Ocular injury with high-pressure paint: a case report.

Chemical injury to the eye is an ophthalmic emergency that can be caused by a work-related accident or common household products. Uradil SZ261 G3Z-65 is a resin containing butyl gycol (2-butoxyethanol) and ethyl ethanol amine (2-dimethyaminoethanol). It is used in stoving enamels for interior and exterior use. The authors report a case of ocular surface injury with a highpressure industrial spray paint-Waterborne Stoving Gentian Blue containing Uradil.

The sea urchin embryo as a model for mammalian developmental neurotoxicity: ontogenesis of the high-affinity choline transporter and its role in cholinergic trophic activity.

Embryonic development in the sea urchin requires trophic actions of the same neurotransmitters that participate in mammalian brain assembly. We evaluated the development of the high-affinity choline transporter, which controls acetylcholine synthesis. A variety of developmental neurotoxicants affect this transporter in mammalian brain. [3H]Hemicholinium-3 binding to the transporter was found in the cell membrane fraction at stages from the unfertilized egg to pluteus, with a binding affinity comparable with that seen in mammalian brain. Over the course of development, the concentration of transporter sites rose more than 3-fold, achieving concentrations comparable with those of cholinergically enriched mammalian brain regions. Dimethylaminoethanol (DMAE), a competitive inhibitor of choline transport, elicited dysmorphology beginning at the mid-blastula stage, with anomalies beginning progressively later as the concentration of DMAE was lowered. Pretreatment, cotreatment, or delayed treatment with acetylcholine or choline prevented the adverse effects of DMAE. Because acetylcholine was protective at a lower threshold, the DMAE-induced defects were most likely mediated by its effects on acetylcholine synthesis. Transient removal of the hyaline layer enabled a charged transport inhibitor, hemicholinium-3, to penetrate sufficiently to elicit similar anomalies, which were again prevented by acetylcholine or choline. These results indicate that the developing sea urchin possesses a high-affinity choline transporter analogous to that found in the mammalian brain, and, as in mammals, the functioning of this transporter plays a key role in the developmental, trophic activity of acetylcholine. The sea urchin model may thus be useful in high-throughput screening of suspected developmental neurotoxicants.

Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos.

BACKGROUND: Choline is an essential nutrient in methylation, acetylcholine and phospholipid biosynthesis, and in cell signaling. The demand by an embryo or fetus for choline may place a pregnant woman and, subsequently, the developing conceptus at risk for choline deficiency. METHODS: To determine whether a disruption in choline uptake and metabolism results in developmental abnormalities, early somite staged mouse embryos were exposed in vitro to either an inhibitor of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), or an inhibitor of phosphatidylcholine synthesis, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH(3)). Cell death following inhibitor exposure was investigated with LysoTracker Red and histology. RESULTS: Embryos exposed to 250-750 microM DMAE for 26 hr developed craniofacial hypoplasia and open neural tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed to 125-275 microM ET-18-OCH(3) exhibited similar defects or expansion of the brain vesicles. ET-18-OCH(3)-affected embryos also had a distended neural tube at the posterior neuropore. Embryonic growth was reduced in embryos treated with either DMAE (375, 500, and 750 microM) or ET-18-OCH(3) (200 and 275 microM). Whole mount staining with LysoTracker Red and histological sections showed increased areas of cell death in embryos treated with 275 microM ET-18-OCH(3) for 6 hr, but there was no evidence of cell death in DMAE-exposed embryos. CONCLUSIONS: Inhibition of choline uptake and metabolism during neurulation results in growth retardation and developmental defects that affect the neural tube and face.

The skin sensitization potential of four alkylalkanolamines.

The skin sensitization potential of 4 alkylalkanolamines (N-methylethanolamine, N,N-dimethylethanolamine, N-methyldiethanolamine and N,N-diethylethanolamine), was evaluated in a guinea pig maximation procedure by the method of Magnusson and Kligman. While all 4 alkylalkanolamines tested were irritating to the guinea pig skin, only N-methylethanolamine showed potential to induce allergic contact dermatitis. None of the remaining 3 alkylalkanolamines exhibited clear skin responses suggestive of sensitization.

Evaluation of the genotoxic potential of alkylalkanolamines.

Three alkylalkanolamines, N,N-dimethylethanolamine, N-methyldiethanolamine, and tert-butyldiethanolamine, were evaluated for potential genotoxic activity using the Salmonella/microsome reverse gene mutation test, the CHO/HGPRT forward gene mutation test, a sister chromatid exchange test in cultured CHO cells, and an in vivo peripheral blood micronucleus test in Swiss-Webster mice. None of the three alkylalkanolamines produced any significant or dose-related increases in the frequencies of mutations, sister chromatid exchanges or micronuclei. These results indicate that N,N-dimethylethanolamine, N-methyldiethanolamine, and tert-butyldiethanolamine are not genotoxic in the tests conducted.

