The purpose of the memorandum is to exchange information and expertise in the area of occupational safety and health. One product of this agreement is the development of documents to provide the scientific basis for establishing recommended occupational exposure limits. These limits will be developed separately by the two countries according to their different national policies. This document on the health effects of occupational exposure to grain dust is the first product of that agreement. The document was written by Michael Brown (DSDTT/NIOSH) and was reviewed by the Criteria Group and by DSDTT/NIOSH.# INTRODUCTION
Adverse health effects from exposure to grain dust were first reported in 1713, when Bernardino Ramazzini noted that grain dust irritated the throats, eyes, skin, and lungs of grain workers (Ramazzini 1713). Workers may be exposed to grain dust during farming operations or while working at grain elevators and flour, feed, and seed mills.
Exposure to grain dust may also occur during the transportation of grain between these facilities. Present-day grain workers have been reported to exhibit both pulmonary effects (including cough, dyspnea, wheezing, asthma, chronic bronchitis, farmer's lung, chronic airway obstruction, mycotoxicosis, and allergic alveolitis) and nonpulmonary effects (including conjunctivitis, rhinitis, grain fever, and dermatitis).
In the United States of America (U.S.A.), the National Institute for Occupational Safety and Health (NIOSH) has previously considered the explosive properties of grain dust and has recommended safe work practices and engineering controls (NIOSH 1983a).

# In Sweden, Lantbrukets
Brandskyddskommitte has issued recommendations on how to prevent the spontaneous combustion and explosion of grain dust (SBK 1977).
Data have also been reported on grain dust contaminants, which include fungal spores, bacteria, mites, and insect body parts (NIOSH 1986a).
This paper addresses the adverse health effects of human exposure to grain dust.
A thorough search of the literature has identified three groups of studies specifically dealing with this type of occupational exposure.
These epidemiologic studies are discussed in detail in Section 5.7.

# CHARACTERISTICS AND COMPOSITION OF GRAIN DUST
Grain dust consists of 60% to 75% organic material and 25% to 40% inorganic material (Yoshida and Maybank 1980), including the following:
(1 ) Fragments of cereal grains (e.g., wheat, oats, barley, rye, and corn), oil seeds (e.g., rapeseed, linseed, and sunflower seed), and pulses (the edible seeds of legumes such as peas and soybeans) (Becklake 1980),
(2) Decomposition products of grains, seeds, and pulses (Chan-Yeung and
(3) Inorganic materials such as soil and traces of chemical elements (Yoshida and Maybank 1980), ( 4) Microorganisms (NIOSH 1986a(NIOSH , 1986b,
(5) Insects, insect parts, and mites (Labour Canada 1981), ( 6) Hairs, feathers, and excreta of rodents and birds (Becklake 1980), ( 7) Fragments of plant matter (Becklake 1980), ( 8) Chemicals such as fertilizers, pesticides, and herbicides (Federal Register 1980), and ( 9) Other contaminants such as metal fragments, lubricating oils, or paint chips that may have accumulated with the grain during the harvesting and subsequent processing or storage (Labour Canada 1981).
Airborne grain dust concentrations in storage and grain-handling facilities are affected by the design of ventilation systems (if present), the intensity and thoroughness of housekeeping efforts, the amounts of contaminants present, the humidity, the age of the grain, the extent to which the grain has been cleaned, and the degree to which the grain has been manipulated.

# .1 Microorganisms
The microbial flora associated with grain dust consist of a wide variety .of fungi and bacteria. The predominant organisms isolated from grain dust depend on the time the dust is produced (during harvest or storage) and factors such as original growing conditions, season of the year, geographical location, water content of the grain, temperature, type of grain, and storage practices. Some organisms invade or contaminate the grain when it is developing in the fields, and other organisms are primarily associated with grain during storage (Lacey 1980;NIOSH 1986a).

