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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented and meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Respiratory Function and Immunological Status in Cocoa and Flour Processing Workers
Author:
Zuskin E., Kanceljak B., Schachter E.N., Godnic-Cvar J., Mustajbegovic J. and Budak A.
Year:
1998
Bibliographic source:
American Journal of Industrial Medicine 33:24–32

Materials and methods

Principles of method if other than guideline:
40 female confectionary workers exposed to cocoa dust. Acute and chronic respiratory symptoms were assessed, and immunological studies (including serum IgE, skin-prick and bronchoprovocation testing) conducted.



Detailed occupational history as well as data about smoking habit was recorded in accordance with the following:

Chronic respiratory symptoms were used as follows:
Chronic cough or phlegm: cough and/or phlegm for a minimum of 3 months a year
Chronic bronchitis: cough and phlegm for a minimum of 3 months a year and for not less than 2 successive years
Dyspnea grades: grade 3—shortness of breath when walking with other people at an ordinary pace on level ground; grade 4—shortness of breath when walking at their own pace on level ground.
Occupational asthma: recurring attacks of dyspnea, chest tightness, and pulmonary function impairment of the obstructive type diagnosed by physical examination and spirometric measurements during exposure to dust at or following work (decrease of FEV 1 > 15%) and confirmed by medical records
Ventilatory Capacity

Lung function testing and calibration were performed in accordance with standards for spirometric measurements [Quanjer et al., 1993].

Bronchoprovocation Testing

One milliliter of cocoa extract or normal saline was placed in a Heyer Picolo nebulizer (Carl Heyer GmbH, Bad Ems, Germany) with an air flow of 15 L/min, which nebulized the fluid during inspiration only. Subjects continued to inhale the solution (cocoa extract or a placebo) during normal quiet breathing until the contents of the nebulizer was completely aerosolized.

Immunological Studies

Cocoa and flour extracts were prepared using a standard immunological technique [Sheldon et al., 1957]. Extracts were made with dust collected from the work areas where workers were examined.

Skin prick testing was performed with cocoa dust extract and flour dust extract in a concentration of 1:50 w/v. In addition, workers were skin tested with histamine base (1 mg/ml), with dermatophagoides pteronnysinus (0.2%) as well as with buffer solution used as controls.

Skin prick testing was performed according to the recommendations of Kjellman et al. [1988] using a lancet with a 1 mm tip. Skin reactions were read after 20 minutes. A test was considered positive if the diameter of the observed wheal was 3 mm greater than that of the buffer solution.

The serum level of total IgE antibody was measured by the PRIST method (Pharmacia Diagnostics, AB, Upsala, Sweden) using a direct radioimmunological ‘‘sandwich’’ technique based on a paper disc as a solid phase.

Specific IgE (RAST) was determined by radioimmunoassay (Phadebas RAST, Pharmacia Diagnostics AB, Uppsala, Sweden), and expressed as PRU/ml (Phadebas Rast Units/ml).

Environmental Measurements

Dust concentrations in the work environment were measured by a two-stage Hexhlet apparatus (Casella, London, UK),

Total and respirable dust particles was collected by the air flow of 60 L/min, (dust samples were taken during an 8-hour work shift in the areas where workers were working). Five samples of dust were collected in the cocoa processing areas and six samples were collected in the flour processing area. These samples were collected over the entire work shift.
GLP compliance:
not specified
Test type:
other: Occupational: End point addressed is Sensitization -inhalation

Test material

Constituent 1
Reference substance name:
cocoa and flour
IUPAC Name:
cocoa and flour
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): cocoa and flour
- Substance type: confectionery industry raw material
- Physical state: Powder (dust)
- Analytical purity: no data available
- Impurities (identity and concentrations): not applicable
- Composition of test material, percentage of components: no data available
- Isomers composition: not applicable
- Purity test date: no data available
- Lot/batch No.: no data available
- Expiration date of the lot/batch: no data available
- Stability under test conditions: no data available
- Storage condition of test material: no data available
- Other: no data available

Test animals

Species:
other: 93 workers from a confectionery plant in Zagreb, Croatia.
Sex:
female

Administration / exposure

Route of administration:
other: airborne
Details on inhalation exposure:
TYPE OF EXPOSURE: Occupational

EXPOSURE PERIOD: mean duration was 8 hour work shifts for an average of 11 years for cocoa workers and 14 years for flour workers.

