Evaluation of teratogenicity and neurotoxicity with maternal inhalation exposure to methyl chloroform

York, Raymond G.; Sowry, Brenda M.; Hastings, Lloyd; Manson, Jeanne M.

doi:10.1080/15287398209530159

Cited by 22 publications

(11 citation statements)

References 11 publications

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“…Based on the results of this study, the authors concluded that Trichloroethane caused no maternal, embryonal, or fetal toxicity (Schwetz et al 1975). York et al (1982) exposed female Long Evans rats to 2100 ppm Trichloroethane before and/or after mating. The animals were divided into four groups: exposure before and during pregnancy; exposure before pregnancy only, with sham exposure during pregnancy; exposure during pregnancy only, with sham exposure before pregnancy; and sham exposure before and during pregnancy (30 rats/ exposure schedule).…”

Section: Reproductive and Developmental Toxicitymentioning

confidence: 93%

“…The authors concluded that prenatal exposure to 2100 ppm Trichloroethane did not produce any persistent maternal toxicity or teratogenicity and that the decreased fetal weights on gestation day 21 in the pre-and postmating exposure groups suggested only delayed development, as the delivered offspring in the same group had a normal growth rate (York et al 1982). Jones et al (1996) studied the developmental effects of intermittent and continuous prenatal exposure to Trichloroethane in mice.…”

Section: Reproductive and Developmental Toxicitymentioning

confidence: 98%

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Final Report on the Safety Assessment of Trichloroethane

2008

Int. J. of Toxicology

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Trichloroethane functions in cosmetics as a solvent. Although Trichloroethane has been reported to the Food and Drug Administration (FDA) to be used in cosmetic products, an industry survey found that it is not in current use in the cosmetic industry. Trichloroethane is considered a Class I ozone-depleting substance by the Environmental Protection Agency (EPA) and its use is prohibited in the United States, unless considered essential. The FDA has stated that Trichloroethane's use in cosmetics is considered nonessential. Trichloroethane is detected by gas chromatography, gas chromatography-mass spectrometry, and gas-liquid chromatography. In rats, Trichloroethane, whether inhaled or injected, is mostly expelled intact from the body through exhalation. A very small percentage is excreted in the urine. In humans, Trichloroethane is rapidly absorbed through the skin and eliminated in exhaled air and a very small percentage is excreted in urine. Inhaled Trichloroethane is eliminated in exhaled air. Acute oral LD(50) values have been reported as follows: 12.3 g/kg in male rats; 10.3 g/kg in female rats; 11.24 g/kg in female mice; 5.66 g/kg in female rabbits; and 9.47 g/kg in male guinea pigs. Acute toxicity studies using other routes of exposure, including subcutaneous injection and inhalation, produced no evidence of significant toxicity, except at very high exposure levels. Continuous inhalation exposure of rabbits to 750 mg/m(3) for 90 days did not produce any signs of toxicity. Continuous exposure of rats, guinea pigs, rabbits, and monkeys to 500 ppm Trichloroethane for 6 months did not produce any signs of toxicity. Other short-term and subchronic inhalation exposures confirmed acute and short-term exposure findings that the toxic effects of inhalation were a function of both concentration and time. Rats receiving 750 or 1500 mg/kg day(- 1) Trichloroethane in corn oil by oral gavage 5 days per week for 78 weeks had reduced body weights and early mortality. Reduced body weights, decreased survival rates, and early mortality (in females) were found in mice dosed with 3000 or 6000 mg/kg day(- 1) (over the last 58 weeks; lower doses were administered for the first 20 weeks). Mice exposed to prolonged periods of Trichloroethane in an inhalation chamber had increased motor activity at levels up to 5000 ppm. Further increase of concentration of exposure resulted in less of an increase of motor activity until motor activity began to fall below normal at 10,000 ppm. Adverse effects on motor activity in rats were seen at exposures as low as 3000 ppm for 4 h. Rabbits had slight reddening and scaling after 10 24-h applications to abdominal skin of Trichloroethane mixed with 2.4% to 3.0% dioxane, and slight to moderate erythema, slight edema, and slight exfoliation was observed when 75% Trichloroethane and 25% tetrachloroethylene were applied to rabbit ears for 11 days. Undiluted Trichloroethane applied to the clipped backs of guinea pigs produced histopathologic damage in the epidermis. A primary irritation index of 5.22 (ou...

