Original Research

Toxic Volatile Organic Hydrocarbons in Chemically Sensitive Patients

William J. Rea, MD, FACSCDirector, Environmental Health Center-Dallas, Dallas,TX

Yaqin Pan, MDCDept. of Allergy Peking Union Medical College Hospital, Beijing, People=s Republic of China

John L. Laseter, PhDCPresident and Chief Executive Officer, Enviro-Health Systems, Inc.; developer of the analytic methods Alfred R. Johnson, DOCEnvironmental Health Center-Dallas, Dallas, TX

Ervin J. Fenyves, PhDCProfessor, Dept. of Physics and Environmental Sciences, University of Texas at Dallas

Source: Rpt. from Clinical Ecology, Volume V, Number 2, 1987.

Key words: blood analysis

chemical sensitivity

hydrocarbons

toxic volatile organic chemicals

Abstract: Blood samples from 134 chemically sensitive patients were studied to determine whether toxic volatile organic chemicals (TVOCs) were contributing to the total pollutant load. All patients had adverse reactions on challenge to low levels of TVOCs typically found in air, food, and water including formaldehyde, petroleum ethanol, chlorine, phenol, and the pesticide 2,4, DNP. For each patient, one aliquot of blood was purged and concentrated at a purging trap combined with GC/MS. The trap was heated to desorb the volatile analyte for elution in the GC column and mass fragments were recorded and quantitated. One hundred and fourteen of the 134 patients had detectable levels of TVOCs, with an average of three TVOCs detectable per patient. The most common chemicals found were tetrachloroethylene (54% of patients), toluene (41% of patients), and xylene (38% of patients). There were no significant sex-related differences in TVOC levels and no differences in symptoms or symptom severity between those with and without detectable TVOCs, although many patients without detectable TVOCs had other toxic chemicals in their blood. The TVOCs found are assumed to be exogenous, and it is possible they have contributed to chemical sensitivity by contributing to the breakdown of enzyme detoxification systems or otherwise interfering with metabolic or immune functions.
************************************
It is uncommon for a sensitive individual to be upset by only one factor. Most are sensitive to several allergens, as demonstrated by skin and inhalant testing. There are several well authenticated instances in which two or more factors have triggered a reaction when each factor alone did not, e.g., the combination of exercise and shrimp has caused an attack of asthma in one patient, while each alone did not. We wondered whether a demonstrable chemical load, such as of toxic volatile organic chemicals (TVOCs) in the blood , might play a part in triggering symptoms in those who appear to be chemically sensitive.

Previous studies from our center have shown reduction in blood levels of chlorinated pesticides in some chemically sensitive persons paralleling a decrease in their symptoms (1). These patients experienced either toxic or allergic effects, or both.
 
 

Materials and methods One hundred and thirty-four Achemically sensitive@ patients were investigated. All had adverse reactions by challenge to toxic chemicals typically found in air, food, and water at ambient levels generally accepted as safe. Fifty-two patients were male and 82 female. Their ages ranged from 1-72 years, with an average of 39 years; age distribution is shown in Table 1. Primary symptoms were cardiovascular (edema, vascular spasm, bruising, petechiae, and arrhythmia), respiratory (rhinorrhea, wheezing, and bronchitis), musculoskeletal (pain and swelling), neurological (headache, memory loss, paresthesias, and vertigo), gastrointestinal (gas, bloating, diarrhea, and constipation), and genitourinary, as well as symptoms of the skin and eye (Table 2).

These patients reacted adversely to challenge with one or more of the following: <0.2 ppm formaldehyde, <0.5 ppm petroleum ethanol, <0.33 ppm chlorine, <0.002 ppm phenol, and <0.0034 ppm pesticide (2,4 DNP). The numbers and percentages of patients reacting adversely to each chemical challenge are shown in Table 3.