POST EXPOSURE PERIOD: No data available

Description/ delineation of exposure groups / categories: No data available

Positive control [only required for robust summary]

Immunological Studies

Workers were skin tested with histamine base (1 mg/ml), and Dermatophagoides pteronnysinus (0.2%) as a control.



Duration of exposure:
ca. 8 h
Remarks on duration:
8 hours/day, 5 days/week for an average of 11 years (1 to 25 years)
Concentrations:
Dust level of 9.1 mg/m3 (2 to 16 mg/m3) of which 2.1 mg/m3 (0.9 to 3.5 mg/m3) was respirable
Control animals:
other: 65 unexposed control workers in the same industry
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): exposure to cocoa dust is linked with various acute and chronic respiratory and allergic symptoms, and eye and respiratory irritation

METHOD OF DATA COLLECTION
- Type: Questionnaire (acute and chronic symptoms), clinical tests (ventilatory function, bronchoprovocation, skin prick and IgE levels)
- Details: chronic respiratory symptoms were recorded for confectionary and control workers using the British Medical Research Council questionnaire for respiratory disease, with additional questions on occupational asthma. Acute symptoms were also recorded, but not in controls. Please see “any other information on materials and methods incl. tables” for details on clinical tests

STUDY PERIOD: no data

SETTING: Croatian plant involved in the production of confectionary

STUDY POPULATION
- Total population (Total no. of persons: 40 cocoa and 53 flour processing workers employed as packers in a confectionary industry asd in 65 unexposed control workers in the same industry): - Selection criteria: n/a
- Total number of subjects participating in study: 40 workers exposed to cocoa dust (and not flour dust; 53 workers exposed to flour dust, but not cocoa dust were also assessed)
- Sex/age/race: Female/32 (mean, range 19-51)/no data
- Smoker/nonsmoker: 6 regular mild smokers (smoking on average 10 cigarettes per day, or less)
- Total number of subjects at end of study: 40
- Matching criteria: n/a (study had no selection criteria)
- Other: individuals had been employed at the plant for an average of 11 years (range 1-25 years)

COMPARISON POPULATION
- Type: Control or reference group (for chronic respiratory symptoms); other comparison group: predicted values for the Croatian population (for ventilatory capacity).
- Details: chronic respiratory symptoms: From a group of 85 unexposed female workers employed by the same plant packing these confectionary products, 65 were available for study as a control group for the prevalence of chronic respiratory symptoms. The age, smoking habits and duration of employment were not significantly different from the confectionary workers.
Predicted values of ventilatory capacity for the Croatian population (including farmers and industrial workers) were from: Mustajbegovic (1992). Ventilatory capacity in farmers, doctoral thesis, Medical School University of Zagreb, Zagreb.

HEALTH EFFECTS STUDIED
- Disease(s): various symptoms (acute effects: cough, dyspnea, throat irritation or dryness, eye irritation, nose dryness or bleeding, headache; chronic effects: chronic cough or phlegm, chronic bronchitis, dyspnea grades 3 and 4, occupational asthma, nasal catarrh, sinusitis)
- ICD No.: no data
- Year of ICD revision: no data
- Diagnostic procedure: no data
- Other health effects: ventilatory capacity; bronchoprovocation testing; skin prick reactions; serum total IgE

OTHER DESCRIPTIVE INFORMATION ABOUT STUDY: The following definitions were used for chronic respiratory symptoms:
Chronic cough or phlegm: “cough and/or phlegm for a minimum of 3 months a year”
Chronic bronchitis: “cough and phlegm for a minimum of 3 months a year and for not less than 2 successive years”
Dyspnea grade 3: “shortness of breath when walking with other people at an ordinary pace on level ground”
Dyspnea grade 4: “shortness of breath when walking at their own pace on level ground”
Occupational asthma: recurring attacks of dyspnea, chest tightness, and pulmonary function impairment of the obstructive type diagnosed by physical examination and spirometric measurements during exposure to dust at or following work (decrease of FEV1 > 15%) and confirmed by medical records”
FEV1 is the forced expiratory volume in one second.
Statistics:
The results of ventilatory capacity measurements were analyzed using the paired t-test to compare across-shift changes. A paired t-test was used to compare baseline lung function (measured before the shift) with predicted values. The chi-square test and Fisher’s exact test were used for testing differences in prevalence data of respiratory symptoms between groups; p<0.05 was considered statistically significant.

