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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for data waiving:
other:
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:
Unnamed
Year:
1961

Materials and methods

Study type:
clinical case study
Endpoint addressed:
acute toxicity: inhalation
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Acase report of chemical pneumonitis from overexposure of smoke containing zinc chloride in three young airmen has been presented.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Zinc chloride
EC Number:
231-592-0
EC Name:
Zinc chloride
Cas Number:
7646-85-7
IUPAC Name:
zinc dichloride
Details on test material:
- Name of test material (as cited in study report): Smoke containing zinc chloride

Method

Type of population:
occupational
Subjects:
- Number of subjects exposed: Three
- Sex: Male
- Age: 17, 17 and 19 yr, respectively
- Demographic information: United States
- Other: Occupation - Airman
Ethical approval:
not applicable
Route of exposure:
inhalation
Reason of exposure:
unintentional, occupational
Exposure assessment:
measured
Details on exposure:
Over exposure to screening smoke containing zinc chloride in first two cases and 5 min. exposure to smoke in third case.

Analysis of air sample at scene of exposure:
Total particulate matter: 800 mg/m3 (average size 0.1 micron.)
Aluminum chloride: 334.2 mg/m3
Aluminum oxide: 134.6 mg/m3
Zinc chloride: 4075.0 mg/m3
Zinc oxide: 107.6 mg/m3
Examinations:
Routine laboratory examinations; chest X-ray; lung functional parameters; zinc urinary excretion; repeated throat and sputum cultures
Medical treatment:
Case 1:
Treatment 1: Supportive therapy upon initial hospitalization
Treatment 2: Saturated solution of potassium iodide and tetracycline initially upon re-admission with intermittent positive pressure breathing with 100 % oxygen.
Treatment 3: 250 mg of hydrocortisone intravenously over the next 14 h with intermittent positive pressure breathing.
Treatment 4: Positive pressure breathing continued intermittently for the next 5 d and steroid administration in the form of oral prednisolone was continued for 12 d.

Case 2:
Symptomatic treatment with elixir of terpin hydrate and aspirin

Case 3:
Symptomatic treatment with elixir of terpin hydrate and salicylates

Results and discussion

Clinical signs:
Case 1: Burning of the throat, paroxysmal coughing, nausea and retching after exposure. Only abnormal physical findings observed upon hospitalisation 1 h after exposure were increased oral temperature (99.6 ºF) and respiratory rate (26 per min.). Symptoms of coughing and nausea disappeared rapidly on supportive therapy (returned to duty). During the next 48 h, increased dyspnea, feverishness, and malaise noticed (re-admitted). The only abnormal physical finding upon re-admission was an oral temperature of 102.6 ºF.
Case 2: Cough, dyspnea and burning of the throat after exposure. Only abnormal physical findings observed upon hospitalization 1.5 h after exposure were increased oral temperature (101.0 ºF), respiratory rate (38 per min), and mildly injected pharyngeal mucosa. Dyspnea, coughing and mild malaise disappeared within 6 h, but temperature remained elevated (up to 101.6 ºF) and a few rales were heard in the left lung base.
Case 3: Breathlessness, nausea, cough and tightness of the chest, shortly after a 5 min exposure. Only abnormal physical findings observed upon hospitalisation shortly after exposure were tachypnea, medium pitched expiratory ronchi and mild obesity. The temperature was normal and no cyanosis was seen. The tachypnea, nausea, and coughing diminished later on the day of hospitalisation, although the temperature rose to 102 ºF in the absence of any new symptom. Except for an occasional ronchus which was heard only early in the hospitalisation, auscultation and percussion of the chest were non-revealing. Mild malaise, dyspnea and a nonproductive cough with slight fever were present during the first 72 h, but thereafter no symptoms were observed.
Results of examinations:
Case 1:
Routine laboratory results: Normal except for white blood count of 11,700 cells/mm3. The differential white blood count showed a shift to the left and a 6 % eosinophilia.
Chest X-ray: A moderately dense, diffuse infiltrative process throughout both lung fields upon re-admission which progressed afterwards. Initial clearing of the infiltrate was not observed for 11 d, and final resolution was delayed for over one month.
Repeated throat and sputum cultures: Normal flora
Lung functional parameters: Only pulmonary ventilatory abnormality was reduced vital capacity (75.8 % of the predicted normal value), which later increased to 99.6 % of the predicted normal value after convalescence.
24 h zinc urinary excretion: 3.02 mg during early convalescence (upper limits of normal 1.0 mg/d).

