Seminar Assignment

GLUTARALDEHYDE

GROUP - 11

1. Roger Ravichandran (C3181014)

2. Suman (C3178307)

3. Poh Hwee Yong (C3177532)

4. Hajamuhaideen Sheik Mohamed (C3177837)

Company

LOGO What is Glutaraldehyde?Glutaraldehyde (GA)

Molecular Formula: C5H8O2

Structural Formula: (CHO)-CH2-CH2-CH2-(CHO)

It is a colourless oily liquid grouped under the aldehyde family. It forms aqueous solution when

cross link with proteins. Glutaraldehyde in vapour state gives of a pungent odour.1

Company

LOGO Uses of GlutaraldehydeMedical (Beauchamp,1992)

• Sterilising of medial equipment's (Endoscope, Bronchoscopes Dialysis instruments)

• Clinical uses (skin treatment, dentistry and tissue implants)

• Preparation for transplantation of grafts and bio-prosthesesOthers (Beauchamp,1992)

• Controlling bacterial growth in cosmetics, toiletries , etc• Development of vaccines against allergens (Grass Pollens) • Tanning of animal skin

Workplace Sources of exposure

Mainly Health Care Industry (source from: http://www.cdc.gov)

Hospital staff involve with cold sterilizing procedure Hospital staff involve in infection control procedure Supply workers whom using glutaraldehyde as a

sterilant Scientist and pharmacy personnel either preparing

alkaline solution or tissue fixing in lab Lab technician whom sterilize benchtops X-ray development workers

Workplace Sources of exposure

Other Industries (source from: http://www.cdc.gov)

Casket company workers (Embalmment) Pulp mill processing Oil and gas industry

Routes of GA Exposure

Inhalation Skin contact Ingestion (very Rare)

GA Exposure and harm Beauchamp (1992) suggested that the followings • Genotoxicity – GA was nonmutagenic • Carcinogenicity – GA was non-carcinogen. Further studies

required• Development toxicity – GA has low hazard in the development

toxicity as indicated that the rate of spontaneous abortion and fetal malformations in the group of Finland health care workers were “low”.

GA Exposure and harm Beauchamp (1992) suggested that the following Human Effects:

• Skin discoloration (contact dermatitis and ulceration) • Eye irritation • Respiratory distress • Secondary infection due to irritation and ulceration • Skin sensitization • Cell death in graft materials• Induce DNA damage

GA Animal Studies – Inhalation There is a higher rate of non-neoplastic lesions in the

nose of rats and mice (Van Birgelen, 2000)• The body weight of all exposed group of male rats were

less than that of the control group (Van Birgelen, 2000)• Exposure to GA results in tissue damage that is

confined to the upper respiratory tract (Van Birgelen, 2000)• Repeated exposure of 2.6 ppm GA to cause upper

respiratory tract disorder in mice. (Zissu, 1994)• 24 hours inhalation exposure up to 133 mg/l of GA

vapour had symptoms of nervous behaviour, excessive washing and panting in six of ten mice. (Beauchamp, 1992)

GA Animal Studies – Contact

Beauchamp (1992) reported the following:• Hypersensitivity was reported in mice and guinea pigs exposure

of 0.3~3% GA.• Moderate irritation was found in rabbit with dermal application. • 25% GA cause severe local inflammation and punctate necrosis • Up to 125 mg/kg per day of GA in male rats for 35 days cause

increase number of white blood cells, decrease level of haemoglobin and lymphocytes.

Werley (1996) reported the following:• local skin irritation mainly erythema and edema was minimal

and present only intermittently and resolved in four week recovery but no sign of systemic toxicity.

GA Animal Studies – Oral Beauchamp (1992) reported the following:• Aqueous solution of GA 0.5 ~ 50% in rats cause sluggish

movement, rapid breathing and diarrhea. • Biopsy of rats fed with GA shows haemorrhagic in stomach wall,

congestion and distension in small intestine and other related damage in digestive system.

Zeiger (2005) reported the following:• The exposure of 500~1000ppm in drinking water in rats cause

high occurrence of bone marrow hyperplasia, irritation in stomach was also observed.

• After 2 years, the rats suffered from large granular lymphocytic leukaemia in the spleen and liver.

