Timed-pregnant Fischer 344 rats were exposed whole body to N,N-dimethylethanolamine vapor for 6 h per day on gestational days 6-15 at mean (+/- SD) analytically measured concentrations of 10.4 +/- 0.86, 29.8 +/- 2.14 and 100 +/- 4.9 ppm. Dams were sacrificed on gestational day 21. There was no maternal mortality in any exposed groups. Maternal toxicity observed in the 100 ppm group included reduced body weight during and after exposures, reduced weight gain during exposure and ocular changes (darkened, cloudy and hazy eyes, slight corneal vascularization and fixed, dilated pupils). Ocular effects were also noted in the other two exposure groups; the effects were quite marked at 30 ppm but only minimal and transient at 10 ppm. There were no effects of treatment on any gestational parameters, including pre- and postimplantation loss or sex ratio. Fetal body weights per litter were statistically significantly increased at 100 ppm relative to controls. There were no increases in the incidences of total malformations by category (external, visceral or skeletal) or individually. The incidence of six skeletal variations out of 120 noted differed in exposed groups relative to that of control. Four of these variations were decreases in incidence; only one fetal variation, the split (bipartite) cervical centrum, was elevated at 100 ppm relative to controls. In the absence of any other indications of delayed ossification or fetal body weights, the observed fetal variation does not suggest a consistent pattern of fetal toxicity. Hence, the no-observed-adverse-effect level is around 10 ppm for maternal toxicity and at or above 100 ppm for embryofetal toxicity and teratogenicity.

Aerosols↗

PubMedDate not supplied

Short-term and subchronic repeated exposure studies with 5-ethylidene-2-norbornene vapor in the rat.

5-Ethylidene-2-norbornene (ENB) is an industrial chemical whose physical properties indicate a likelihood for vapor exposure to humans. The potential for target organ or cumulative toxicity was investigated in rats exposed for 6 h per day for 9 days over an 11-day period, or 66 or 67 days over 14 weeks; 4- week recovery animals were added to the 14-week study. Mean analytically measured ENB vapor concentrations (+/-SD) were 52 +/- 1.5, 148 +/- 2.3 and 359 +/- 4.2 ppm for the 9-day study and 4.9 +/- 0.14, 24.8 +/- 1.23 and 149 +/- 4.40 ppm for the subchronic study. There were no mortalities, and clinical signs were limited to periocular swelling and/or encrustation, and urogenital area wetness. Body weight gain was decreased in the 9-day 359 ppm females and in the subchronic 24.8 and 149 ppm males. A minimal macrocytic anemia was present in subchronically exposed males, which resolved during the recovery period. In the 9-day study increased liver weight was associated with minimal centrilobular hepatocytomegaly and cytoplasmic basophilia with no degenerative or serum biochemical liver function changes, suggesting an adaptive response. Only relative liver weights were increased in the subchronic 149 ppm males, and no histopathological findings were observed. Principal target organ effects were to the thyroid gland, which showed an exposure concentration-related, but not exposure time-related, depletion of follicular colloid that resolved during the recovery period, together with light microscopic evidence for a hypertrophic and hyperplastic response in the follicular epithelium that resolved more slowly. The thyroid colloid depletion was a graded effect without a clear no-effect concentration, but was not accompanied by any clinical or clear biochemical evidence for thyroid dysfunction. A no-effect concentration of 4.9 ppm was established for the follicular cytological effects.

Administration, Inhalation↗

PubMedDate not supplied

Comparative acute toxicity and primary irritancy of the ethylidene and vinyl isomers of norbornene.

The acute toxicity and primary irritancy of the industrial chemicals 5-ethylidene-2-norbornene (ENB) and 5-vinyl-2-norbornene (VNB) were studied. They are of moderate acute peroral toxicity in the rat, with LD50 values for ENB of 2.54 (male) and 5.66 (female) ml kg(-1), and for VNB of 5.90 (male) and 11.9 (female) ml kg(-1). Percutaneous toxicity is slight in the rabbit by 24-h occluded contact, with no mortalities for ENB up to 8.0 ml kg(-1) and only one mortality (male) at 16.0 ml kg(-1) VNB. Dynamically generated saturated vapor atmosphere LT50 values for ENB in the rat were 75 (male) and 125 (female) min, and for VNB they were 28 (male) and 37 (female) min. The 4-h LC50 values for ENB were 2717 (male) and 3015 (female) ppm, and for VNB they were 2231 (male) and 2518 (female) ppm. Intravenously, the ENB LD50 ranged from 0.09 (male rabbit) to 0.11 ml kg(-1) (female); corresponding LD50 values for VNB were 0.10-0.05 mg kg(-1). Acute neurotoxic signs were seen by the intravenous and inhalation routes of exposure, including tremors, ataxia and convulsions; the latter were sufficient to cause vertebral column luxation or fracture, producing spinal cord compression and resultant hindlimb paralysis. Both ENB and VNB are moderately irritating to the skin (rabbit), causing erythema and edema, but not necrosis. Both materials cause slight conjunctival hyperemia and chemosis in rabbits, but not corneal injury.

