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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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, limitations in study design, nevertheless results are considered sufficiently robust for DNEL derivation.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Experimental human exposure to tetrachloroethylene
Author:
Stewart RD, Baretta ED, Dodd HC and Torkelson TR
Year:
1970
Bibliographic source:
Arch Environ Health. 20; 224-229.

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
eye irritation
respiratory irritation
neurotoxicity
Principles of method if other than guideline:
study with human volunteers
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tetrachloroethylene- Analytical purity: 99.6%

Method

Type of population:
other: human volunteers
Subjects:
- Number of subjects exposed: 17- Sex: 16 males (technical engineers) and 1 female (nurse)- Age: 24-64 yearsEach subject had been under careful medical suveillance for six years and each was given a complete medical examination immediately prior to the series of exposure.
Ethical approval:
not specified
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
100 ppm (690 mg/m3) tetrachloroethylene for 7 hours.A series of five experimental exposures of seven hours each were conducted on consecutive days to simulate a work week. In each of the five experiments groups of 6-8 subjects were exposed. 5 male subjects were repeatedly exposed on each of the five days.Exposure chamber: An interior room measuring 41x6x7.5 feet high served as the exposure chamber. The incoming air was passed through activatedcharcoal filters and then humidified prior to entering the chamber. A dual-action syringe pump was used to introduce the solvent into the chamber's recirculation system, a series of inlet and outlet duets spanning the length of the chamber. The system was capable of maintaining a relatively constant atmospheric concentration of solvent-contaminated air (in 5 experiments the mean value was 101 ppm (SD 9.8, range 62-137)).The concentration of the tetrachloroethylene in the chamber atmosphere was recorded continuously by an infrared spectrometer equipped with a 10-meter path-length gas cell which was continuously flushed with air drawn from the chamber through a 1/4-inch inside diameter saran tube. For added assurance, the chamber atmosphere was also monitored by a Dow-modified Davis Halide meter with a continuous recorder and a gas chromatograph equipped with a hydrogen flame detector. Calibration standards of tetrachloroethylene in air were prepared in 70-liter bags made of saran and were analysed by the three analytical methods before, at midpoint, and at the conclusion of each experiment.
Examinations:
Pre-exposure: Each subject was given a repeat physical examination one hour before entering the exposure chamber. The blood pressure, pulse rate, respiratory rate, timed vital capacity, tidal volume, and temperature was measured. A pre-exposure venous blood sample was obtained for heamatology analysis. A complete urinalysis and a 24-hour urine collection were obtained. Alveolar breath samples for tetrachloroethylene analysis completed the pre-exposure evaluation.During exposure: Subjective responses of each individual were recorded every 60 minutes. At these times a neurological examination which included a modified Romberg test (subject balancing on one foot with his eyes closed and with both arms at his side), heel-to-toe, and finger-to-nose test were performed. After five hours of exposure, the Crawford manual dexterity tests and the Flannagan coordination, arithmetic, and inspection tests were performed. A two-hour postlunch blood glucose was obtained on each subject. After six hours of exposure on the fourth and fifth days, an electrocardiogram was obtained on each of the five chronically exposed subjects. At this time, their visual acuity and depth perception were measured. Subjects were queried every hour as to whether they were experiencing light-headedness, headache, eye, nose and throat irritation, speech difficulty, sleepiness, nausea, abdominal pain, or chest discomfort. After exposure: The subjects collected serial samples of alveolar breath for tetrachloroethylene analysis. 16 and 72 hours after exposure the urinalysis, hematology and blood chemistry studies were repeated. 24-hors postexposure urine specimens were collected for analysis. Analysis of alveolar breath: the breath samples were collected in both 50 ml glass pipettes and 7-liter bags made of saran. The samples were analyzed by gas chromatography within 16 hours following collection. These included the samples collected by the individuals at home in the postexposure period. The breath samples collected in the bags were obtained immediately following the pipette breath collections and were analyzed by an infrared spectrometer within two hours.

Results and discussion

Clinical signs:
Subjective effects including headache, sleepiness, difficulty with speech and light-headedness were each affirmed in 25-40% of the subjects. Mild eye and nasal irritation developed within the first 2 hours and usually subsided before the end of the 7 hour exposure. Two of 5 subjects who were given 7-hour exposures on 5 consecutive days consistently reported mild eye irritation in this study. Subjects repeatedly exposed had fewer subjective complaints.A decreased balancing ability (modified Romberg test) was obtained in 4 subjects, and 3 of these gave a normal test when it was repeated. All of the other clinical tests (Crawford, Flannagan, neurological and pulmonary) were unequivocally normal. All of the laboratory tests performed on the blood and urine specimens were completely within the range of normal for each of the subjects.
Results of examinations:
Tetrachloroethylene concentrations in alveolar air samples showed an exponential decrease with time, with a low level still being present 16 hours after the end of the exposure. During consecutive exposures there was a slight but definite accumulation, with exhaled breath concentrations approaching but never reaching a state of equilibrium. Following the fifth exposure there was a prolonged exponential decay of tetrachloroethylene levels in the exhaled air, with mean concentrations of about 8, 5, 3, 2 and 1 ppm recorded for 15, 71, 111, 231 and 303 hours respectively.Subjective effects including headache, sleepiness, difficulty with speech and light-headedness were each affirmed in 25-40% of the subjects. Mild eye and nasal irritation developed within the first 2 hours and usually subsided before the end of the 7 hour exposure. Two of 5 subjects who were given 7-hour exposures on 5 consecutive days consistently reported mild eye irritation in this study. Subjects repeatedly exposed had fewer subjective complaints.A decreased balancing ability (modified Romberg test) was obtained in 4 subjects, and 3 of these gave a normal test when it was repeated. All of the other clinical tests (Crawford, Flannagan, neurological and pulmonary) were unequivocally normal. All of the laboratory tests performed on the blood and urine specimens were completely within the range of normal for each of the subjects.Some volunteers exposed to 100 ppm (690 mg/m3) tetrachloroethylene complained of mild eye irritation that developed within the first 2 hours andusually subsided before the end of the 7-hour exposure. Two of 5 subjects who were given 7-hour exposures on 5 consecutive days consistently reported mild eye irritation in this study.In the same volunteer study conducted at 100 ppm (690 mg/m3) tetrachloroethylene, some subjects complained of mild nasal irritation that developed within the first 2 hours and usually subsided before the end of the 7-hour exposure.

Any other information on results incl. tables

Although there were no control exposures in this study, only one concentration was tested and the reported symptoms are rather unspecific, an incidence of 40% for subjective CNS effects is too high to be considered a chance finding.

Applicant's summary and conclusion