Indium trihydroxide

Endpoint summary

Description of key information

Repeated dose toxicity inhalation studies:

An increasing number of cases of severe lung effects (characterized by pulmonary alveolar proteinosis and/or interstitial fibrosis) in ITO-exposed workers has been reported in several publications in the Far East and USA. The lung effects appear to have a fast onset, in some cases within one year of exposure.

In an extensive occupational exposure study in an IO and ITO production facility in the USA, Cummings et al., 2013 - 2016 have studied the exposure to indium by the worker population over several years. The study included medical surveillance, levels of indium detected in the blood of workers and investigation on the use and efficiency of respiratory protective equipment (RPE) employed at the site, since indium lung disease appeared in 2 workers.

 

The plant activities are shown in the Figure of Cummings et al 2013. It is assumed that the indium oxide production area is the refining area referred to in the publications of Cummings et al.

Legend figure: ITO production began with indium metal, which was used to make indium oxide powder. Indium oxide, tin oxide, and other compounds were mixed and the resulting liquid cast into molds to harden. The castings were sanded by hand and then fired. The sintered tiles, or targets, were ground and cut to the customer’s specifications for sputtering. Indium metal was reclaimed from used targets and waste materials (cuttings, grindings, and rejected tiles) generated in the production process.  

 

Medical Surveillance Information

Medical surveillance and lung function tests were carried out in approximately 100 workers from all areas of the site and effects on lung function were found in the workers from the tile making area, grinding area and the reclaim area, but not the indium oxide production area (refinery). At the start of the studies two cases of pulmonary alveolar proteinosis were found in two workers from the tile making and reclaim area. There were no reported cases of workers having adverse effects on lung function from the refinery area but this should be confirmed by the authors.

Air Indium levels

The authors investigated the blood and plasma indium levels in all workers including administration staff on the site. They developed a very sensitive method to detect indium in air samples at levels of 0.375 µg/sample (Cummings et al, 2016). They also calculated the current indium levels in the workers and predicted the "cumulative" levels. The current exposures were assigned to jobs in each worker's work history regardless of calendar time, as detailed historical information on workplace conditions, processes, and representative historical exposure estimates were not available to assess or account for differences in exposure over time. The exposure associated with each job in the work history was then multiplied by the duration (in years) that the job was performed and summed across all jobs held to obtain cumulative exposure for each worker. It should be considered that the accuracy of the cumulated levels (shown in Table below) is questionable and indeed the authors themselves indicated that there were several uncertainties surrounding their assumptions.

Table (taken from Cummings et al., 2016) -Personal Respirable Indium Exposure Levels by Department at an Indium-Tin Oxide (ITO) Production Facility ^(a)

					Years to accumulate 22 µg-years/m^3(range for jobs) ^(d)	Years to accumulate 22 µg-years/m^3(range for jobs)^(d)	Years to accumulate 22 µg-years/m^3(range for jobs)^(d)
Department	N	Mean µg/m^3 (b)	Min-Max µg^3	% ≤10 µg/m^3 (c)	No respirator	N95 FFPR	PAPR
ITO	25	81.9	9.9-518.3	4	0.3 (0.2-1.9)	2.7 (2.4-18.8)	6.7 (5.9->40)
Planar bond	5	9.1	3.2-17.6	60	2.4	24.2	>40
Planar grind	8	27.2	4.6-148.4	50	0.8 (0.6-1.2)	8.1 (6.0-11.7)	20.2 (15.1-29.3)
Reclaim	12	108.4	4.8-796.6	17	0.2 (0.1-2.5)	2.0 (0.7-24.7)	5.1 (1.8->40)
Refinery	6	26.3	10.9-40.9	0	8.8	8.4	20.9
Rotary bond	9	3.7	0.7-6.4	100	5.9	>40	>40
Rotary grind	4	39.4	20.9-59.3	0	0.6	5.6	14.0
Engineering	9	4.9	1.7-23.2	89	4.5 (2.3-12.2)	>40 (23.4->40)	>40 (>40)
Maintenance and facilities	8	8.6	2.2-16.0	62	2.6 (1.7-6.5)	25.6 (17.2->40)	>40 (>40)
Forming	8	5.7	1.3-12.4	87	3.9	38.6	>40
QC lab	6	3.5	1.9-5.4	100	6.3 (6.1-6.5)	>40 (>40)	>40 (>40)
R&D	8	35.5	2.1-111.1	50	0.6 (0.4-10.5)	6.2 (4.5->40)	15.5 (11.2->40)
Shipping and receiving	2	1.9	1.7-2.1	100	11.6	>40	>40
Administrative^(a)	1	0.4	-	100	>40	>40	>40

N, number of measurements.

(a)– All results shown are from personal sampling,with the exception of those for the Administrative Department,which was valuated with area sampling.
(b) – Represents the minimum variance unbiased estimate (MVUE) of the arithmetic mean. These measurements do not reflect the actual use of respiratory protection during exposure monitoring.
(c) – None of the measurements was below 0.3 mg/m3. The remainder of measurements were all greater than 10 mg/m3 concentration requiring immediate actions to be taken to reduce exposures (process enclosures, ventilation, process changes, respiratory protection, etc.).
(d) – Number of years it would take at the mean exposure level for the department and jobs within department to reach cumulative exposure of 22 mcg-years/m3, the lowest cumulative exposure at which a significant effect on health outcomes was noted with no respirator use, or using a disposableN95filtering face piece respirator (FFR) with an assigned protection factor (APF) of10 or a powered air purifying respirator (PAPR) with an APF of 25. For departments with more than one job, the range of values for those jobs is shown in parentheses. For departments with one job, no range is shown.

Conclusion of the available human data

This exhaustive investigation at an IO and ITO production plant gives good evidence of the need for RPE and exposure controls to reduce/eliminate exposure to ITO. The results indicated that higher indium exposures were not necessarily associated with greater lung function and radiographic abnormalities. There did seem to be a difference in the time taken to reach a critical cumulative dose between the IO activities (refinery) and the ITO associated activities. However, the significance of these findings is unclear.

Indium oxide producers had among the highest airborne indium exposures and serum indium concentrations, but virtually no respiratory impairment, while ITO tile makers had the lowest airborne indium exposures and apparently lower serum indium concentrations, but a larger burden of respiratory abnormalities.

Indium blood and serum plasma concentration and indium airborne concentration (respirable indium) alone cannot distinguish the form of indium (i.e. indium metal, indium hydroxide, indium oxide, or ITO) to which a worker has been exposed, nor does it appear to directly link to respiratory impairment. It only indicates that workers have been exposed to some form of indium during their work activities, but it does not directly relate to adverse findings in the workplace.