Germanium dioxide

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Study type:

cross sectional study

Endpoint addressed:

basic toxicokinetics

repeated dose toxicity: inhalation

Principles of method if other than guideline:

- Principle of test and parameters analysed: cross sectional study in which exposure was characterised by measuring air ad urine concentrations of the element during a typical working week. Health was assessed by a questionnaire, clinical examination, lung function testing, chest radiography and clinical chemistry in serum and urine, including high and low molecular weight urinary proteins.

GLP compliance:

not specified

Specific details on test material used for the study:

the study monitored Ge-levels in air and urine, blood of occupationally exposed workers. No test material used.

Type of population:

occupational

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

STUDY POPULATION:
- Total population :
Exposed group: 75 males out of a total of 80 employees in a plant in which germanium was extracted and worked up in various pyro- and hydrometallurgical processes as a by-product of zinc processing. They were exposed to dusts: 50 to metallic germanium dust, six to germanium metal dust and GeO2, six to GeO2 and GeCl4 dust, and 13 had variable exposures.
Control group: 79 persons served from the same establishment without occupational exposure to germanium. In addition, a group of 11 former employees aged 20-35 years in Germanium production and an equal paired control group were also examined.
- age (arithmetic mean): Control group: 38.8 (27.5-54.6, 6.0); Exposed group 38.8 (27.1-55.0, 6.5)
- sex: male
- Smoker/nonsmoker: Control group: 27/26; Exposed group: 27/24
- Matching criteria: control and exposed group were matched for age, height, weight, and smoking habits

METHOD OF DATA COLLECTION
-personal air sampling was carried out during a whole work shift (about 8h usually from 6.00 to 14.00h) on Monday and Friday; collection of inhalable fraction of the aerosols
-blood, urine samples: collection of urine, blood samples before and after the shift, on the same day as the air sampling

HEALTH EFFECTS STUDIED:
clinical examination, lung function tests, radiographs and clinical chemistry in serum and urine

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: occupational

TYPE OF EXPOSURE MEASUREMENT: Personal air sampling /Biomonitoring (urine) / Biomonitoring blood

Statistical methods:

Statistical analyses were by NCSS procedures (NCSS 6.0 Statistical System for Windows, Washington, DC, USA)
When variables were not normally distributed, analysis was performed on log transformed data and nonparametric tests were used when log transformation did not normalise the distributions.
For stratification analyses, ex-smokers were combined with current smokers. Means were compared by Student’s t test or by analysis of variance (ANOVA) complemented by Dunnett’s multiple comparison test.
Proportions were compared with a ÷2 test. A p value <0.05 (two sided) was considered as the criterion of significance.

Results:

-Germanium in air: the geometric mean exposure of germanium to respirable dust was 0.92µg/m3 (Fridays, GSD 3.98) and 1.07 µg/m3 (Mondays, GSD 3.21), respectively, in the inhalable dust on both days 5.11 µg/m3. In a control group of more than 70 adult men (79) without occupational exposure to germanium, the ambient measurement were below the detection limit (<10ng/m3).
-Germanium in urine : the geometric mean on the last working day of the week (before shift start) was significantly higher at 3.16 µg/g creatinin than at the first day (1.36 µg/g creatinin). On both days (Monday and Friday), the end shift (post shift) was significantly higher than the pre-shift: 4.22 and 4.34 µg/g creatinin, respectively. In a control group of more than 70 adult men (79) without occupational exposure to germanium, the germanium concentration in the urine was below the detection limit (<0.25 µg/g creatinin).
-Lung, liver, and haematological variables were not significantly different between referents and workers exposed to Ge.
-A slightly higher urinary concentration of high molecular weight proteins (albumin and transferrin) was found in workers exposed to Ge, possibly reflecting subclinical glomerular changes.
- No dose-effect relation was found between urinary albumin and exposure as assessed by Ge in air, Ge in urine, or duration of exposure
- No difference between referents and workers exposed to Ge was found for other renal variables (ß2- and α1-microglobulin, RBP, NAG, kallikrein).
- For retired workers: the concentration of albumin and transferrin was higher on average in the exposed than in the control, however, the serum creatinine was lower in the former employees with Ge exposure than in the control group.

