Objectives. First study. Second Study. Determination of Unspecific Sensitivity

Transcription

1 Institute and Outpatient Clinic for Occupational and Social Medicine University of Heidelberg Formaldehyde and chemosensory effects in normal, hyper and hyposensitive volunteers G. Triebig, I. Lang, J. U. Mueller, T. Bruckner Objectives to examine chemosensory effects of formaldehyde on normal, hyper and hyposensitive healthy, non smoking men and woman symptoms and findings on eyes, nose and olfactory function exposed to concentrations typical for workplaces: up to. ppm th International Congress on Occupational Health March 8, Cancun, Mexico Studies were approved by the Ethics Committee of the Medical Faculty of the University of Heidelberg First study Exposure/ Concentrations men and woman 6 +/ 6 years old students, unemployed persons Subjects Exposure Monday to Friday Two consecutive weeks (= days) Four hours daily Random order and double blind fashion Masking with ethylacetat Examinations after min, min and 9 min of exposure Scenario Formaldehyde Continuous exposure (ppm) Formaldehdye peaks (ppm) x.6 x. x. EA (ppm) men +/ years old unemployed persons Second Study Subjects Exposure Exposed on consecutive days (Monday Friday), hours daily followup examinations at oneweekintervals five randomized formaldehyde concentrations: concentration A:. ppm (control group) concentration B:. ppm with.6 ppm peak ( x min) concentration C:. ppm with.8 ppm peak ( x min) concentration D:. ppm concentration E:.7 ppm Determination of Unspecific Sensitivity COthreshold measurement / Separation into Sensitivity Groups CO offers possibility to determine irritation of trigeminal nerve (=sensible nerve supply e.g. of the nose) COapplication at nasal mucosa evokes stinging, painful sensations (concentration and sensitivitydependent) provoked subjective pain intensities marked on a VAscale (by participant) were used for mathematical calculation of individual sum score ( individual sensitivity score ), and for evaluation of mean value, median and quartiles. on basis of these individual sum scores of our volunteers Separation into two subgroups. at median hyposensitive and hypersensitive participants. at upper/ lower quartile resp. extremely hypo / hypersensitive subjects

2 Examinations: examinations and volunteers Subjective rating Swedish Performance Evaluation System (SPES) by Gamberale et al. 989, German version by Seeber et al. Digital slit lamp photography: conjunctival redness grading scale of the Cornea and Contact Lens Research Unit (CCLRU) Measurement of blinking frequency new developed method by Ziegler et al. 7 (Exposure chamber) Tear film break up time (stopwatch measurement) Olfactory function (nbutanol threshold, SniffinSticks) Active anterior rhinomanometry nasal flow and resistance (Volunteers on cycle ergometer in exposure chamber) examinations and volunteers SPES I (Video recording of eyeblinking frequency) (Test of olfactory function Sniffin Sticks ). Blurred Sight. Feeling of fainting or vertigo. Pain or pressure over the chest. Bad taste in the mouth. Sensation of bad air (quality) 6. Irritation of the throat 7. Headache 8. Coughing spells 9. Sensation of unpleasant taste. Nasty smell. Irritation of the skin. Dizziness. Shortness of breath. Nasty taste. Palpitations 6. Sensation of unpleasant smell 7. Nausea 8. Stink 9. Irritation of the nose. Itching nose. Dry nose. Running nose. Smarting nose. Diplopic images. Eyestrain 6. Itching eyes 7. Smarting eyes 8. Irritation of the eyes 9. Dry eyes. Watering eyes. Redness of the eyes = not at all = hardly at all = somewhat = rather much = considerably = very, very much SPES II SPES III S y m p to m g r o u p S y m p to m s O lfactory sym ptom s Sensation of bad air (quality ) N a s ty s m e ll S e n s a tio n o f u n p le a s a n t s m e ll S tin k Nasal irritations Irritation of the nose Itc h in g n o s e D ry n o s e R u n n in g n o s e S m a rtin g n o s e O c u la r irrita tio n s E y e s tra in Itc h in g e y e s S m a rtin g e y e s Irritation of the eyes D ry e y e s W a te ry e y e s R e d n e s s o f th e e y e s S h a m e s y m p to m s P a lp ita tio n s D ip lo p ic im a g e s Symptom group Unspecific symptoms Not classified Taste symptoms Respiratory symptoms Symptoms Feeling of fainting or vertigo Dizziness Nausea Blurred sight Irritation of the throat Irritation of the skin Bad taste in the mouth Sensation of unpleasant taste Nasty taste Pain or pressure over the chest Coughing spells Shortness of breath

