Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
other information
Study period:
No data
Reliability:
other: Not applicable
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure
Author:
Meggs, W.J.; Elsheik, T.; Metzger, W.J.; Albernaz, M. and Bloch, R.M.
Year:
1996
Bibliographic source:
Clinical Toxicology, 34(4):383–396

Materials and methods

Type of sensitisation studied:
respiratory
Study type:
case report
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Biopsies were taken of the nasal mucosa in patients with reactive upper airway dysfunction syndrome and in some cases reactive airways syndrome developing in temporal association with a chlorine dioxide exposure, to see if a histological basis for the persistent rhinitis and sensitivity to chemical irritants could be determined.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Chlorine dioxide
EC Number:
233-162-8
EC Name:
Chlorine dioxide
Cas Number:
10049-04-4
Molecular formula:
ClO2
IUPAC Name:
Chlorine dioxide generated from sodium chlorate and hydrogen peroxide in the presence of a strong acid
Details on test material:
No data

Method

Type of population:
occupational
Subjects:
The clinical evaluation was performed on the patients 5 years after a documented occupational exposure to chlorine dioxide associated with a leak in a pipe of a water purification system.

- Number of subjects exposed: 12 female, 1 male plus control subjects for biopsies
- Age: Mean age 48 years, range 30 to 61
- Known diseases: Healthy
Clinical history:
No data
Controls:
No data
Route of administration:
inhalation
Details on study design:
Examinations: Nasal biopsies were performed by otolaryngologists under local anaesthesia. A biopsy forcep was used to remove tissue from the inferior aspect of the right middle nasal turbinate. Specimens were fixed and stained using haematoxylin and eosin, Giemsa stain or periodic acid Schiff stain. Immunohistochemical studies were performed on paraffin fixed tissue by the use of Avidin-Biotin complex technique. Stains for S-100 protein, substance P VIP, L-26 (a marker for B-lymphocytes) and MT-1 (a marker for T-lymphocytes) were performed. Some biopsies were stained for neutral endopeptidase (NEP).

Results and discussion

Results of examinations:
Clinical signs: Nasal examination was abnormal in all patients and included injection, telangectasia, paleness, cobblestoning, edema and thick mucous. Depression, fatigue and dyspnea were reported.

Examinations: Nasal biopsies obtained from symptomatic subjects showed a spectrum of changes ranging from congestion and edema and mild inflammation to severe inflammation. In the majority of cases there was chronic inflammation with lymphocytes and plasma cells present within the lamina propria. Occasionally lymphocytes infiltrated the overlying mucosa. Reactive epithelial changes were seen in the overlying mucosa and submucosal glands. T-lmphocytes comprised the predominant lymphoid cell population. Nonspecific nuclear staining of mucosal and acinar epithelial cells. Nerve fibres were present mainly in the lamina proparia, mostly concentrated around blood vessels. Fibrosis was seen in two patients with mild inflammation.

Any other information on results incl. tables

No data

Applicant's summary and conclusion

Conclusions:
Inflammation ratings of exposed individuals were higher than for the non-exposed individuals. The study suggests a mechanism by which ongoing low level exposures perpetuate airway inflammation after inducing toxic inhalation.
Executive summary:

In a poisonning accident study, 12 female patients and one male were exposed unintentionally by inhalation to Chlorine dioxide.

The clinical evaluation was performed on the patients 5 years after a documented occupational exposure to chlorine dioxide associated with a leak in a pipe of a water purification system.
Biopsies were taken of the nasal mucosa in patients with reactive upper airway dysfunction syndrome and in some cases reactive airways syndrome developing in temporal association with a chlorine dioxide exposure, to see if a histological basis for the persistent rhinitis and sensitivity to chemical irritants could be determined. Biopsies were also taken from control patients.

Nasal examination was abnormal in all patients and included injection, telangectasia, paleness, cobblestoning, edema and thick mucous. Depression, fatigue and dyspnea were reported.

Nasal biopsies obtained from symptomatic subjects showed a spectrum of changes ranging from congestion and edema and mild inflammation to severe inflammation. In the majority of cases there was chronic inlflammation with lymphocytes and plasma cells present within the lamina propria. Reactive epithelial changes were seen in the overlying mucosa and submucosal glands. Nerve fibres were present mainly in the lamina proparia, mostly concentrated around blood vessels.

Inflammation ratings of exposed individuals were higher than for the non-exposed individuals. The study suggests a mechanism by which ongoing low level exposures perpetuate airway inflammation after inducing toxic inhalation.