# Ashley 1978),
Under field conditions, fungi such as Cladosporium, Alternaria, Fusarium, Diplodia, Chaetomium, Rhizopus, and Absidia are predominant, but bacteria such as Erwinia herbicola, Pseudomonas, Bac i11 u s , and Streptomyces are also found (NIOSH 1986a).
Though microorganisms from the field can still be isolated after the grain has been stored, the number of field organisms usually declines over time, and some are replaced by other fungi and bacteria (Lacey 1980). Aspergi11 us and Pen i c i 11i um species are the predominant fungi associated with storage, but grain that has become moist or heated often contains Micropolyspora, Thermoactinomyces vulgaris, and yeasts such as Cand i d a , Mucor pusi11 u s , and Absidia (NIOSH 1986a).
Appendix Table A-1 lists the predominant microorganisms identified in selected reports.

# Pesticides
Grain may be fumigated with pesticides at a number of points between the field and storage facility to prevent spoilage or loss from pests.
Fumigation frequently occurs during transportation by truck or freight car to large elevators. Grain may be fumigated again during transfer into elevators, during storage, and also during discharge into barges, ships, or rail cars. Grain in long-term storage is subjected to periodic preventive fumigation and treatment if pest infestation occurs.
Pesticides that are currently banned for use with grain in the U.S.A. are ethylene dibromide (Federal Register 1984), carbon disulfide, ethylene dichloride, and carbon tetrachloride (Federal Register 1985). Pesticides that are currently being used are methyl bromide (EPA 1986), and aluminum or magnesium phosphide (EPA 1987). Malathion has an EPA label registration that permits it to be used for protecting grain from future infestation.
Sampling has been conducted for carbon disulfide, ethylene dibromide, and carbon tetrachloride (McMahon 1971;NIOSH 1977NIOSH , 1984aNIOSH , 1985aNIOSH , 1985b; chloroform and 1 ,2-dichloroethylene (NIOSH 1984a(NIOSH , 1985a; methyl bromide and ethylene dichloride (NIOSH 1977(NIOSH , 1985a; carbon disulfide (NIOSH 1977(NIOSH , 1985b; malathion (Palmgren and Lee 1984;NIOSH 1985c); 1 ,2-dibromoethane (Berck 1974;Panel on Fumigant Residues in Grain 1974;Heikes 1985); phosphine (NIOSH 1977(NIOSH , 1985c(NIOSH , 1987; ethylene dichloride (Berck 1974;NIOSH 1984a); carbon tetrachloride (NIOSH 1976a); trichloroethylene, and chloroform (Panel on Fumigant Residues in Grain 1974); and diazinon (Palmgren and Lee 1984). None of these pesticides are known to cause the major health effects identified with exposures to grain dust. NIOSH has recommended that some pesticides (e.g., carbon tetrachloride, trichloroethylene, and ethylene dibromide) be regarded as potential occupational carcinogens, and that efforts be made to substitute or take appropriate control measures (NIOSH 1976b(NIOSH , 1978(NIOSH , 1983b.

# Inorganic compounds
Wirtz and Olenchock (1984a) characterized the elemental composition of airborne grain dusts from six different grains and the settled dust from grain elevators.
The data from this study demonstrated that differences exist between the elemental compositions of the airborne grain dusts generated by different grains and between the compositions of settled and airborne grain dusts.
Concern exists about the silica content of grain dust. Silica has been reported to constitute 9.96% of dusts with a particle size <44 yim (Heatley et al. 1944). Stepanov et al. (1967) reported that up to 70% of the grain dust from the elevator and threshing floor of a grain elevator consisted of organic material and that the mineral fraction of the dust was composed of 8% to 18% free silica. When available, silica concentrations are reported in the epidemiologic studies in Section 5.7.

# ANALYTICAL METHODS
Because of the variety of contaminants occurring in grain dust, the analytical methods for their determination cannot be reviewed in this brief document.
The reader is referred to standard textbooks on analysis of organic chemicals in the workplace. Whether or not the specific components of the dusts are measured, the exposure measurement should involve the collection of the total and respirable fractions. These can be collected using standard methods for total nuisance dust (NIOSH Method 0500) and respirable nuisance dust (NIOSH Method 0600) (NIOSH 1984b).
Several methods are available for sampling the microflora of both settled and airborne grain dust. These methods vary in their degree of precision, sophistication, and suitability (Lacey 1980;NIOSH 1986a (Table I). Data on exposure to grain dust are listed by occupational group, process, or area monitored in Appendix Tables A-2 and A-3 for Canada and the U.S.A.
In Sweden, the concentration of grain dust ranged from 4 to 53 mg/m in five grain pits (ASF 1985).