3 Results Study I: Eye Irritation Results Study II: Eye Irritation A = ppm B =.ppm C =.ppm D =.ppm + peaks with.6ppm E =.ppm F =.ppm + peaks with.ppm G = ppm + EA H =.ppm + EA I =.ppm + EA K =.ppm + peaks with.ppm + EA * compared to FA # compared to FA + EA Postexposure Eye Irritation scores are predominantly increased compared to values before exposure, however, without statistical significance and without a concentrationresponserelationship. Comparison to the zero concentration and comparison between the sensitivity groups also revealed no statistical significant difference. Results Study I: Nasal Irritation Results Study II: Nasal Irritation (= combined organ related items/symptoms; e.g. burning, running or dry nose) A = ppm B =.ppm C =.ppm D =.ppm + peaks with.6ppm E =.ppm F =.ppm + peaks with.ppm G = ppm + EA H =.ppm + EA I =.ppm + EA K =.ppm + peaks with.ppm + EA * compared to FA # compared to FA + EA We found no uniform trend and no significant changes in postexposure values. No concentrationresponse relationship could be detected. Comparison to the zero concentration and comparison between the sensitivity groups also revealed no consistent tendency. Results Study I: Olfactory Symptoms (= combined organ related items/symptoms; e.g. stench, unpleasant smell or perception of impure air) Olfactory Symptoms is the very SPESSubgroup with strongest increase of symptomscores after exposure A = ppm B =.ppm C =.ppm D =.ppm + peaks with.6ppm E =.ppm F =.ppm + peaks with.ppm G = ppm + EA H =.ppm + EA I =.ppm + EA K =.ppm + peaks with.ppm + EA * compared to FA # compared to FA + EA Results Study II: Olfactory Symptoms Generally, all volunteers indicate an increase of olfactory symptoms after exposure (including controlgroup) Higher increases were found in hypersensitive and extremely hypersensitive volunteers compared to hypo / extremely hyposensitive counterparts. However Comparison with zeroconcentration reveals only few statistically significant differences and no consistent concentrationresponse relationship. rather a situational effect than attributable to formaldehyde effects see following page

4 Results Study I: Conjunctival Redness Eye redness according to CCLRU Eye redness grade A = ppm B =.ppm C =.ppm D =.ppm + peaks with.6ppm E =.ppm F =.ppm + peaks with.ppm G = ppm + EA H =.ppm + EA I =.ppm + EA K =.ppm + peaks with.ppm + EA * p <. = very slight = slight = moderate = severe Results Study I: Blinking Frequency Blinking frequency per 9 sec Results Study I: Correlation between blinking frequency and eye irritations Formaldehyde concentration (ppm) Mean blinking frequency ±SD Median Range... + peaks at.6 8. ±.. ±. 7.8 ±.7. ± ρ=.6; y =.9x +.7 p=... + peaks at. + EA. + EA. + EA. + peaks at. + EA 9. ± ±.6 *# 8.6 ± ±.. ±.. ±. *# Results Study II: Blinking Frequency Results Study II: Tearfilm BreakUp Time No concentrationdependent increase of eye blinking frequency after FA exposure No statistically significant differences between pre and postexposure values in comparison with zero concentration between different sensitivity groups We found an increase rather than a decrease of tear film breakup time after exposure. Comparison with control group and comparison between the sensitivity groups revealed no consistent tendency and no concentrationeffect relationship

5 Results Study I: Nasal Flow Results Study II: Olfactory Funktion nbutanol threshold (performed daily before/after exposure and during the followup examinations) 6 A = ppm B =.ppm C =.ppm D =.ppm + peaks with.6ppm E =.ppm F =.ppm + peaks with.ppm G = ppm + EA H =.ppm + EA I =.ppm + EA K =.ppm + peaks with.ppm + EA 6 A B C D E F G H I K No consistent, concentrationdependent pre/postexposure change of nbutanol thresholds No significant differences compared to control group and no concentrationeffect relationship detectable. No significant variation of nbutanol thresholds between different sensitivity groups Conclusion: no specific FAeffect detectable! Results Study I: Time course A) Ocular irritation A = No exposure B =. ppm plus peaks of. ppm C = Next morning (about 6hrs after exposure) * p<. Conclusions () Eye irritations are the most critical effects induced by formaldehyde vapors Blink frequency and redness of the eyes increased significantly at a concentration of. ppm with peaks of. ppm Peak exposure is more relevant to induce conjunctival effects B) Olfactory irritation A = No exposure B =. ppm plus peaks of. ppm C = Next morning (about 6hrs after exposure) * p<. Eye and olfactory symptoms started at concentrations of. ppm without peaks Conclusions () Acknowledgement No influence of gender on results No significant differences of specific effect parameters between hypo and hypersensitive persons NOAELs of. ppm (constant exposure) and,8 ppm (shortterm peaks) are recommended Our results are in accordance with former review articles of Paustenbach et al. (997) () and Arts et al. (6) () We gratefully acknowledge the volunteers for their participation and the following colleagues for assistance and study advice: Lutz Buchholz, Gudula Christ, Armin Gamer, HeinzPeter Gelbke, Joerg Haisser, Thomas Hummel, Michael Kentner, Christoph Klingmann, Stefan Knohl, Thomas Krczal, Heidi Ludwig, Jutta Martin, Sylvana Müller, Wolfgang Rosenberger, Manuel Ruehle, Benno Schuster, Guenter Speit, Rho Thiel, Andrea Vinzens und Holger Zimmer. The authors thank the FormaCare sector group of CEFIC, Brussels, the European Panel Federation, Brussels, and the Verband der Deutschen Holzwerkstoffindustrie e.v., Gießen, for their financial support of this study. J.Toxicol.Environ.Health (997) 76 Regul.Toxicol.Pharmacol. (6) 6

6 Publications Isabelle Lang, Thomas Bruckner, Gerhard Triebig: Formaldehyde and chemosensory irritation in humans: A controlled human exposure study, Regulatory Toxicology and Pharmacology (8) 6. Joerg U. Mueller, Thomas Bruckner, Gerhard Triebig: Exposure study to examine chemosensory effects of formaldehyde on hyposensitive and hypersensitive males, International Archives of Occupational and Environmental Health, DOI.7/s79. Thank you for your attention! 6