Confounding factors:

Considered confounders:
- age, height, weight, and smoking habits
- Other simultaneous exposures: Ge, GeCl4

Strengths and weaknesses:

no information

none

Conclusions:

In summary, minimal changes in glomerular functional parameters were found, but no changes in markers that indicate tubular effects. No significant difference between controls and the exposed group is found for kidney tubular markers.
Evidence of a manifest restriction of renal function did not show.

Executive summary:

This study aimed to assess occupational exposure to inorganic germanium (Ge) in workers from a producing plant, and to assess the health of these workers, with a special focus on respiratory, kidney, and

liver functions.In a cross sectional study of 75 workers exposed to Ge and 79 matched referents, exposure was characterised by measuring air and urine concentrations of the element during a typical working

week, and health was assessed by a questionnaire, clinical examination, lung function testing, chest radiography, and clinical chemistry in serum and urine, including high and low molecular weight urinary proteins.

The airborne concentrations of Ge (inhalable fraction) ranged from 0.03 to 300 μg/m3 , which was reflected by increased urinary excretion of Ge (0.12–200 μg/g creatinine, after the shift at the end of

the working week). Lung, liver, and haematological variables were not significantly different between referents and workers exposed to Ge. A slightly higher urinary concentration of high molecular weight proteins (albumin and transferrin) was found in workers exposed to Ge, possibly reflecting subclinical glomerular changes. No relation was found between the intensity or duration of exposure and the urinary concentration of albumin. No difference between referents and workers exposed to Ge was found for other renal variables.

In conclusion, the measurement of urinary Ge can detect occupational exposure to inorganic Ge and its compounds. It is prudent to recommend the monitoring of renal variables in workers exposed to Ge.

Data source

Reference

Reference Type:

publication

Title:

Determination of germanium in urine and its usefulness for biomonitoring of inhalation exposure to inorganic germanium in the occupational setting

Author:

Roels H and Buchet JP

Year:

2001

Bibliographic source:

J Environ Monit, 2, 67-73

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

basic toxicokinetics

Principles of method if other than guideline:

Investigation of urinary elimination kinetics in workers exposed to airborne dust of either metallic Ge or GeO2

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Germanium dioxide

EC Number:

215-180-8

EC Name:

Germanium dioxide

Cas Number:

1310-53-8

Molecular formula:

GeO2

IUPAC Name:

Germanium dioxide

Test material form:

solid

Specific details on test material used for the study:

the study monitored Ge-levels in air and urine of occupationally exposed workers. No test material used.

Method

Type of population:

occupational

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

STUDY POPULATION: 75 persons from a plant active in the processing of germanium-containing concentrates from the zinc ore processing, and in germanium recovery. These were exposed to dusts: 50 to metallic germanium dust, six to germanium metal dust and GeO2, six to GeO2 and GeCl4 dust, and 13 had variable exposures

METHOD OF DATA COLLECTION
-personal air sampling was carried out during a whole work shift (about 8h usually from 6.00 to 14.00h) on Monday and Friday; collection of inhalable fraction of the aerosols
-urine samples: collection of spot-urine samples before and after the shift, on the same day as the air sampling

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: occupational

TYPE OF EXPOSURE MEASUREMENT: Personal air sampling /Biomonitoring (urine)

Statistical methods:

standard descriptive statistics: for analysis biological and air sampling data.
The distributions of the concentrations of atmospheric and urinary germanium were positively skewed. They were normalised by logarithmic transformation
Parametric tests on Log-transformed values were used (Bonferroni multiple comparison test)
Regression analysis

Results and discussion

Results:

