Occup Environ Med 2000;57:837-839 837



# SHORTREPORT



# Two cases ofparaoccupational asthma due to



# toluene diisocyanate (TDI)

RDe Zotti, AMuran, F Zamb?n

Institute of Occupational Medicine, Trieste General Hospital and University ofTrieste, Via d?lia Piet? 19, 1.34129 Trieste, Italy RDe Zotti AMuran F Zamb?n
Correspondence to: Dr Renata De Zotti dezotti @univ.trieste.it Accepted 6July2000 Abstract Two cases of paraoccupational asthma 

## caused by toluene diisocyanate (TDI) are reported. The first patient was a metal worker in amachine shop situated near a factory producing polyurethane foam. Symptoms at work were not explainable by any specific exposure to irritants or allergens in the work site. As the patient recalled previous occasional work in the adjacent polyurethane factory with ac companying worsening of respiratory 

## symptoms, a specific inhalation (SIC) test

was performed with TDI, which con 

## firmed the diagnosis ofTDI asthma. The second case was a woman working part time as a secretary in the offices of her son's factory for varnishing wooden chairs. TDI was present in the products 

## used in the varnishing shed. The SIC test confirmed the diagnosis of TDI asthma, despite the fact that the patient's job did not present risk of exposure to the sub stance. In both patients, symptoms disap peared when further exposure was avoided. These two cases confirm that paraoccupational exposure to TDI must be considered when evaluating patients with asthma not mediated by immu 

## noglobulin E. They also suggest the need for more prospective studies evaluating 

## the health risk for the general population living near polyurethane factories or other 

## firms that use TDI. (Occup Environ Med 2000;57:837-839)
Keywords: paraoccupational exposure; toluene diisocy anate; asthma

Occupational exposure to diisocyanate var nishes or to polyurethane foam are the main
causes ofTDI asthma, that affects 5%-10% of workers exposed to diisocyanate.12 Paraoccu pational exposure to TDI has seldom been reported, but this possibility must be consid ered when evaluating patients with asthma not 

## mediated by immunoglobulin E (IgE).3 4Iden tifying the aetiology of the symptoms means improving the prognosis of the disease by avoiding further exposure. The patient, how ever, may be hampered by the difficulties involved inhaving the exposure toTDI recog

www. occenvmed. com nised as an occupational hazard. We report two recent cases.

CASE i 

## Amen aged 60had no personal or family his tory of atopy or pre-existing asthma, and had been an ex-smoker for 21 years (previously 15 

## cigarettes/day for20 years). He was employed asabricklayer for38years and then for9years as ametal worker in amachine shop near a fac tory producing polyurethane foam. In 1990, after a few weeks' work in themachine shop, he began to complain of upper respiratory irrita tion with adry and then productive cough, and 

## self limiting episodes ofwheezing and short
ness of breath. Symptoms progressively wors 

## ened, both atwork and during the night. In September 1998, hewent sickbecause of these respiratory symptoms. At that point his symp 

## toms improved, but he stilltook short and long ?2 agonists, mucolytics, and antihistamines. A chest x ray film and spirometric evaluation during this period were within normal limits. He resumed work, but soon after re-exposure 

## in theworkplace he complained again of the

same respiratory symptoms. The patient was admitted to our department 4 months later, once again off work sick. He had stopped taking antihistamines and ?2 ago nists as required 3weeks earlier. On admission, 

## hisgeneral condition was good and thephysical examination was normal. Baseline spirometry was normal. The log cumulative dose ofmeta 

## choline producing a20% fall inforced expired volume in 1 second (FEV\) was low (meta choline PD20FEV1=570.6 ]ug), suggesting air way hyperresponsiveness. Skin prick test was positive toDermatophagoides species. Total IgE 

## antibodies (PRIST) were 78.8 U/ml. Blood tests were normal. Ear, nose, and throat (ENT) examination was normal. During the history 

## taking, thepatient recalled that inthepast he had occasionally performed maintenance work in the adjacent polyurethane factory and that, in these occasions, his dyspnoea and wheezing had worsened. Inside or outside the machine shop the respiratory symptoms were less severe, and not related to any specific job or exposure. The patient confirmed our sugges tion that the proximity of the polyurethane foam factory might be a factor in causing his illness. We then decided to perform a specific 