# EFFECTS IN HUMANS
This document deals with the adverse health effects of exposure to grain dust. The occurrence of these adverse health effects has been documented in the literature since 1713.

# Uptake and deposition in human lungs
No information has been found regarding the uptake and deposition of grain dust in human lungs.

# Acute effects
Acute exposure to grain dust has resulted in pruritic skin reactions, conjunctivitis, rhinitis, asthma, and grain fever (symptoms of the latter may include cough, chest tightness, wheezing, dyspnea , expectoration, fever, chills, flushed face, and pain in the joints and muscles). See also Section 5.7, Epidemiologic studies.

# Chronic effects
Chronic exposure to grain dust has resulted in chronic bronchitis and hyperreactive airways. See also Section 5.7, Epidemiologic studies.
Neuropsychiatric effects have been seen in grain elevator workers exposed to carbon disulfide (Peters et al. 1982). Grain elevator -2.5 to 19.9 NIOSH (1977) Grain elevator -2 . 0 to 118.8 NIOSH (1977) Grain elevator -0 . 2 to 6 . 6
NIOSH (1977) Grain elevator -0.7 to 35.9 NIOSH (1977) Grain elevator -0.28 to 9.5 NIOSH (1985c)
Grain elevator -0.34 to 30.0 NIOSH (1985c)
Grain elevator 13 0.96 to 9.48 NIOSH (1986a) *Area dust concentrations. "^PersonaI dust concentrations.

# Critical effects
No specific adverse health effect can be recognized as always occurring first in workers exposed to grain dust.
The first effect could be manifested as irritation of the throat, eyes, skin, or lungs.

# Dose response/dose effect
Table II lists the reported human health effects at various grain dust exposure concentrations.

