Experimental Exposure to Propylene Glycol Mist in Aviation Emergency Training: Acute Ocular and Respiratory Evects

Occup Environ Med 2001;58:649–655 649 Experimental exposure to propylene glycol mist in aviation emergency training: acute ocular and respiratory eVects

G Wieslander, D Norbäck, T Lindgren

Abstract Keywords: acoustic rhinometry; aviation medicine; pro- Objectives—Propylene glycol (PG) (1–2 pylene glycol; respiratory symptoms; tear film stability propanediol; CAS No 57–55–6) is a low break up time toxicity compound widely used as a food additive, in pharmaceutical preparations, in cosmetics, and in the workplace—for Main messages example, water based paints, de-icing flu- x Propylene glycol is is a low toxicity com- ids, and cooling liquids. Exposure to PG pound widely used in many products. mist may occur from smoke generators in x The concentration of propylene glycol discotheques, theatres, and aviation mist in aviation emergency training can emergency training. Propylene glycol may be high compared with other occupa- cause contact allergy, but there is sparse tional exposure to this compound. Mist from artificial smoke generators may information on health eVects from occu- x cause ocular and upper airway irritation pational exposure to PG. in non-asthmatic subjects. Methods—Non-asthmatic volunteers x A few may also react with cough and (n=27) were exposed in an aircraft simula- slight airway obstruction. tor to PG mist over 1 minute, during real- istic training conditions. Geometric mean concentration of PG was 309 mg/m3 (range 176–851 mg/m3), with the highest concen- Policy implications trations in the afternoon. The medical x Awareness should be spread that expo- investigation was performed both before sure to high concentrations of propylene and after the exposure (within 15 min- glycol in workplaces and public places utes). It included an estimate of tear film may cause ocular and respiratory irrita- stability break up time, nasal patency by tion, and that sensitive subjects should be acoustic rhinometry, dynamic spiro- protected or avoid extreme or prolonged metry, and a doctor’s administered ques- exposure. tionnaire on symptoms. Results—After exposure to PG mist for 1 minute tear film stability decreased, ocu- Propylene glycol (PG) (1–2 propanediol; CAS lar and throat symptoms increased, forced nr 57–55–6) is a widely used compound 1 expiratory volume in 1 second/forced vital because of its low toxicity and lack of carcino- genic or mutagenic eVects.23It is used as a food capacity (FEV1/FVC) was slightly reduced, 4 5 and self rated severity of dyspnoea was additive, in pharmaceutical preparations, and in cosmetics.3 Rarely, allergic contact sensitisa- slightly increased. No eVect was found for 6–8 nasal patency, vital capacity (VC), FVC, tion to PG in consumer products may occur, and one case of systemic skin reactions in a PG nasal symptoms, dermal symptoms, smell Department of sensitised subject after ingestion of food of solvent, or any systemic symptoms. Medical containing PG has been reported.9 Also skin Those exposed to the higher concentra- Sciences/Occupational irritation from PG in tooth paste10 as well as and Environmental tions in the afternoon had a more pro- Medicine, Uppsala nasal and throat irritation related to PG in nounced increase of throat symptoms, and 11 12 University, University nasal spray has been reported. Transdermal a more pronounced decrease of tear film 13 Hospital, S-751 85, adsorption of PG may occur. There are a few Uppsala, Sweden stability. In four subjects who reported case reports on severe systemic reactions from G Wieslander development of irritative cough during PG in humans, including one case of coma in a D Norbäck 14 exposure to PG, FEV1 was decreased by premature infant and two cases of acute renal T Lindgren 5%, but FEV1 was unchanged among those tubular cell injury from pharmaceuticals dis- 15 16 Scandinavian Airline who did not develop a cough. Those who olved in PG. The premature infant went System (SAS), developed a cough also had an increased into coma after treatment for burns with STOIM-O, S-195 87 perception of mild dyspnoea. antiseptic dressings containing unusually high Stockholm, Sweden Conclusion—Short exposure to PG mist concentrations of PG. Ending the topical treat- T Lindgren from artificial smoke generators may ment resulted in complete recovery.14 Correspondence to: cause acute ocular and upper airway irri- Propylene glycol is metabolised to lactic acid Dr G Wieslander tation in non-asthmatic subjects. A few and pyromaleic acid, normal intermediates in gunilla.wieslander@medsci may also react with cough and slight human metabolism, either by oxidisation or .uu.se airway obstruction. phosphatisation.4 Metabolic formation of PG Accepted 1 June 2001 (Occup Environ Med 2001;58:649–655) and 2,3-butanediol has been reported in

