Chromium - Toxicology of Metals - page 482

7.1.2.5 Local Effects in the Lungs
7.1.2.5.1 Local Effects in the Lungs Mancuso and
Hueper (1951) reported on a spotty, moderately severe
not nodular pneumoconiosis in chromate workers. Sluis-
Cremer and du Toit (1968) reported on fi ne nodular
pneumoconiosis—somewhat more radiopaque than in
simple coal miner's pneumoconiosis—in a few chromite
workers in South Africa, who might also have been
exposed to crystalline quartz. The results in these reports
have never been confi rmed in other studies.

the mitochondria. Schubert et al . (1971) demonstrated
similar changes in the proximal tubuli after subcutane-
ous administration of 15 mg/kg potassium dichromate
to rats, and Langård (1979) showed perivascular edema
and focal necrosis of the proximal tubuli 4 days after
intravenous administration of as low a dose as 0.56 mg/
kg sodium chromate. No dose-effect or dose-response
relationship has been established for tubular damage
after administration of Cr(VI).

7.2.1.2 Effects on the Liver
Few studies have focused on hepatotoxic effects of
Cr compounds. Tandon et al . (1978) compared the hepa-
totoxic effects of Cr(III) and Cr(VI) by intraperitoneal
administration of 1.3 mg Cr/ kg to rabbits for 6 weeks
as Cr nitrate and potassium dichromate, respectively.
The Cr(VI) compound resulted in thickening of the
liver capsule, congestion in the central vein, and adja-
cent sinusoids and coagulation necrosis of hepatic cells
throughout the parenchyma. The Cr(III) compound also
resulted in congestion in the central vein and necrosis
of the hepatocytes, but less extensive. The mechanisms
of hepatotoxicity were not clarifi ed in this study, and
some untoward effects may be secondary to intravascu-
lar microthrombi. Dinu and Boghianu (1973) suggested
that potassium chromate given to rats in the diet at
100 ppm concentration inhibits the activity of glucose-
6-phosphatase. The biochemical mechanisms involved
in hepatocellular necrosis are not fully explained, but
inhibition of this enzyme may result in hypoglycemia
that may bear some relation to the toxicity. No dose-
response relationship has been established for the hepa-
totoxic effects of Cr(VI) or for Cr(III) compounds.

7.2 Systemic Effects and Dose-Effect
and Dose-Response

7.2.1 Animals

Although some toxic effects of chromates in humans
have been known for more than 100 years (Brieger,
1920; Major, 1922; Reischer and Glesinger, 1922), rela-
tively few experiments were carried out in animals.
Most of the reports based on animal experiments have
considered untoward effects in more than one organ,
and some of these effects may be secondary to effects in
other organs. Tandon (1982) reviewed systemic effects
in animals resulting from Cr compounds.

7.2.1.1 Effects in the Kidneys
Hunter and Roberts (1933) administered potassium
dichromate in high doses subcutaneously to rhesus mon-
keys and found necrosis of the proximal and the distal
tubules, as well as diminution in the number of glomeru-
lar epithelial and endothelial cells, and some effect on
the capillary basement membrane. Later, a large number
of studies demonstrated necrosis of the proximal tubular
epithelium after intravenous administration of chromate
doses ranging from 0.5-30 mg/kg (Tandon, 1982). In an
extensive study, Evan and Dail (1974) administered 10
and 20 mg of aqueous sodium chromate/kg intraperi-
toneally to rats and found lysozymuria and proteinuria
6 hours after the 20 mg/kg dose and 24 hours after the
10 mg/kg dose, respectively. By use of electron micros-
copy techniques, they showed that sodium chromate at
these dose levels selectively caused damage in the con-
voluted portion of the proximal tubuli, with no evidence
of damage to glomeruli, most of the nephrons being
affected. The sequential changes were (1) sealing and
loss of microvilli; (2) formation of intracellular vacuoles
of varied sizes; (3) mitochondria in the orthodox confi g-
uration; (4) appearance of cytosegresomes; (5) pyknosis
of the nuclei; (6) mitochondrial swelling; (7) cytoplasmic
liquefaction; and (8) rupture of the cell membrane. Evan
and Dail (1974) suggested that many of the observed
effects are related to an induced impairment of the
electron-transport system and the phosphorylation in

7.2.1.3 Effects on the Airways
Akatsuka and Fairhall (1934) exposed cats to 80-
115 mg/m 3 Cr(III) salts 1 hour daily for 4 months and
fed another group a diet containing high amounts of
chromic salts. No adverse effects were observed in the
airways. Nettesheim et al . (1971) observed enhance sub-
epithelial connective tissue and fl attened epithelium in
the large bronchi when exposing mice to calcium chro-
mates by inhalation. Also, they observed morphological
changes in tracheal and submandibular lymph nodes.
To examine whether observations in humans could
be confi rmed, indicating that inhalation of chromite
dust may induce pneumoconiosis, Swensson (1977)
introduced 40 mg chromite particulates suspended in
Ringer's solution intratracheally to rats, but did not
observe pneumoconiosis.

7.2.1.4 Effects in the Digestive Tract
After administering potassium chromate to small
animals by various routes, the total dose varying from