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Allergies affect over 20% of the population in the UK and “recent epidemiological studies have indicated that many chemical pollutants are allergenic ...and the incidence of atopic allergy is increasing with pollution”. Allergies are difficult to diagnose and it is hard to get a clear indication of all the allergens implicated. One of the oldest tests is Skin Prick Testing involving the introduction of allergen extract into the upper layer of skin - gives immediate results. However disadvantages include poor quality, unstable, non-standard solutions that may also contain irritants. Also, the assessment is subjective and skin response variable and may be influenced by medication. The test carries the risk of serious adverse reactions. [1]

Skin Patch testing is diagnostic for skin allergies. It is not diagnostic for inhaled allergens. I am most familar with fragrance materials. Many fragrance materials are also skin irritants. The concentrations are formulated to provide enough exposure to trigger a reaction if the person is allergic to the material, but not high enough for concentration to cause an irritant reaction or cause sensitization if the allergy did not exist. Patch tests that covered larger areas (so there was more exposure) had greater positive results. (Gefeller O, et al. The association between size of test chamber and patch test reaction: A statistical reanalysis. Contact Dermatitis. 1999 Jan, 4, 1, 14-8.)

....The size of the reaction is the gauge of how allergic a person is to the substance. The larger the area of reaction, the more sensitive. There are a few people that are so highly sensitive to an allergen that an anaphalactic reaction is a real possibility from a scratch test. For this reason scratch tests are not usually used if a person is suspected of having very severe allergies to a particular substance. RAST tests are done on the blood instead.

All allergy tests have limits. There are false positives and false negatives. A person can have respiratory sensitisation to a substance and the tests be negative. In the case of isocyanates

only about a third have positive antibodies to the substance, but have positive respiratory challenge tests. Results of allergy testing are manifested as a local reaction in the case of skin testing and as elevated antibodies in blood testing (IgE, IgG).”

Some SNFTAAS members show a reaction to glutaraldehyde with skin testing but many do not; many have wider, delayed testing responses.

Nethercott et al[2] looked at contact dermatitis due to GA in health care workers. Allergic contact dermatitis due to GA was found in 13. Concomitant sensitivity to other chemicals was noted in 10. The positive patch test was only evident for every 2 in 4. In 5, the skin disease forced the worker to leave his occupation. Garcia, 1972[3] described a prosecutor’s assistant who showed glutaraldehyde/formaldehyde cross-reactivity on SPT but had apparently had no contact with glutaraldehyde.

From Glasgow, Scotland: Skin testing done in 1987/8 by Dr Forsythe, Dermatologist, at Glasgow Royal Infirmary, of 12 radiographers and technicians with darkroom disease.

A control group of OTs was done at the same time but this weren't followed up at the time. Recently one of the Glasgow technicians who was retested now patch tests positive to almost all perfumes and a large variety of household cleaners. She also has mucous membrane reactions (swelling) to plastics which didn't show up on the skin test of her back.[4]

Betty Bridges (see above): “Challenge testing is different from allergy testing. The person is exposed to the substance in question, then observed and tested to see what happens. This has definite risks and is sometimes difficult to do. If the substance being tested has an odor, it is difficult to do a blinded test. A blinded test is necessary to determine that it is not the odor that triggers the response. In general in a challenge test, the least amount of the substance needed to cause a reaction is used.”

From Our Toxic Times, (April 1999, Vol 10, No 4). Dr Patrick Williams (Benchmark Genetics, USA

ph 507- 645-2378) has a good explanation of how the immune system reacts with chemicals following the traditional toxicological model: “CHEMICALLY INDUCED IMMUNE RESPONSE EXPLAINED”. It covers Innate Immunity (the body’s physical and chemical barriers; blood proteins; phagocytic macrophages, neutrophils, and natural killer cells) and Acquired Immunity - a specific immune response to each foreign agent. Also Chemical Irritants, Toxicants and Allergens. “Toxic effects sre not produced by a chemical agent unless that agent or its metabolites reach susceptible cells tissues, or organs within the body. In addition, the concentration and longevity of the chemical in the body are critically important to the production of a toxic effect...and the susceptibility of the body. As in the case of chemical irritants, cellular and tissue toxicity results in an inflmmatory response. If this occurs on the external surface, redness, swelling, heat, and pain will be observed. These same indications of inflammation occur inside the body as well.”

