B.K.J. Leong

The effect of maternally inhaled trichloroethylene, perchloroethylene, methyl chloroform, and methylene chloride on embryonal and fetal development in mice and rats☆

Abstract These studies evaluated the effects of trichloroethylene, perchloroethylene (tetrachloroethylene), methyl chloroform (1,1,1-trichloroethane) and methylene chloride (dichloromethane) on mouse and rat embryonal and fetal development at a concentration two times the maximum allowable excursion limit for human industrial exposure as defined by ACGIH, 1973 (300, 300, 875, 1250 ppm, respectively). Groups of pregnant Sprague-Dawley rats and Swiss Webster mice were exposed to each solvent 7 hr daily on days 6–15 of gestation. None of these solvents caused significant maternal, embryonal or fetal toxicity and none was teratogenic in either species of animal at the concentrations studied. Elevated carboxyhemoglobin content was observed in mice and rats exposed to methylene chloride.

Embryo- and fetotoxicity of inhaled chloroform in rats

Abstract This study evaluated the effects of inhalation of subanesthetic concentrations of chloroform on rat embryonal and fetal development. Pregnant Sprague-Dawley rats were exposed to 30, 100 or 300 ppm chloroform for 7hr/day on days 6 through 15 of gestation. Exposure to chloroform caused an apparent decrease in the conception rate and a high incidence of fetal resorption (300 ppm), retarded fetal development (30, 100, 300 ppm), decreased fetal body measurements (30, 300 ppm) and a low incidence of acaudate fetuses with imperforate anus (100 ppm). Chloroform was not highly teratogenic but was highly embryotoxic. The results of this study disclosed no relationship between maternal toxicity and embryo or fetotoxicity as the result of exposure to chloroform by inhalation.

Embryo- and fetotoxicity of inhaled carbon tetrachloride, 1,1-dichloroethane and methyl ethyl ketone in rats

Abstract These studies evaluated the effects of subanesthetic concentrations of carbon tetrachloride, 1,1-dichloroethane and methyl ethyl ketone on rat embryonal and fetal development. Groups of pregnant Sprague-Dawley rats were exposed to each solvent 7 hr/day on days 6 through 15 of gestation. All 3 solvents caused some degree of retarded fetal development, such as delayed ossification of sternebrae. In addition to this degree of embryotoxicity, exposure to methyl ethyl ketone, but not to carbon tetrachloride or 1,1-dichloroethane, also caused a low incidence of acaudia, imperforate anus and brachygnathia. These studies do not reveal a correlation between the toxicity incurred by the mother exposed to these solvents and that incurred by the embryos or fetuses.

Testicular atrophy from inhalation of ethylene oxide cyclic tetramer

Abstract The inhalation toxicity of ethylene oxide cyclic tetramer vapor (EOCT), a synthetic compound, has been evaluated. Rats were exposed to 0.5 and 1.0 ppm ethylene oxide cyclic tetramer vapors for 7 hr/day, 5 days/week for 3 weeks. Both concentrations produced marked testicular atrophy which was associated with degeneration of the germinal epithelium. This effect appeared to be long lasting since testicular atrophy persisted for as long as 4 months post exposure. Even though the rats exhibited normal sexual activity, they remained sterile. Atrophy of the prostate gland and seminal vesicles was also noted immediately following exposure. However, within 2–3 weeks these organs returned toward normal appearance and size. Administration of testosterone, 10 mg/kg, prevented atrophy of the prostate and seminal vesicles but not that of the testes. Exposure to 1.0 ppm of EOCT vapor produced a prominent degradation of conditioned behavioral performances, depression of food and water intake, retardation of growth and body tremors. These effects were reversible. At 0.5 ppm of EOCT vapor, these latter effects were much less severe.

The effects of maternally inhaled vinyl chloride on embryonal and fetal development in mice, rats, and rabbits.

Abstract These studies evaluated the effects of inhaled vinyl chloride on mouse, rat, and rabbit embryonal and fetal development. Groups of pregnant CF-1 mice, Sprague-Dawley rats and New Zealand white rabbits were exposed to 500 ppm of vinyl chloride 7 hr daily during the period of major organogenesis. Subsequently, other groups of mice were similarly exposed to 50 ppm of vinyl chloride and rats and rabbits were exposed to 2500 ppm of vinyl chloride. While maternal toxicity was observed, vinyl chloride alone did not cause significant embryonal or fetal toxicity and was not teratogenic in any of the species at the concentrations tested. Maternal toxicity was more prominent among mice than among rats and rabbits. Simultaneous exposure of some of the pregnant animals to vinyl chloride by inhalation plus 15% ethanol in the drinking water resulted in toxic effects greater than those associated with exposure to vinyl chloride alone in the three species. The maternal toxicity was enhanced to an extent greater than the embryotoxicity.