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alcoholic subjects, both in the presence and history of atopy, whereas three women and 16 absence of alcohol,17 in premature infants,17 in men did not have atopy, a non-significant but diabetic patients,17 and with specific enzyme numerically higher occurrence of atopy among deficiencies (congenital propionic and methyl- the women. None had ever had any respiratory malonic acidaemia). Also, alcohol related diols disorders, including asthma or chronic bron- (PG and 2,3-butanediol) have been shown to chitis diagnosed by a doctor, and none had any cause insulin resistance in rats.18 febrile respiratory infection the week before the Occupational exposure to PG may occur in investigation. The subjects were naive, in that many occupational settings. The phasing out of none had previous occupational exposure to organic solvents at work has increased the use PG. The investigations were done at normal of PG in Sweden, as it is commonly used in aviation emergency training, during 1 week in many water based products—such as water March 1998, before the pollen season had based paints.19–22 The annual Swedish con- started in mid-Sweden. The flight simulator sumption (8 million inhabitants) of PG is belonged to a training centre of the flight acad- between 13 200 and 13 300 tonnes, and it is emy of the Scandinavian Airline System (SAS). used in 1183 products. It is the 17th most The artificial smoke generator was placed in common chemical counted as number of the flight simulator, with a commercial PG products in which it is used.19 Other sources of solution for smoke generation. The exposure occupational exposures include aircraft de- was performed as a part of the regular training icing work, where both ethylene glycol23 and schedules for pilots, aiming to train pilots for PG are used,23 and exposure to glycol based evacuation at fire emergency situations. cooling liquids in car engines.24 Also, PG is commonly used in artificial ASSESSMENT OF PERSONAL FACTORS smoke generators in discotheques, theatres, One general medical questionnaire was used to and emergency training. In connection with gather information on personal factors, includ- use of smoke generators in aviation emergency ing medical disorders, medication, occupa- training, being a part of the basic education of tional data, the home environment, and smok- pilots and flight attendants at Scandinavian ing habits.28–30 Atopy was defined as having a Airline Systems (SAS), concern was raised history of childhood eczema or current history about possible respiratory eVects from this of allergy related to exposure to common IgE exposure mediated allergens in Sweden (tree pollen, There is sparse published information on grass pollen, or furry animals). Current smoker irritative or respiratory eVects of PG in was defined as reporting actual smoking in the humans.25 Recently, clinical methods that can interview (>1 cigarette/day), or stopping smok- be applied in exposure studies have become ing less than 1 year ago. available, including measurement of tear film 26 27 stability break up time, and nasal patency INFORMATION ON CURRENT SYMPTOMS by acoustic rhinometry.28–30 These methods Information on current symptoms was ob- have been applied to study transient physi- tained from two questionnaires used in previ- ological eVects at controlled exposures to vola- ous investigations. The first questionnaire con- tile organic compounds. Decreased nasal tained 10 rating scales on current ocular, nasal, patency has been reported at exposure to a throat symptoms, dyspnoea, malodour, and mixture (4 h; 10 mg/m3)of22diVerent volatile systemic symptoms.33 Answers were given on a organic compounds, not including PG.31 In 100 mm visual analogue rating scale (VAS- another experimental study, exposure to a mix- scale) adapted from Kjellberg et al,34 graded ture of PG and three glycol ethers induced from “not at all” to “almost unbearable” . The ocular symptoms, but did not aVect tear film second questionnaire contained 23 yes or no stability, nasal patency, or lung function.32 questions on diVerent types of ocular, respira- The aim of the investigation was to study tory, and dermal symptoms, as well as systemic eVects of an experimental exposure to PG mist, symptoms—for example, headache, nausea, at exposure levels occurring during normal and fatigue.30 Both questionnaires were admin- aviation emergency training. The physiological istered before and after the exposure to PG. eVects studied included tear film stability, nasal patency, and lung function, as well as subjective ASSESSMENT OF TEAR FILM STABILITY symptoms. The study was approved by the eth- Tear film stability was estimated by a standard- ics committee of the Medical Faculty of ised method, self reported tear film stability Uppsala University. break up time measuring the time the subject could keep the eyes open without pain, when Material and methods watching a fixed point at the wall. The method STUDY POPULATION is mentioned in our introduction as tear film Healthy non-asthmatic volunteers (n=27), 22 stability and has been used previously. It has men and five women, were examined medically been shown to correlate well with the fluores- before and after exposure to PG mist. Most ceine method for detection of tear film were pilots working in civil aviation. Mean stability.26 27 Moreover, it has been shown that (SD) age of the group was 44 (11) years, 22% tear film stability is lower in subjects reporting were current smokers, 44% were ex-smokers. ocular symptoms.28 In total, 30% had a history of atopy, 15% had hay fever, 15% had a history of childhood ACOUSTIC RHINOMETRY eczema, but none reported allergy to furry ani- Acoustic rhinometry (Rhin 2000; wideband mals. In total, two women and six men had a noise; continuously transmitted) was applied to

