca-sep, Virasan, Visco, Wavicide (sterilant), Zenicide Plus, Zexocide. 

Other nomenclature:  Glutardialdehyde; glutaric (di)aldehyde; Glutaral; 1,3-Diformylpropane; pentanedial; 1,5-pentanedione; potentiated acid glutaraldehyde; succin-dialdehyde.

GA is purported to have an "odour threshold" of 0.04 ppm. However, in a series of NIOSH investigations of hospitals, even though most of the air samples indicated that glutaraldehyde concentrations were at or below 0.04 ppm, workers still complained about its irritating odor. This reinforces the general caution that odour is a poor indicator of exposure or predictor of toxicity.

[3]GA is highly soluble in water and hence in the mucous membranes of the respiratory tract, (and blood).  NIOSH (USA) became concerned about GA in 1991 when questions were raised about the carcinogenic potential of acetaldehyde, malonaldehyde and formaldehyde and the mutagenicity of other low molecular weight aldehydes.

[4]Glutaraldehyde toxicity.  NIOSH data, Dec 1997,  "Class:  Tumorigen;  Mutagen;  Reproductive Effector;  Primary Irritant."   The draft Toxicology and Carcinogenesis Studies of Glutaraldehyde in F344/N Rats and B6C3F1 Mice (Inhalation Studies) NIEHS/NIH  presented 30 Oct, 1998, states that under the 2 yr inhalation studies there was no evidence of carcinogenic activity in the mice exposed to up to 250ppb. Incidences of nonneoplastic (non-tumorous) lesions of the nose were significantly increased in rats and mice.

Antec International web site: "In a Soviet study, repeated oral doses of glutaraldehyde evidently had effects on the heart, kidneys and liver. Repeated oral doses given during pregnancy to rabbits caused foetotoxicity and an increased incidence of malformations was seen at maternally toxic doses. DNA damage, mutations and some evidence of chromosome damage were found in mammalian cells in culture following treatment with glutaraldehyde. It was mutagenic in Ames bacterial assays. DNA damage was not induced in the liver cells of rats treated orally. A dominant lethal mutation assay where female rats were treated orally gave a negative result.

The USA PEL - Permissable Exposure Limit of  0.2 ppm;   NZ WES - Workplace Exposure Standard of  0.2 ppm (10 minute period);   UK  OES  (Occupational Exposure Standard),  measured over a 10 minute period, of  0.2 ppm  [or  0.7 mg/m³]  in air  (conditions under which workers may be exposed day after day without adverse effect) was based on its irritant effects on eyes, nose and throat. These limits are under major revision:                

TheACGIH (USA) Notice of Intended Change (NIC) is to lower the existing TLV of  0.2 ppm to a TLV ceiling of  0.05 ppm.

The British Health and Safety Executive (HSE)  has issued a Chemical Hazard Alert Notice.  Their Advisory Committee has recommended that a  Maximum Exposure Limit  (MEL)  of   0.05 ppm, expressed as a time weighted average, and 0.05 ppmexpressed as a 15-minute reference period,  should be set.  "A MEL places a duty on the employer to reduce exposure as low as is reasonably practicable, and in any case below the MEL".  They state:  The independent committee of occupational health experts

"could not identify a safe level of exposure where it could be certain that there would be no risk of serious health effects."  (Sept 1997)

A further Chemical Hazard Alert Notice, Feb 98 states:  "Because of information now available on the health effects of glutaraldehyde, the committee could no longer identify a level which is both safe and practicably achievable and the OES was withdrawn in Jan 98."  [The Occupational  Exposure Standard  is set at a level at which there are thought to be no adverse effects.]  Copies of Gluteraldehyde and You: Guidance for the Healthcare Sector  are available from:  HSE Books, PO Box 1999, Sudbury, Suffolk, CO10 6FS, England,   ph: 01787-881165   f: 01787-313995.

GA is absorbed into the body if the vapour is breathed in.  In addition, the vapour and liquid are readily absorbed through the skin. (Chemical Hazard Alert Notice, Sept 1997).  For substances assigned a short-term MEL in the UK, the employer  MUST:

2)  keep the exposure as far below it as reasonably practical

3)  measure airborne concentrations (unless a formal risk assessment shows the MEL is very unlikely to be breached).

4)  keep a record of individuals with work-related symptoms.

"Only about 40 compounds in the UK have been assigned MELs so this reclassification is very significant.  So is reducing the limit by a factor of four.  MELS are most often allocated to carcinogens and to other substances for which no 'safe' health threshold can be identified and for which there is no doubt about the seriousness of the effects of the exposure."  (Geof Care, Managing Director, Photosol, London; personal communication, Nov, 1997). Measurement down to a few ppb is straightforward with a high performance liquid chromatograph. The measurement of airborne glutaraldehyde by high-performance liquid chromatography (HPLC) shows 3ppb may be detected with improved eluent and more robust calibration under this system.  MBTH measurement of aldehydes detects non-selectively all aldehydes in the environment. The DNPH method (4.4ppb)  is more sensitive than MBTH (165 ppb).