A lifetime study of rats and mice exposed to vapors of bis(chloromethyl)ether

Abstract Groups of rats and mice were exposed to 100, 10, and 1 parts per billion (ppb) of bis(chloromethyl)ether (BMCE) 6 hr/day, 5 days/week for 6 months and subsequently observed for the duration of their natural lifespan. Evaluation of groups of rats sacrificed at the end of the 6-month exposure period revealed no abnormalities in hematology, exfoliative cytology of lung washes, or cytogenetic parameters of bone marrow cells. However, 86.5% of the surviving rats which had been exposed to 100 ppb of BCME subsequently developed nasal tumors (esthesioneuroepithelioma) and approximately 4% of the rats developed pulmonary adenomas. This tumorigenic response was not observed in rats exposed to 10 or 1 ppb of BCME. Mice exposed to 100 ppb of BCME did not develop nasal tumors, but showed a significant increase in incidence of pulmonary adenomas over the control mice. Mice exposed to 10 or 1 ppb of BCME did not show a significant increase in incidence of pulmonary adenomas. These data demonstrated the existence of nontumorigenic or no-observable-effect-levels of BCME vapor for a 6-month inhalation exposure in rats and mice.

Subchronic Toxicity Study of 1,2,4-Trichlorobenzene in the Rat, Rabbit and Beagle Dog

Male rats, rabbits and dogs were exposed to 0, 30 or 100 ppm of 1,2,4-trichlorobenzene (TCB) for 7 hours/day, 5 day/week for 30 exposures in 44 days. In all 3 species, there were no significant effects on body weight gain, hematologic and serum biochemical tests or gross and histopathologic appearance of tissues. At 100 ppm TCB, both rats and dogs had increased liver weights, and the rats also had increased relative kidney weight at this higher exposure level. Urinary excretion of porphyrins were increased in rats exposed to 30 or 100 ppm TCB, most likely as a result of hepatic induction by TCB. In view of the reversibility of this porphyrin induction noted in a companion study, and the absence of other indications of discernible toxicity, this increased urinary excretion of porphyrins is best considered more of a compound-specific physiologic effect rather than a toxic effect.

Repeated inhalation toxicity of diphenyl oxide in experimental animals

Abstract Repeated inhalation studies using rats, rabbits, and dogs were conducted at mean exposure concentrations of 0, 4.9, and 10.0 ppm diphenyl oxide (DPO) vapor. Exposures were 7 hr per day, 5 days per week for a total of 20 exposures. Additional groups of rats were exposed 7 hr per day to 0 or 20 ppm DPO vapor for a total of 20 exposures. No signs of toxicity or irritation were observed in animals exposed to 4.9 ppm. Eye and nasal irritation were observed in rats and rabbits but not dogs exposed to 10.0 ppm and in rats exposed to 20 ppm. Aside from this irritation no other signs of toxicity were discerned.

Utilities and Limitations of Behavioral Techniques in Industrial Toxicology

When a manufacturer proposes to produce a new chemical, he has an obligation to the health of his workers and customers. Our laboratory, one of the first industrial toxicology and industrial hygiene laboratories in this country, was established in 1933 to help meet this obligation. As a result, we were ready when the enactment of the Occupational Health and Safety Act of 1971 made these research efforts legally obligatory.

Tissue response to ceramic foam dust following intratracheal and intraperitoneal administration

Abstract Ceramic Foam (CF) is manufactured by The Dow Chemical Company from an illitic clay for use as a thermal insulator. The pathologic response following intratracheal or intraperitoneal (ip) administration of 40 mg of CF dust (1–11 μ particles) was characterized in rats killed serially up to 177–187 days post-administration. CF did not alter the pulmonary architecture and was rapidly cleared from the lung. Thus, CF can be classified as a nonfibrogenic nuisance dust. The ip administration of CF invoked only a minimal nonprogressive inflammatory response. In contrast to CF, either ip or intratracheal administration of silica, a classical fibrogenic dust, induced a progressive inflammatory response with the deposition of abundant reticulum stroma.