Table 1. Age distribution of chemically sensitive patients

Age
Number below detectable limit
Number with positive findings
1-10
 

4

11-20
3
9
21-30
1
13
31-40
8
36
41-50
4
26
51-60
1
17
61-70
3
8
71-80
 

1


 

Table 2

Primary Symptoms of 114 Patients with Detectable Levels of TVOCs in Blood

Symptoms
Number
Cardiovascular
36
Respiratory
35
Musculoskeletal
35
Neurological
18
Gastrointestinal
27
Genitourinary
4
Skin
15
Eye
1

Table 3

Numbers and Percentages of Patients Reacting to Each Chemical on Double-blind Inhaled Challenge

Chemical
Number and Percent Reacting
Number Patients Challenged
Phenol <0.002 ppm
107 (80%)
134
Petroleum ethanol <0.5 ppm
102 (76%)
134
Pesticide 2,4 DNP <0.0034 ppm
111 (83%)
134
Formaldehyde <0.2 ppm
121 (90%)
134
Chlorine <0.33 ppm
75 (56%)
134
Xylene <0.17 ppm
3 (100%)
3
Toluene <0.7 ppm
1 (100%)
1
Tetrachloroethylen <0.7 ppm
1 (100%)
1
Pentachlorophenol <0.1 ppb
1 (100%)
1

  Tests were performed between May 1993 and December 1986 to detect those TVOCs listed in Table 4. Blood was drawn in special decontaminated tubes and syringes. One aliquot of a specimen was purged and concentrated at a purging trap combined with GC/MS (2). The trap was then heated to desorb the trapped volatile compounds directly onto the GC column. The volatile analytes separate from other components during elution through the GC column. Mass fragments of each were recorded and quantitated (3).
 
 
Results One hundred and fourteen of the 134 patients had detectable levels of TVOCs in the blood, with an average of three TVOCs detectable per patient (Table 4). The most common chemical, tetrachloroethylene, was found in 72 of the patients. This was followed by toluene in 55, and xylene in 51 (Table 4).

There were no differences in symptoms or symptom severity between those with and without detectable levels of TVOCs. However, many patients without detectable TVOCs had other toxic chemicals in their blood such as organochlorine pesticides, polychlorinated biphenyls, or other solvents. This may account for their chemical sensitivity. There were differences relating to exposure patterns: all persons who worked near certain chemicals had these in their blood, while those who were not heavily exposed did not. There were no differences between urban and rural populations.

We compared levels of TVOCs in males and females and found no significant differences (Table 5). It seems that sex does not affect the exposure or degradation of TVOCs in the body, at least in this series.

Table 4

Toxic Volatile Organic Chemicals Found in 134 Chemically Sensitive Patients, Compared with Overall Patient Population Studied by the Laboratory

Compound Number of patients below detection limits of 0.1-0.3 ppb (all volatiles negative) Number and percent of 134 patients with detectable TVOC levels (0.3 ppb-36.2 ppb) Percent of patient population (>500 persons) tested
Volatile aromatic hydrocarbons
 

 

Benzene

20
16 (11.9%)
23.4
Toluene
20
55 (41.0%)
63.2
Ethylbenzene
20
22 (16.4%)
39.2
Xylenes
20
51 (38.1%)
59.7
Styrene
20
7 (05.2%)
22.0
Trimethylbenzenes
20
10 (07.5%)
3.2
Volatile chlorinated hydrocarbons
 

 

Chloroform

20
13 (09.7%)
36.9
Dichloromethane
20
21 (15.7%)
49.7
1,1,1-Trichloroethane
20
42 (31.3%)
50.5
Trichlorethylene
20
14 (10.4%)
8.6
Tetrachloroethylene
20
72 (53.7%)
83.1
Dichlorobenzenes
20
17 (12.7%)
10.5

 
 

Table 5

Comparison of TVOC levels between male and female patients

 

Patient (n=114)

Male (n=47) Female (n=67)  

 

 

Chemical

X SD X SD X SD Ttest P
Significance
 

(ng/ml, ppb)

(ng/ml, ppb) (ng/ml, ppb)  

 

 

Benzene

0.1175 0.3431 0.1128 0.3633 0.1209 0.3324 0.1233 >0.05
No
Toluene 0.4211 0.9701 0.4553 1.1008 0.3970 0.8749 0.3146 >0.05
No
Ethylbenzene 0.1368 0.4101 0.0872 0.3097 0.1716 0.4670 1.0821 >0.05
No
Xylenes 0.5895 1.1058 0.5532 1.2205 0.5851 0.9690 0.1553 >0.05
No
Styrene 0.0360 0.1619 0.0362 0.1811 0.0358 0.1484 0.0129 >0.05
No
Trimethylbenzenes 0.0851 0.3400 0.0830 0.3338 0.0866 0.3468 0.0554 >0.05
No
Chloroform 0.1947 0.7755 0.1426 0.5340 0.2313 0.9097 0.5993 >0.05
No
Dichloromethane 0.6219 3.3390 0.8766 4.7238 0.4433 1.8596 0.6804 >0.05
No
1,1,1-Trichloroethane 0.4482 1.2052 0.3553 1.1721 0.4354 1.0843 0.3729 >0.05
No
Trichloroethylene 0.0921 0.3366 0.0766 0.3184 0.1030 0.3507 0.4106 >0.05
No
Tetrachloroethylene 0.9298 3.9485 0.8809 2.2349 0.9642 4.4042 0.1104 >0.05
No
Dichlorobenzenes 0.1939 0.7069 0.0723 0.2902 0.2791 0.8826 1.5467 >0.05
No

