PMID- 9179724 OWN - NLM STAT- MEDLINE DCOM- 19970724 LR - 20190920 IS - 0260-437X (Print) IS - 0260-437X (Linking) VI - 17 Suppl 1 DP - 1997 May TI - Developmental toxicity evaluation of methyl tertiary-butyl ether (MTBE) by inhalation in mice and rabbits. PG - S21-9 AB - Pregnant CD-1 mice (30 per group) and female New Zealand White rabbits (15 per group) were exposed by inhalation to 0, 1000, 4000 and 8000 ppm methyl tertiary-butyl ether (MTBE) vapor for 6 h a day during gestational days (GD) 6-15 and 6-18, respectively. Maternal body weights, clinical observations and food consumption were recorded throughout gestation for both species. At scheduled euthanization (GD 18 for mice and GD 29 for rabbits), fetuses were weighed, sexed and examined for external, visceral (including craniofacial) and skeletal alterations. For both species, the pregnancy rate was high and equivalent across all groups; no pregnant animals died or aborted. There were no does that delivered early, but there were three mouse dams in the control group and two dams in the 4000 ppm group that delivered early and were removed from the study. In mice, maternal body weights, body weight gain, corrected maternal gestational weight change and food consumption were significantly reduced in mice at 8000 ppm. Hypoactivity and ataxia were observed in dams exposed to 4000 and 8000 ppm. Gestational parameters affected at 8000 ppm included post-implantation loss (due to increased late resorptions and dead fetuses) and altered sex ratio (decreased males); fetal body weights per litter were reduced at 4000 and 8000 ppm. There was a significantly increased incidence of cleft palate at 8000 ppm; this resulted in increased incidences of pooled external and visceral malformations and of total malformations at this exposure concentration. There were also treatment-related increases in the incidence of individual skeletal variations at 4000 and 8000 ppm. In rabbits, maternal weight gain and food consumption were significantly reduced at 4000 and 8000 ppm. Relative liver weights were also reduced at 8000 ppm. All gestational parameters were equivalent across all groups, including pre- and post-implantation loss, fetal sex ratios, litter size and fetal weights/litter. There was no evidence of treatment-related teratogenicity observed at any dose tested in rabbits. The no-observed-effect levels (NOELs) for maternal and developmental toxicity were both 1000 ppm in mice and 1000 ppm and at least 8000 ppm, respectively, in rabbits. FAU - Bevan, C AU - Bevan C AD - Exxon Biomedical Sciences, Inc., East Millstone, NJ 08875, USA. FAU - Tyl, R W AU - Tyl RW FAU - Neeper-Bradley, T L AU - Neeper-Bradley TL FAU - Fisher, L C AU - Fisher LC FAU - Panson, R D AU - Panson RD FAU - Douglas, J F AU - Douglas JF FAU - Andrews, L S AU - Andrews LS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (Air Pollutants) RN - 0 (Methyl Ethers) RN - 29I4YB3S89 (methyl tert-butyl ether) SB - IM MH - Abnormalities, Multiple/*chemically induced MH - Administration, Inhalation MH - Air Pollutants/*toxicity MH - Animals MH - Atmosphere Exposure Chambers MH - Dose-Response Relationship, Drug MH - Female MH - Fetal Resorption/chemically induced MH - Fetus/*drug effects MH - Male MH - Methyl Ethers/*toxicity MH - Mice MH - Pregnancy MH - Rabbits EDAT- 1997/05/01 00:00 MHDA- 2000/06/20 09:00 CRDT- 1997/05/01 00:00 PHST- 1997/05/01 00:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1997/05/01 00:00 [entrez] AID - 10.1002/(SICI)1099-1263(199705)17:1+3.0.CO;2-E [pii] AID - 10.1002/(sici)1099-1263(199705)17:1+3.3.co;2-5 [doi] PST - ppublish SO - J Appl Toxicol. 1997 May;17 Suppl 1:S21-9. doi: 10.1002/(sici)1099-1263(199705)17:1+3.3.co;2-5.