Response of pulmonary macrophages to lead.

The intratracheal instillation of moderate doses of PbO to Long-Evans strain rats resulted in a significant increase in the number of recoverable pulmonary alveolar macrophages. The viability of recovered cells was remarkably constant throughout the experimental period of 40 days. The results obtained indicate a low order of toxicity of PbO to alveolar macrophages and show that the mucociliary escalator is a significant route of excretion of PbO from the respiratory tract. The in vitro survival of macrophages from PbO-treated rats was significantly reduced. Survival of cells from both treated and control animals was somewhat enhanced by the addition of formalinized lymphocytes to the culture medium. Morphological changes and evidence of phagocytosis are discussed.

Dominant lethal studies with technical chlordane, HCS-3260, and heptachlor: heptachlor epoxide.

Male albino mice in groups of eight were each given single doses, either by gavage or by intraperitoneal injection, of either technical chlordane (50 or 100 mg/kg), HCS-3260 (50 or 100 mg/kg), or heptachlor:heptachlor epoxide (25:75) (7.5 or 15 mg/kg). The males were subsequently mated with three untreated females for six consecutive weeks. No dominant lethal changes among females that had mated with the treated males were produced.

Reproductive and teratologic studies with isoflurane.

The volatile anesthetic, Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), was investigated at anesthetic concentrations to determine its effects on reproduction in rats treated prior to mating, on fetal development in rats and rabbits when administered during various stages of gestation, and on fetal survival in rats treated during late pregnancy. No adverse reproductive effects were observed, and no evidence of teratogenic activity was obtained. Fetal survival was low in rats exposed during late pregnancy but whether or not this finding is related to Isoflurane exposure requires confirmation.

Reproductive and peri- and postnatal studies with hexachlorophene.

PIP: Hexachlorophene (HCP) in dosages of 0, 5, or 10 mg/kg/day was administered by gavage to 30 male and 60 female rats for 63 and 14 days, respectively, prior to mating. Dosing was continued until Day 14 of gestation for 1/2 the females and until after weaning for the other 1/2. Mating and fertility were not affected, and progeny were delivered in normal numbers, were free of structural abnormalities, and developed normally throughout lactation. A slight reduction in pup survival was observed at the 10 mg/kg dose level. Treatment of females with either 15 or 30 mg HCP/kg/day during the last third of gestation and until weaning caused reductions in the body weights and survival of the progeny. Reduced body-weight gain and some deaths were found among the maternal animals treated with 30 mg HCP/kg/day. At this level, an increase in stillbirths was seen, although all progeny, viable and stillborn, were structurally normal.^ieng

Subacute toxicity studies with sodium saccharin and two hydrolytic derivatives.

The subacute toxicity of sodium saccharin and 2 hydrolytic derivatives, o-sulfamoylbenzoic acid (Compound I) and ammonium o-carboxybenzene sulfonate (Compound II) was evaluated by feeding each of the compounds alone at a dietary level of 20 000 ppm to both beagle dogs and albino rats. Additionally, groups of dogs and rats were fed combinations of the 3 materials at levels up to 20 000 ppm (2000 ppm sodium saccharin, 9000 ppm of both Compound I and II). Dogs were maintained on the test diets for 16 weeks, rats for 13 weeks. No signs of a pharmacotoxic response to the test materials were observed. Parameters determined for treated animals, including growth, food consumption, hematologic profiles, clinical blood chemistry studies, urinalyses, organ weight and ratio data, and both gross and microscopic pathologic evaluation, were not significantly different from control values. From these findings, it is suggested that there is little toxicologic hazard associated with ingestion of the 2 hydrolytic derivatives of sodium saccharin.

Reproductive, teratologic, and mutagenic studies with some polydimethylsiloxanes.

The purpose of these studies was to evaluate the effects of selected polydimethylsiloxanes on reproduction and fetal development in rats and rabbits and to determine the mutagenic potential of one such material in mice. In two separate three-phase studies in rats and rabbits with a 350 centistoke medical grade fluid, the only significant effect noted was an apparent dose-related incidence of in utero mortality at dose levels of 200 and 1,000 mg/kg sc in rats in one study. No evidence of fetotoxicity was obtained in the second study at the same dose levels. The incidence of talipes varus at a sc dose level of 200 mg/kg in rabbits (8.8%) is at or above that expected for control populations. The nonoccurrence of talipes varus at the higher level of 1,000 mg/kg and the absence of this defect in the companion study casts doubt on the significance of this finding. A 7-cs pump fluid was nonteratogenic in rats at oral doses as high as 1,000 mg/kg and was nonmutagenic in ma1e mice at ip doses of 5 and 10 g/kg. A 10-cs fluid was nonteratogenic in rabbits at a dermal dose level of 200 mg/kg.

Reproductive and teratologic studies with halothane.

PIP: 9 groups of 10 male and 20 female Charles River albino rats were used in a 3-phase study to determine the effect of 2-bromo-2-chloro-1,1,1,-trifluroethane (halothane) in anesthetic concentrations, on reproduction in rats treated prior to mating, on fetal development in rats and rabbits when administered during various stages of gestation, and on fetal survival in rats treated during late pregnancy. Exposures were conducted in a 250-liter Plexiglas chamber. Food consumption and body weights were determined at 5-day intervals. At 100 days of age, females were caged with a male from the same group on a rotating basis until fertilization was confirmed. Half of the females from each group were sacrificed on Day 14 of gestation and the ovaries and uterus examined, corpora lutea, implantation sites, resorption sites, and fetuses counted. The remaining females were allowed to go to term. In teratologic studies, pregnant rats in 3 groups, were exposed on gestation Days 1-5 to mean halothane concentrations of 1.35%, on Days 6-10 to concentrations of 1.43% and on Days 11-15 to 1.43%. Rabbits were exposed to 2.16, 2.16 and 2.3% on respective gestation days. Perinatal and lactation performance in rats was tested after inhalation of halothane at a mean concentration of 1.44% for 1 hour/day on gestation Days 15-20. Adverse reproductive effects were absent as was evidence of teratologic activity. There was a suggested effect on fetal survival in rats exposed during late pregnancy, but further research is required to give significant results.^ieng

Investigation of hexachlorophene for dominant lethal effects in the mouse.

Hexachlorophene (HCP) was studied for mutagenic effects in the dominant lethal test on mice. Groups of male mice were treated with either 2.5 or 5.0 mg hexachlorophene per kg body weight as a single intraperitoneal injection. Control animals were treated with the propylene glycol vehicle. Each male was mated with 3 untreated females for each of 8 consecutive weeks with the uterus of the females examined at mid-pregnancy for signs of early embryonic death. Treatment did not alter mating capacity and fertility of the males. The administration of hexachlorophene had no influence on pre- or post-implantation losses. An increase in early resorptions among female mice bred to males treated with the reference compound, methyl methanesulfonate (MMS) given a single i.p. injection of 100 mg/kg, indicated the susceptibility of the mouse strain used to a known mutagen. It is concluded that hexachlorophene at maximally tolerated doses is not mutagenic in the dominant lethal test in mice.