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Technical Report 
Integrated criteria document chromium: effects 
Janus, JA; Krajnc, EI 
Human Toxicity: Cr(III) - being present in biological material as an organic compound, the so-called "glucose tolerance factor" - is an essential trace element for mammals. It is estimated that the minimal requirement for adults is provided by a daily dietary intake of 2 to 8 ug Cr(III), corresponding with 0.03 to 0.13 ug Cr(III).kg There is conclusive evidence that Cr(VI) is carcinogenic to mammals, including man. Because of the mutagenic activity, Cr(VI) is considered to be a genotoxic carcinogen. Therefore, a dose-without-effect with regard to carcinogenicity can not be established. After parenteral administration of either Cr(VI) or Cr(III) to pregnant hamsters and mice in specific teratogenicity studies, developmental effects (including malformations) have been reported. However, developmental toxicity tests in which animals were exposed orally or by inhalation are very limited and, therefore, do not allow an evaluation of the risk to humans which are exposed only orally or by inhalation. The oral studies available with regard to Cr(III) are considered to be too limited to establish an acceptable daily intake. Based on feeding studies with insoluble chromic oxide pigment (Cr2O3), a dose-without-effect (DWE) of 1,210 mg Cr(III).kg-1 was established; assuming a fractional absorption of 0.5%, this DWE corresponds with 6 mg absorbed-Cr(III).kg-1 Based on a study in which animals were exposed to relatively soluble chromic chloride (CrCl3) in drinking water, a DWE of 2.5 mg Cr(III).kg-1 was established; assuming a fractional absorption of 5%, this DWE corresponds with 0.125 mg absorbed-Cr(III).kg-1 Data on the daily dietary intake of chromium in The Netherlands are not available. Based on foreign data ("total diet studies") summarized in the Criteria Document, the average daily dietary intake is estimated to be 100 ug, with a range of 50 to 200 ug Data on the speciation of chromium in the diet are not available. Based on the speciation of chromium in biological material [organic Cr(III)] and the small contribution of drinking water [containing 0.1-0.8 ug total-Cr.l-1 in The Netherlands] to the chromium level in the total diet, it is assumed that by far most chromium in the diet is present as Cr(III). Therefore, the upper limit of 200 ug is corresponding with 0.83 ug absorbed-Cr(III).kg-1 (based on a fractional absorption of 25% and a body weight of 60 kg). The two above-mentioned DWE-values (125 and 6,000 ug absorbed-Cr(III).kg-1, respectively) based on long-term animal experiments are 150 times and 7000 times, respectively, higher than the upper limit of human intake (0.83 ug absorbed-Cr(III).kg-1 Based on these "margins of safety" adverse effects are not expected to occur at the current exposure levels. Because of data on the speciation of chromium in surface water in The Netherlands, it must be noticed that it can not be excluded that chromium in drinking water may be present partially as Cr(VI). If so, Cr(VI) will be converted partially to Cr(III) due to intragastric reduction; quantitative data on this reduction are not available. The available studies in which animals were orally exposed to Cr(VI) are too limited for a risk assessment for man. Because Cr(VI) is considered to be a genotoxic carcinogen, exposure to Cr(VI) should be as low as possible. Exposure to Cr(III) by inhalation results in a daily intake which is less than 0.1% of the dietary intake, assuming an airborne concentration of 5 ng.m-3 and a respiration volume of 12 m3 per day. Because exposure to Cr(III) by inhalation is not expected to result in different effects than oral exposure, exposure to Cr(III) by inhalation is considered relevant. Therefore, this risk assessment is limited to Cr(VI). Although there appear to be differences in the carcinogenic potency of different Cr(VI) compounds, it is not possible to quantify these differences. Moreover, data on the speciation of Cr(VI) in air are not available. The "unit risk" of 40 x 10E-3, calculated by the World Health Organization (WHO, 1987), is considered to be the best estimate of the carcinogenic potency of Cr(VI). The "unit risk" is defined as "the additional lifetime cancer risk occurring in