Deoxyribonucleic acid reassociation was used to determine relatedness among protei and providenciae and between these organisms and other members of the family Entero bacteriaceae. Ewing described four biogroups in Prov. alcalifaciens and two biogroups in Prov. stuartii. These are based on the production of gas from glucose and the fermentation of adonitol and inositol (17; see Table 12).Several other taxonomic proposals for Proteus and Providencia have been reviewed by Rauss (38). The best known of these is Kauffmann's recommendation of four genera: Proteus, Morganella, Rettgerella, and Providencia (26). Kauffmann included Prot. mirabilis and Prot. vulgaris in the species Prot. hauseri. The fourgenus concept with Prot. hauseri was endorsed by Rauss (38)) and Coetzee (7) endorsed the four-genus system while retaining P. mira bizis and P. vulgaris. In a review (7), Coetzee documented serological differences in enzymes among protei. Therefore, there are antigenic, structural, and biochemical data that suggest genetic divergence among protei. With the exception of Prot. morganii (50 mol% guanine plus cytosine [G+C] in the deoxyribonucleic acid [DNA]), Proteus and Prouidencia species have substantially lower G+C ratios than other Entero bacteriaceae, whose DNA contains 50 to 58 mol% G+C. Prot. mirabilis and Prot. vulgaris contain 38 to 40 mol% G+C (19, 23, 29), Prot. rettgeri has 39 to 41.5 mol% G+C, and providenciae are reported to have 40 to 42 mol% G+C. 269

Octamethylcyclotetrasiloxane, D4, is a low viscosity, silicone fluid consisting of four dimethyl-siloxy units ((CH3)2SiO)4 in a cyclic structure. It is primarily used as a building block in the industrial synthesis of long chain silicone polymers. The combination of D4 with decamethylcyclopentasiloxane (D5) is commonly referred to as cyclomethicone which has a wide range of applications as a formulation aid in personal care products. To extend the existing database regarding the biological activities of D4, a 28 day whole body vapor inhalation study was conducted using Fischer 344 rats at 0 (room air), 7, 20, 60, 180 and 540 ppm for 6 hours/day, 5 days/week. Parameters measured included body weights, organ weights, gross pathology, histopathology, serum chemistries, and urinalysis. In addition to these standard toxicological endpoints, the ability of D4 exposed animals to mount an IgM antibody response was evaluated by a splenic antibody forming cell (AFC) assay and a serum enzyme-linked immunosorbant assay (ELISA). The results of this 28-day inhalation study indicate that D4 exposure caused no adverse effects on body weight, food consumption, or urinalysis parameters. In addition, there were no exposure related histopathological alterations at any site for any exposure group. A statistically significant increase in liver weight and the liver to body weight ratio was observed in both male (180-540 ppm) and female (20-540 ppm) rats, which was not observed in the 14-day recovery group animals. There were no other significant organ weight changes. Although statistically significant changes were observed in several hematological and serum chemistry parameters in both the terminal and 14-day recovery animals, the changes were marginal and within the normal range of values for the rat. Under these experimental conditions, there were no alterations noted in immune system function at any of the D4 exposure levels.

Previous investigations from our laboratories have demonstrated that cannabinoids possess immunosuppressive properties. The present studies were designed to determine whether these agents decrease host resistance to infections with Listeria monocytogenes and herpes simplex virus type 2. Host resistance was measured by changes in the 50% lethal dose of the pathogen in cannabinoidtreated and control mice. The effect of cannabinoids on resistance to L. monocytogens was dose dependent. Delta-9-tetrahydrocannabinol at doses of 38, 75, and 150 mg/kg suppressed resistance to infection by 10-, 17-, and 657-fold, respectively. Marijuana extract was less active but significantly reduced resistance to L. moncytogenes at all tested doses. Resistance to systemic herpes simplex virus type 2 infection was decreased 96-fold by delta-9-tetrahydrocannabinol, although marijuana extract was inactive. The doses and regimen of treatment with cannabinoids that produced significant decreases in host resistance were similar to those which caused suppression of delayed-type hypersensitivity to sheep erythrocytes. The possible mechanisms and public health aspects of the decreased host resistance produced by marijuana extract and its cannabinoids are discussed.

D5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to assess potential toxic and immunomodulatory consequences of inhalation exposure to D5. Male and female Fischer 344 rats (25/group) were exposed by whole body inhalation to 0, 10, 25, 75, or 160 ppm D5 6 h/day, 7 days/week for 28 days. Clinical signs, body weights, and food consumption were recorded. On the day following the final exposure, 10 rats/group/sex were euthanized and a complete necropsy performed. Following a 14-day nonexposure recovery period, the remaining 5 rats/sex/group were necropsied. Body and organ weights were obtained and a complete set of tissues was taken for histopathology. Samples were also collected for serum chemistry, hematology, and urinalysis. Immunotoxicology-designated rats (10/sex/group) were immunized with sheep erythrocytes (sRBC) 4 days prior to euthanasia and cyclophosphamide (CYP) was administered i.p. to positive controls on days 24 through 28. The anti-sRBC antibody-forming cell (AFC) response was evaluated in a standard plaque assay. Blood was also collected for examination in the anti-sRBC enzyme-linked immunosorbant assay (ELISA). D5 exposure did not modulate humoral immunity, while the internal control, CYP, produced the expected suppression of the AFC response. D5 exposure caused no adverse effects on body weight, food consumption, or urinalysis parameters. Serum alkaline phosphatase (SAP) was significantly decreased in females at terminal (12%, 160 ppm) and recovery sacrifice. A significant increase in the liver-to-body weight ratio was observed in female animals at the end of exposures (13%, 160 ppm), but was not noted in recovery animals from the same exposure group. In males, significant increases in liver-to-body weight (5%) and thymus-to-body weight (14%) ratios were also noted at the high dose at terminal sacrifice and were not present at recovery. At recovery only, a significant increase in spleen-to-body weight ratios (14 and 17%; 25 and 160 ppm, respectively) was noted. At the end of exposure, histopathological analysis indicated an increased incidence and severity of nasal (Level 1) goblet cell proliferation. Focal macrophage accumulation in the lung was also observed to be increased in incidence in both sexes at 160 ppm. At the end of the recovery period, the effects in both of these organs appeared to be reversible. In summary, D5 inhalation exposure did not alter humoral immunity and caused only minor, transient changes in hematological, serum chemistry, and organ weight values. Histopathological changes were confined to the respiratory tract and appeared to be reversible. The no observed effect level for systemic toxicity, based primarily on the liver weight changes, was 75 ppm.

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