EXPOSURE TO GLUTARALDEHYDE

ALONE OR IN A FUME MIX:

A REVIEW OF 26 CASES

 

Bill Glass, FAFOM, FFOM (Lond.) FFOM (I.) Occupational Medical Specialist

Presented to the Marjorie Gordon Memorial Seminar, March 1997.

Published in SHADOWS, Journal of the NZMRT, VOLUME 40, NO 2, 13-17. JUNE, 1997

I would like to begin with a personal tribute to Marjorie Gordon.

She recognised the reality of the relationship between an illness and work. She was tenacious in the face of disbelief.

She had an open mind.

She was not blinded by prejudice, ignorance or the security of the status quo. These are the qualities and attitudes which take society forward.

Thank you Marjone.

This paper reviews the effect of glutaraldehyde on the health of 26 referred patients over a 6 year period.

The patients fall into 2 groups. Group A includes those who worked predominantly with glutaraldehyde, Group B those who worked with a chemical cocktail which included glutaraldehyde, with the exception of two cases where formaldehyde and benzaldehyde replaced glutaraldehyde.

Referrals came from either the ACC, lawyers or general practitioners. They thus tend to reflect those more seriously affected.

Group A patients worked with glutaraldehyde used as a cold sterilant or, on occasions, as a bench wipe and comprised nurses and technicians employed in hospitals or general practice.

Group B patients worked predominantly in photographic or x-ray departments in hospitals. They were exposed to a mix of chemicals in the developing and fixing processes. In the developer there was glutaraldehyde, acetic acid, hydroquinone, a glycol ether, potassium hydroxide, sodium sulphite and 1 phenyl-3 pyrazolidone. In the fixer there was acetic acid, aluminiurn sulphate, ammonium thiosulphate, sodium acetate, sodium sulphite and a glycol ether.

The method of processing has evolved over time from a predominantly hands on process with mixing and diluting of chemicals and manually removing the film to automatic processing systems.

METHODS OF USE AND EXPOSURE LEVELS

1. Glutaraldehyde as a Cold Sterilant

Glutaraldehyde is a volatile irritating chemical which can also act as a sensitiser. The odour threshold is 0.04ppm and the irritant threshold 0.3ppm. The workplace exposure standard (short term, 10 minutes) is 0.2ppm.

The chemical is used as a 2% solution and is activated for use by buffering with sodium bicarbonate which enhances its irritating effects. It has been frequently used in open containers, buckets and shallow dishes and for cleaning surfaces (bench wipe).

A Scandinavian study(1) recorded glutaraldehyde in air levels as follows:

-When used as a bench wipe in a 0.5% and 3% solution, 0.04 to 0.7ppm.

-During manual procedures, <0.01 to 0.2ppm.

-With automatic sterilisers, <0.01 to 0.06ppm.

-In poorly ventilated rooms, 0.04 to 0.06ppm.

-In well ventilated rooms, up to 0.01ppm.

An investigation in the UK(2) produced results similar to those reported above. However, a NIOSH investigation recorded 6 out of 13 tests greater than 0.2ppm.

2. Glutaraldehyde as a Hardener During Film Processing

In a review of use in the UK(3) it was noted that dark rooms and processing areas are typically very small with little attention to design, drains are often open, local exhaust ventilation poor and general dilution ventilation inadequate. Skin contact can occur during mixing of the chemicals, cleaning of the equipment and cleaning of the floors. Hands on use is gradually being replaced with more automatic systems.

An investigation into levels of pollutants in automated processing units indicated that only acetic acid and sulphur dioxide were detected at measurable levels (<0.lppm) although still below the exposure standards. It was not possible to investigate workplaces where health problems had occurred.

IN SUMMARY

Results from overseas studies have shown both high and low air levels when glutaraldehyde has been used either as a cold sterilant or in photographic processing. Few measurements in New Zealand workplaces have been carried out; one will be presented in a case history.

CLINICAL FINDINGS

The tables which follow list the reported symptoms and the frequency of occurrence of the symptoms in the two groups.

TABLE 1
FREQUENCY OF OCCURRENCE OF SYMPTOMS IN THE TWO GROUPS
.

Eye Irritation

Blocked Nose

Sore Throat

Chest Tightness

Shortness of Breath

Confirmed Asthma

Skin Irritation 10 4

Confirmed Dermatitis

Headache

Fatigrue

Muscle aches and pains

Palpitations

Nausea

Diarrhoea

Ear Problems

Cross Sensitivity

(Neuropsychological ) Mood

Memory

Concentration

GROUP A

10

10

11

9

2

 2

10

2

7

10

6

7

 3

 3

3

7

12

12

12

GROUP B

9

8

8

7

1

3

4

2

2

10

 5

3

5

1

2

8

7

7

7

     

From Table 1 there is clearly little difference in the frequency of occurrence of symptoms between Group A and Group B except for skin irritation. The most commonly occurring symptoms are those which are irritative to the eye, nose, throat, lower respiratory tract and skin, together with headache and fatigue.