[5]Glutaraldehyde is also a sensitiser. A sensitiser notation (SEN) for GA has also just been given.

[6] In the USA 0.2ppm threshold limit was set by OSHA is the 1980s.  In 1992, the US Court of Appeals struck down those limits on the grounds that  OSHA had not done the degree of investigation that the court thought that the law required.  OSHA expects its new standards to be published early 1999. (Letter from Assistant Attorney General to S Sowers and J Kenepp,  Oct 1, 1998.)

From  <http://www.cdc.gov/niosh/ipcs/0158.html>  -  International Chemical Safety Cards (WHO/IPC...):  "Anyone who has shown symptoms of asthma due to this substance should never again come into contact with this substance"

The proposed WES for Australia is 0.1ppm.  OSH NZ has sent out a Chemical Alert Notice for GA, stating that a level below the current  0.2ppm WES  is  to be considered.  Andrea Eng, formerly OSH's  Senior Occupational Health Scientist, says that it is likely that this will be 0.05 ppm for NZ  not 0.1ppm as first proposed.  The OSH Notice states that "the fact that the WES is likely to be lowered  reinforces the need for a review of processes that use glutaraldehyde to ensure that all practicable steps have indeed been taken to prevent or control exposure".  If an unsafe environment is suspected,  OSH or the equivalent Health and Safety Inspectors should be called in to make accurate readings of chemicals present  BEFORE  the environment is cleaned up (and preferably without too much warning).  This is important if cases for compensation are to succeed. 

LEVELS

The problem with glutaraldehyde has continued to be the fact that people have become sensitised at levels well below "safe" limits  (and react subsequently to minute quantities).  The only glutaraldehyde detected by Scobbie et al  (1996) in all of:  (a) a survey of  8 typical X-ray locations,  (b) the exhaust duct of a Dupont Cronex processor,   (c) made-up working strength solutions in a laboratory,  (d) a created worst case scenario of a one-time problem area with room ventilation switched off,   was  "directly above the solution in the developer tank in the problem area where the concentration was about  0.13 ppm....  Other studies of X-ray facilities, although limited, have reported glutaraldehyde concentrations in the range 0.003-0.006 mg/m-³ (0.0009-0.002 ppm) (Leinster et al, 1993)."

[7]  (OES of the time  0.2ppm).

Higher levels are detected when glutaraldehyde is used as a sterilant or bench wipe.  A Scandinavian study

[8] recorded glutaraldehyde in air levels:    Used as a bench wipe in a 0.5% and 3% solution < 0.04 to 0.7 ppm;        During manual procedures  <0.01 to 0.2 ppm;        With automatic sterilisers  < 0.01 to 0.06 ppm;              In poorly ventilated rooms  0.04  to 0.06 ppm;        In well-ventilated rooms  up to   0.01 ppm.

Scobbie and Groves:  "An investigation of the atmosphere above an activated sterilising solution suggests that the concentation of  up to 2 ppm glutaraldehyde can be formed."

[9]In a 1986 investigation (86-226-1769) of the use of Cidex 7® in a Pennsylvania hospital,  NIOSH found breathing zone samples of from 0.1ppm to 0.4 ppm collected over a five to seven minute period. GA use was also investigated at a Denver hospital (85-257).  In the radiology department glutaraldehyde solution was applied to the tables using a rag soaked with the solution.  Concentrations determined by personal monitoring ranged from 2.0 ppm to about 2.8 ppm (1.98 mg/m3).  In the emergency department both personal and area sampling revealed concentrations that ranged from about 1- 2.7 ppm.  A West Virginia hospital (90-296-2149) found airborne glutaraldehyde exposures of  0.005 ppm - 0.08 ppm.NIOSH has also conducted investigations in hospitals in Alaska (97-0062-2662) and Montana (87-176-1826). In the Alaskan hospital no GA was detected in any of the samples taken in the X-ray processing dark room. In the Montana hospital GA was used to sterilize sigmoidoscopes; all samples revealed air borne concentrations of glutaraldehyde well below the NIOSH REL of 0.2 ppm (0.03 ppm - 0.07 ppm).  The findings from the Montana investigation document the efficacy of local exhaust ventilation in maintaining glutaraldehyde concentrations below those which have been demonstrated in other hospitals.

[10]

[2]Allergic contact dermatitis to glutaraldehyde in a hair conditioner.  Jaworski C, et al. Cleveland Clinic Journal of Medicine, 54, 5 1987