GA Environmental – Fresh water Organism

Larissa (2005) suggested that:• There is a strong evidence proof that toxicity of GA is

influenced by the temperature. Lower environmental temperature decrease the toxicity and higher temperature increase the toxicity of GA. Toxicity depends on the rates of GA degradation and dispersion in the environment.

GA Human Studies – Inhalation• Exposure to <1ppm of GA caused irritation of the

mucus membrane and eye irritation. When expose to >1ppm of GA cause respiratory distress and secondary infection due to severe irritation. (Beauchamp, 1992)

• Symptoms may observe eye discomfort, excess tearing, discomfort of nose and chest, nose mucus secretion and cough or sneezing when the odor recognition threshold (>0.04ppm) is exceeded. (Ballantyne, 2001)

• The epidemiological study was indicated that overexposure of GA may cause occupational asthma. (Ballantyne, 2001)

GA Human Studies – Skin Contact • Exposure to <1ppm of GA caused contact dermatitis

and skin discoloration. When expose to >1ppm of GA cause respiratory distress and secondary infection due to severe irritation. (Beauchamp, 1992)

Dose effects and Dose Response

source from: http://www.glerl.noaa.gov/res/Task_rpts/1997/aqland06-2.html

Graph 1: Inhibitory curve of marine bacteria over a period of 5 minutes and 15 minutes of GA exposure.

Dose Effects and Dose Response

source from: http://www.glerl.noaa.gov/res/Task_rpts/1997/aqland06-2.html

Graph 2: Survival rate of rainbow trout embryos

Threshold of Harm

Limit of Exposure Effects0.032 ppm Respiratory sensitization (Asthma) to human

0.04 ppm Odor threshold

0.1ppm No effect to human

0.3ppm Irritation threshold to human

0.38ppm Eye irritation, throat & nasal discomfort, chest thickness and cough & head ache to human

0.63ppm GA vapour mortality to human

<1 ppm Irritation in mucus membrane and eye to human

>1ppm Respiratory distress and secondary infection to human

2.6ppm Upper respiratory disorder to mice

125ppm Cause white blood cells, decrease level of haemoglobin and lymphocytes to rat

133ppm Nervous behaviour and excessive washing to rat

500~1000ppm Mixture with drinking water cause high occurrence of bone marrow to rat

Threshold of Harm• Based on the research studies and analysis the threshold of

harm is determined to be less than 0.3ppm. However the skin and respiratory sensitization was noted as 0.032 ~0.04 ppm for human. The ACGIH has established the threshold limit for skin, nose, throat sensitization and contact dermatitis as 0.05 ppm for human. Respiratory distress and secondary infection was noted when the threshold limit is exceed >1 ppm for human.

• upper respiratory disorder have been reported in mice expose to 2.6ppm

Occupational Exposure Limit • Prior to 1986, there was no limit of occupational exposure set by

OHSA . In 1986, ACGIH recommended set up the exposure limit up to 0.2ppm, which was adapted by OHSA.

• In 1989, NIOSH agreed to the 0.2ppm limit and adopted it. • In Singapore the Ministry of Manpower (MOM) also adopted the

limit of 0.2 ppm. • In 2001, ACGIH determined the Threshold limit value for GA is

0.05 ppm. (10)

Occupational Exposure Limit [10] Exposure Limit Limit Values Health Factors and Target

Organs

National Institute of Occupational Safety and

Health (NIOSH) recommended exposure limit

0.2ppm

(0.8 mg/m³)

Eye, nose and throat irritation

American Council Governmental of Industrial

Hygienist (ACGIH) Threshold limit value (TLV)

0.05ppm

(0.2 mg/m³)

Eye, nose, skin and throat irritation; skin sensitization and contact dermatitis

OHSA exposure limit value 0.05ppm

(0.02 mg/m³)

Respiratory sensitization, allergic sensitization, asthmatic sensitization.

• The Ministry of Manpower (MOM) in Singapore (13) established the permissible exposure Limit for GA is 0.2 ppm (0.82 mg/m³) [13]

Threshold Differences• According to OHSA the GA odor threshold limit is 0.04 ppm

and the irritation response level is 0.3ppm. ACGIH threshold for GA is 0.2ppm because of its irritation properties from activated or unactivated solutions. (11)

• Frequent exposure of GA to level as low as 0.05 ppm can cause asthma. Small amount of GA exposure can effect the person who has developed asthma. (12)

• For this reason OHSA and ACGIH have set GA exposure limit to 0.05ppm.