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900 the deviation between the two best tests were less than 5%. The results were expressed as a 800

) percentage of normal values based on stand- 3 700 ardisation to age, sex, height, smoking habits, and body mass using reference values from 600 Uppsala.35 500

400 TEST SEQUENCE All physiological measurements and question- 300 naires were administered by a physician, in a 200 modern oYce building, with a general ban on

Propylene glycol (mg/m smoking indoors. Moreover, smokers were not 100 allowed to smoke during the test period, which 0 started 15 minutes before the exposure, when the subject was asked to sit down. During this time, the tear ﬁlm stability test was performed 1:20 PM 1:50 PM 2:20 PM 2:50 PM

12:20 PM 12:50 PM first, then the two symptom questionnaires. 10:20 AM 10:50 AM 11:20 AM 11:50 AM Time After about 5 minutes, acoustic rhinometry was performed, then the dynamic spirometry. Air concentration of propylene glycol at aviation emergency training (1 minute point measurements), as a function of time of the day. Then the subjects entered the smoke training unit, were exposed to PG mist for 1 minute, Table 1 Average ratings on 10 questions* on smell before and went out to sit down and wait for repeated and after 1 minute of exposure to propylene glycol mist (n=27) medical investigation. The same test sequence was applied before and after the exposure to 10 min before 10 min after Two PG, and was completed within 15 minutes of exposure mean exposure tailed p Type of rating (SD) mean (SD) value† the exposure. When all testing was finished, the general medical questionnaire was answered. Ocular irritation 5(10) 14(13) <0.001 The tests were performed during 2 days from Nasal irritation 7(10) 10(11) 0.17 Throat irritation 7(9) 20(14) <0.001 0930 to 1500, with a lunch break from 1200 to DiYculty in 3(4) 7(10) 0.048 1300. breathing Solvent smell 3(6) 4(7) 0.43 Headache 4(6) 4(6) 0.46 ASSESSMENT OF EXPOSURE Fatigue 6(10) 5(8) 0.40 Room temperature and relative air humidity Nausea 3(3) 2(3) 0.33 Dizziness 2(3) 5(7) 0.10 was measured by an Assman psychrometer. Intoxication 2(3) 4(6) 0.24 Propylene glycol in the flight simulator was sampled by pumped sampling, on a synthetic *Visual analogue rating scales 0–100 mm (Nihlen et al33). †Calculated by Students t test for paired comparison. polymer tube (XAD-7; SKC 226–95, SKC, USA). The sampling time was 1 minute, and measure nasal patency. The measurements the sampling rate was 200 ml/min. The XAD-7 were made under standardised forms (sitting), tube was desorbed with 1 ml of methylene after 5 minutes of rest. By means of acoustic chloride, and analysed for PG, with a method reflection the minimum cross sectional areas described already.36 A recovery of 100% of PG (MCAs) on each side of the nose were on the XAD tube was assumed, as was demon- measured from 0 and 22 mm (MCA1) and strated for higher concentrations of PG in ear- from 23 and 54 mm (MCA2) from the nasal lier desorbtion eYciency tests.36 To control for opening. The volumes of the nasal cavity on the possible overloading of the sorbent tubes by right and the left sides were also measured from PG, both the measuring layer and the control 0 and 22 mm (VOL1) and from 23 to 54 mm layer of the tubes were analysed. As it was a (VOL2). The mean values were calculated possibility that particulate PG mist could be from three subsequent measurements on each adsorbed on the glass wool plug in the inlet of side of the nose. Data on nasal dimensions in the sampling tubes, the glass wool was the present study are presented as the sum of desorbed separately with another 1 ml of the values recorded for the right side and the methylene chloride. left side. Exposure to formaldehyde in the flight simulator was measured by pumped sampling LUNG FUNCTION TESTS on glass fibre filters impregnated with 2,4- Respiratory function was studied by dynamic dinitrophenyl hydrazine (2,4-DNF), at a flow spirometry. Vital capacity (VC), forced vital rate of 200 ml/min for 4 hours.37 The filters capacity (FVC), peak expiratory flow (PEF), were analysed by liquid chromatography. To

and forced expiratory flow in 1 second (FEV1) detect other specific volatile organic com- were measured with a Vitalograph (Vitalo- pounds in the flight simulator, pumped sam- graph, Buckingham, England) which was pling on a conventional charcoal sorbent tube

calibrated daily. Also, FEV1/FVC was calcu- (SKC 226–01) was performed (4 h; 200 lated. All the tests were carried out in a stand- ml/min). The charcoal tube was desorbed with ardised way with the same spirometer, by a 1 ml carbon disulﬁde. Both PG and other spe- trained nurse. To avoid disturbance of nasal ciﬁc compounds were analysed by means of a patency, a nose clip was not used. The Hewlett Packard 5890 gas chromatograph measurements were performed three times on equipped with a mass selective detector (HP each subject, and the highest values were 5970) (GC-MS), using a 50 metre cross linked noted. A test was considered adequate when methyl silicone capillary column (HP-1,