Administration, Inhalation↗

PubMedDate not supplied

Investigations on the in vitro and in vivo genotoxic potential of 5-vinyl-2-norbornene.

5-Vinyl-2-norbornene (VNB: CAS no. 3048-64-4), an industrial chemical that produces hyaline droplet nephropathy in the male rat with associated alpha2u-globulin increases, was investigated in vitro and in vivo for its genotoxic potential. A Salmonella typhimurium reverse mutation assay (strains TA98, 100, 1535, 1537, 1538) was negative both without (dose range 0.003-0.3 mg per plate) and with (0.003-0.3 mg per plate) metabolic activation. A forward gene mutation test in Chinese Hamster Ovary (CHO) cells (HGPRT locus) did not show any significant concentration-related increases in mutation frequencies in the absence (0.01-0.1 mg ml[-1]) or presence (0.005-0.1 mg ml[-1]) of metabolic activation. In a sister chromatid exchange (SCE) test, VNB did not produce statistically significant or dose-related increases in the incidence of SCEs in the absence (0.02-0.06 mg ml[-1]) or presence (0.005-0.03 mg ml[-1]) of metabolic activation. A bone marrow chromosome aberration test was conducted in groups of 10 male and 10 female Sprague-Dawley rats exposed for 6 hr/day for 5 consecutive days to mean (+/- SD) VNB vapor concentrations of 0 (air control), 48.1 +/- 1.29, 146 +/- 9.2, or 336 +/- 8.5 ppm. Marrow was collected 6 and 24 hr after the final exposure. No statistically significant or dose-related increases in chromosomal aberrations occurred in the VNB-exposed animals. 5-Vinyl-2-norbornene did not show any potential for genotoxic activity with this in vitro-in vivo battery of tests.

Animals↗

PubMedDate not supplied

Subchronic inhalation toxicity of 3.5-microm diameter carbon fibers in rats.

No effects were seen when rats were exposed for 6 h day(-1), 5 days per week, for 16 weeks to an atmosphere of 20 mg m(-3) of carbon fibers (25 x 10(6) fibers m(-3)) and small amounts of fiber particulate resulting from preparation of the ultimate test material. The carbon fibers were made from polyacrylonitrile fiber. They were 3.5 microm in diameter and 72% were 10-60 microm long. Histopathological evaluations were made after each of 4, 8, 12 and 16 weeks of exposure and after 36 and 80 weeks of recovery. No effects due to the exposure were seen, as judged by clinical signs, body weight, organ weight, organ-body weight ratios, organ-brain weight ratios, gross and microscopic examination of internal organs, special stains of lung tissue for fibrous tissue, reticulin and fat and pulmonary function measurements. Non-fibrous particles were seen in the pulmonary lymphoid clearance system and in alveolar histiocytes (macrophages) at each histopathological evaluation period. Non-fibrous particles were seen in histiocytes in the mucociliary clearance system after 12 and 16 weeks of exposure. Fibers were seen in the nasal cavity at each histopathological examination. Fibers also occasionally were seen in tissue sections from the lower respiratory tract, but their exact location in life could not be determined. There was no indication of fibrosis.

Animals↗

PubMedDate not supplied

Developmental toxicity evaluation of rats dosed orally or cutaneously with octoxynol-9.

Pregnant CD rats were dosed cutaneously (530, 1600 or 4270 mg kg-1 day-1) or fed diets containing octoxynol-9 (70 or 340 mg kg-1 day-1) during the major period of organogenesis. Monitors for maternal toxicity included clinical observations, body weight, organ weight and food consumption. Fetuses were evaluated for body weight and for external, visceral and skeletal abnormalities. Maternal effects were noted in dams dosed cutaneously with 4270 mg kg-1 day-1 octoxynol-9, and included excoriation, exfoliation/desquamation in the area of treated skin, urine stains, perinasal encrustation and audible respiration. In addition, maternal weight gains were reduced during the dosing period. Octoxynol-9, dosed orally or cutaneously to gravid rats, had no effect on pregnancy performance but increased the incidences of a number of developmental abnormalities in the offspring. Most notable was the induction of supernumerary ribs arising from the lumbar and cervical regions. Other skeletal abnormalities included decreased incidences of poorly ossified supraoccipital and hyoid bones and zygomatic arches, suggesting an enhanced ossification in the neck and head regions. Increased incidences of two fetal visceral abnormalities, displaced tests in dams dosed orally with 340 mg kg-1 day-1 and atelectasis in dams dosed cutaneously with 1600 or 4270 mg kg-1 day-1 were also observed.

Abnormalities, Drug-Induced↗