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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:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study fulfills basis scintific principles; acceptable restrictions: no constant concentrations in the inhalation chamber, no data about statistical evaluation, additional exposure via smoking, aerosol particle size measurement questionable

Data source

Reference
Reference Type:
publication
Title:
Inhalation of aerosolized ethylene glycol by man
Author:
Wills JH, Coulston F, Harris ES, McChesney EW, Russell JC, Serrone DM
Year:
1974
Bibliographic source:
Clinical Toxicology 7:463–476

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
respiratory irritation
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Controlled whole body inhalation study on systemic and local adverse effects
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no details

Method

Type of population:
other: male prisoners
Subjects:
20 male healthy prisoners in the treatment group and 14 male prisoners in the control group, no further details
Ethical approval:
not specified
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
20 volunteers (19 finished the treatment period) exposed 20-22 h per day for 30 days in a closed room to ethylene glycol aerosol (particle size 1–5 μm, microscopical analysis of slide); the concentration (measured by colorimetrical methods) varied markedly between 0.8 and 75 mg/m3 (the mean daily concentration varied between 3 and 67 mg/m3), giving average weekly concentrations between 17 and 49 mg/m3. In the last week the volunteers were exposed for brief periods to higher concentrations. Controls were held under the same conditions without ethylene exposure in another room.
Examinations:
Blood samples were collected on day 0, 1, 3, 5, 8, 12, 19, 22, 26, and 29 for haematology (hematocrit, hemoglobin, total and differential leucocyte counts, and prothrombin time) and clinical chemistry. Morning urine (daily) and 24h-urine (twice weekly) were analysed. Subjective clinical symptoms recorded. Psychological tests prior to initiation of exposure and at termination.
Medical treatment:
No

Results and discussion

Clinical signs:
No clinical signs at mean daily concentrations of up to 67 mg/m3; in short sessions of unaware higher concentrations the volunteers reported upper respiratory tract irritation which became common at approximately 140 mg/m3; irritation was tolerated for only 15 minutes at 188 mg/m3, 2 minutes at 244 mg/m3, and one or two breaths at 308 mg/m3 due to symptoms like burning sensation in the trachea and cough.
Results of examinations:
No adverse systemic effects in haematology, clinical chemistry and urinalysis. No changes in psychological tests.

Any other information on results incl. tables

Little evidence for absorption of ethylene glycol in blood and urine samples (daily intake of about 0.8 g ethylene glycol calculated for test persons with the highest urinary ethylene glycol concentrations)

Applicant's summary and conclusion

Conclusions:
Exposure of volunteers to concentrations up to 67 mg/m3 for 30 days resulted in no subjective local effects or systemic effects but short-term exposure to >= 140 mg/m3 induced upper respiratory tract irritation.
Executive summary:

In a clinical inhalation study 20 male volunteers (14 non-exposed control) were exposed 20 -22 h per day for 30 days to ethylene glycol aerosol (particle size 1–5 μm). The daily mean concentrations varied between 3 and 67 mg/m3 (highest measured concentration 75 mg/m3). No clinical symptoms were noted and no systemic adverse effects in haematology, clinical chemistry, urinalysis and psychological tests were detected. In short sessions of unaware higher concentrations, however, the volunteers reported upper respiratory tract irritation which became common at approximately 140 mg/m3; irritation was tolerated for only 15 minutes at 188 mg/m3, 2 minutes at 244 mg/m3, and one or two breaths at 308 mg/m3 due to symptoms like burning sensation in the trachea and cough. The authors of a review (ATSDR, 2010) allocated a NOAEL of 26 mg/m3 for this study.

Conclusion: Exposure of volunteers to concentrations up to 67 mg/m3 for 30 days did not result in systemic or subjective local effects but short-term exposure to >= 140 mg/m3 induced upper respiratory tract irritation. Systemic effects in humans are not expected at concentrations inducing irritation of the upper respiratory tract.