a hypothetical population in which all individuals are exposed continuously from birth throughout their lifetimes to a concentration of 1 ug.m-3 of the agent in the air they breathe". Assuming an acceptable risk of 1 x 10E-6 (one extra case of lung cancer per million persons exposed lifetime), this risk corresponds with an airborne concentration of 25 x 10E-6 ug Cr(VI).m-3 [0.025 ng Cr(VI).m-3]. Aquatic organisms: Accumulation and food chain transfer: Chromium is accumulated to a limited extend by aquatic animals. The concentrations in aquatic organisms decrease with increasing trophic level. In general, concentrations up to 10 and 5 1 fresh weight have been reported in invertebrates and vertebrates (fish), respectively. These concentrations are based on both freshwater and seawater organisms. Based on these data it is concluded that biomagnification (the occurrence of a substance at successive higher concentrations with increasing trophic levels in food chains) of chromium is of no-account. Toxicity to freshwater organisms: Short-term "single species" tests with most species of invertebrates have resulted in L(E)C50-values of 2,000 to 60,000 ug.l-1, based on tests with both Cr(III) and Cr(VI). Crustaceans, especially cladocerans (Daphnia sp.) are more sensitive, with L(E)C50-values of 10 to 500 ug.l-1. In general, fish are less sensitive than invertebrates: LC50-values for fish are 3,000 to 190,000 ug.l-1. The toxicity of Cr(VI) increases with decreasing pH and hardness of the water. Long-term "single species" tests with Cr(VI) have resulted in NOEC-values of 0.35 to 6,650 ug.l- 1. Relatively low values have been reported for organisms of different, important taxonomic groups, namely algae, crustaceans and fish. In general, fish are less sensitive than invertebrates. Long-term tests with Cr(III) have resulted in NOEC-values of 48 to 330 ug.l-l. In experimental micro-ecosystems (algae) a concentration of 100 ug Cr(VI).l-1 has resulted in a reduction of diatom abundance and diversity. Toxicity to marine organisms: Short-term "single species" tests with Cr(VI) have resulted in L(E)C50-values of 2,000 to 105,000 ug Cr(VI).l-1; these values are based on tests with both invertebrates and vertebrates. The lowest values have been reported for crustaceans and polychaete worms. L(E)C50-values based on tests with Cr(III) are 10,000 to 56,000 ug Cr(III).l-1. Long-term "single species" tests with Cr(VI) have resulted in NOEC-values of 13 to 770 ug Cr(VI).l-1. The only available NOEC resulting from a test with Cr(III) is 50,400 ug Cr(III).l-1; in this test only 20 ug Cr(III).l-1 was found to be dissolved (0.1 um). Based on these NOEC-values and additional data it is concluded that Cr(III) is less toxic than Cr(VI) in sea water. Terrestrial organisms: Toxicity: In some short-term experiments effects on microbes (numbers, diversity) and microbe-mediated processes (respiration, ammonification, nitrification, enzym-activities) have been reported at concentrations of 25 to 100 dry weight [Cr(III) or "chromium"] and 1 to 10 mg Cr(VI).kg-1. However, in most short-term experiments and in long-term experiments no effects have been reported at concentrations up to 200 (dry weight) [Cr(III) or "chromium"]. In a test with the earthworm Eisenia Andrei, a concentration of 1,000 mg Cr(III).kg-1 dry weight resulted in adverse effects on growth and reproduction. The resulting NOEC is 300 mg Cr(III).kg- 1 dry weight. In two tests in which other earthworm species were exposed to Cr(VI), concentrations of 2 and 10 mg Cr(VI).kg-1, respectively, resulted in increased mortality. Relevant data on other terrestrial organisms are not available. 
ANIMAL; acute toxicity; subacute toxicity; subchronic toxicity; chronic toxicity; carcinogenicity; carcinogens; genetic toxicity; mutagens; reproductive and developmental tests; teratogens; embryo-fetal toxicity; toxicokinetics; liver; urinary tract; HUMAN; epidemiological study; occupational exposure; acute effect; carcinogenic effect; genetic effect; gastrointestinal system; cardiovascular system; respiratory system; skin; ENVIRONMENT; TERRESTRIAL TOXICITY; invertebrate; plant; microorganisms; AQUATIC TOXICITY; fish; algae; ENVIRONMENTAL CONCENTRATIONS; biota; BIOACCUMULATION; aquatic; terrestrial 
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