Threshold Differences• Animal experiment have concluded that on mice the

exposure levels of GA inhalation from 0.03ppm to 0.1ppm caused sensory irritation.

• Zissu (1994) also supported that OHSA and ACGIH exposure limit of GA is 0.05ppm. Therefore the study concluded that GA permissible exposure limit is 0.2ppm would not be adequate to prevent irritation of the human respiratory tract.

• Ministry of Manpower (MOM) adopts a semi quantitative method to assess the occupational exposure to harmful chemical. The assessment does not take into account persons who have hypersensitivity and also not consider the dermal exposure (or) ingestion.

References 1. International Programme on Chemical Safety [Online] [cited 2014 Mar 16]; Available from: URL: http://

www.inchem.org/documents/sids/sids/111308.pdf2. BEAUCHAMP R, STCLAIR M, FENNELL T, CLARKE D, MORGAN K, KARI F. A CRITICAL-REVIEW OF

THE TOXICOLOGY OF GLUTARALDEHYDE. Critical Reviews In Toxicology [serial on the Internet] 1992 [cited 2014 Mar 16]; 22(3-4): 143-74. Available from: Science Citation Index.

3. Centers for Disease Control and Prevention [Online] [cited 2014 Mar 16]; Available from: URL: http://www.cdc.gov

4. Van Birgelen A, Chou B, Renne R, Grumbein S, Roycroft J, Bucher J, et al. Effects of Glutaraldehyde in a 2-Year Inhalation Study in Rats and Mice. Toxicological Sciences [serial on the Internet]. 2000 May [cited March 16, 2014]; 55(1): 195-205. Available from: Environment Complete.

5. Zissu D, Gagnaire F, Bonnet P. Nasal and pulmonary toxicity of glutaraldehyde in mice. Toxicology Letters [serial on the Internet]. 1994 Mar [cited March 16, 2014]; 71(1): 53-62. Available from: Scopus®.

6. Werley M, Ballantyne B, Neptun D, Losco P.Four-Week Repeated skin contact study with glutaraldehyde in rats. Cutaneous and Ocular Toxicology [serial on the Internet]. 1996 [cited March 16, 2014]; Available from: URL: http://0-informahealthcare.com.library.newcastle.edu.au/doi/pdf/10.3109/15569529609048872

7. Zeiger E, Gollapudi B, Spencer P. Genetic toxicity and carcinogenicity studies of glutaraldehyde -- a review.(Report). Mutation Research - Reviews In Mutation Research [serial on the Internet]. 2005 [cited 2014 Mar 16]; (2): 136-51. Available from: Academic OneFile.

References 8. Larissa L. Sano, Ann M Krueger, Peter F Landrum, Chronic toxicity of glutaraldehyde: Differential

Sensitivity of three freshwater organisms. Journal of aquatic Toxicology [Serial on the Internet]. 2004 Dec [Cited 2014 Mar 17]; 71 (2005) 283-296. Available from Science Citation Index

9. Ballantyne B, Jordan S. Toxicological, medical and industrial hygiene aspects of glutaraldehyde with particular reference to its biocidal use in cold sterilization procedures. Journal Of Applied Toxicology [serial on the Internet]. 2001 [cited 2014 Mar 16]; 21(2): 131-51. Available from: Science Citation Index.

10. Occupational Safety and Health Administration (OSHA) [Online] [Cited 2014 March 14]; Available from : URL: https://www.osha.gov/dts/chemicalsampling/data/CH_243400.html

11. Occupational Safety and Health Administration OHSA [Online] [Cited 2014 March 17] ; Available from: URL: https://www.osha.gov/dts/sltc/methods/organic/org064/org064.html

12. Hazard evaluation system and information service [Online] [Cited 2014 March 17]; Available from: URL http://www.cdph.ca.gov/programs/hesis/Documents/glutaral.pdf

13. Ministry of Manpower (MOM) [Online] [Cited 2014 March 17]; Available from: URL: http://www.mom.gov.sg/Documents/safety-health/factsheets-circulars/A%20Semiquantitative%20Method%20to%20Assess%20Occupational%20Exposure%20to%20Harmful%20Chemicals.pdf