# Case studies
The following health effects have been reported in workers exposed to grain dust: silicosis in a worker who unloaded grain from rail cars (Heatley et al. 1944), pneumoconiosis in dock laborers who primarily handled grain (Dunner et al. 1946), farmer's lung in farmers who handled grain (Dickie and Rankin 1958;Patterson et al. 1974;Kotimaa et al. 1984), neuropsychiatrie disorders in grain storage workers (Peters et al. 1982), pulmonary mycotoxicosis (now referred to as organic dust toxic syndrome ) in farmers who handled moldy silage (Emanuel et al. 1975), and grain fever and severe dyspnea in grain elevator workers (Skoulas et al. 1964 A logistic regression analysis produced the odds ratios (i.e., the probability of having a symptom divided by the probability of not having the symptom) listed in Table IV. These ratios indicate that the odds of developing respiratory symptoms from grain dust exposure are independent of and usually greater than the odds of developing them from smoking.   , (1983).
283 grain elevator workers and 192 city service workers (comparison population). The two groups were comparable with respect to age, sex, height, weight, and smoking habits.
The workers were given a limited physical examination and were administered medical and occupational questionnaires to obtain information on the frequency of eye, nasal, and respiratory symptoms and their perceived level of dust exposure ("less than average," "above average," or "average"). Spirometrie measurements were obtained for FVC, F E V^ FEFgo^, and FEF^g^.
Other tests included (1) oral temperature, (2) skin tests using pollen, mixed feathers, cat and rat epithelium, grass, and mixed grain dusts, and (3) venous blood samples for total leukocyte count.
During the work shift, 209 total dust measurements (8 -hr TWA's)
were made. Ninety-three percent of the grain dust concentrations were 3 3 below 10 mg/m , and 8 6% were below 5 mg/m , with a mean concentration of 3.3 mg/m^. Statistically significant differences (p<0.05) existed in the prevalence rates of the following symptoms among all grain workers and all comparison workers, respectively: cough, 48% and 32%; expectoration, 38% and 19%;
wheezing, 13% and 9%; dyspnea, 12% and 6%; nasal stuffiness, 38% and 26%; and eye irritation, 13% and 6 %.
In the comparison group, workers who smoked had a significantly greater prevalence (p<0.05) of cough, expectoration, and nasal symptoms than did nonsmokers. Grain elevator workers who reported that their perceived exposure to grain dust was "average" had a significantly greater occurrence (p<0.05) of cough than those who reported "less than average" exposures.
Those who assessed their exposure as "greater than average" had a significantly greater prevalence (p<0.05) of dyspnea, wheezing, and eye symptoms than those reporting "average" or "less than average" exposures.
An analysis of the relationship between dust concentrations and symptom prevalence was conducted for 209 grain workers (no explanation was given for the reduced number of workers). At total grain dust concentrations 3 >5 mg/m , grain workers had a significantly greater prevalence of cough (p<0.005), expectoration (p<0.0001), dyspnea (p<0.001), and eye irritation (p<0 .0 0 0 1 ) than did city service workers.
An analysis of pulmonary function values for 241 grain workers and 191 comparison workers was conducted (no explanation was given for the reduced number of workers). Grain workers experienced a significant pre-shift to post-shift percentage change for FVC (p<0.05), ^5 0% (p<0.01), and FEF?5 % (p<0.001).
A multiple regression analysis correcting for age, height, and smoking habits revealed that the grain dust concentration had a statistically significant (p<0.05) effect on the pre-shift to post-shift percentage changes in FVC, FEF^q^, and FEF^^. The significant effect noted for FVC limits the validity of the flow rate measurements, as the lung volume shifted the volume at which the flow measurements were made.  The average respirable dust 3 concentration was 0.9+0.7 mg/m , and the average nonrespirable dust 3 concentration was 5.7+10.9 mg/m . Note that the standard deviation for the nonrespirable dust concentration is larger than the mean because the data are greatly skewed; the validity of the data is not affected, however.
Pulmonary function analyses were based on results from 34 of the 47 grain elevator workers (the remaining 12 workers were either unable to report for the tests or had results that were rejected on technical grounds). The FVC decreased from Monday to Wednesday, and the Wednesday change was sustained on Friday (p<0.001).
The These data were used to examine a dose-effect relationship for grain dust exposure.
Results showed that 50% of the workers underwent a daily decrease of at least 923 ml/sec in (p=0.004) and of 310 ml/sec in FEF2 5% (p=0.08) for each 1 mg/m^ increase in the concentration of respi rable dust.
5.7.2. 3 Broder et al. (1983) In a report based on information collected in the 1977 survey (Broder et al. 1979), Broder et al. (1983  No results were reported for the chest radiographs.
On the basis of skin tests results, two subsets of grain workers were established for further study: (1 ) 18 grain handlers with positive reactions to one or more grains and a comparison group of 18 grain workers with no reaction, and (2 ) 21 grain handlers with positive reactions to one or more fungal antigens and a comparison group of 21 grain workers with no reaction.
Workers were matched for age, duration of employment, smoking status, and pack years of smoking. No significant differences were found for demographics, respiratory symptoms, or pulmonary function.
On the basis of results of the inhalation challenge tests, three subsets of grain workers were established for further analysis: (1 ) 12 nonsmoking grain workers with chronic cough and 12 grain workers with no cough (internal comparison group),
(2) 9 grain workers with a decrease in FEFgQ^ from Monday to Friday and 9 grain workers with no decrease in FEFgo^ (internal comparison group), and (3) 10 grain workers whose baseline FEV^ was 100%
(internal comparison group). Insofar as possible, the internal comparison workers were matched with the other grain workers for age, duration of employment, and smoking history. No significant differences were found for demographic variables, respiratory symptoms, or pulmonary function. For the longitudinal analysis, 14 workers who were laid off and 14 who were not laid off were matched as closely as possible for age and smoking habits. The laid-off workers were examined in January and February before being rehired; they were subsequently examined between April and June.
Steadily employed workers were examined at the same intervals. After they were rehired, workers who had been laid off reported an increase in cough (p<0.04), rhinitis (p<0.03), and sputum production (p<0.05), and a decrease in shortness of breath (p<0 .0 1 ) and respiratory illness (p<0 .0 2 ). Workers who were steadily employed had an increase in cough (p<0.04), rhinitis (p<0.03), and sputum production (p<0.05) during the same time period.
Compared with these workers, those who had been laid off reported significantly less cough (p<0.05) and sputum production (p<0.01) in February, and less shortness of breath (p<0.05) after they were rehired.
Workers who had been laid off showed improvement in FEV^ (p<0.001) and FEFgo^ (p<0.001) in February followed by a decline after they were rehired. For that same period, steadily employed workers had an increase in FEV.J (p<0.002) in February followed by a decline.
An analysis covering the maximum consecutive period of reduced employment (January to March) included 15 workers who were laid off and 24 steadily employed workers. The subjects were not matched for age or smoking habits. The steadily employed workers had a significant increase in cough (p<0 .0 2 ) and sputum production (p<0 .0 0 1 ).
Though low ambient temperature may have had an effect on the respiratory symptoms, adverse symptoms continued to increase as the temperature increased. The longitudinal changes in respiratory variables are partially reversible and are consistent with the effects of grain dust exposure.  (Broder et al. 1985). The grain handlers who had left employment were significantly younger (p<0 .0 0 1 ), had a shorter duration of employment (p<0.001), and reported a greater prevalence of eye irritation (p<0.04), cough (p<0.04), and shortness of breath (p<0.003) than those grain workers who remained employed. The groups were compared using multiple logistic analyses of the symptoms and multiple regression analyses of pulmonary function measurements with adjustments for age, pack years of smoking history, and duration of employment. These adjustments increased the differences in prevalence rates for the aforementioned symptoms but they did not change the statistical significance.
The adjustments also increased the significance of the reported sputum prevalence from p=0.04 to p<0 .0 2 . Civic workers who left the job were significantly younger (p<0 .0 0 1 ), had a shorter duration of employment (p<0 .0 0 2 ), had decreased pack years of smoking history (p<0 .0 0 1 ), included a lower percentage of current smokers (p<0 .0 2 ), had a lower prevalence of coughing (p<0 .0 2 ), and had a lower FVC (p<0.002), a higher F E V^F V C ratio (p<0.02), and a higher ^7 5% (p<0.005) than those civic workers who remained employed. When adjusted for age, pack years of smoking history, and duration of employment, the differences were no longer statistically significant.
Data obtained in the 1977 survey (Broder et al. 1979) for the grain and civic workers who remained employed and were reexamined were compared with data obtained from those workers who remained employed but did not report for the 1980 survey (Broder et al. 1985). The grain workers who declined participation in the 1980 survey were significantly older (p<0.007), had a longer duration of employment (p<0.009), and had a greater number of pack years of smoking history (p<0.006) when compared with those grain workers who were reexamined in the 1980 survey.
The grain workers who declined participation in the 1980 survey had a higher prevalence of sputum production (p<0.01), lower FEF^q (p<0.009), and F E V^F V C (p<0.006) when compared with those grain workers who were reexamined in the 1980 survey.
However, the significance for these pulmonary parameters declined when adjusted for number of pack years of smoking.
The civic workers who declined to participate in the 1980 survey were significantly older (p<0.03) than those civic workers who were reexamined.
There was a statistically significant greater prevalence of wheezing in nonsmoking civic workers compared with nonsmoking grain workers in 1977 (p<0.03) and in 1980 (p<0.001).
In 1977, increased eye irritation (p<0.01) and a higher FEF^g^ (p<0 .0 2 ) was measured in grain workers who smoked compared with civic workers who smoked. For grain and civic workers whose smoking status remained constant from 1977-80, Table V shows demographic characteristics, symptom prevalence, and measures of pulmonary function. The changes in pulmonary function from 1977 to 1980 show (1) a significant increase in FEV^/FVC (p<0.04) among grain workers who were ex-smokers compared with civic workers who were ex-smokers, and (2 ) a decline in FEF7 5% (P<0 -0 0 2 ) among grain workers who were current smokers compared with civic workers who were current smokers.
A multiple regression analysis of change in pulmonary function from 1977 to 1980 demonstrated an inverse relationship between age in 1980 and the level of pulmonary function in 1977.
The longitudinal study by Broder (1980) showed that there was an increased prevalence of rhinitis, cough, and sputum production among rehired grain workers compared with continuously employed grain workers. However, the rehired workers showed a decrease in the prevalence of shortness of breath and respiratory illness compared with the continuously employed grain  (1985) reported the results of special tests and/or analyses performed by Tabona et al. (1984) on subsets of these populations. These reports followed portions of the same populations of grain workers and controls for periods as long as 6 years (Table VI).
For the first health survey,   1977. Candidates identified for study included 642 workers from five grain elevators, 206 civic workers, and 302 noncedar sawmill workers (1980).
Because there were no female grain elevator workers, women were excluded from the two comparison populations. Nonwhite workers were eliminated the crystalline silica content of the dust ranged from 3.8% to 5.0%. The average total dust concentration in the sawmills was 1.9 mg/m (the range was not reported).
There were no statistically significant differences between grain workers and civic workers with regard to the prevalences of eye, nasal, and chest symptoms when workers were matched for smoking habits. Grain workers and sawmill workers had statistically significant differences in the prevalences of these symptoms (Table VIII).
Cough, sputum, wheezing, and breathlessness were more prevalent in smokers than in nonsmokers in all