## inhalation challenge (SIC) testwith TDI. In838 De Zotti,Muran, Zamb?n



## line with SIC test standards, the test was preceded by a control test, which ensured a stable FEVl over an 8 hour period.5 Exposure 

## toTDI was generated inthechamber byblow ingairover the surface ofTDI (20ml) ina200 ml glass bottle. The airflow rate was controlled by a rotameter, calibrated at 2 1/min. The con centration of atmospheric TDI was measured with isocyanate detection equipment in the 

## same room (MDAModel 7100 GETEC MDA Scientific, Glenview, IL,USA). Exposure was stopped after 5minutes because of dyspnoea and cough. The median TDI concentration 

## was 5.5ppb.The FEV\ wasmonitored at5, 15, 30, and 60 minute intervals after the end of 

## exposure, and thenhourly for8hours. The SIC test was positive for early asthma (fig 1). At a subsequent examination, 3 months later, the patient was still free from respiratory symp toms but off work.

CASE 2 

## A women aged 42 had no personal history of allergic disease. She had smoked one pack of cigarettes a day for 15 years, and for the past 7 

## yearshadhad chronic rhinitiswith sporadic but not seasonal relapses. She had been employed as a cotton spinner for 2 years and then as a packer in a confectionery factory for 17 years. In 1993, she began towork 2-3 days aweek as
a secretary in the offices of her son's factory, where wooden chairs were varnished. The office was on the same floor as the varnishing sheds, but not next to them. After 6months, the woman began to complain of cough, wheezing, and shortness of breath, and to use ?2 agonists and a corticosteroid inhalant. The symptoms started just a few minutes after arriving in the office and improved only after long periods away from work. A chest x ray film ordered by the family doctor at the time was negative. On admission to our department, she 

## had been offwork fora month andhad stopped taking drugs a week earlier, but still com 

## plained of sporadic fits of dry coughing. Baseline spirometry was normal, metacholine 

## PD20 FEX^ was 473 jug.Skin prick testwith

common allergens was negative; IgE antibodies
were 66.9 U/ml; blood tests were normal and ENT examination showed evidence of vasomo 

## torrhinitis.After thepresence ofTDI had been ascertained in the varnishes used in the factory where she worked, we suggested an SIC test

o 105 100 95 90 85 80 75 70 65 60 55 50 45 c /b |? CD 

## TDISIC Control

J_L 0 1 5 15 30 1 Minutes 3 4 5 Hours 7 8

Figure 1 Case 1:man 60years, ex-smoker, metal worker for 9years. Specific inhalation test:TDI 5.5 ppbfor 5 minutes.

www. occenvmed. com 

## TDISIC

-- Control



## 1 1 1_I_I_1 1 0 1 5 15 30" 1 2 3 4 5 6 7 8 Minutes Hours Figure 2 Case 2:woman 42years, smoker, secretary for <1 year. Specific inhalation test:TDI 12ppbfor 5minutes. 

## with TDI, which thepatient accepted solely for diagnostic purposes. Exposure was stopped after 5 minutes because of dyspnoea and cough. The median TDI concentration was 12 

## ppb.The SIC testwas positive forearly asthma (fig2) and thepatient decided tostopworking in her son's factory.

Discussion A non-occupational TDI asthma may be 

## caused by hobbies involving the use of varnishes, concrete sealers, glue, and other
sources of diisocyanates. As well as these expo sures, there are some paraoccupational situa tions, where the TDI does not come from the actual indoor occupation, but from other
sources. Some of these cases have been ascribed to emissions from neighbouring facto ries where TDI is used.3 6 Moreover, other studies have shown that TDI concentrations in 

## the residential ambient air in thevicinity of a factory producing polyurethane foam were alarmingly high. These findings arouse con
cern about the health risks for the general 

## population living near this kind of establish ment.7 8
In the first case described, a paraoccupa tional exposure toTDI coming from a nearby factory producing polyurethane foam can be considered the cause of the patient's persistent respiratory symptoms. However, the first sensi 