HYPOTHESIS TESTED: To investigate the respiratory function and immunological status in cocoa and flour processing workers.

STUDY PERIOD: No data available

STUDY POPULATION: 93 workers from a confectionery plant in Zagreb, Croatia.

HEATLTH EFFECTS STUDIED: Sensitization

Results and discussion

Other findings:








Ventilatory Capacity

Tables III presents across-shift differences and chronic changes in ventilatory capacity among the cocoa and flour workers. There were statistically significant reductions across the work shift for all ventilatory capacity tests. These were particularly pronounced for FEF50 (cocoa: - 17.5%; flour:-21.6%) and FEF75 (cocoa: - 22.6%; flour: - 26.7%).
Comparison of the actual measured with predicted ventilatory capacity parameters revealed significantly lower than predicted FEF50 and FEF75 in cocoa and flour workers. There were no differences in across-shift reductions in ventilator capacity measurements noted for these workers by specific skin tests: cocoa workers (positive skin tests FVC - 2.8%, FEV1 - 9.1%, FEF50 - 18.7%, FEF 75 - 23.7%; negative skin tests: FVC - 2.1%, FEV1 - 7.9%, FEF50 - 16.4%, FEF75 - 19.7%;); flour workers (positive skin tests FVC - 4.9%, FEV1 - 10.5%, FEF50 - 23.1%, FEF75 - 28.3%; negative skin tests FVC - 2.5%, FEV1 - 7.8%, FEF50 - 19.3%, FEF75 - 23.2%). Analysis of the individual ventilatory capacity data demonstrated that among exposed workers FEF50 was, 70% of predicted in four (10.0%) cocoa workers and in four (8.9%) flour workers. FEF75 was lower than 70% of predicted in six (15.0%) cocoa workers and in eight (15.1%) flour workers.




Effect of Disodium Cromoglycate (DSCG)

In the nine workers selected for this study, the control across-shift difference in FEF50 varied from - 25% to -29% and for FEF75, from - 26% to - 34%. There was a significant decrease (p< 0.05) in the magnitude of these across-shift reductions when the workers were pre-treated with DSCG. For the FEF50 across-shift values varied from - 5% to - 9% and for the FEF75, across shift values varied from - 10% to - 14% (p< 0.05).

Bronchoprovocation Testing

Table IV shows the results of bronchoprovocation testing with cocoa extract in three cocoa workers. Two workers demonstrated consistent immediate decreases in FEV1 ranging up to - 15.2% and up to - 25.3% for FEF25 -75. The third worker did not experience reductions of FEV1 or FEF 25 -75 following cocoa dust extract inhalation. None of these three workers reacted to the inhalation of the buffer control solution. There were no late reactions noted at 24 hours after challenge testing.
Bronchoprovocation testing with wheat flour dust in two flour workers showed a marked decrease in FEV1; the largest decrease occurred 10 minutes after exposure in the three subjects. The maximal immediate FEV1 decrease (as a percent of baseline) following exposure to wheat flour was 55.6% and 40.5% following rye exposure. There were mild late reactions demonstrated in all three tested subjects.



Immunological Studies

The prevalence of immediate skin tests sensitivity to cocoa or flour dust extract in exposed and in control workers are presented in Figure 2 below.