# groups.
The predicted values for FEV1 and FVC (mean percentage) were significantly lower for nonsmoking or ex-smoking grain workers than for nonsmoking or ex-smoking civic or sawmill workers (p<0.05). The more non-atopic status of grain workers compared with civic workers suggests that a self selection (healthy worker effect) occurs.
On  IX).
In addition to tests conducted in the primary study, other tests performed were (1 ) methacholine broncochallenge tests, with FEV1 and FVC measured before and after the tests, (2) serum precipitin responses to grain dust extracts, (3) bronchial inhalation challenge to grain dust and grain dust extract, with FEV^ and FVC measured before and after the tests, and (4) venous blood samples for determination of absolute eosinophil counts. On the basis of these test results, the 33 workers were divided into three groups. Twenty-two of these workers (Groups A and B) reported respiratory symptoms (cough, sputum production with or without wheezing, and breathlessness) and demonstrated decrements in lung function. Group A consisted of 6 workers who also had a +PC2 0 =Provocation concentration of methacholine to induce a 20% fal I in FEV-j.
the workers in Group B demonstrated bronchial reactivity to methacholine at a level similar to that of patients with symptomatic occupational asthma.
The remaining workers in Group B showed bronchial reactivity to methacholine challenge within the range seen in patients with chronic bronchitis. Groups A and B had evidence of airway obstruction, indicated by the decline in FEV1 , FEF25-75%' an(- FEV-|^VC (Table X). Group A had an absolute eosinophil count of 244/mm'- compared with 156/mm^ for Group B. None of the subjects reacted to skin tests or responded to grain dust extracts with serum precipitins. Although grain dust did not cause a bronchial reaction in all the workers, it cannot be excluded as the causative agent for the asthma and chronic bronchitis. Asthma is not a graded uniform response across exposed groups; rather it is an incident frequency response. Also, the results of exposure to the settled grain dust may not be indicative of those that may occur with fresh grain dust.   5.7.3.4 Tabona et al. (1984) In the fourth report of the series, Tabona et al. (1984) conducted a health survey in October and November 1981 using workers from the same worker populations studied in the first three reports (Chan-Yeung et al. 1980, 1981. The characteristics of 267 grain workers who had not changed their smoking habits over the 6 -year study period were compared with the characteristics reported in the first health survey (Chan-Yeung et al. 1980 5.7.3.5 Enarson et al. (1985) In the fifth report, Enarson et al. (1985) analyzed the respiratory functions of 81 of the grain workers described by Tabona et al . (1984).
These workers were matched for age and smoking habits. Twenty-seven of the

