Arsenic and its Inorganic Compounds (with the Exception of Arsine) [MAK Value Documentation, 2014]

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated arsenic and its inorganic compounds, with a special focus on gallium arsenide. Available publications and study reports are described in detail. Arsenic and its inorganic compounds are carcinogenic in humans. From the available studies in workers in the semiconductor industry probably exposed to gallium arsenide, no increased cancer risk can be derived. Carcinogenicity studies with inhalation exposure to gallium arsenide revealed lung tumours, mononuclear leukaemia and benign phaeochromocytomas in the adrenal glands in female rats. In animal studies, increased levels of arsenic in blood were determined after exposure to gallium arsenide. The metabolites are the same as those found after exposure to arsenite and arsenate. Although the bioavailability of gallium arsenide is much lower than that of arsenic trioxide, it cannot be completely neglected. Therefore, the classification of arsenic and its inorganic compounds including gallium arsenide as carcinogenic in man (Carcinogen Category 1) has been retained. In vitro genotoxicity studies with inorganic arsenic(III) compounds yielded mostly positive results in tests for sister chromatid exchange, chromosomal aberrations and micronuclei. In in vivo studies with somatic cells, arsenic(III) compounds induced an increase in DNA strand breaks, chromosomal aberrations and micronuclei. In humans exposed long‐term to arsenic, increased incidences of micronuclei, chromosomal aberrations, sister chromatid exchange and DNA damage were observed. Gallium arsenide was not genotoxic in vitro and in vivo. Gallium arsenide, like arsenic, is systemically available and forms the same metabolites as arsenic and its inorganic compounds. For this reason the suspected germ cell mutagenicity of gallium arsenide cannot be unequivocally excluded. Arsenic and its inorganic compounds including gallium arsenide therefore remain in Category 3A for germ cell mutagens which produce mutagenic effects in somatic cells of mammals in vivo and have been shown to reach the germ cells. No MAK value has been derived and thus also no peak limitation has been established, and classification into one of the Pregnancy Risk Groups is not possible. Skin contact is not expected to contribute significantly to systemic toxicity. Sensitizing effects of arsenic and its inorganic compounds cannot be derived from the available data.

Safety Assessment of Zinc Salts as Used in Cosmetics

“…25,123 In a guinea pig maximization test of Zinc Sulfate (0.1% for intradermal induction; 50% for epidermal induction and challenge), weak reactions were reported in 5/10 treated animals and 2/5 control animals; following a second challenge, reactions noted in 4/10 treated animals and 2/5 controls. 63 Zinc Chloride (in formulation, effective test concentrations of 0.229% 124 and 0.326% 125 ; n = 55 and 52, respectively), Zinc Laurate (7% in formulation; n = 104), 126 and Zinc Myristate (in formulation, effective test concentration 14%; n = 49) 127 were not irritants or sensitizers in human repeated insult patch tests (HRIPTs).…”

“…62 Smaller amounts of zinc are located in the skin and hair (∼8%), liver (∼5%), and gastrointestinal tract and pancreas (∼3%). 36,63 Zinc Carbonate. The naturally occurring minerals smithsonite and zincspar contain Zinc Carbonate.…”

“…In humans, inhalation exposure via aerosol (exposure duration not specified) to 40 mg/m 3 Zinc Chloride (19.2 mg/m 3 of free zinc) produced a metallic taste; the particle size and other details were not provided. 63 Another study reported that in human subjects exposed via inhalation to 4800 mg/m 3 Zinc Chloride (2302.5 mg/m 3 of free zinc) for 30 minutes, pulmonary effects were induced (no further details).…”

“…In humans, depending on the amount of zinc ingested, approximately 70-80% of zinc is excreted in feces; urine, saliva, hair, breast milk, and sweat are other routes of elimination. 63,79 Zinc can be reabsorbed from the small intestines. 62 ADME studies summarized below are detailed in Table 9.…”

Towards an ecological modelling approach for assessing ionizing radiation impact on wildlife populations

“…The exercise was carried out for a hypothetical contamination scenario involving gamma radiation in combination with sodium arsenate in the soil, inhabited by a population of small mammals (for which the parameters of the vole model were used). The LD 50 for sodium arsenate is 112 mg kg −1 (or 40 mg kg −1 in terms of elemental arsenic) [58]. Figure 4 demonstrates the effect of adding a progressively higher chemical dose for a range of radiation dose rates between 0 and 10 −1 Gy d −1 .…”