Significantly higher prevalence’s of positive skin tests were seen in the 93 exposed workers for cocoa (56/93; 60.2%) than for flour (24/93; 25.8%) (p<0.01). The prevalence’s of positive skin tests to cocoa and flour were significantly higher in exposed workers than in control workers (cocoa: 3/65; 4.6% and flour: 8/65; 12.3%) (p<0.01). All tested workers reacted to histamine and none reacted to the buffer control solution.
A separate analysis of workers with positive skin tests by exposure group demonstrated that among cocoa workers, 29/40 (72.5%) reacted to cocoa and 4/40 (12.5%) to flour. Among the 53 flour workers, 27 (50.9%) had a positive skin test to cocoa and 19 (35.8%) to flour. Cocoa workers had significantly higher prevalence’s of positive skin tests to cocoa than did flour workers (p< 0.05); flour workers had a significantly higher prevalence’s of positive skin tests to flour than cocoa workers (p< 0.05). An increased total serum IgE level was found in 7 (17.5%) of the cocoa workers and in 10 (18.7%) of the flour workers. None of the control group workers had increased serum levels of IgE. All exposed workers with increased serum IgE level had positive skin reactions to cocoa or flour
dust extract. The two cocoa workers and the three flour workers with occupational asthma had positive skin tests to cocoa or flour dust extract accompanied by increased serum IgE level
(range: 260–470 kU/L).

Environmental Measurements

In the cocoa processing area, the mean total dust level was 9.1 mg/m3 (range: 2–16 mg/m3) and the mean respirable fraction was 2.1 mg/m3 (range: 0.9–3.5 mg/m3). In the flour processing area, the mean total dust was 12.3 mg/m3 (range: 2.4–17.1 mg/m3) and the mean respirable fraction was 1.9 mg/m3 (range: 0.5–2.7 mg/m3). These measured mean total and respirable dust concentrations were higher than those allowed by the Croatian Federal standards for organic dust (total dust: 3 mg/m3; respirable dust fraction: 1mg/m 3). Correlation with health parameters were not found, presumably because workers changed jobs in the factory frequently.

The data demonstrate that work with cocoa and flour dust may be associated with acute and chronic respiratory symptoms, including occupational asthma. Taytard et al. [1988] described a high incidence of cough and chronic bronchitis as well as hypersensitivity in flour workers. Similarly, Jarvinen et al. [1979] and El Karim et al. [1986] reported chronic bronchitis, chronic productive cough, chest tightness, and bronchial asthma in workers exposed to grain and flour dust.