-Germanium in air: the geometric mean exposure of germanium to respirable dust was 0.92µg/m3 (Fridays, GSD 3.98) and 1.07 µg/m3 (Mondays, GSD 3.21), respectively, in the inhalable dust on both days 5.11 µg/m3.
-Germanium in urine : the geometric mean on the last working day of the week (before shift start) was significantly higher at 3.16 µg/g creatinin than at the first day (1.36 µg/g creatinin). On both days (Monday and Friday), the end shift (post shift) was significantly higher than the pre-shift: 4.22 abd 4.34 µg/g creatinin, respectively. In a control group of more than 70 adult men without occupational exposure to germanium, the germanium concentration in the urine was below the detection limit. This suggests that the exposure-free time over the weekend is not sufficient for a complete elimination of germanium.
-The urinary elimination rate of germanium studied in seven workers, was characterised by half-times ranging from 8.2 to 18.1 h (on average 12 h 46 min) showing a fast urinary elimination kinetics for inhalation exposure to dust of metallic Ge and GeO2. The elimination half-times in urine was 12.4 -18.1 h in 3 persons exposed to elemental germanium, and 8.2 - 14.4 h in 4 persons exposed to GeO2 dust.
There was a significant correlation between exposure to inhalable germanium-containing dust and urinary germanium excretion.

Confounding factors:

Considered confounders:
- Smoking: no
- Other simultaneous exposures: Ge, GeCl4

Strengths and weaknesses:

no information

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:

In Roels and Buchet (2001) urine samples were collected at the beginning and at the end of the day shift from workers occupationally exposed to Ge or GeO2 by inhalation. The urinary elimination rate of germanium studied in seven workers, was characterised by half-times ranging from 8.2 to 18.1 h (on average 12 h 46 min). The study did not allow discrimination between the germanium species to which the workers were exposed, but it showed fast urinary elimination kinetics for inhalation exposure to dust of metallic Ge and GeO2.

Executive summary:

This study aimed to assess whether urinary germanium concentration can be used as a biomarker of inhalation exposure to airborne dust from metallic germanium (Ge) or GeO2 in the occupational setting. The investigation included 75 persons from a plant for the processing of germanium-containing concentrates from the zinc ore processing and for germanium recovery. These were exposed to dusts: 50 persons to metallic germanium dust, six to germanium metal dust and GeO2, six to GeO2 and GeCl4 dust, and 13 had variable exposures. On Monday and Friday, the external dust exposure during the working shight with dust collectors was recorded, as well as the internal exposure based on the germanium excretion in the spot urin, which was collected before and after the shift. Seven of the employees also collected urine samples over the weekend until the beginnning of the next working week.

The geometric mean exposure of germanium to respirable dust was 0.92µg/m3 (Fridays, GSD 3.98) and 1.07 µg/m3 (Mondays, GSD 3.21), respectively, in the inhalable dust on both days 5.11 µg/m3.

The germanium content in the urine (pre-shift) was at the beginning of the working week for 10 persons and for six person on the last working day below the detection limit (0.25 µg/l).

The geometric mean on the last working day of the week (before shift start) was significantly higher at 3.16 µg/g creatinin than at the first day (1.36 µg/g creatinin). On both days (Monday and Friday), the end shift (post shift) was significantly higher than the pre-shift: 4.22 abd 4.34 µg/g creatinin, respectively. In a control group of more than 70 adult men without occupational exposure to germanium, the germanium concentration in the urine was below the detection limit. This suggests that the exposure-free time over the weekend is not sufficient for a complete elimination of germanium.

The urinary elimination rate of germanium studied in seven workers, was characterised by half-times ranging from 8.2 to 18.1 h (on average 12 h 46 min). The elimination half-times in urine was 12.4 -18.1 h in 3 persons exposed to elemental germanium, and 8.2 - 14.4 h in 4 persons exposed to GeO2 dust. There was a significant correlation between exposure to inhalable germanium-containing dust and urinary germanium excretion.