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Table 2 DiVerent types of symptoms* before and after 1 minute of exposure to propylene were analysed by Student’s t test for paired glycol mist (n=27) comparisons. As the tear film stability was not normally distributed, change in tear film Symptoms 10 min Symptoms 10 min Proportion developing before exposure after exposure a particular symptom† stability was analysed by Wilcoxon matched pairs signed rank test. Changes in symptoms, Type of symptoms n(%)n(%)n(%) measured as a dichotomous outcome variable, Sore eyes 1 4 6 22 5/26 19 were measured by the McNemar test. Itching in the eyes 1 4 4 15 3/26 12 Dry eyes 1 4 9 33 8/26 31 Gritty eyes 2 7 3 11 1/25 4 Results Eye redness 0 0 0 0 0/27 0 EXPOSURE MEASUREMENTS Swollen eyelids 0 0 0 0 0/27 0 Room temperature was 22.0ºC–22.5ºC, and At least one ocular symptom 2 7 11 41 9/25 36 mean relative air humidity in the flight simula- Nasal catarrh 1 4 2 7 1/26 4 tor was 34%. Eleven 1 minute measurements Nasal itch 0 0 2 7 2/27 7 of PG were performed. The geometric mean Sneezing 0 0 0 0 0/27 0 Nasal obstruction 1 4 1 4 0/26 0 concentration of PG in the flight simulator was At least one nasal symptom 2 7 3 11 1/25 4 309 mg/m3 (GSD=1.7). Arithmetic mean concentration of PG was 360 mg/m3 (range Throat dryness 4 15 17 63 14/23 61 3 Sore throat 1 4 1 4 0/26 0 176–851 mg/m ), with an arithmetic mean At least one throat symptom 4 15 18 67 14/22 64 exposure of 220 mg/m3 in the morning, and 520 mg/m3 in the afternoon. The distribution Irritative cough 2 7 6 22 4/25 16 DiYculties in breathing 1 4 1 4 0/26 0 of the 11 point measurements over the day can At least one lower 2 7 6 22 4/25 16 be seen in figure 1. Most detected PG was in respiratory symptom the measuring layer of the sampling tube, only Sensation of catching a cold 1 4 1 4 1/26 4 5%–10% was detected in the control layer, and Headache 1 4 1 4 0/26 0 <1% was found in the glass wool plug in the Nausea 0 0 0 0 0/27 0 Fatigue 1 4 1 4 1/26 4 inlet of the tube. Low concentrations of At least one general 2 7 2 7 0/25 0 formaldehyde were detected in the flight simu- symptom lator (29 µg/m3), but no other volatile organic Facial itching 0 0 0 0 0/27 0 compounds. Facial rash 1 4 0 0 0/26 0 Itching on the hands 0 0 1 4 1/27 4 SYMPTOMS Rashes on the hands 2 7 2 7 0/25 0 Eczema 2 7 2 7 0/25 0 The most common annoyance after the At least one dermal 4 15 3 11 0/23 0 exposure were ocular and throat irritation as symptom measured by the VAS scales (table 1). When *Yes/no questions from a detailed symptom questionnaire (Wålinder et al29). analysing changes of VAS ratings, a significant †Calculated for those not reporting the particular symptom before the exposure. increase of ocular irritation (p<0.001), throat irritation (p<0.001), and dyspnoea (p=0.048) Table 3 Rhinometric measurements before and after 1 minute of exposure to propylene glycol mist (n=27) was found, but there were no eVects on solvent smell or other symptoms. 