Occupational allergy (asthma and rhinitis) was seen in 58% of workers occupationally exposed to flour as reported by Debelic and Sarvan [1982]. A case of baker’s asthma due to wheat flour was reported by Walker et al. [1989]. In this study, occupational asthma was determined in 2 (5%) of the cocoa workers and in 3 (5.7%) of the flour workers. Their symptoms started 2–3 years after theiremployment in the confectionery industry. Brisman and Jarvholm [1995] noted that Swedish bakers exposed over a 10-year period have approximately double the risk of developing asthma than the general population. Musk et al.[1989] reported chest tightness and nasal symptoms in 38% of British bakery workers. Interestingly, in this study a large number of cocoa and flour workers complained of upper respiratory symptoms such as acute dryness of the nose (cocoa workers: 45.0%; flour workers: 47.2%). Ventilatory capacity testing in the workers demonstrated acute and chronic reductions following exposure to cocoa and flour dust. These changes were particularly pronounced for FEF50 and FEF75, suggesting obstructive changes located in smaller airways. These data are similar to those found in industrial workers exposed to other dusts, such as those associated with the processing of coffee, tea, spices, soy, and confectionery (Zuskin et al., 1981, 1985, 1988, 1991, 1994). Across-shift changes averaging nearly 10% in FEV1 were described for this group of workers. These are significant changes, since previous work by Ghio et al. [1991] demonstrated that unexposed blue collar workers do not decrease their lung function (FEV 1) by 2–3% over a shift. Similarly, Zuskin et al. [1994, 1996] demonstrated that unexposed (control) workers demonstrated even a slight across-shift increase of FVC, FEV1, FEF50, and FEF75. Confectionery workers in the study with more marked across-shift changes are not more likely to have positive skin tests or more symptoms than are their less reactive co-workers. Pugliese [1973] and Schultze-Werninghaus and Schwarting [1974] described the inhibitory effect of DSCG in preventing FEV1 decreases in bakers with occupational asthma. In the study, five cocoa workers and six flour workers with large-across shift FEF50 reductions (range: 25–29%) and FEF75 reductions (range: 26–34%) inhaled DSCG before their work shift. In all tested workers, the reductions were considerably decreased by the DSCG prophylaxis: FEF50: range 5–8%; FEF25 : range 7–11%. Such data suggest that mast cell mediator release may play an important role in the bronchoconstrictor effect on airways in cocoa and flour dust exposure. Bronchoprovocation testing in symptomatic workers demonstrated hyperreactivity to cocoa dust extract in two out of three workers with positive skin tests to cocoa dust allergen. Bronchoprovocation with flour dust (wheat and rye) in three workers caused a marked reduction in FEF25-75, possibly related to small airway obstruction. Mild late reactions were recorded in all three workers tested with flour. The two workers responding to cocoa extract did not exhibit late reactions. Palczynski et al. [1996] indicated that in patients with bronchial asthma, both neutrophils and eosinophils take part in allergic reaction in the mucosa following bronchial challenge with flour. Hendrick et al. [1976] described that bronchial provocation tests with occupational exposure to flour precipitated dual asthmatic reactions accompanied by rhinitis. Skin tests with aqueous extracts of flour produced positive immediate reactions in these workers. These findings suggest that specific bronchoprovocation may play a role in identifying workers at risk for occupational asthma due to cocoa and flour. Immunological testing in the workers demonstrated that significantly more of the exposed workers demonstrated positive skin tests to cocoa or flour dust extract than did control workers. Zotti et al. [1994] described atopy in 23.4% of bakers. In their study, many workers complained of work-related asthma, rhinoconjuctivitis, and chronic bronchitis. Skin sensitization to occupational allergens was significantly associated with atopy, smoking habit, and work seniority. Zeitz [1990] suggested that the main mechanism for occupational asthma in bakers is an IgE-mediated immune response. Chocolate allergy was described by Maslansky and Wein [1971]. The authors reported that 2% of allergic individuals manifested specific allergic symptoms after eating chocolate. In this study, 17 of 93 exposed workers (18.3%), including five with occupational asthma, had increased serum IgE level. Increased levels were found only in those with positive skin prick tests to cocoa or flour dust extract. As in the previous study [Zuskin et al., 1994] of confectionery workers, we have demonstrated frequent respiratory findings in workers exposed to the food products used in this industry. The current study extends the previous findings in that the workers in the present investigation had frequent and consistent exposure to cocoa and flour. These workers had more positive specific skin tests than those in a previous study and these skin tests correlated with the finding of occupational asthma (but not with nonspecific reactivity to these dusts). Interestingly, significant protection from across-shift changes was obtained using DSCG pre-treatment in both studies. This study of cocoa and flour workers suggests frequent lung function and immunological abnormalities in this group. However, despite a high prevalence of positive skin tests in these workers, airway responsiveness was not predicted by skin tests results. In contrast, the five workers with occupational asthma did have positive immunologic findings and DSCG appeared to be effective in protecting workers. These findings suggest that immunologic markers may help to identify workers at risk for occupational asthma caused by cocoa and flour, but not those workers who develop nonspecific reactivity to these dusts. It is most likely that the high dust levels in this plant account for the nonspecific airway findings. We suggest that both environmental control measures and medical surveillance including immunologic testing would be indicated in this industry.

Any other information on results incl. tables

Ventilatory capacity:

The ventilatory capacity of the 40 workers was assessed by recording at least three maximum expiratory flow-volume (MEFV) curves per subject (with the “best” value used), from the forced vital capacity (FVC), 1-second forced expiratory volume (FEV1) and maximum flow rates at 50% and 25% of the vital capacity (FEF50and FEF75). Readings were taken before and after a Monday daytime shift, and compared to predicted values for the Croatian population (ventilatory capacity readings were not taken concurrently from control workers).

 

Skin prick tests:

Skin prick tests were performed with specific occupational and common allergens. Tests were performed on the 40 cocoa workers, the 65 controls, and 53 flour workers, apparently not exposed to cocoa dust. Cocoa dust extract was tested at 2%, with reactions read after 20 minutes. Tests were considered positive if the wheal diameter was at least 3 mm greater than that of the negative control (buffer solution).

 

Serum IgE:

Serum total IgE was measured, with specific IgE determined by radioallergosorbent test (RAST). Total serum IgE below 125 kU/L, and serum specific IgE below 0.035 PRU/ml were considered normal.