 
 
 

Discussion

For some time, people have diagnosed chemical sensitivity based on the patient=s history and confirmed by the response to avoidance and challenge. Only recently has accurate technology made it possible to measure these chemicals in the blood and to assess the total body burden.

We assume the TVOCs found in our patients were all exogenous in origin, and that had it been possible to carry out similar studies before the industrial revolution, no TVOCs would have been found. This is reinforced by the fact that 20 patients had no detectable levels of TVOCs in their blood, and not all patients with TVOCs present had every chemical in their blood. We know that heavy exposure to TVOCs may cause illness, e.g., chlorinated solvents can cause severe liver injury and death. We also know that some chlorinated solvents can be mutagenic and carcinogenic, after repeated Alow level@ exposure over a prolonged period. This suggests that there may be no safe level of TVOCs.

Whether the levels of TVOCs found in our patients did or did not contribute to their illness is unclear. The levels found were certainly not in the acutely toxic range. They may, nevertheless, have contributed to the patients= illness indirectly by interfering with metabolic or immunologic functions, or directly by adding to the patient=s total body load. There may have been an increased demand for nutrients otherwise needed for detoxification or cell repair, eventually leading to breakdown of enzyme detoxification systems and an accumulation of toxic chemicals. This could account for the increased sensitivity seen in such patients to chemicals such as formaldehyde and pesticides. This seems probable int he patients studied, as symptoms were triggered in a high percentage by chemicals inhaled during double-blind challenges. If TVOCs contribute to the patient=s total body load, it should be possible to expedite recovery by accelerating their removal by avoiding them in the home and at work and by increasing their excretion in the breath, sweat, urine, and feces.

Compounds are found in patients= blood because of their ubiquitous presence in our environment. Higher levels correlate with increased exposures in the workplace, home, water source, or diet (4). Some of these chemicals are found indoors, as emission products from building materials (floor coverings, furnishings, and paint) and consumer products (polishes, cleaners, and solvents), as well as from combustion (cigarette smoking, kerosene heaters, wood stoves). For example, dichlorobenzene is used as a chemical intermediate in deodorants, disinfectants, insecticides, fumigants, metal polishes, and moth-proofing materials. It has applications in lacquers and paint products (5). The most common application of benzene is in the manufacture of detergents, polymers, pesticides, pharmaceuticals and paint products; it is also found in processed food, petroleum products, and cigarette smoke (6). Toluene is commonly found in solvents for gums, fats, adhesives, as well as in petroleum products and paint products (7). According to their histories, most of our patients did not work directly with Ahigh levels@ of these compounds but they were exposed to them on a daily basis. Ethylbenzene is used as an anti-knock additive for gasoline (8). Trimethylbenzenes are used as solvents and intermediates for chemical synthesis, in the manufacture of paint thinners, perfumes, dyes, and as motor fuel additives (9). Benzene compounds were found in the blood of chemically sensitive patients: 11.9% of the patients had detectable levels of benzene and 16.4% had detectable levels of ethylbenzene. There may be a relationship between these cancer-causing hydrocarbons and chemical sensitivity. This is not surprising, for toxic chemicals can produce both malignant and nonmalignant tissue damage.

Xylenes are found in a variety of solvents for gums, synthetic resins, rubbers, paints, and inks. They are also used in photographic processes in the manufacture of insecticides and plastics, and are present in degreasing agents, cleaners, and petroleum products (10). Xylenes were present in 38% of the 134 patients studied. Styrene is used as a solvent for resins and synthetic rubber, and as an intermediate in the chemical synthesis of polymerized synthetic materials (11).