10 min before 10 min after The most common symptoms were a sensa- Rhinometric exposure mean exposure mean Two tailed parameter (SD) (SD) p value* tion of sore and dry eyes, throat dryness, and irritative cough, as measured by the more MCA1 (cm2) 1.31 (0.20) 1.32 (0.32) 0.40 detailed symptom questionnaire, requesting a MCA2 (cm2) 1.43 (0.36) 1.37 (0.32) 0.36 VOL1 (cm3) 4.44 (0.73) 4.36 (1.05) 0.33 yes or no answer (table 2). When grouping the VOL2 (cm3) 8.35 (2.01) 7.90 (1.81) 0.36 symptoms for diVerent organs, a significant *Calculated by Student’s t test for paired comparison. increase was found for ocular (p=0.005) and throat symptoms (p<0.001). Nine subjects Table 4 Dynamic spirometry values before and after 1 without previous symtoms (36%) developed at minute of exposure to propylene glycol mist (n=27) least one ocular symptom after exposure to 10 min before 10 min after PG, and 14 (64%) developed throat symptoms. Lung function exposure mean exposure mean Two tailed Two reported appearance of nasal catharr and parameter (SD) (SD) p value* one got nasal itching, but none reported sneez- VC 4.92 (0.93) 4.92 (0.91) 0.48 ing or nasal obstruction after the exposure. FVC 4.66 (0.89) 4.70 (0.96) 0.23 None reported appearance of headache, nau- FEV 4.01 (0.71) 3.98 (0.78) 0.29 1 sea, or breathing diYculties after exposure to FEV1/FVC 86.8 (7.3) 84.8 (6.5) 0.049 PEF 650 (179) 638 (183) 0.45 PG, and there was no net change in reporting of fatigue. One subject reported the appear- *Calculated by Student’s t test for paired comparison. ance of itching on the hands, and another Hewlett Packard) with an inner diameter of reported disappearance of facial skin rash after 0.32 mm and a film thickness of 1 µm. The the exposure to PG mist. oven temperature was programmed for an ini- There were some indications that women tial hold for 5 minutes at 35oC after which the and those with a history of atopy seemed to be temperature increased to 200oCatarateof more sensitive to exposure to PG, for some 15oC/min. Carrier gas (helium) flow rate was 1 types of symptoms, but the number of women ml/min. For each substance, a mass spectrum (n=5) and subjects with atopy (n=8) were and retention time was assessed.36 small. In total, 29% of men and 80% of women reported the development of throat symptoms, STATISTICAL ANALYSIS but there were no sex diVerence for develop- DiVerences in VAS scales, nasal patency, and ment of ocular symptoms. Moreover, 50% of lung function before and after exposure to PG those with atopy, and 11% of those without