 

Bronchoprovocation tests:

Bronchoprovocation testing was performed on three cocoa workers with suspected occupational asthma (with “respiratory symptoms”, a positive skin prick test reaction to cocoa dust extract and an increased total serum IgE level). FEV1, FEF25and FEF75were measured 1, 10 and 20 minutes after the inhalation of 1ml of nebulised cocoa dust extract [no further details] or saline. A drop in baseline FEV1of at least 15% was considered significant.

Applicant's summary and conclusion

Conclusions:
Working in an environment with total dust level in the cocoa processing area in the range 2-16mg/m3 (mean level of 9.1.mg/m3) was linked in a sub-section of long-term confectionery factory workers to a significantly increased incidence of a number of chronic respiratory symptoms, significant reductions in ventilatory capacity, and two cases of occupational asthma. The mean respirable fraction was 2.1 mg/m3 (range 0.9-3.5 mg/m3). Both the mean total and respirable dust concentrations were several times higher than those allowed by the Croatian Federal Standards for organic dust (total dust: 3mg/m3, respirable dust fraction: 1mg/m3).

Overall, this data suggests that that there were relatively few cases of respiratory effects among workers repeatedly inhaling high levels of cocoa and dusts. The symptoms were consistent with the inhalation of any organic dust and not necessarily a specific effect of cocoa. [INDCRESA WORKERS EXPOSURE-Cocoa powder summary and communication to the Cocoa Consortium, 2012].

Executive summary:

A number of health effects were assessed in 40 female confectionary workers occupationally exposed to cocoa dust levels at about 9.1 mg/m3(of which about 2.1 mg/m3was respirable). On average, workers had been employed at the plant for 11 years.(range 1-25 years)

 

A questionnaire was used to assess the presence of chronic respiratory symptoms (chronic cough, phlegm and bronchitis, nasal catarrh, sinusitis, shortness of breath (dyspnea grades 3 and 4), and occupational asthma) in exposed workers, and in 65 control workers from a region of the plant not exposed to cocoa dust. Acute symptoms (including cough, headache and eye and throat irritation) were assessed only in exposed workers (i.e. the significance of results could not be assessed), with high incidences reported e.g. for cough (57.5%) and eye irritation (50%). For all chronic respiratory symptoms, except occupational asthma, incidence was significantly higher in the exposed workers, compared to controls.

 

Clinical testing was used to assess the ventilatory capacity of the 40 exposed workers, before and after a daytime shift. Forced vital capacity (FVC), 1-second forced expiratory volume (FEV1) and maximum flow rates at 50% and 25% of the vital capacity (FEF50and FEF75) were measured. Results were compared to predicted values for the Croatian population. Significant reductions in ventilatory capacity were seen after the work shift. Compared to predicted values, FEV1, FEF50and FEF75were significantly reduced in exposed workers [it is not clear whether ventilatory capacity was compared to predicted values before, or after, the shift].

 

Skin prick testing with cocoa dust extract (at 2%) was performed on the 40 cocoa dust-exposed workers, as well as 53 flour dust workers, apparently not exposed to cocoa dust, and the 65 control workers. Reactions were read after 20 minutes. 72.5% of the cocoa workers and 50.9% of the flour workers gave positive skin reactions to cocoa dust extract, compared to 4.6% of control workers.

 

Serum total IgE was measured in control and exposed workers, and was significantly raised in 17.5% of cocoa workers, and none of the control workers. Apparently serum specific IgE levels were determined by radioallergosorbent testing (RAST), but no results for this are reported.

 

Three cocoa dust workers exhibited respiratory symptoms, a positive skin prick test for cocoa dust extract, and increased total serum IgE. These individuals were subject to bronchoprovocation testing. FEV1, FEF25and FEF75were measured 1, 10 and 20 minutes after the inhalation of cocoa dust extract.Two of the tested workers demonstrated consistent immediate decreases in FEV1of up to -15.2%, and FEF25-75­of up to -25.3%.These were considered to be two cases of occupational asthma due to cocoa dust.

 

This study linked occupational exposure to cocoa dust with significant increases in the incidence of chronic respiratory symptoms, and significant reductions in ventilatory capacityin some workers exposed long-term to cocoa and/or other organic dusts.[i1] Two cases of occupational asthma due to cocoa dust were identified using skin prick, bronchoprovocation and skin prick testing..

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