# . ANIMAL STUDIES
The animal studies cited here identify the mechanism(s) of lung response to grain dust exposure. Mice exposed to grain dust concentrations ranging from 1200+500 to 5400+700 mg/m^ total dust for 2 to 28 days developed an increased pulmonary macrophage response (Armanious et al. 1982). Rabbits exposed to grain dust at 20 mg/m for 24 weeks, 5 days a week, developed inflammation of the alveoli and interstitium (Stepner et al. 1986).
Exposure to mycotoxin produced noncytotoxic histamine release in rat peritoneal cells (Warren and Ho Iford-Stevens 1986) and inhibited several critical cellular functions in rat alveolar macrophages (Sorenson et al. 1986).
In rats, intratracheal instillation of grain dust initiated an acute inflammatory reaction as evidenced by an influx of neutrophils into the airspaces and later into the lung interstitium (Keller et al . 1987).
Rats do not respond to histamine, yet histamine is the major pharmacologic mediator of acute bronchoconstriction in man.
The allergic anaphylactic response of guinea pigs is mediated by a subtype of IgG (heterocytrotropic IgG) which is unlike the human IgG mediated responses. Human allergy is IgE mediated (Bass et al. 1988).
Limited conclusions have been drawn from the rodent animal modeling studies of human etiopathogenes. However, these studies support the proposed immunologic mechanism(s) presented in this document.

