efsa-opinion-chromium-food-drinking-water

7.3.2.1. Acute oral toxicity
Chromium in food and drinking water
Most studies identified on acute toxicity are case reports from intentional and accidental poisoning.
Those case reports on the consequences of high doses of Cr(VI) allow the identification of the type
and nature of possible effects of Cr(VI) in humans when describing a range of effects from mild to
serious and life-threatening and lethal effects (see Appendix I1) Clinical effects included
haematological, hepatic and renal injury as well as respiratory and gastrointestinal lesions.
Accidental ingestion has been reported for Cr(VI) compounds including chromic acid (Fristedt et al.,
1965; Saryan and Reedy, 1988; Loubières et al., 1999), potassium chromate (Goldman and Karotkin,
1935; Partington, 1950; Kaufman et al., 1970; Sharma et al., 1978; Iserson et al., 1983; Clochesy,
1984; Hanston et al., 2005), and ammonium dichromate (Reichelderfer, 1968; Hasan, 2007) resulting
in a large variety of clinical presentations such as abdominal pain, nausea, and vomiting; hematemesis
and bloody diarrhea; caustic burns of the mouth, pharynx, esophagus, stomach, and duodenum and GI
hemorrhage; anemia, decreased blood Hb, abnormal erythrocytes, and intravascular hemolysis;
hepatotoxicity (hepatomegaly, jaundice, elevated blood bilirubin, and liver enzymes activities); renal
failure (oliguria and anuria); cyanosis; and metabolic acidosis, hypotension, and shock (see also
ATSDR, 2012). Fatty degeneration in the liver and tubular degeneration and necrosis in the kidney
were observed in biospies (Reichelderfer, 1968; Kaufman et al., 1970; Sharma et al., 1978; Loubières
et al., 1999).
Doses of Cr(VI) ranging 4 to 360 mg/kg b.w. were reported to be lethal (Kaufman et al., 1970; Iserson
et al., 1983; Clochesy, 1984; Saryan and Reedy, 1988; Loubières et al., 1999).
Paustenbach et al. (1996) investigated the kinetics of Cr(VI) in a male volunteer who ingested 2 L per
day of water containing 2 mg/L for 17 consecutive days. Kerger et al. (1996) studied four adult male
volunteers ingesting a single dose of 5 mg Cr (in 0.5 liters deionized water) in three choromium
mixtures: (1) Cr(III) chloride (CrCl 3 ), (2) potassium dichromate reduced with orange juice (Cr(III)-
OJ); and (3) potassium dichromate [Cr(VI)]. Kuykendall et al. (1996) report on four adult male
volunteers ingested a bolus dose of 5000 micro chromium in a 0.51 volume of water (10 ppm),
Corbett et al. (1997) examined the systemic uptake of chromium in four human volunteers immersed
below the shoulders in water at 91 +/- 2.5 degrees F. following three hours of contact with water
containing Cr(VI) at a concentration of 22 mg/L. Finley et al., 1997 studied adult male volunteers
ingesting a liter (in three volumes of 333 ml, at approximate 6-hr intervals) of deionized water
containing Cr(VI) at concentrations ranging from 0.1 to 10.0 mg/L. Kerger et al. (1997) investigated
in adult male volunteers the oral exposure to 5 and 10 mg Cr(VI)/L in drinking water administered as
a single bolus dose (0.5 L swallowed in 2 min) or for 3 days at a dosage of 1 L per day (3 doses of
0.33 L each day, at 6-h intervals). None of these reports presented indications of clinical effects.
In conclusion, at high doses Cr(VI) exerts acute health effects in the respiratory, haematological,
hepatic and renal system and in the gastrointestinal tract where acute effects include abdominal pain,
vomiting, ulceration, hemorrhage, necrosis, and bloody diarrhea.
7.3.2.2. Subchronic and chronic toxicity excluding cancer
Haematological effects have been inconsistently reported in the literature such that haemotoxicity after
oral exposure cannot be assessed. It was suggested that those effects originate from primary exposure
to Cr(VI) and its accumulation in erythrocytes and subsequent reduction to Cr(III) via the reactive
intermediates Cr(V) and Cr(IV) and their binding to hemoglobin and other ligands. The Crhaemoglobin
complex is relatively stable and remains sequestered within the cell over the life-span of
the erythrocyte (Lewalter et al., 1985). Haematological effects observed in some cases of accidental or
intentional ingestion of high doses Cr are detailed in Appendix I2. A cross-sectional study from an
alloy plant in the People's Republic of China (summarised below) reports associations between Cr(VI)
and the occurrence of leukocytosis and immature neutrophils.
Gastrointestinal effects observed in occupational studies may occur due to exposure via mouth
breathing or other means of ingestion of Cr (e.g., mucociliary clearance of inhaled Cr particles to the
gastrointestinal tract and/or ingestion secondary to hand-to-mouth activity). In particular, epigastric
EFSA Journal 2014;12(3):3595 98