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Table 5 Changes† of symptom ratings and physiological measurements stratified for FEV1 among those who did not develop a diVerent levels of exposure cough. Moreover, those four subjects had an increase in self rated dyspnoea of 13% on the Morning test (lower Afternoon test exposure) (n=18) (higher exposure) analogue scale, whereas those who did not mean (SD) (n=9) mean (SD) develop cough only had a 1% increase of VAS scales: dyspnoea, a significant diVerence between the Change in ocular symptom rating (%) 9 (12)** 8 (11) two groups (p<0.01). Change in nasal symptoms rating (%) 1 (10) 8 (14) Change in throat symptoms rating (%) 11 (17)** 18 (15)*** Change in rating of dyspnoea (%) 3 (9) 7 (14) DOSE-EFFECT RELATIONS Physiological measurements: The investigation was not a controlled expo- Change in tear film stability (break up time) −6 (24) −13 (28)* Change in MCA1 (cm2) −0.01 (0.22) 0.06 (0.34) sure chamber test, but a physiological investi- Change in MCA2 (cm2) −0.08 (0.30) −0.02 (0.40) gation performed during exposure conditions Change in VOL1 (cm3) −0.10 (0.90) −0.04 (0.89) 3 occurring when PG mist was used in aviation Change in VOL2 (cm ) −0.51 (2.21) −0.31 (2.80) training. The mean exposure measurements Change in FEV1 (% of predicted value) −1 (6) −1 (10) showed that there were higher exposures (520 *p<0.05; **p<0.01; ***p<0.001, change after the exposure (Student’s t test for paired comparisons). mg/m3 ) in the afternoon than in the morning, †Calculated as diVerence between values after and before exposure. before the lunch break (220 mg/m3). These atopy reported development of least one ocular diVerences made it possible to evaluate possi- symptom. Finally, 100% of those with atopy, ble dose-eVect relations comparing changes but only 28% of those without atopy reported from before to after exposure in those nine development of throat symptoms after expo- subjects exposed in the afternoon with those 18 sure to PG. exposed in the morning. A dose-eVect relation was found for tear film break up time, with a 6 PHYSIOLOGICAL INVESTIGATIONS second average decrease in the low exposure All participated in the acoustic rhinometry and group and a 13 second decrease in the high the lung function test. One could not partici- exposure group. Moreover, 47% in the low pate in the measurement of tear film stability exposure group but 100% in the high exposure due to nervous blinking. A significant decrease group reported development of throat dryness, of tear film stability was found after exposure to and the rating of throat symptoms on the VAS PG, with a reduction of mean tear film stability scale were higher in the highly exposed group. break up time from 38 to 29 seconds (p=0.02), By contrast, no dose-eVect relations were and the decrease of tear film stability was simi- found for ocular or nasal symtoms, dyspnoea,