Chlorinated compounds also are ubiquitous. Dichlorobenzene was discussed previously with the aromatic group. Chloroform is used in the preparation of pharmaceuticals, artificial silks, insecticides, floor polishes, lacquers, and cleaning solvents (12). Wallace has demonstrated an average of 10 mg/m3 chloroform in New Jersey homes (13). It is a common by-product of water chlorination. Dichlormethane is a major component of paint strippers and degreasers. It is also used as a solvent for oils, fats, and waxes (14). 1,1,1-Trichloroethane (methyl chloroform) applications include use as a degreaser, dry cleaning agent, and as a solvent in paint products (15). Trichloroethylene is commonly used in manufacturing computer chips and electrical components and has been used as a degreaser for metals, and as a dry cleaning agent. It can be found in lacquers, printing inks, and paints and has been used as a refrigerant and as an extracting agent in the removal of caffeine from coffee (16). It has been used in the manufacture of pharmaceuticals, as a metal degreaser, and as a grain fumigant (17). Even though most of our patients were not occupationally exposed to tetrachloroethylene, 72 (54%) of the 134 patients had this substance in their blood. This is probably due to its presence in food and in dry cleaned clothes present in most patients= houses.

TVOCs may pollute indoor air more frequently than outside air. This was pointed out by Randolph in 1961 (18). Mølhave reported from 1978 measurements that TVOCs were higher inside new Danish homes than outside (19). Later work by Wallace (13), Lebret (20), Jarke (21), Seifert (22), DeBortoli (23), and Mage (24) have confirmed this in the U.S., Italy, and Germany. Total TVOCs in new homes have been found to be as high as 19 mg/m3, but levels are 1,000 times lower in homes more than three years old (25).

Since 1974, we have demonstrated effects on humans using ambient doses of phenol (<0.002 ppm), chlorine (<0.33 ppm), petroleum derived alcohols (<0.50 ppm) and pesticides (2,4 DNP, <0.0034 ppm) with controlled double-blind inhaled challenges on different vascular entities (26-29). Mølhave, in 1984 (30), demonstrated acute neurolgical changes from a mixture of 22 TVOCs found in Danish homes at levels ranging from 5 mg/m3 to 0.25 mg/m3.

TVOCs share certain characteristics: all are easily vaporized, dissolve in liquids, are transported across cell membranes, and are absorbed by the lungs, skin, and gastrointestinal tract. Environmental Protection Agency (EPA) studies have shown up to 300 different TVOCs in homes (25). Our previous studies have shown a variety of effects on challenge, including symptoms related to the cardiovascular, gastrointestinal, genitourinary, respiratory, neurological, and dermatological systems (26-29, 31). We have found that effects can better be demonstrated with challenge if there is at least a four-day reduction of total load by avoidance, allowing deadaptation. The systems affected depend not only on the toxic chemicals involved, but more particularly on the individual response to that chemical. According to the EPA Carcinogen Assessment Group, chronic lifetime exposure to benzene, carbon tetrachloride, chloroform, methylene chloride, dinitro-toluene, nitrosamines, and phenols increases the probability of developing cancer (25).

The presence of these toxic chemicals in chemically sensitive patients should be of concern to the clinician.
 
 

References 1. Laseter JL, Deleon IR, Rea WJ, Butler JR. Chlorinated hydrocarbon pesticides in environmentally sensitive patients. Clinical Ecology 2:3-12, 1983.

2. Dowty BJ, Carlisle DR, Laseter JL, Storer JS. Halogenated hydrocarbons in New Orleans drinking water and blood plasma. Science 187:75, 1975.

3. Laseter JL, Dowty BJ. Association of biorefractories in drinking water and body burden in people. Ann NY Acad Sci 298:546-57, 1977.

4. Seba, DB, Milan MJ, Laseter JL. Uptake, measurement and elimination of synthetic chemicals by man. In Brostoff J, Challacombe SJ (eds.) Food Allergy and Intolerance. London: Baillière Tindall, 1986:401-15.

5. Sax NI (ed.) Dangerous Properties of Industrial Materials Report. New York: Van Nostrand Reinhold Co., 4(2):45-8, 1984.

6. Parmeggiani L (ed.) Encyclopedia of Occupational Health & Safety, 3rd ed. Geneva: International Labour Office, 1983, 1:257-61.