Developmental toxicity study in Fischer 344 rats by whole-body exposure to N,N-dimethylethanolamine vapor.

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.

Effect of lifetime administration of dimethylaminoethanol on longevity, aging changes, and cryptogenic neoplasms in C3H mice.

The effects of lifetime treatment with dimethylaminoethanol on longevity and cryptogenic neoplasm formation were studied in females of two mouse sub-lines, the C3H/HeN which carries a germinal mammary tumor provirus and the C3H/HeJ(+) which also carries the exogenous mammary tumor virus. Administration in the drinking water of 10 mM dimethylaminoethanol to the C3H/HeN mice or 15 mM to the C3H/HeJ(+) mice did not result in significant differences between treated and untreated groups in average survival. No changes in age-related organ structure or morphology were observed with dimethylaminoethanol treatment, except for an apparent decrease in the amount of lipofuscin in the liver judged in histological sections. Among untreated C3H/HeJ(+) females, 89% developed neoplasms of the mammary gland, ovary, liver, lung and reticuloendothelial system, while the incidence was 88% in the treated mice. In C3H/HeN females, neoplasms of the mammary gland, ovary, liver, lung and lymphatic system occurred in 57% and in 60% of treated mice. Also, there was no statistically significant difference between control and treated animals in the age of onset or the type of specific neoplasms. Dimethylaminoethanol did not induce any neoplasms.

Dimethylethanolamine: acute, 2-week, and 13-week inhalation toxicity studies in rats.

Dimethylethanolamine (DMEA) is a volatile, water-soluble amine that has applications in the chemical and pharmaceutical industries. These studies evaluated the acute and subchronic inhalation toxicity of DMEA. Acute (4-hr) exposures of Wistar rats to DMEA vapor resulted in an LC50 value (95% confidence limits) of 1641 (862-3125) ppm. Clinical signs of nasal and ocular irritation, respiratory distress, and body weight loss were observed in rats exposed to 1668 ppm DMEA and higher. In the 2-week study, F-344 rats exposed to 98, 288, or 586 ppm DMEA for 9 days (6 hr/day) during an 11-day period also exhibited signs of respiratory and ocular irritation (except the 98 ppm group). All animals of the 586 ppm group and 4 of 15 male rats of the 288 ppm group died. Body weight values for the 288 ppm group were reduced to about 75% of preexposure values, while the 98 ppm group gained 35% less weight than controls. Statistically significant differences in clinical pathology parameters (288 ppm group) and in organ weight values (288 and 98 ppm groups) probably resulted from the decreased food consumption and not from specific target organ toxicity. In the groups evaluated histologically (the 98 and 288 ppm groups) the eye and nasal mucosa were the primary target organs. In the 13-week subchronic study, F-344 rats were exposed to 0, 8, 24, or 76 ppm DMEA for 6 hr/day, 5 days/week for 13 weeks. The principal exposure-related changes were transient corneal opacity in the 24 and 76 ppm groups; decreased body weight gain for the 76 ppm group; and histopathologic lesions of the respiratory and olfactory epithelium of the anterior nasal cavity of the 76 ppm group and of the eye of several 76 ppm group females. Rats maintained for a 5-week recovery period only exhibited histological lesions of the nasal tissue, with the lesions being decreased in incidence and severity. DMEA acts primarily as an ocular and upper respiratory tract irritant and toxicant at vapor concentrations of 76 ppm, while 24 ppm or less produced no biologically significant toxicity in rats. Thus, 24 ppm was considered to be the no-observable-effect level.

Effects of dietary choline and N,N-dimethylaminoethanol on lung phospholipid and surfactant of newborn rats.

Pups delivered by rats fed during pregnancy a choline-deficient (CD) diet containing 1% N,N-dimethylaminoethanol (DME) die within 36 hr of birth. The concentrations of sphingomyelins, phosphatidyl cholines, and disaturated phosphatidyl cholines in the lungs of these pups are lower than those in the lungs of pups delivered by dams fed a choline-supplemented diet (CS). The amount of surfactant isolated from the lung of the pups was also reduced. These changes were accompanied by alterations in the activity of enzymes (choline kinase, EC 2.7.1.32; choline phosphotransferase, EC 2.7.8.2) involved in the synthesis of lung lecithins. These results strongly suggest that pups delivered by dams fed a CD diet containg 1% DME die of respiratory distress syndrome due to altered metabolism of lung surfactant.