Human health hazard profile

• Author: Clemm, Christan; Löw, Clara; Baron, Yifaat; Moch, Katja; Möller, Martin; Köhler, Andreas R; Gensch, Carl-Otto; Deubzer, Otmar
• Pages: 22-23

RoHS Annex II Dossier, final

Indium phosphide

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4 HUMAN HEALTH HAZARD PROFILE

The human health hazard of indium phosphide has been reviewed for the purpose of the harmonised

classification. In the following the main results from the Annex XV dossier proposing the harmonised

classification for indium phosphide prepared by France in 200959 are briefly summarised.

4.1 Critical endpoints

The substance has CMR properties as follows:60

Carcinogenicity: In the dossier, two cohort studies in the semiconductor industry are described:

One study reports an excess of risk of melanoma and rectum cancer whereas the other study reports

a significant excess of lung cancer in women and non-significant excess of stomach and breast

cancer in women. Due to the limited size of the two cohorts, the limited information on exposure

history and co-exposures and the lack of consistency of results between the two cohorts, it is not

possible to draw a conclusion on the carcinogenic effect of indium phosphide in humans.

In animal studies, tumours of lungs, adrenal gland and other less significant tumours are induced by

indium phosphide in mice, rats and hamsters. Development of tumours outside lungs after inhalation

exposure suggests that the mechanism does not only rely on a local inflammatory and proliferative

effect.

France (2009) concluded that indium phosphide may cause cancer, which is in line with the

conclusion of the International Agency for Research on Cancer (IARC)61 that considered indium

phosphide as probably carcinogenic to humans (Group 2A) because of inadequate evidence in

humans and sufficient evidence in experimental animals.

Reproductive toxicity: In an animal study, a decrease in reproductive organs is observed that was

more important than the general decrease of body weight. The study provides evidence that indium

phosphide induces toxic effects on the male reproductive system. Interpretation of the study is

however limited by the single dose used and the absence of direct assessment of fertility function.

Toxicokinetic data shows that indium can accumulate in testes after inhalation and raises a concern

on potential accumulation of high concentrations due to chronic exposure. Therefore, indium

phosphide was concluded as suspected of damaging fertility.

Besides the CMR properties, acute and repeated toxicity data were also reported in the dossier. The

data on repeated dose toxicity indicated that indium phosphide causes damage to lungs by

prolonged exposure through inhalation: Studies, using inhalation or intratracheal instillation, show

that indium phosphide induces severe inflammation in lungs. Particles accumulate in lungs but can

also be found in bronchial and mediastinal lymph nodes. Modification of the anti-oxidative potential

of the cells by indium phosphide could lead to different lesions and to hyperproliferation. The

proportion of the substance which passes into systemic circulation is unknown, but at higher doses,

other organs can be reached, such as liver, where necrosis is observed. Severe effects (death,

moribund condition and hepatic necrosis) are found in animal studies.

59 Op. cit. France (2009)

60 Op. cit. France (2009)

61 IARC International Agency for Research on Cancer (2006), to be found under http://publications.iarc.fr/104 (last

accessed 10.01.2020)