PRINCIPLES OF TOXICOLOGY

396 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTS
umbilical cord blood at quantities greater or equal to maternal blood levels, indicating transplacental
acquisition.
Although the toxicity of chloroform and carbon tetrachloride has been ascribed to their solubility
in cellular lipid, metabolism appears necessary to explain their toxicity. Since chloroform does not
form the free radical CCl 3 , it would not be expected to be as toxic as carbon tetrachloride. However,
the mechanisms and paths of metabolism are still not certain and both enzymatic and nonenzymatic
processes may be important. No metabolite has been identified in the blood or urine that can be
considered as a useful guide for evaluating occupational chloroform exposure. Chloroform does not
appear to induce chromosome breakage or sister–chromatid exchanges in human lymphocytes and
failed to produce mutagenic changes in cultures of Chinese hamster lung fibroblast cells.
Carbon tetrachloride (see Figure 16.23) (or tetrachloromethane) has seen widespread industrial
uses, including: fire extinguishers, refrigerants, metal degreasing, semiconductor production, and as a
chemical raw material. Significant amounts were used in grain fumigant mixtures. Carbon tetrachloride
is an active insecticide and is effective in suppressing the flammability of more flammable fumigants.
The odor is one to which individuals often becomes adapted, and odor is not a satisfactory warning of
excessive exposure. Carbon tetrachloride is not significantly teratogenic, but can be shown to be
variably embryotoxic and fetotoxic to animals at high exposure levels. Carbon tetrachloride is not
considered to be strongly mutagenic. Hepatocellular carcinomas and adrenal tumors developed in mice
that received gavaged doses of 2500 or 1250 mg/kg per day for 78 weeks of carbon tetrachloride. The
substance is regulated as a potential carcinogen by a number of occupational and environmental
regulatory agencies.
Figure 16.23 Carbon tetrachloride.
Acute exposure to carbon tetrachloride may result in systemic effects including CNS depression,
loss of consciousness, dizziness, dyspnea, cyanosis, proteinuria, optic neuritis, vertigo, headache, mental
confusion, incoordination, nausea, vomiting, abdominal pain, diarrhea, visual disturbances, ventricular
fibrillation, kidney and/or liver injury, oliguria, albuminuria, edema, and anorexia. From the available clinical
evidence carbon tetrachloride is suspected of causing retrobulbar neuritis, optic neuritis, and optic atrophy,
although no experimental demonstration of retinal or optic nerve injury has been made.
Hepatic and renal injury may occur from a single acute exposure, but is more likely following
repeated exposures. The lower the exposure level, the greater the likelihood that the injury will occur
predominantly in the liver. The concurrent intake of significant amounts of alcohol with exposure to
carbon tetrachloride may greatly increase the probably of liver injury. In nonfatal poisoning, recovery
of renal function occurs in three phases. In the first, after 1–3 days, oliguria stops, but creatinine and
urea plasma concentrations remain elevated. The second phase begins with a decline in these
concentrations. In the third phase, about 1 month after the initial injury, renal blood flow and glomerular
filtration begin to improve and renal function is recovered after 100–200 days.
PHYSIOLOGIC RESPONSE TO CARBON TETRACHLORIDE IN HUMANS
Concentration (ppm) Response
21–79 Odor threshold
200 Severe toxic effects with strong odor
1000–2000 Reported lethal concentration