# POSSIBLE MECHANISMS OF ACTION
Grain dust is a complex mixture of organic and inorganic compounds. dust as a source of material for the RAST assay, and found that the prevalence of IgE antibodies to grain dust antigens was significantly higher than the prevalence of IgE antibodies to grain antigens. In Sweden, febrile reactions occurred in 19% of farmers exposed to unusually moldy grain (Malmberg et al. 1985). This variability of the agents in dust may be partially responsible for the variations in hypersensitivity noted in the reports cited above; or other causal mechanisms may be involved such as irritant effects or toxic reactions (e.g., activation of the alternative pathway of complement activation).
Allergic reactions to grain mites and weevils have been described. Ingram et al. (1979) obtained responses to bronchial provocation after farmers inhaled storage mite extract. Warren et al . (1983) Olenchock et al. (1978Olenchock et al. ( , 1980aOlenchock et al. ( , 1980b and Olenchock and Major (1979) have suggested that grain dust induces activation of the alternative complement pathway in man and that the activity appears to vary depending on the type of grain dust exposure. Though a number of potential mechanisms or interactions have been activated  the specific grain dust component that activates the alternative complement pathway is yet to be identified. Moldy hay has been shown to induce activation of the alternative pathway in human (Edwards 1976) and rabbit serum (Edwards et al. 1974).

# Microbial Toxins
Bacteria are ubiquitous in grain dust (Outkiewicz 1978;DeLucca et al.1984;Lacey 1980 exposure to a 1% weevil extract. (Olenchock et al 1978;Wirtz et al 1984b) as well as in settled dust.
DeLucca and Palmgren (1987) reported a seasonal variation in endotoxin concentration in both respirable and settled grain dust. Endotoxin levels in settled dusts were lowest in January and highest in November.
Respirable samples collected in the fall months (September and October)
showed significantly higher levels than those collected on other sampling dates.
Mycotoxins such as aflatoxin are commonly found in grain. They are considered to be carcinogenic as well as hepatotoxic (WHO 1979).
Mycotoxins are products of secondary fungal metabolism; they may be located within the hyphae and spores and may be excreted into the grain (Palmgren and Lee 1986).
Mycotoxins are usually associated with a toxic reaction that occurs as a result of food ingestion. Burg and Shotwell (1984) measured the aflatoxin level of corn dust during harvest at a farm in Georgia, U.S.A., where the level of contamination was known to be high.
Airborne dust samples collected at the front of the combine had an average aflatoxin concentration of 3,850 ng/g, and the operator was exposed to aflatoxin concentrations up to 1,360 ng/g in the combine cab. Sorenson et al. (1981) analyzed samples of airborne grain dust for aflatoxin.
Samples were collected from grain terminals in Duluth, Minnesota, Superior, Wisconsin, and from a corn dumping station in Georgia.
No aflatoxin was detected in the samples from the Superior-Duluth area, but the airborne corn dust from Georgia contained 130 ppb aflatoxin B^. Dashek et al. (1983) later confirmed the absence of aflatoxin in grain from the Superior-Duluth area.