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Section: Reproductive and Developmental Toxicitymentioning

confidence: 93%

Section: Reproductive and Developmental Toxicitymentioning

confidence: 98%

Final Report on the Safety Assessment of Trichloroethane

2008

Int. J. of Toxicology

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“…Planned comparisons among the concentrations of toluene were also used, as well as Tukey’s B post hoc analyses, as appropriate ( p <0.05). Frequency data for malformations were analyzed with Kruskal-Wallis one-way ANOVA by ranks [56]. …”

Section: Methodsmentioning

confidence: 99%

Binge toluene exposure in pregnancy and pre-weaning developmental consequences in rats

Bowen

Hannigan

2013

Neurotoxicology and Teratology

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The persistent rate of abuse of inhaled organic solvents, especially among women of child-bearing age, raises the risk for teratogenic effects of maternal toluene abuse. In this study, timed-pregnant Sprague Dawley rats were exposed from Gestation Day (GD) 8 to GD20 to 12,000 or 8,000 parts per million (ppm) toluene, or 0 ppm (controls) for 30 min twice daily, 60 min total daily exposure. Pups were assessed from postnatal day (PN) 4 to PN21 using a developmental battery measuring growth (i.e., body weight), maturational milestones (e.g., eye opening & incisor eruption), and biobehavioral development (e.g., negative geotaxis & surface righting). Pups exposed in utero to 12,000 ppm or 8,000 ppm toluene weighed significantly less than the non-exposed control pups beginning at PN4 and PN12 (respectively) until PN21. Toluene resulted in significant increases in an index of poor perinatal outcome, specifically a composite of malformations, defined “runting” and neonatal death. No significant delays were observed in reaching maturational milestones. The results reveal that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth retardation and malformations in rats. A comparison of the present, conservative results with findings in previous studies implies that binge patterns of toluene exposure in pregnant rats modeling human solvent abuse can result in developmental and morphological deficits in offspring. These results do not exclude the possibility that maternal toxicity as well as teratogenic effects of toluene may contribute to outcomes. The results suggest that abuse of inhaled organic solvents like toluene may result in similar early developmental outcomes in humans.

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“…Trichloroethane (TCE), is widely used as an industrial solvent and a degreasing agent (12)(13)(14). It is reported that TCE is well absorbed by all exposure routes (15). Several studies with developmental exposure to lower doses than the "safe" dose suggest that TCE exposure can cause various detrimental defects, such as low fetal weight, birth defects, developmental disorders.…”

Section: Introductionmentioning

confidence: 99%

Transgenerational Genetic Effect of Trichloroethane (TCE) on Phenotypic Variation of Acrosomal Proteolytic Enzyme and Male Infertility Risk

Al-Griw¹

2015

IJGG

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Exposure to trichloroethane (TCE), a ambiguous environmental toxicant, has been negatively associated with male reproductive performance. The objective was to investigate, in-vivo, the mutagenic, carcinogenic or teratogenic effect of TCE maternal exposure on sperm quality and testicular cytoarchitecture of F1 generation of mice. A motile sperm separation technique was used to estimate sperm motility and a gelatin slide technique was used to measure the number of the halo around the acrosome of individual sperm as an acrosomal proteolytic enzyme (APA). Animals were followed up for signs of toxicity and mortality. Alterations in testicular tissues have been histopathology investigated. No adverse signs, symptoms and mortality were observed in the animals treated with TCE. Moreover, significant changes were seen in body and testis weight. Results of semen analysis revealed that TCE lead to low sperm count, abnormal sperm morphology, and frequently of sperm motility. These results were correlated with decrease in APA when pre-leptotene or spermatogonial cells were tested, indicating a transgenerational toxic effects. Histopathological examination revealed that TCE insult marked alterations in the microstructures of testicular tissues appeared as severe morphological abnormal spermatozoa and vacuoles. Taken together, these results suggest that early exposure to TCE causes testicular toxicity and poor semen quality. The sperm phenotypes utilized in this study may increase the value of sperm for detection mutagenic developmentally active agents, and agent with anti-fertility effects in mammals. This in-vivo animal model represents a unique platform for assessing human reproductive toxicity potential and genetic risk of various environmental mutagens, carcinogens and teratogens in a rapid, efficient, and unbiased format.

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Evaluation of teratogenicity and neurotoxicity with maternal inhalation exposure to methyl chloroform

Cited by 22 publications

References 11 publications

Final Report on the Safety Assessment of Trichloroethane

Final Report on the Safety Assessment of Trichloroethane

Binge toluene exposure in pregnancy and pre-weaning developmental consequences in rats

Transgenerational Genetic Effect of Trichloroethane (TCE) on Phenotypic Variation of Acrosomal Proteolytic Enzyme and Male Infertility Risk

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