“Chemical allergy is an immunologically mediated adverse reaction resulting from previous exposure (sensitisation) to a specific chemical or structurally similar one (hypersensitivity). Most chemicals and their metabolic products are not large enough to be recognized by the immune system as a foreign substance.” However, when a chemical binds with a “self” protein (called a hapten) it forms an antigen and can now be recognized by the immune system ... “This hapten-protein complex (antigen) is then capable of stimulating the formation of antibodies, which occurs over a 7-14 day period. This process is called sensitization.”

Hypersensitivity can be classified into four types on the basis of immune mechanisms and mediator molecules (this is a simplification): TYPE 1 Immediate Hypersensitivity - typically mediated by IgE (eg isocyanates). TYPE 2 Antibody-Mediated Cytotoxic Hypersensitivity - antibodies against haptens bound to cell surfaces (eg heavy metals). TYPE 3 Immune Complex Mediated Hypersenstivity - deposition of antigen-antibody complexes in various tissues (blood vessels and joints). TYPE 4 Cell Mediated Hypersensitivity - sensitized T cells (typically in skin) release cytokines in response to a secondary exposure (eg allergic contact dermatitis which represents a true allergy with minute amounts of chemical causing reactions. This is distinct from irritant contact dermatitis where the severity of the reaction is related to the dose applied.) 50% of chemically sensitive patients display Type 4 (Rea, 1992.)

Dr Sherwood Burge, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, England (ph 0121 766 6611, fax 0121 685 5558) has done a great deal of work on glutaraldehyde and occupational asthma. He has developed the hapten for GA. He can do specific allergy testing to GA. It must be done fairly quickly after exposure - at least within the first 6 months. He has set up booth challenges for X-ray chemistry and GA.

is available in Adelaide, Australia through Dr Judy Ford. She writes: “There are positive findings in more than 70% with glutaraldehyde exposure, with no limit to the time between exposure and blood-testing. The test looks at the rate of “sporadic” chromosome abnormalities. The rate found per cell is about 1 cell per 1,000 analysed. This is elevated 30 times in people who have been chemically exposed, so so there are usually 1 or more abnormal cells in 50. This is like a fingerprint left at the scene of the crime. It is damage that we can observe but obviously indicates a far greater level of damage to the mitochondrial DNA (the energy system for the cell). The DNA in mitochondria cannot be repaired and so damage is permanent.

The test takes about 10 days -2 wks. We have recently analysed our data on (a) past exposures - analysed by chromosome analysis and (b) current exposures - measured by the micronucleus test. Most of the people with legal claims belong to the first group. Whilst I write reports, legal cases usually require an extra report which explains the particular relevance of the findings to the particular case. I charge $150 per hour for the writing of these reports but they are well recieved by the lawyers. There can be a delay with Customs/Quarantine so if you wish to go ahead with testing I will send you some labels to attach to the outside of packages. Please send a specimen of heparinised blood (never clotted - about 10 mls in a lithium heparin tube) with some sealant around the top - we usually use Parafilm. This stops problems with pressure changes in the plane. The blood tube then needs to be packaged appropriately for international air transport (we can return packaging). Hopefully one of your Pathology Companies can assist. On the outside of the package put “Human blood, pathogen-free, for genetic testing” and mark it URGENT. Just send a letter (or Pathology Form) of referral with patient's name and address, doctor's name and address/fax number for the report plus date of birth. If the details of the exposure, when, for how long, how much are known, please include them.

Contact: DOVE Australia. Email: <info@mtx.net.au> or search for <http://www.mtx.net.au> or:

Dr Judy Ford, Genetic Consulting and Testing, 8 Butler Dr, Hendon, Adelaide, Australia.

In A Brief Overview of MCS, Cynthia Wilson, CIIN, says: “One key element that is emerging is that chemical sensitivity is probably not an immune system dysfunction or related to allergies. The latest research strongly suggests that chemical sensitivity is most probably some combination of CNS damage and enzyme deficiencies that can cause problems with the endocrine and immune systems....”

“While most MCS research has focused on an immune system mechanism, MCS critics have repeatedly pointed out that much of what MCS sufferers claim simply cannot be immune system mediated. Especially controversial have been reactions which begin immediately upon exposure to chemicals or immediately upon the cessation of an exposure. With the exception of a histamine response and some IgE-mediated responses such as anaphylactic shock, the immune system is not generally capable of reacting as fast as the symptoms appear. This has led some researchers to look at the central nervous system because it can and does have the capacity to respond within the time-frame most patients experience. For example, if your immediate reaction is nausea or vomiting, these reactions are most probably being neurologically mediated. Neurologic testing is finally proving subtle nervous system dysfunction and damage...”