## tisation toTDI probably occurred during the short periods when he did maintenance work
on themachines in this factory.9 The symptoms 

## were not immediately correlated with TDI; only after an accurate clinical history did the patient recall his previous sporadic direct exposure toTDI. Two considerations led us to suspect a causative role of the TDI used in the nearby factory in the symptoms of this patient. The first was the earlier relation between the worsening of symptoms and direct exposure to TDI, and the second was the positive stop-start relation between symptoms and his worksite, where there was no significant exposure to irri tants or allergens. Unfortunately, data about TDI concentrations in the ambient airwere not available. Nevertheless, diagnosis was con 

## firmed by the outcome of SIC test and the remission of symptoms after he stopped work ing near the polyurethane foam factory. In the patient who worked as a secretary, the absence of awork related hazard for exposure to TDI is even more evident. However, low 100 

## ^ 95 it 90

> 85 

## ?? 80
c 75 "cd 70 

# ? 65 I 60 u 55 50Two cases ofparaoccupational asthma due totoluene diisocyanate (TDI) 839

TDI concentrations in the ambient air could have come from the shed where the substance
was used. The diagnosis of paraoccupational 

## TDI was based on the fact that even very low TDI concentrations may cause asthma in sen 

## sitised subjects12 6on the result of theSIC test and on the remission of respiratory symptoms when the patient stayed away from work. For both subjects, stopping exposure restored good 

## health, but unfortunately lost them their jobs. For the first patient, compensation was claimed, and he iswaiting for an answer. For understandable reasons, the second patient refused tomake a claim for compensation. The cases described suggest that there may be cases of non-occupational exposure toTDI that cause asthma. As it can be difficult to identify the source of exposure, there is aneed for careful evaluation of possible sources of 

## indirect exposure both inside and outside the workplace. Moreover, itisimportant toidentify the stop-start relation between symptoms and hobbies, between symptoms and temporary jobs done in other factories, and between symptoms and being in places near factories where the substance is used. Confirmation of 

## diagnosis based on the specific inhalation test improves the prognosis for the patient, who

www. occenvmed. com 

## would otherwise bediagnosed ashaving intrin sic asthma. Paraoccupational TDI asthma also suggests the need for better assessment of 

## health risks of the general population through
more prospective studies evaluating the resi 

## dential populations living around polyurethane factories or other firms that use TDI.

1 White WG, Sugden E,Morris MJ, etal. Isocyanate-induced asthma inacarfactory. Lancet 1980;ii:756-60. 2Mapp CE, Butcher BT, Fabbri LM. Polyisocyanates and theirprepolymers. In:Bernstein IL,Chang-Yeung M,Malo JL, etal,eds.Asthma intheworkplace.Marcel Dekker, New York 1999:457-78. 3Kopferschmitt-Kubler MC, Bessot JC, Charles P, et al. Asthme aux isocyanates ?un poste th?oriquement non expose. RevMal Respir 1991;8:240-1. 4 Sartorelli E, Innocenti A. Asma da isocianati. In:Masson, ed.Asma bronchialeprofessionale.Milano, Italy:Collana di medicina del lavoro: 1988:55-61. 5Cartier A,Malo JL.Occupational challenge tests. In:Bern stein IL,Chang- Yeung M, Malo JL, etal.Asthma in the workplace.New York:Marcel Dekker, 1999:211-33. 6 Carrol KB, Secombe CJP, Pepys J. Asthma due to non-occupational exposure to toluene (toluene di isocyanate). ClinicalAllergy 1976;6:99-104. 7Nuorteva P,Assmuth T,Haahtela T, etal.The prevalence of asthma among inhabitants inthevicinity ofapolyurethane factory inFinland. Environ Res 1987;43:308-16. 8Orloff KG, Batts-Osborne D, Kilgus T, etalAntibodies to toluene diisocyanate inanenvironmental exposed popula tion.EnvironHealth Perspect 1998;106:665-6. 9Hery M, Diebold F,Hecht G. Exposure of contractors to chemical pollutants during themaintenance shut-down of achemical plant. RiskAnal 1996;16:645-55.