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The inhalation toxicity of 25-, 100-, and 250-ppm morpholine was investigated by 6 hr/day, 5 day/week exposures to Sprague-Dawley rats for 13 weeks. Irritant effects of morpholine exposures were evident mostly in the high exposure group; a reddish discharge was observed around the nose and mouth in the 250-ppm group rats after the first week; salivation was also observed. Ten rats/sex/dose level were sacrificed after 7 weeks. The high-level (250-ppm) exposure resulted in focal erosion and focal squamous metaplasia of the maxilloturbinates; effects were observed in 6 10 male rats and 2 10 female rats. There was also a sporadic increase of secretions in the Harderian gland sections. Almost all high-level rats sacrificed after 13 weeks demonstrated comparable effects; the lesions, which were increased in incidence and severity, involved the nasal septum and anterior nasal cavities in addition to the nasoturbinates and maxilloturbinates. Lesions of chronic murine pneumonia were increased in severity in the 250-ppm group. The only compound-related histomorphologic alterations observed in the 100-ppm group consisted of focal necrosis and necrotic cell debris in the nasal cavity of two female rats at terminal sacrifice. No exposure related effects were observed in the 25-ppm group. No significant compound-related effects on body weight, clinical chemistry, hematology, or organ weight data were observed.

Adult, Sprague-Dawley albino rats of four different ages (6, 18, 32 and 52 weeks) were exposed to 940 ppm vinyl chloride by inhalation for 24 weeks, 5 days/week, 7 hr/day. In each age group, there were 110 to 128 males and the same number of females. The similarly housed control group, which was not exposed to vinyl chloride, consisted of the same number of males and females in each age group. All animals that died spontaneously, or were sacrificed moribund, or were killed at scheduled times (3, 6 and 9 months after initial exposure) were autopsied. All organs were examined grossly, and several tissues from each animal were examined microscopically. The older the rats were when they were first exposed, the greater the incidence of angiosarcomas. The incidences of angiosarcomas in the four age groups (from youngest to oldest) in the exposed males in the nonscheduled sacrifice groups were: 0/37 (0%); 0/44 (0%); 3/45 (6.7%); and 13/55 (24%). Similarly, for the females, these incidences were: 2/38 (5.3%); 7/47 (15%); 23/49 (47%); and 11/54 (20%). Most of the angiosarcomas were highly anaplastic, primary tumors in the livers that metastasized to the lungs. Only one angiosarcoma was seen in all the control rats; that occurred in subcutaneous tissue. This study demonstrated that older adult animals and females are more susceptible to the angiosarcoma-inducing effects of vinyl chloride than young adult animals and males, respectively.

Cynomolgus monkeys exposed 6 hr daily, 5 days/week for 6 months to atmospheres containing synthetic detergent dust at 1, 10, or 100 mg/m 3 together with enzyme dust at 0.001, 0.01, 0.1, or 1 mg/m 3 , or to the detergent dust alone at 100 mg/m 3 , or to the enzyme dust alone at 1 mg/m 3 . The enzyme was a mixture of two enzymes manufactured for use in commercial detergents: Novo Alcalase and Milezyme 8X. The mass median (aerodynamic equivalent) diameter of the dust particles was ⋍3 μm. No evident adverse effects were produced by any of the mixtures of 1 mg/m 3 detergent dust with as much as 0.1 mg/m 3 enzyme dust. The detergent dust alone at 100 mg/m 3 produced gross signs of respiratory distress, pulmonary histopathological effects, and pulmonary function impairment. This impairment, measured by the nitrogen washout method, was indicative of constricted small airways. Exposure to 10 or 100 mg/m 3 detergent dust together with 0.01 or 1 mg/m 3 enzyme dust produced the same effects along with diminished weight gain or weight losses. The 100 mg/m 3 level of detergent dust, alone and with enzyme, caused some mortality. At least one animal in each group exposed to enzyme dust had precipitating antibodies to the enzyme. Evidence of respiratory toxicity diminished greatly in animals that were held for 4 to 6 weeks after their last exposure to the dust, but single 6-hr reexposures of some of these animals reinstated many of their overt symptoms. The dust exposures had no apparent effects on total respiratory system flow resistance, diffusion capacity, hematology, clinical chemistry, urinalysis, intradermal or skin-prick challenge test results, or chest radiographs.

In a study to evaluate its acnegenic potential, increasing concentrations of 1,2,4-trichlorobenzene were applied topically to the ventral surface of the rabbit ear three times weekly for 13 weeks. Additional groups of rabbits received similar treatment with petroleum ether (solvent controls), received no treatment (negative controls), and received four once-weekly treatments with hexachlorodiphenyloxide, a known chloracnegenic agent (positive controls). Skin response to 1,2,4-trichlorobenzene was characterized grossly by dermal irritation directly related to the concentration of test material; there were the associated histologic changes of acanthosis and hyperkeratosis; there was no primary follicular involvement characteristic of acneform dermatitis. Dermal responses to hexachlorodiphenyloxide consisted of gross follicular enlargement, with waxy excretion on pressure, and severe scaling. The affected ear appeared thickened up to three times normal size and histologic sections showed primary follicular involvement characterized by marked thickening of the sheath and marked distention of the follicles with keratin, with resultant comedone formation, typical of chloracne.

Pilot laboratory experiments were conducted to assess preliminarily the possibility of effects on biota from exposures of various durations to electric fields of 10 and 20 volts per meter and magnetic fields of 1.0 and 2.0 gauss at two extremely low frequencies, 45 and 75 Hz. In some experiments the electric field was set up in a conductive medium (moist soil, water, or nutritive medium) and in others in the air. In one study, 0.5 mA current at these frequencies was passed through the bodies of dogs concurrent with the application of the fields. The laboratory studies consisted of the following with possible electromagnetic effects indicated, if any: Rat Fertility Studies - no effects; Rat Avoidance Learning Study - no effects; Canine Physiology Study - possible elevated blood pressure and rectal temperature; Insect Mutagenic Study - possible dominant lethal mutation rate increase; Bacteria Mutagenesis Study - no effects; Plant Cytogenetic Study - no effects; Seed Germination and Early Growth Study - possible growth inhibition in one of three species; Multiple-Species Electric Field Preception and Preference Study - no preference effects except in a few turtles which reacted to the onset of 20 v/m fields. Fish 'preceived' the onset of 10 v/m fields.