“The neurological phenomenon known as time-dependent sensitisation (TDS),...has an amazing and uncanny similarity to MCS and not only helps to explain how the brain becomes sensitized to low-level chemical exposures in the first place, but the role that stress plays in adverse reactions. It also provides a mechanism for cross sensitization to unrelated chemicals... thought to be impossible by MCS adversaries because no immune system mechanism has ever been established for it. Because classical toxicology makes no allowances for cross sensitization either, the impossibility of cross sensitisation became a critical element in most theories of why MCS had to be a psychological rather a physiological disorder...” (For TDS, see also Cross Sensitisation p40.)

“...in 1994, testing showed that over 90% of MCS sufferers have developed ..Disorders of Porphyrinopathy...The porphyrias are a group of rare metabolic, enzyme deficiency disorders involving the production of heme (for producing haemoglobin and cytochrome P-450), and liver and/or bone marrow damage. They have many symptoms in common with MCS, the most significant being chemical intolerance/sensitivity and the fact that any estrogen mimicking chemical or drug can trigger an attack...this estrogen connection may be one reason females are more susceptible... A recent study of Gulf War veterans discovered that plasma butyrylcholonesterase enzyme deficiencies were playing a significant role in how people get poisoned. A Danish study found that women in their 30s and 40s are at an all time low for the production of this enzyme. Plasma butyr..s are scavenger enzymes for removing toxins from the body...I believe that these metabolic problems will provide the tie that binds all of the chemically injured communities together. ...Autoimmune disorders are ...suspected as a consequence of being poisoned...”.

From Our Toxic Times, Aug 1998: Clinical similarities of MCS to porphyria include: “Apparent neurological basis for many of the symptoms, familial pattern of susceptibility thought to relate to probable genetic enzyme deficiency, and symptoms exacerbated by many medications.” For a good explanation of porphyria, see Defining Multiple Chemical Sensitivity, Bonnye L. Matthews, McFarland 1998. (This book also contains chapters by Dr Donald Dudley on Evoked Potential Testing, and Dr Gunnar Heuser on SPECT brain scanning.) Blood testing for chemically-induced porphyria needs to be done through the Mayo Clinic, Rochester, Minnesota, when a person is “normal” and after an exposure. Articles on porphyrins appear in CIIN’s Our Toxic Times, April, August, October 1998.

The Chemical Information Injury Network (CIIN) has a marvellous Resource Directory and EARN provides computer literature searches etc at very reasonable cost. CIIN, P.O. Box 301, White Sulphur Springs, Montana 59645-0301. Ph: (406) 547-2255 F: -2455. Web: http://biz-comm.com/CIIN

Abnormal body levels of 2 and 3 methylpentane and n-hexane have been detected in radiographers/MRTs/nurses. The mechanism for their presence is not explained.

From the WASTE web page: “Last summer (mid ’97) a member of WASTE had a two inch yellow staining with a wicking line across her bra and at both armpits. This was followed by sleepness night and then a horrible two weeks of toxic illness. The lab felt this indicated the chemicals could still be active and recommended a blood analysis. Methyl pentane showed 4x higher than normal. Testing for methyl pentane and hexane in a further 10 USA nurses and MRTs affected by GA has shown all with abnormal levels of methyl pentane ranging from 7 to 102 (with normal being 4.5), some with and n-hexane, from 20 to 152 (with normal being 2). Methanol is added to gluteraldehyde (pentanedione). [See also p14 for methanol.] They suspect that is where glut metabolises to methylpentane.”

Explanations/theories are currently being sought.Geof Care (Photosol) writes: “N-hexane and methylpentane are not constituents of water-based photographic processing chemicals. Both are immiscible with water and so would be useless for any purpose including the removal of water after fixation. The UK HSE found no trace of either in their exhaustive study of fume components above fresh and used X-ray chemicals which identified over 50 other compounds, often impurities in raw materials or incompletely removed solvents etc from the manufacture of film base (Scobbie & Groves: Chemical pollutants in X-ray film processing departments, Ann.Occup.Hyg., 40, 423-435, 1996.)

Sample 4: Anne W: methyl pentane 29.4, n-hexane 21.1; she has not been working for a year.

Sample 5: Methylpentane 7. She never worked with the chemical but was a floor above an X-ray dept with linking air conditioning. She is still working. The Xray facility is gone.