There were 5 cases of asthma confirmed by respiratory physicians, 2 among Group A and 3 among Group B. There were 4 cases of dermatitis confirmed by dermatologists, 2 in each Group. I was also diagnosed as having scleroderma (See Gase Study.)

Symptoms of a neuropsychological nature involving mood, memory and concentration occurred more frequently among the Group A cases than Group B.

10 of the 13 cases in Group A were also given Questionnaire 16 and the results are shown in Table 2.

Questions 1, 2, 3, and 4 involve memory, question 6 understanding, question 6 concentration and questions 7 and 8, mood.

More detailed short battery psychological tests were completed by 4 patients (Table 3) and a full clinical neuropsychological

evaluation was carried out on 6 patients. These further tests confirm the neuropsyochological damage suffered by the patients.

TABLE 2                          Questionnaire 16

A Questionnaire for CNS Symptoms

NO. QUESTIONS  YES NO
1 Do you have a short memory?  9 4
2 Have your relatives told you that you have a short memory?   6 7
3 Do you often have to make notes about what you have to remember? 9 4
4

Do you often have to go back and check things you have done such as turned off the stove, locked the door etc? 

10  3
5

Do you generally find it hard to get the meaning from rcading newspapers and books? 

6
6 Do you often have problems with concentrating?  10  3
7 Do you often feel irritated without any particular reason?  5
8 Do you often feel depressed without any particular reason?  7
9 Are you abnormally tired?  10  3
10 Are you less interested in sex than what you think is normal?  7  6
11 

Do you have palpitations of the heart even when you don't exert yourself?  

7 6
12  Do you sometimes feel oppression in your chest?  6
13  Do you perspire without any particular reason?  7
14  Do you have a headache at least once a week?  6
15  Do you often have painful tingling in some parts of your body?  6
16  Do you have problems with buttoning and unbuttoning?  3  10

TABLE 3

NEUROPSYCHOLOGICAL - SHORT BATTERY TESTS

TEST

PATIENT RESULTS

                

     GROUP A     

     GROUP B     

Case l 
Male 46 
Case 2 
Male 46 
Case 3 
Female 44 
Case 4
Female 47
Attention (Digit Span) 5F 3B 7F 3B 5F 4B 8F 4B
Normal Range for age: .9 /4.3 6.9/4.3 6.9 /4.3 6.9 /4.3
(S.D. 1.12 /1.11) Sensory Motor (Digit Symbol) 52 47  54  62
 Normal for age:  33+   33+  33+ 33+ 
Memory        
a) Verbal (Associated Learning)    121/2  91/2 91/2 121/2
Normal for age  15  15  15  15
b) Short Term (Digit Span) .            See above        

c) Long Term (Controlled Oral Word Fluency)

23  43  32  30

Normal for age 

44  44  44   44

d) Visual    (Visual Reproduction) 

N

DISCUSSION

Exposure to glutaraldehyde and consequential health effects have been well documented in the medical literature(7) since the original work of Marjorie Gordon(8). The effects of exposure are both irritative and allergic with symptoms predominantly on the upper and lower respiratory tract(9-14) and the skin(15-17). Undue fatigue and headache have also been reported.

However, it is clear from the review of these 26 cases that other symptoms have occurred to a significant degree and include neuropsychological symptoms and cross sensitivity reactions. It is of interest that these symptoms were not recorded in the paper by Spicer and Gordon in 1986(18).

NEUROPSYCHOLOGICAL SYMPTOMS

Questionnaire 16 is a screening questionnaire developed initially by Hogstedt et al(19) to test for early disturbance in central nervous system function.

A recent study in New Zealand (in publication) has validated Questionnaire 16 as a useful tool. It suggested that Q16 effectively screens men with suspected Type 2 occupational solvent neurotoxicity (WHO classification of mild toxic encephalopathy with symptoms of abnormality of performance on neuropsychological testing).

While not all of the 26 cases were tested with Q16, among those ten who were tested in Group A, evidence of memory, mood and concentration impairment was evident. Confirmation by a short battery neuropsychological test procedure or complete neuropsychological assessment was shown in 6 of these 10.

In an interesting paper by Teo(20) given at the Australian Institute of Occupational Hygienists Conference in 1994, three staff exposed to glutaraldehyde in a theatre while cleaning endoscopes were tested by the auditory evoked potential method. They showed prolongation of the response time (p3 latency) a dysfunction related to the depression of the cortical function of the brain.