7. Angerer J. Occupational chronic exposure to organic solvents. VII. Metabolism of toluene in man. Int Arch Occup Environ Health 43:63-7, 1979.

8. Bardoedj Z, Bardodejova E. Biotransformation of ethylbenzene, styrene, and alphamethylstyrene in man. Am Ind Hyg Assoc J 31:206-9, 1970.

9. Caperow, JR, Fernandez JG. Simultaneous determination of toluene and xylene metabolites in urine by gas chromatography. Br J Ind Med 34:229-33, 1977.

10. Bonnichsen R, Maehly AC, Moeller M. Poisoning by volatile compounds. I. Aromatic hydrocarbons. J Forensic Sci II:186-204, 1966.

11. Astrand A., Kilbom P, et al. Exposure to styrene. Work Env Health 11:69-85, 1974. 12. Bonnichsen R, Maehly AC. Poisoning by volatile compounds. II. Chlorinated aliphatic hydrocarbons. J Forensic Sci 11:414-27, 1966.

13. Wallace L, Pellizzari E, Hartwell T. Analysis of exhaled breath of 355 urban residents for volatile organic compounds. In Proceedings of the 3rd International Conference on Indoor Air Quality and Climate. Stockholm, 1984, 4:15-20.

14. Proctor, NH, Hughes JP. Chemical Hazards of the Workplace. USA: JB lippincott Co, 1978: p 243. 15. Astrand I, Kilbom A, Wahlberg I, Ovrum P. Methychloroform exposure. Work Env Health 10:69-81, 1973.

16. Parmeggiani L (ed.) Encyclopedia of Occupational Health and Safety, 3rd ed. Geneva: International Labour Office, 1983, 2:2214-6.

17. Baselt RC. Biological Monitoring Methods for Industrial Chemicals. Davis, CA: Biomedical Publications, 1980:39-40.

18. Randolph TG. Human Ecology and Susceptibility to the Chemical Environment. Springfield, IL: Charles C. Thomas, 1962.

19. Mølhave L, Moller J, Anderson I. Air concentrations of gases, vapours and dust in new houses. Ugeskr f Laeger 141:956-61, 1979.

20. Lebret E, Vande Weil HJ, Bos HP, et al. Volatile hydrocarbons in Dutch homes. In Proceedings of the 3rd International Conference on Indoor Air Quality and Climate. Stockholm: 1984, 4:169-74.

21. Jarke FH. Organic contaminants in indoor air. ASHRAE Report No. 183, IITRI project No. C8276. Chicago: IIT Research Institute.

22. Seifert B. Results of the 1984 Saltzjoabaden WHO Meeting on Indoor Air Pollution. Report on the Third Annual International Symposium on Man and His Environment in Health and Disease, Dallas, TX 1985.

23. DeBortoli M, Knöppel H, Pecchio E, et al. Integrating real life measurement of organic pollution in indoor and outdoor air of homes in northern Italy. In Proceedings of the 3rd International Conference on Indoor Air Quality and Climate. Stockholm: 1984, 4:21-6.

24. Mage DT, Gammage RB. Evaluation of changes in indoor air quality occurring over the past several decades. In Gammage RB, Kaye SV, Jacob VA (eds.) Indoor Air and Human Health. Chelsea, MI: Lewis, 1985.

25. Ammann HM, Berry MA, Childs N, Mage DT. Health effects associated with indoor air pollutants. US EPA, RTO, NC27711, May 1986:1-26.

26. Rea WJ. Environmentally triggered small vessel vasculitis. Ann Allergy 38:245-51, 1977. 27. Rea WJ, Bell IR, Smiley RE. Environmentally triggered large vessel vasculitis. In Johnson F, Spence JT (eds.) Allergy. Chicago: Symposia Specialist, 1975:185-98. 28. Rea WJ. Environmentally triggered cardiac disease. Ann Allergy 40:243-51, 1978.

29. Rea WJ. Environmentally triggered thrombophlebitis. Ann Allergy 37:101-9, 1976.

30. Mølhave L, Bach B, Pederson OF. Human reactions during exposures to low concentrations of organic gases and vapors known as normal indoor air pollutants. In Proceedings of the 3rd International Conference on Indoor Air Quality and Climate. Stockholm: 1984, 4:431-6.

31. Rea WJ. Review of cardiovascular disease in allergy. In Frazier CA (ed.) Bi-Annual Review of Allergy. 1979-80:282-347.