lar in men and women. The diVerence in tear nasal patency, or FEV1% (table 5). film stability before and after the exposure was the same (mean decrease 6 s) in those who Discussion developed and those who did not develop ocu- The design was experimental and showed lar symptoms. When comparing tear film acute eVects on ocular and throat symptoms, stability after the exposure, however, those who and decreased tear film stability in non- developed ocular symptoms had numerically asthmatic subjects after 1 minute exposure to lower tear film stability (mean 27 s) than those PG mist from an artificial smoke generator. A who did not (mean 34 s). The two people with few reacted with a small lower airway obstruc- ocular symptoms before the exposure had the tion, cough, and mild dyspnoea. Moreover, greatest decrease of tear film stability (mean there were indications of a dose-eVect relation decrease 38 s). for throat symptoms and impairment of tear No significant changes in any measures of film stablility. There were some indications that nasal patency were found after exposure to PG women and subjects with a history of atopy (table 3). Most of the lung function values reported more of some types of symptoms after remained unchanged after exposure to PG, but the exposure. These results agree with a popu-

there was a minor numerical decrease of FEV1 lation study, suggesting that women and from 103% to 102% at exposure, and a small subjects with atopy are more sensitive to emis- 38 but signiﬁcant decrease of FEV1/FVC sions from indoor paint. (p=0.049). Mean VC was unchanged after the The physiological methods in the chosen exposure, whereas FVC was slightly increased acute eVect test battery have been used in pre- (table 4). None of the 27 participants had an vious epidemiological30 and experimental in- 31 initial lung function value (FEV1) below 80% vestigations. As there were few subjects of predicted value, but one got a 77% value for participating in this type of emergency training

FEV1 after the exposure. The mean decrease of at each time, the number of participants was

FEV1 and FEV1/FVC was similar in subjects limited. The study was based on non-asthmatic with and without a history of atopy. Moreover, volunteers, participating in the exposure as a there were no signiﬁcant association between a part of their occupational training. The expo-

decrease in FEV1, and development of mild sure time was short, but relevant to the dyspnoea (measured by the rating scales) in the exposure time used in aviation emergency total material training. Despite the limitations of the study, A few, however, reacted with cough, mild limited power, short exposure time, and exclu- airway obstruction, and mild dyspnoea. There sion of asthmatic people, we showed signiﬁcant were four subjects (16%) who developed irrita- eVects of airborne exposure to PG mist. tive cough after the exposure. All were The exposure concentration of PG (geomet- non-smoking men, without any history of ric mean 309 mg/m3) was quite high, compared allergies. They had an average reduction in with other exposure measurements of this

FEV1 of 5%, compared with a 0% reduction of compound in work environments. Exposure