TABLE 4 FULL NEUROPSYCHOLOGICAL ASSESSMENT

GROUP A      GROUP B    
56 YRS  39YRS  40 YRS  48 YRS  49 YRS  44 YRS
MALE  MALE  FEMALE  FEMALE  FEMALE  FEMALE
TEST             
PRE-MORBID
INTELLECTUAL CAPACITY (NART)
Above av  Above av  Above av  Above av  Average  Above av
GENERAL INTELLECTUAL ABILITY (WAIS-R) VERBAL AND PERFORMANCE Above av  Above av generally.  Verbal abstraction reduced Performance better than verbal.  Digit span similarities reduced Memory retrieval abstract thought reduced Digit span reduced Below predicted on sub-tests
             
Verbal Memory Assoc learning  reduced. Selective reminding reduced Assoc learning good. Logical memory reduced Unimpaired  Assoc learning reduced. Immediate recall reduced  Assoc learning reduced Assoc learning reduced
NON-VERBAL MEMORY WVR good REY figure  fair. Delayed  test poor. WVR & REY figure good Both results good WVR reduced WVR average. REY figure difficulty WVR & REY figure reduced
REACTION    Not Assessed Good Good Impaired  Impaired  Impaired

TIME - VERBAL -VISUOMOTOR      

Not assessed Av Good Impaired Impaired Impaired
FRONTAL LOBE  Impaired  Impaired  Impaired  Impaired  Impaired  Impaired
-VERBAL FLUENCY  Reduced  Reduced  Reduced latter half Reduced Not assessed Not assessed

CROSS SENSITIVITY

Cross sensitivity, a term used to categorise those who developed a reaction to other chemicals, was a disturbing reaction in a number of patients. There were 7 cases among Group A and 8 cases among Group B. Common substances to which patients reacted included petrol fumes, cigarette smoke, deodorants, hairsprays. paper and household cleaners. Many of these substances contain formaldehyde, a chemical relative of glutaraldehyde.

Tachycardia and palpitations were noted by 7 patients in Group A and 3 patients in Group B. A report by Connaughton(2l) in Australia recorded a similar finding. However, "unusual heart rhythms" were also noted in the survey by Spicer and Gordon in 18 out of 367 radiographers.

Questions have arisen as to whether the cause of radiographers' illnesses is glutaraldehyde alone, given that other hazardous chemicals are present. For example, sulphur dioxide, a respiratory irritant, and acetic acid are more commonly found in detectable quantities in air sampling than is glutaraldehyde. In fact in one report an analogy is made between the symptoms of radiographers and those who suffer sick building syndrome(22).

Certainly working circumstances for many radiographers are dreadful with confined space and inadequate ventilation, both local and general, being frequent findings.

It is a well accepted premise in occupational medicine that the toxic effects of a chemical are more severe when the dose is high and dose is a consequence of concentration and exposure time, with the former being influenced by confined space conditions. It is also well accepted that working in poorly ventilated work areas, even when the chemical concentration is modest, will lead to symptoms such as headache and perhaps fatigue.

As is so often the case, a specific causative agent for illnesses which occur to workers exposed to a mixture of chemicals is rarely isolated but this does not invalidate the "mix" as causative. Smelter asthma in the aluminum industry, solvent neurotoxicity (when the solvent is frequently a solvent mix) and chronic bronchitis from welding fumes, are well known examples.

Energy and money spent on providing good working conditions and better technical systems is more effective in these cases than fruitless research on trying to identify a single causative agent.

I will conclude, therefore, by reminding us all that the essence of the law in New Zealand, The Health and Safety in Employment Act 1992, is compliance with a few basic principles. These include:

- hazard identification

- hazard assessment (measuremeut)

- hazard significance (is it a health risk?)

- intervention.

Principles of intervention for significant hazards are:

- elimination

- isolation

- minimisation and monitoring.

The emphasis of the Act is that employers shall take all practicable steps to ensure the safety of employees while at work.

More detailed assistance is provided by the 0SH booklet "The Safe Occupational Use of Glutaraldehyde in the Health Industries", 1992 and the ACC booklet "Guidance Notes to the Provision of a Safe Work Environment and Safe Work Practice for Radiographers and Darkroom Technicians", 1986.

Specific control measures include

1. Attention to workplace design, size, construction, and surfaces.

2. Attention to local and general ventilation principles.

3. Engineering solutions to handling and decanting, i.e. process change.

4. Good housekeeping and hygiene practice.

5. Planned contingencies for spillages.

6. Proper waste disposal.

7. Education and training.

8. Personal and protective equipment.

9. Health surveillance and environmental monitoring.

10. Compliance with the law.

Finally, given the history of the management of glutaraldehyde in photographic chemicals to date and the disastrous outcomes for many workers, there is clearly a need for a new technological approach for both cold sterilising and film processing.

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