Cardiovascular Effects in Rats following Exposure to a High-Boiling Coal Liquid

In previous work, increased blood pressure was observed in anesthetizedrats following a subchronic aerosol exposure to solvent-refinedcoal heavy distillate (HD). To determine if this increase isa permanent, dose-related response, 11-week-old male rats wereexposed by inhalation to 0, 0.24, or 0.70 mg/liter (control,low-exposure, and high-exposure groups, respectively) of HDfor 6 hr/day, 5 days/week, for 6 weeks. In addition to bloodpressure, select cardiovascular parameters were measured toobtain information on other possible toxic effects of the HDand also to gain some insight into potentially altered regulatorymechanisms that could be affecting the blood pressure. The angiotensin–aldosteronehormonal system, body fluid regulation, cardiac function andregulation, and pulmonary gas-exchange capabilities were examined.Two weeks after the end of exposure, mean blood pressures andheart rates of anesthetized animals in the low- and high-exposuregroups were elevated relative to the controls. Plasma angiotensinconcentrations decreased with increasing dose, whereas aldosteroneconcentrations were unaffected. In the high-dose group, bloodand plasma volumes were 20 and 28%, respectively, higher thanthose of controls. Seven weeks after exposure, all measuredcardiovascular parameters were similar to control values. Resultsfrom this study show that a 6-week exposure to HD resulted indose-dependent, transient changes in a variety of physiologicalfactors considered important in cardiovascular function.     

Comparison of Fetotoxic Effects of a Dermally Applied Complex Organic Mixture in Rats and Mice

A high-boiling (288–454?C), coal-derived complex organicmixture (COM) has been shown to be teratogenic in rats followinginhalation and oral routes of exposure. To determine whethersimilar changes also occur after dermal exposure to this COM,pregnant rats and mice were exposed during periods of organogenesis(Days 11 to 15 of gestation). Shaved backs were painted with0, 500, or 1500 mg/kg of the COM (control, low, or high dose,respectively); the exposed area was not occluded. Maternal weightgain during the gestation period decreased with increasing dosein rats but not in mice. Examination of rat fetuses on Day 20of gestation showed that resorptions had occurred in more than90% of low-and high-dose litters (vs 6% in the control group).In mice, fetal examinations on Day 18 of gestation showed thatresorptions occurred in 71% of litters from both exposure groups(vs 14% in the controls). Fetal measurements indicated thatboth the weight and the length of rat fetuses decreased withincreasing dose, but mouse fetuses were unaffected. Cleft palates,absent in the control groups, were observed in 50 to 55% ofthe high-dose group and 5 to 8% of the low-dose fetuses of bothspecies. Small fetal lungs occurred in nearly 100% of the exposedrat fetuses and in 25% of the high-dose mice; the incidenceof small lungs was 1% in control animals. Other variations observedin exposed groups included edema and reduced ossification inthe rat and renal pelvic cavitation in the mouse. In conclusion,dermal exposure of dams to COM resulted in life-threateningmorphological alterations in fetuses of both species similarto those seen following exposure by Other routes.