# . RESEARCH NEEDS
Research is needed in the following areas:
(1) Establish the relationship between the recognized health effects of exposure to grain dust and the various constituents of the dust, including the possible effects of pesticides, fumigants, endotoxins, and mycotoxins.
(2) Determine the relationship between the various acute and chronic clinical effects of grain dust exposure.
(3) Identify the importance of the host factor in modifying the workers' response to grain dust exposure.
(4) Determine the relationship between levels of grain dust exposure, smoking, and respiratory disorders.
(5) Determine the role and mechanism of action of grain dust components. (7) Determine the feasibility and efficacy of using small amounts of mineral oil to reduce grain dust in elevators.

# CONCLUSIONS
From epidemiologic studies it is evident that grain dust is associated with respiratory symptoms (i.e., cough, dyspnea, rhinitis, wheezing, and chronic airway obstruction) and nonpulmonary disorders (i.e., conjunctivitis, grain fever, and dermatitis).
Epidemiologic data indicate an excess risk of chronic obstructive and restrictive pulmonary disease in workers with chronic exposure to grain dust, although the mechanism(s) responsible for the lung abnormalities is not known. Worker exposure to grain dust has resulted in increased incidences of chronic bronchitis, asthma and chronic obstructive pulmonary disease. These adverse health effects are likely to result from repetitive acute inflammatory responses to grain dust exposure.
Epidemiologic and animal studies support the hypothesis that immunologic mechanism(s) cause the adverse health effects seen in grain workers.
Although thorough characterization of allergenicity (Type I )
is lacking, it can be concluded that potent immunologic responses evoke inflammatory-mediated responses in airway smooth muscle.
A number of animal studies have been conducted to examine the mechanisms of response to grain dust, but the modeling approaches taken do not study the same physiologic parameter of response. For instance, all human studies evaluate forced expiratory flowrate (FEV, FVC, FEFgg 75^. yet the animal studies cited do not evaluate these parameters.
If they did, it would be possible to compare animal and human responses almost directly.
Because exposure to grain dust results in an immunologic response in some individuals, it is presently impossible to recommend an exposure concentration at which all workers would be protected from adverse health effects. However, reducing exposure to grain dust will decrease exposure to the agent(s) in grain dust that elicit the adverse health effects.

# SUMMARY IN SWEDISH

# ASF.
Dammfria mottagningsgropar for spannmal (Dust-free pits for grain).
Enarson DA, Vedal S, Chan-Yeung M.
Rapid decline in FEV^ in grain handlers. Am Rev Respir Dis 132 (1985)  No. PB87-117172 Washington, DC 1-257 (January 1987) 1-257.
Farant J-P, Moore CF. Dust exposures in the Canadian grain industry. Am Ind Hyg Assoc J 39 (1978) 177-194. Federal Register. 45 FR (No. 33); 10732-10737, February 1980. U.S.
Department of Labor, 29 CFR, Parts 1910, 1918, 1926, and 1928  Grain dust from an elevator and threshing floor was cul tured to determine the types of microorganisms present and the number of organisms per gram of dust. The total microbial count per gram of grain dust ranged from 168,000 to 544,000 in five samples.
(Stepanov 1967) A 10-year study in Poland that measured the viable microorganisms in the air at a variety of worksites   Five grain elevators along the M ississippi River near New Orleans were sampled over a 2-year period to determine thei r bacter ial samples were col breathing zones using personal a ir samplers and s te rile filte rs of 0.45-mm pore size. Twenty dust samples were also collected from various sections of the elevators where grain dusts were deposited. Settled grain dust had popula tions of bacteria that ranged from 1.9 to 53.4 x 10/g (total plate counts). The range was 0.9 to 14.8 x 10/g for gram-positive bacteria and 0.1 to 5.0 x 106/g for gram-negative bacteria.
(DeLucca et a I . 1984) Airborne dust samples were taken from 21 farms of farmers who were undergoing a study to determine the occurrence of symptoms (feb rile and airway-obstructive) and their immune statu s. Twenty-four samples were collected from the breathing zone on a 0.1-m filte r while the subject was handling grain or hay. (Malmberg et a l. 1985)