American Journal of Industrial Medicine 25:13%140 (1994)

Endotoxi n and (1 +3)-P-D-G I u can

David Pratt, MD, Maria Fernanda Carvalheiro, MD, Jacek Dutkiewicz, PhD, Hajlme Goto, PhD, Robert Jacobs, PhD, Jyrki Liesivuori, PhD, Eric Melbostad, PhD, Anna Rask-Andersen, PhD, and Deogratias Sekimpi, PhD

Key words: animal models, airborne endotoxin, organic dusts, occupational exposures

RATIONALE

There is an abundance of literature on the effects of endotoxin after inhalation both in animal and human models. An evaluation of all this information was con- sidered beyond the purview of the work group; the discussion centered on questions relating to the determination of airborne endotoxin in organic dusts.

Although there is a substantial literature which demonstrates the effects of (1+3)-P-D-glucan on the immune system, only a few reports are available address- ing the effects of inhaled glucan. Further studies must be conducted before the relevance of (1-3)-P-D-glucan in organic dusts can be assessed. The members of the workgroup concurred that there was sufficient evidence to conclude that endotoxins in the atmosphere of the workplace are capable of causing human illness in exposed subjects. Thus there is a need to characterize levels of endotoxin exposures in dif- ferent environments.

DETERMINATION OF AIRBORNE ENDOTOXIN

0 At the present time, the reporting of endotoxin levels in the work environ- ments is not consistent in the literature. The results of scientific investigations

Corporate Medical Department (D.P.). Hershey Foods Corporation, Hershey, Pennsylvania. Hospital de Pulido Valente (M.F.C.), New University of Lisbon, Department of Pneumology, Lisbon, Portugal. Institute of Agricultural Medicine (J.D.), Lublin, Poland. Department of Pulmonary Disease (H.G.), Tokyo Metropolitan Komagome General Hospital, Tokyo, Japan. School of Public Health (R.J.), University of Alabama, Birmingham, AL. Kuopio Regional Institute of Occupational Health (J.L.), Kuopio. Finland. The National Work Environment Institute (E.M.), Oslo, Norway. Department of Occupational Medicine (A.R.-A,), University Hospital, Uppsala, Sweden. Medical Department (D.S.), Kampala, Uganda. Address reprint requests to David Pratt. MD, Corporate Medical Director, Corporate Medical Depart- ment, Hershey Foods Corporation, 100 Crystal A Drive, Hershey, PA 17033. Accepted for publication March 15, 1993.

0 1994 Wiley-Liss, Inc.

140 Prattet al.

are variously reported in endotoxin units or amounts of endotoxin. At times, the results of scientific inquiries are reported in weight units. The literature would be improved if exposure to endotoxin was reported in endotoxin units, as well as a measure of concentration, e.g., nanograms per liquid volume or per air volume. The group was reminded that this was also suggested at Skokloster I.

0 The quality control of endotoxin analysis needs to be improved. A recent WHO collaborative study showed considerable variation in test results using identical samples of study material. At the present time, scientific papers often do not report standard errors of the mean or ranges around the mean for results obtained in investigations. Increased rigor should be put into the test methodology and to the reporting of quality assurance for these tests. An international standard for endotoxin analysis should be established. In the United States, the Food and Drug Administration uses Escherichia coli 5 as the standard of endotoxin in testing. It was recommended that the WHO might consider this for its standard in endotoxin measurement.

0 The methods chosen to sample environments for the presence of airborne endotoxin should be carefully designed and reported in detail in published papers. Often, the literature provides only a sketchy account of how the sampling methodology was designed and how the results were obtained. Reproducible experiments to verify the dangers of work environments are therefore much more challenging and much more difficult. It was noted in the group that, in considering the role of endotoxin in illness, measurements of peaks and means are both important.

0 (1~3)-P-D-glucan and endotoxin may cross-react in the Limulus assay. Test methodologies that will clearly differentiate between endotoxin and ( 1+3)- P-D-glucan are important for the further study of problems associated with inhaling (1+3)-P-D-gIucans, as well as other toxins. A more specific, non- biological test method should be explored and developed.

0 Expanded research is needed to address the possible synergy between endo- toxins and allergens, molds, and bacteria as imtants in the work environ- ment. Relatively little is known about how these agents might interact and impact on the immune system, airways, and mucous membranes.

0 The physical and chemical presentation of endotoxin to human hosts may be important. Studies are needed to assess the many ways in which endotoxins are presented to the airways, lung, and mucous membranes in humans.

0 The chronic effects of breathing high levels of endotoxins have not been sufficiently studied. The potential existence of high levels of endotoxins in saw mills, grain elevators, animal feed storage systems, and fish farming need to be studied and dose-response relationships evaluated for different effects.