Sample 6: Rose S’s tests were done 10 mnths after she was terminated from work; methylpentane 7.4, n-hexane 1.8

Sample 7: X-ray tech had the highest levels - 102 for methylpentane and n-hexane 152. She is currently working in an x-ray dept.

Sample 8: Had only a slight elevation, 3 methyl pentane - 4.7, working part time, 20 yrsin dept with unventilated processor. (Also male).

Sample 9: Just stopped work with dermatitis and asthma. 3-Methylpentane 17 and n-hexane 41.6.

Synonyms: Also called pentane, 2-methyl-iso-hexane, 1,2-dimethylbutane. May be shipped as Hexane. Used as solvent for paints, adhesives. Reduced health hazard replacement for n-hexane.

Acute health Effects: In general, the branched hexanes are much less toxic than n-hexane. Based on structural and physicochemical similarities, hexane isomers are expected to be adsorbed, distributed and excreted like n-hexane. Adipose (fatty) tissue has a high affinity for all C6 alkanes. Solubility of hexane isomers in adipose, brain, liver, kidney, heart and muscle tissues was found to be higher than in blood.

Inhaled: Acute effects from inhalation of high concentrations of vapour are pulmonary irritation, including coughing, with nausea; central nervous depression - characterised by headache and dizziness; increased reaction time, fatigue and loss of co-ordination....Symptoms of moderate poisoning may include giddiness, headache, dizziness and nausea...

Hexane and related aliphatic hydrocarbons exhibit only slight acute toxicity by all routes of exposure... inhalation at high concentrations may result in light-headedness, giddiness, nausea and headache... Chronic exposure may cause central nervous system toxicity...

Use: An incidental component of many aliphatic solvent mixes used as lacquer, paint and enamel thinners; also in ink reducers and cleaning solvents. Also used for solvent extraction of oil seeds [eg soya]and in pesticide residue analysis and gas chromatography.

Chronic Health Effects: Principal routes of exposure are usually by inhalation of vapour and skin contact with the material. Chronic inhalation or skin exposure to n-hexane may cause peripheral neuropathy, (eg damage to nerve ends in extremities with loss of sensation); and characteristic thickening. Nerve damage has been documented with chronic exposures of greater than 500ppm. Improvement in condition does not immediately follow removal from exposure and symptoms may progress for two or three months. Recovery may take a year or more depending on severity of exposure, and may not always be complete. Exposure to n-hexane with MEK will accelerate the appearance of damage. Other isomers of hexane do not cause nerve damage.

Dr William L. Marcus, Ph.D., D.A.B.T. EPA. Test interpretation: toxdoc@crosslink.net Aug 15, 1998

“There is no simple answer to your questions. The methyl pentanes appear to adversely affect the kidneys by forming branched chain aldehydes and or keytones that block the descending tubules, so it is important to monitor your kidney function. N-Hexane is extremely dangerous. It attacks the nervous system causing various peripheral nervous system problems. It also attacks the central nervous system causing many different subtle problems ranging from changes in personality to loss of recent memory. Many of these symptoms are peripheral neuropathies (stocking glove syndrome) and motor problems [which] appear to most practising physicians unrelated. There are also problems with vision. Headache and sleep disorders are also not uncommon. They are all related. The mechanism is well described. N-hexane’s metabolite, hexane dione causes an interruption in axion-plasmic flow causing a condition known as die-back syndrome. Since none of these materials are normal, any level in the blood is upsetting. However, I am surprised to see that they can be measured at all. They are readily metabolized into far more toxic metabolites. They are stored in fat in large amounts especially if exposure has taken place over long periods of time. That portends worsening problems that are difficult to ameliorate.”

Contact Accu Chem Labs, Richardson, Texas - Ph 0168 1800 747 2878 (Jerry Laporte, Ext 12). Cost - US $155. The samples need to arrive in 3 days - phone first for the Aliphatic Volatile Solvent Test Kit.

Urine testing of 3 SNFTAAS members in NZ for the metabolite of n-hexane (hexanedione) was negative.

[1]Evans G, Shaw S. Alternatives to the Skin Prick Test. Lab Equip Digest. Aug 1990.

[2]Nethercott J R, Holness D L, Page E. Occupational contact dermatitis due to glutaraldehyde in health care workers. Contact Dermatitis. 1988, 24, 1, 9-12.

[3]Reported in Fisher A A, Reactions to glutaraldehyde with particular reference to radiologists and technicians. Cutis. 1981, 28, 113.

[4]Personal communication. Marlene Barrie. 5 Jan 1999.