Teratological assessment of methanol and ethanol at high inhalation levels in rats

Nelson, B. K.; Brightwell, W.S.; Mackenzie, Deborah R.; Khan, Amir; Burg, JeAnne R.; Weigel, Walter W.; Goad, Phillip T.

doi:10.1016/0272-0590(85)90197-6

Cited by 96 publications

(15 citation statements)

References 7 publications

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“…This observation is consistent with that of (Nelson et al, 1985b), who reported that exposed rats consumed less food during the first week of exposure but maintained normal body weights. When dietary intake was scaled to body weight in the present study, the control group consumed an average of 225 kcal/kg 0.75 /day while the 21,000 ppm group consumed~10% less, 202.4 kcal/kg 0.75 /day.…”

Section: Maternal Exposures and Effectssupporting

confidence: 94%

“…Moreover, the behavior of the exposed rats during maintenance operations after exposures was not obviously different from controls. These observations contrast with those of Nelson et al (Nelson et al, 1985b), who reported that after 7-h ethanol inhalation exposures, pregnant Sprague-Dawley rats were "completely narcotized" after 20,000 ppm, and "appeared to be hyperactive" after 10,000 and 16,000 ppm.…”

Section: Maternal Exposures and Effectscontrasting

confidence: 84%

“…5 are unlikely to be a consequence of exposure, given that the BECs achieved in the pregnant dams were less than 200 mg/dL. Consistent with this suggestion, Nelson et al (1988) reported no effects on neuromotor coordination or activity levels in offspring of dams exposed to 10,000 or 16,000 ppm ethanol during gestation, which were associated in those studies with BECs of~3 and~40 mg/dL, respectively in a companion paper (Nelson et al, 1985b).…”

Section: Assessments Of Offspring: Unconditioned Behaviorsupporting

confidence: 50%

“…Nelson et al (1985b) measured maternal BECs of about 3, 84, and 193 mg/dL after the first 7-h exposure and 3, 42 and 148 mg/dL after 19 daily exposures to 10,000, 16,000 and 20,000 ppm ethanol vapor, respectively. These values are consistent with the BECs estimated for the current study, suggesting that the Long-Evans rats in our study were less sensitive to the narcotizing effect of ethanol.…”

Section: Maternal Exposures and Effectsmentioning

confidence: 99%

See 3 more Smart Citations

Toxicological outcomes in rats exposed to inhaled ethanol during gestation

Beasley

Evansky

Martin

et al. 2014

Neurotoxicology and Teratology

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Section: Maternal Exposures and Effectssupporting

confidence: 94%

Section: Maternal Exposures and Effectscontrasting

confidence: 84%

Section: Assessments Of Offspring: Unconditioned Behaviorsupporting

confidence: 50%

Section: Maternal Exposures and Effectsmentioning

confidence: 99%

See 2 more Smart Citations

Toxicological outcomes in rats exposed to inhaled ethanol during gestation

Beasley

Evansky

Martin

et al. 2014

Neurotoxicology and Teratology

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“…The increased susceptibility of humans and other primates to methanol poisoning has been attributed to their lower capacity to metabolize formate, the putative toxic metabolite, by the tetrahydrofolate (THF)-dependent pathway (McMartin et al, 1980). Studies with rats (Nelson et al, 1985;Stanton et al, 1995) and mice (Bolon et al, 1993;Dorman et al,1995) indicated that maternal exposure to methanol vapor at 10,000 to 20,000 ppm during gestation produces developmental toxicity. Rogers et al (1993) reported that some effects on fetal development can be detected in mice exposed to 2000 ppm methanol on day 6-15 gestation, and determined the NOAEL on developmental toxicity to be 1000 ppm.…”

Section: Introductionmentioning

confidence: 98%

Inhalation Toxicity of Methanol/Gasoline in Rats: Effects of 13-Week Exposure

et al. 1998

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The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate glands in the high dose males. No other significant microscopic changes were observed in the tissues of treated animals. Based on the marked increase in urinary ascorbic acid and albumin in the high dose males and the decreased forelimb grip strength in the high dose females, we concluded that the no-observed adverse effect level (NOAEL) of methanol/gasoline vapour is 500/30 ppm.

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Influence of maternal folate status on the developmental toxicity of methanol in the CD-1 mouse

Sakanashi

Rogers

et al. 1996

Teratology

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Methanol, which is detoxified via a folic acid‐dependent pathway, has been shown to be teratogenic in mice. Given recent observations that the level of dietary folic acid intake may be inversely related to the occurrence of select birth defects in humans, we tested the hypothesis that dietary folic acid intake would influence the developmental toxicity of methanol. Virgin female mice were fed one of three diets containing 400 (low), 600 (marginal), or 1,200 (adequate) nmol folic acid/kg diet for 5 weeks prior to and following mating. On gestation days (GD) 6–15, dams were administered by gavage either vehicle (distilled, deionized water) or methanol at 2.0 or 2.5 g/kg body weight, twice daily. On GD 18, mice were weighed and killed and the liver, kidneys, and gravid uteri removed and weighed. Implantation sites, live and dead fetuses, and resorptions were counted; fetuses were weighed individually and examined for cleft palate and exencephaly. One third of the fetuses in each litter were examined for skeletal morphology. Maternal liver folate concentrations were approximately 40–50% lower in the low dietary folic acid groups than in the marginal and adequate groups; methanol did not affect maternal liver folate concentration at term. Maternal net gestational weight gain was lowest at the lowest dietary folate level but was not affected by methanol. Gravid uterus weights were lowest in the low dietary folic acid groups exposed to the high methanol dose and the number of live fetuses per litter was lowest in the low folic acid groups. Fetal body weights were lowest in the low folic acid groups and significantly lower in the methanol groups relative to vehicle‐treated animals. Fetal crown‐rump lengths were shorter in the methanol‐treated groups; this parameter was not affected by folic acid treatment. Both methanol and low dietary folic acid increased the incidence of cleft palate, with the highest number of affected litters in the low dietary folic acid group. These results support the concept that maternal folate status can modulate the developmental toxicity of methanol. Teratology 54:198–206 © 1997 Wiley‐Liss, Inc.

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Teratological assessment of methanol and ethanol at high inhalation levels in rats

Cited by 96 publications

References 7 publications

Toxicological outcomes in rats exposed to inhaled ethanol during gestation

Toxicological outcomes in rats exposed to inhaled ethanol during gestation

Inhalation Toxicity of Methanol/Gasoline in Rats: Effects of 13-Week Exposure

Influence of maternal folate status on the developmental toxicity of methanol in the CD-1 mouse

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