Occup Environ Med 2000;57:837-839 837 

SHORT REPORT 

Two cases of paraoccupational asthma due to 

toluene diisocyanate (TDI) 

R De Zotti, A Muran, F Zamb?n 

Institute of 

Occupational 

Medicine, Trieste 

General Hospital and 

University of Trieste, 

Via d?lia Piet? 19, 

1.34129 Trieste, Italy 

R De Zotti 

A Muran 

F Zamb?n 

Correspondence to: 

Dr Renata De Zotti 

dezotti @univ.trieste.it 

Accepted 6 July 2000 

Abstract 

Two cases of paraoccupational asthma 

caused by toluene diisocyanate (TDI) are 

reported. The first patient was a metal 

worker in a machine 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 of TDI 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 of TDI 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 

4 Iden 

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 in having the exposure to TDI recog 

www. occenvmed. com 

nised as an occupational hazard. We report two 

recent cases. 

CASE i 

A men aged 60 had 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 for 20 years). He was employed 

as a bricklayer for 38 years and then for 9 years 

as a metal worker in a machine shop near a fac 

tory producing polyurethane foam. In 1990, 

after a few weeks' work in the machine shop, he 

began to complain of upper respiratory irrita 

tion with a dry and then productive cough, and 

self limiting episodes of wheezing and short 

ness of breath. Symptoms progressively wors 

ened, both at work and during the night. In 

September 1998, he went sick because of these 

respiratory symptoms. At that point his symp 

toms improved, but he still took 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 the workplace 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 3 weeks earlier. On admission, 

his general condition was good and the physical 

examination was normal. Baseline spirometry 

was normal. The log cumulative dose of meta 

choline producing a 20% fall in forced expired 

volume in 1 second (FEV\) was low (meta 

choline PD20FEV1=570.6 ]ug), suggesting air 

way hyperresponsiveness. Skin prick test was 

positive to Dermatophagoides 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, the patient recalled that in the past 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) test with TDI. In 
838 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 

to TDI was generated in the chamber by blow 

ing air over the surface of TDI (20 ml) in a 200 

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 (MDA Model 7100 GETEC MDA 

Scientific, Glenview, IL, USA). Exposure was 

stopped after 5 minutes because of dyspnoea 

and cough. The median TDI concentration 

was 5.5 ppb. The FEV\ was monitored at 5, 15, 

30, and 60 minute intervals after the end of 

exposure, and then hourly for 8 hours. 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 

years had had chronic rhinitis with 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 to work 2-3 days a week 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 6 months, 

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 off work for a month and had 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 test with 

common allergens was negative; IgE antibodies 

were 66.9 U/ml; blood tests were normal and 

ENT examination showed evidence of vasomo 

tor rhinitis. After the presence of TDI 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 

TDI SIC 

Control 

J_L 

0 1 5 15 30 1 

Minutes 

3 4 5 

Hours 

7 8 

Figure 1 Case 1: man 60 years, ex-smoker, metal worker 

for 9 years. Specific inhalation test: TDI 5.5 ppb for 5 

minutes. 

www. occenvmed. com 

TDI SIC 

-- 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 42 years, smoker, secretary for 

<1 year. Specific inhalation test: TDI 12 ppb for 5 minutes. 

with TDI, which the patient 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 test was positive for early asthma 

(fig 2) and the patient decided to stop working 

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 the vicinity 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 to TDI 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 to TDI probably occurred during the 

short periods when he did maintenance work 

on the machines 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 to TDI. 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 air were 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 a work 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 

50 
Two cases of paraoccupational asthma due to toluene 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 

6 

on the result of the SIC 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 is waiting for an answer. For 

understandable reasons, the second patient 

refused to make a claim for compensation. 

The cases described suggest that there may 

be cases of non-occupational exposure to TDI 

that cause asthma. As it can be difficult to 

identify the source of exposure, there is a need 

for careful evaluation of possible sources of 

indirect exposure both inside and outside the 

workplace. Moreover, it is important to identify 

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 be diagnosed as having 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. 

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asthma in a car factory. Lancet 1980;ii:756-60. 

2 Mapp CE, Butcher BT, Fabbri LM. Polyisocyanates and 

their prepolymers. In: Bernstein IL, Chang-Yeung M, Malo 

JL, et al, eds. Asthma in the workplace. Marcel Dekker, New 

York 1999:457-78. 

3 Kopferschmitt-Kubler MC, Bessot JC, Charles P, et al. 

Asthme aux isocyanates ? un poste th?oriquement non 

expose. Rev Mal Respir 1991;8:240-1. 

4 Sartorelli E, Innocenti A. Asma da isocianati. In: Masson, 

ed. Asma bronchiale professionale. Milano, Italy: Collana di 

medicina del lavoro: 1988:55-61. 

5 Cartier A, Malo JL. Occupational challenge tests. In: Bern 

stein IL, Chang- Yeung M, Malo JL, et al. 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). Clinical Allergy 1976;6:99-104. 

7 Nuorteva P, Assmuth T, Haahtela T, et al. The prevalence of 

asthma among inhabitants in the vicinity of a polyurethane 

factory in Finland. Environ Res 1987;43:308-16. 

8 Orloff KG, Batts-Osborne D, Kilgus T, et al Antibodies to 

toluene diisocyanate in an environmental exposed popula 

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9 Hery M, Diebold F, Hecht G. Exposure of contractors to 

chemical pollutants during the maintenance shut-down of 

a chemical plant. Risk Anal 1996;16:645-55.