For evaluation of subchronic toxicity of the two single-ring nitroaromatics,
p-nitroaniline (PNA) and
p-nitrochlorobenzene (
PNCB), groups of 10 male and 10 female Sprague-Dawley rats were exposed to an
aerosol/vapor of PNA in
isopropanol at target concentrations of 0, 10, 30, or 90 mg/m3 or to
PNCB vaporized from a
solution in
ethylene glycol monoethyl ether at target concentrations of 0, 5, 15, or 45 mg/m3 for 6 hr/day, 5 days/week for 4 weeks. Clinical signs of toxicity,
body weights, results of ophthalmoscopic exam, hematology and clinical chemistry tests, organ weights, gross and histopathological changes were recorded. Exposure to PNA or
PNCB resulted in a dose-related increase in blood
methemoglobin levels. Mean red blood cell counts, hematocrit, and
hemoglobin were significantly decreased in mid and high level animals exposed to
PNCB. Mean spleen weights (absolute and relative to
body weight) were significantly increased at the high dose levels in the two studies. A slight increase in spleen weights was also observed at the low concentration level in the PNA study. Absolute and relative liver weights also were increased among animals exposed to 45 mg/m3
PNCB. Microscopic changes were observed mainly in the spleen and included an increase in intensity of extramedullary hematopoiesis and
hemosiderosis with both compounds. Spleens of animals exposed to
PNCB also exhibited congestion. Neither PNA nor
PNCB exhibited significant toxicological effects other than those of
methemoglobinemia,
anemia, and splenic changes classically associated with nitroaromatics at levels significantly above presently accepted occupational standard. Our data suggest that the current TLV for PNA which is 3 mg/m3 will provide adequate protection to the workers. OSHA's PEL of 1 mg/m3 for
PNCB is to be preferred over the current TLV of 3 mg/m3 to provide a comparable margin of safety.