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measurements in house painters who used measured by acoustic rhinometry, or lung water based paints36 showed exposure concen- function were found.32 In another study, 18 trations of PG ranging from <0.1 to 12.7 non-asthmatic subjects were exposed for 2 mg/m3 (mean 2.6 mg/m3), but no measurable hours to emissions from two diVerent formula- exposure to PG was found in motor servicing tions of water based paint, with emissions from work.24 The exposure measurements showed viscosed water as a control. The exposure to that the concentrations of other volatile organic PG was 0.13 mg/m3 with the old formulation, compounds in the flight simulator were very and 0.03 mg/m3 in the new formulation, low, and the concentration of formaldehyde expressed as toulene equivalents. The new for- was similar to that found in mid-Swedish mulation had a reduced emission of other vola- dwellings.39 tile organic compounds, including 2-methyl-1- To our knowledge, this is the first study of propanol, 2-butoxy-ethanol, and diisobutyl irritative and respiratory eVects of occupational glutarate. None of the two paint formulations exposure to airborne PG. There are some ear- had a significant eVect on tear film stability, lier exposure studies in animals. In one study, nasal patency measured by acoustic rhinom- 19 rats were exposed by nose only inhalation to etry, or concentration of biomarkers of inflam- 0, 160 (low), 1000 (medium), and 2200 (high) mation in nasal lavage. The old paint formula- mg/m3 concentrations of PG, 6 hours/day 5 tion induced some acute symptoms, had more days/week for 90 days. There was a significant smell, and induced a minor acute airway increase in the number of goblet cells in the obstruction, whereas the new paint had no nasal passages of the medium and highly such eVects.43 Finally, 17 asthmatic subjects exposed animals. It was concluded that this with previous exacerbation of symptoms on exposure to PG caused nasal haemorrhage and exposure to paint or other odours were exposed ocular discharge in a high proportion of to emissions from two diVerent formulations of animals, possibly due to dehydration of the water based paints. The new formulation, a 40 nares and eyes. volatile organic compound free paint, caused In one study of the eVects of organic solvents less wheeze and breathlessness, and less airway to induce erythema, no eVect was found on obstruction.44 dermal blood flow measured by Doppler flow- Despite the common use of PG in many metry, after dermal application of concentrated commercial and industrial products, there are 41 PG in humans. In another study, children few studies on irritative eVects in humans from were exposed to airborne PG (mean concen- airborne exposure to this compound. As PG is 3 3 tration 69 mg/m , maximum 94 mg/m )atair commonly used in artificial smoke generators sterilisation, continuously during several in discotheques, theatres, and emergency weeks. No negative eVects were found on training, possible adverse eVects of such expo- mucous membranes in the upper respiratory 42 sure can be of public interest, particularly for tract. sensitive subjects. Our measurements showed There are some indications that PG in tooth that exposure to PG can be high from smoke paste and nasal spray may cause mucosal generators, higher than in other occupational irritation in humans, but the relevance of these applications. We conclude from our results that findings for occupational exposure to PG is short exposures to PG mist from smoke unclear. When comparing dermal irritation generators may cause acute irritative ocular from four commercial toothpastes, three with and upper airway eVects in non-asthmatic sub- PG and one without PG, less irritation was 10 jects, and some symptoms were more common found for the toothpaste without PG. When in women and subjects with atopy. A few may comparing airway symptoms in subjects with also react with minor lower airway obstruction, allergic rhinitis who used two diVerent nasal cough, and mild dyspnoea. Recent experimen- sprays, less nasal burring, stinging, and throat tal studies have shown that there are subjects irritation was found when the concentration of with with increased sensitivity to trigeminal PG was reduced in the newer formulation of 12 irritants (sensory hyperreactivity). These sub- nasal spray. Similar results were found in jects react with cough after provocation with another study that showed improved nasal air- capsaicin solutions, and the reaction can be flow, decrease of nasal eosinophilia, and less blocked by lidocain, which inhibits nerve nasal burning and stinging with a new 45 11 transmission in the sensory nerves. Moreover, formulation of nasal spray containing less PG. such subjects may react with cough and Also, one recent case report describes asthma 25 asthma-like symptoms after provocation to crisis and cough induced by PG. irritants.46 Thus, sensory hyperreactivity could There are three experimental studies on be one mechanism behind the development of acute eVects of emissions from water based a combination of cough, slight airway obstruc- paints containing both PG and other volatile tion, and mild dyspnoea in a few of those organic compounds—for example, glycol exposed to PG mist. As exposure to PG mist ethers. In one study, 30 non-asthmatic subjects may occur both in workplaces and certain pub- were exposed for 4 hours to a mixture of PG lic places, studies on respiratory eVects of PG (10 mg/m3), texanol (2,2,4-trimethyl 1,3- 3 in subjects with obstructive respiratory disor- pentanediol monoisobutyrate) (5 mg/m ), di- ders or sensory hyperreactivity seem relevant. ethylene glycol monobutyl ether (5 mg/m3), diethylene glycol monobutyl ether (5 mg/m3), and dipropylene glycol monomethyl ether (5 This study was supported by grants from the Swedish Council 3 for Worklife Research, the Swedish Foundation for Health Care mg/m ). EVects on ocular symptoms, but no Sciences and Allergy Research, and the Swedish Association eVect on tear film stability, nasal patency against Asthma and Allergy.

www.occenvmed.com Propylene glycol in aviation emergency training and ocular and respiratory eVects 655

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