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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
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Occupational exposure to indium: what does biomonitoring tell us?
Author:
Hoet P, De Graef E, Swennen B, Seminck T, Yakoub Y, Deumer G, Haufroid V and Lison D.
Year:
2012
Bibliographic source:
Toxicology Letters 213(1):122-128

Materials and methods

Study type:
cross sectional study
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
Investigation of the kinetics of indium in urine (In-U) and plasma (In-Pl) in workers manufacturing In ingots and mainly exposed to hardly water-soluble In compounds
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Zinc chloride
EC Number:
231-592-0
EC Name:
Zinc chloride
Cas Number:
7646-85-7
Molecular formula:
ZnCl2
IUPAC Name:
Zinc dichloride
Details on test material:
- Name of test material (as cited in study report): indium metal

Method

Type of population:
occupational
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
STUDY POPULATION: indium ingot production plant where workers are mainly exposed to In2O3, but also to In(OH)3, indium metal and to a certain extent to indium chloride [InCl3]
E: 9 (M) current workers (mean age: 43; range: 22-56 years) , seniority: 1month to 12 years (mean: 5.7 years) + 5 (M) former workers (mean age: 50; range: 46-53 years) with last exposure dated from 3.5 up to 14 years
C: 20 subjects from the laboratory not occupationally exposed to In

METHOD OF DATA COLLECTION
-personal breathing zone air was collected throughout the work shift on Monday and Friday; collection of inhalable fraction of the aerosols
-blood and urine samples: collection before and after the shift, on the same day as the air sampling and on pre-shift the next Monday after a non-working weekend. Former workers: 1 sampling time : Monday morning
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: occupational

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

Statistical methods:
standard descriptive statistics: for analysis demographic characteristics, biological and air sampling data.
Most variables showed a skewed distribution and were Logtransformed. Parametric tests on Log-transformed values were used. For concentrations below the LOQ, a value of half the LOQ was assigned.
-Student’s unpaired t-test on Log values: for comparison between exposed workers and unexposed controls
-In levels in pre- and post-shift samples were compared at the individual level using paired t-tests on Log values and at the group
level using unpaired t-test on Log values.
-Data were analysed by simple linear regression on Log values. Two-tailed p-values < 0.05 were considered to be of statistical significance

Results and discussion

Results:
-indium in air: Air (µg/m3) AM (range): 190 (10-1030), median: 55
-indium in plasma: Serum/plasma (µg/L) AM (range):
current workers: 5.411(0.32-12.61)
former workers: 1.72 (<0.08-4.38)
controls: <0.08
-indium in urine: urine (µg/L) AM (range):
current workers: 1.69 (0.13-8.68)
former workers: 0.71 (<0.05-3.02)
controls: <0.05
--> Higher In-Pl and In-U concentrations in both current and former workers compared with controls
-In-Pl and In-U highly correlated but no correlation found between In-air and In-Pl or In-U
-normalizing In urinary concentration for creatinin concentration reduced inter- and intra-variability of the levels
-stronger correlations between In-Pl and In-Ucreat (r=0.8052) as compared with In-U unadj (r=0.5935)
-Neither In-Pl nor In-Ucreat increased significantly during the day of the week; In-Pl remained remarkably stable and displayed a much lower intraindividual variability compared with In-Ucreat
-several years after withdrawal from occupational exposure, biological levels were still higher than in controls; no clear relationship between current concentration of In-air and In-Pl or In-U indicating these indices do not reflect recent exposure
Confounding factors:
Considered confounders:
- Smoking: no
- Other simultaneous exposures: In2O3, in(OH)3, InCl3
Strengths and weaknesses:
no information

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
This study shows that in workers exposed to hardly soluble In compounds, In-U and In-Pl are very sensitive to detect exposure and mainly reflect long-term exposure. In-Pl levels are particularly stable for a given individual. In-U might be more influenced than In-Pl by recent exposure. Both parameters remained high years after withdrawal from exposure, indicating a possible endogenous exposure and a prolonged risk of pulmonary and systemic diseases even after work exposure has ceased.
Executive summary:

This study aimed at investigating the kinetics of indium in urine (In-U) and plasma (In-Pl) in workers manufacturing In ingots and mainly exposed to hardly water-soluble In compounds. All nine workers from the In department of a large metallurgical concern participated in the study as well as 5 retired workers and 20 controls.

Personal breathing zone air was collected throughout the work shift on Monday and Friday. Blood and urine samples were collected, before and after the shift, on the same day as the air sampling and on preshift the next Monday after a non-working week-end.

Higher In-Pl and In-U concentrations were found in both current and former workers compared with controls. Both biological parameters were highly correlated but no correlation was found between In-air and In-Pl or In-U. Normalizing In-U by the urinary creatinine concentration reduced the inter- and intra-individual variability. In-Pl remained remarkably stable along the working week . Neither In-U nor In-Pl significantly increased during the day or the week. A week-end without occupational exposure was not sufficient to reach the background In-Pl and In-U levels measured in controls. The results of the experimental investigations confirmed the hypothesis that inhalation of hardly soluble In compounds may cause accumulation of In in the body leading to a prolonged “endogenous exposure” from both a lung depot of “insoluble” particles that are progressively absorbed and from a retention depot in other internal organs.

In conclusion: This study shows that in workers exposed to hardly soluble In compounds, In-U and In-Pl are very sensitive to detect exposure and mainly reflect long-term exposure. In-Pl levels are particularly stable for a given individual. In-U might be more influenced than In-Pl by recent exposure. Both parameters remained high years after withdrawal from exposure, indicating a possible endogenous exposure and a prolonged risk of pulmonary and systemic diseases even after work exposure has ceased.