Case 2:
Routine laboratory results: Normal except elevated white blood count of 11,800 cells/mm3 and an increase in the % of polymorphonuclear cells on differential count.
Chest X-ray: Normal on second day of hospitalisation. Faint, diffuse infiltrate in the left mid-lung field next day. Increase in the patchy infiltration in the left mid-lung field with a fainter infiltration in the opposite side after 5 d. Radiographic resolution was virtually complete in one month.
Lung functional parameters: Borderline normal vital capacity (82 % of predicted normal levels), and a resting blood oxyhemoglobin saturation of 97.7 % at the height of lung infiltration. After recovery the vital capacity improved to the level of 95 % of predicted normal.
24 h Zinc urinary excretion: 1.74 mg (highest)

Case 3:
Routine laboratory results: Normal
Chest X-ray: Infiltrative process involving the left lower lung field and lingula and mild dorsal scoliosis after 24 h of hospitalization. More generalised extension of the infiltrate after 4 d. Radiographic resolution was virtually complete in 16 d.
Lung functional parameters: The only pulmonary ventilatory function abnormality was reduced vital capacity (65.8 % of the predicted normal value), which improved to 87.3 % after recovery. Resting blood oxyhemoglobin saturation was 94.5 % at the height of the clinical illness.
Repeated throat and sputum cultures: Normal bacterial flora. Absence of cold agglutinins and non-significant titres of respiratory virus agglutinations indicated non-viral pneumonitis.
Effectivity of medical treatment:
Case 1:
Treatment 1: Symptoms of coughing and nausea disappeared rapidly. However, during the next 48 h, increased dyspnea, feverishness, and malaise.
Treatment 2: Only a rare non-productive cough, temperature climbed to 105.2 ºF and developed tachypnea and definite cyanosis. A repeat chest x-ray film after treatment showed progression of infiltrate, definite cyanosis. Intermittent positive pressure breathing showed little effect.
Treatment 3: The temperature dropped 2 ºF within 1 h of this treatment and was normal within 6 h. Tachypnea decreased and color improved concomitantly.
Treatment 4: A low grade tachypnea and sporadic temperature elevations (up to 101.0 ºF) continued for the first 72 h. After this, the patient was essentially asymptomatic. In spite of marked earlier clinical improvement, initial clearing of the infiltrate was not observed for 11 d, and final resolution was delayed for over one month.

Case 2: Only symptomatic treatment was given. Patient was virtually asymptomatic after 4 d.

Case 3. Only symptomatic treatment was given. Patient was virtually asymptomatic after 72 h.
Outcome of incidence:
Case 1: Asymptomatic within a wk but radiographic resolution was delayed over 1 month.

Case 2: Afebrile and asymptomatic after 4 d and radiographic resolution was virtually complete in one month.

Case 3: Virtually asymptomatic after 72 h and radiographic resolution was virtually complete in 16 d.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Not applicable
Executive summary:

Three cases of severe, generalised chemical pneumonitis resulting from exposure to zinc chloride smoke were presented.

In all three of them, the initial symptoms such as nausea, paroxysmal cough, dyspnea and tightness of the chest, disappeared after 6 h of conservative care. However, fever, tachypnea and cyanosis developed later and were particularly noticeable in the first patient. Later, in the course of the illness, coughing was non-productive and infrequent despite the presence of marked parenchymal infiltration on the X-rays. Auscultation of the lungs revealed only occasional ronchi and a few medium rales in one patient despite the density of the pneumonitis suggested by the x-ray film. The depressed vital capacity during the acute illness reverted to normal in all patients.

Two responded to symptomatic treatment while under close observation and one showed rapid progression and demanded the most aggressive measures. Despite the generalised involvement in all three patients and the relatively long persistence of infiltrate on chest x-rays, no lasting effects were detected by analysis of follow-up symptoms, chest x-ray films, ventilatory function tests or blood gas studies.

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