Gestation day

Rat DBTC Gestation days 4-7 at 3.8 mg/kg body weight and above impiantation faiiure LOAEL = 3.8 Harazono and Ema (2003)... 

Dimethyltin Rat DMTC Gestation days 7-17 at 0,5, 10, 15, and 20 mg/kg body weight Maternal toxicity reduction in fetal body weight reduced thymus weight in dams LOAEL=15 NOAEL=10 Noda (2001)... 

Monobutyltin Rat MBTC Gestation days 7-17at0, 50, 100, 200, and 400 mg/kg body weight Maternal toxicity thymic atrophy dose-dependent developmental toxicity fetuses with visceral or skeletal abnormalities NOAEL >400 Noda etal. (1992)... 

Dibutyltin Rat DBTC Gestation days 7-15at0, 2.5, 5, 7.5, and 10 mg/kg body weight Maternal toxicity body weight gain Teratogenicity LOAEL = 7.5 NOAEL = 5 LOAEL = 5 NOAEL = 2.5 Ema et al. (1991)... 

Monooctyltin/ dioctyltin Mouse DOT stabilizer mix (DOT(IOMA) MOT(IOMA) 80 20) Gestation days 6-17 at 0,20, 30, 45, 67, and 100 mg/kg body weight Embryo/fetal malformations Maternal thymus weight LOAEL = 67 NOAEL = 45 LOAEL = 45 NOAEL = 30 Faqi et al. (2001)... 

Rat MOT DOT thio- glycolates (67 33) Gestation days 6-15 at 0,20, 60, and 120 mg/kg body weight No adverse effects NOAEL= 120 Ciba-Geigy Ltd (1983)... 

Noda T, Nakamura T, Shimizu M, Yamano T, Merita S (1992b) Critical gestational day of teratogenesis by di-normal-butyltin diacetate in rats. Bulletin of Environmental Contamination and Toxicology. 49(5) 715-722. 

In rats, daily administration of 5 or 10 mg/kg doses of endosulfan by gavage in corn oil during gestational days (Gd) 6-14 or 6-19 produced a dose-related increase in maternal deaths in these test groups (FMC 1980a Gupta et al. 1978). 

GO) = gavage in oil (GW) = gavage in water Gd = gestation day Hemato = hematological LD50 = lethal dose, 50% kill LOAEL = lowest-observable-adverse-effect level M = male Metab = metabolic Musc/skel = musculoskeletal NOAEL = no-observable- adverse-effect level ... 

An unspecified number of pregnant rats was administered a single dermal dose of 670 or 1,000 mg endosulfan/kg on clipped skin on gestation day 1, and exencephaly was observed in 5 and 3 pups, respectively (the total number of live pups at these dose levels was not clearly indicated) (El Dupont deNemours Co. 1973). Maternal death was reported at higher dose levels (1500 and 2250 mg/kg), no effects were reported at lower dose levels (0 and 450 mg/kg), and no increase in embryolethality was observed at any dose level. Further study details were not provided. 

Figure 3. Section of intestine from fetus whose mother was dosed orally with 1 fj g/kg/day of 2,3,7,8-tetrachlorodihenzo-p-dioxin during gestation days 6-15 (Note hemorrhage in intestinal lumen) (lOOX)...

Table III. Tissue Distribution in Dams Following a Single Oral Dose of 200 /Ag/kg of C -2,3,7,8-Tetrachlorodibenzo- >-Dioxin on Gestation Day 16, 17, or 18 (/ g/gram of tissue)...

Oral treatment of pregnant dams with 0.25 /xg (or more) /kg/day of 2,3,7,8-tetrachlorodibenzo-p-dioxin for 10 days during gestation resulted in adverse effects on rat development. No adverse effects were seen at the 0.125 ju,g/kg/day. When C-2,3,7,8-tetrachlorodibenzo-p-dioxin (2.99 fjLc/mg) was given at 2 /xg/kg/day there was activity, primarily in liver and to a lesser extent, in fat and brain. When a single oral dose of 200 /Ag/kg was administered on gestation days 16, 17, or 18 and was followed 6 hours later with tissue sampling, the label was also observed in the fetus and placenta. Placenta had approximately twice as much label as the fetus. 

Acute oral LDjgS have been determined for mice (2,402 mg/kg) (Tucker et al. 1982) and rats (7,208 mg/kg) (Smyth et al. 1969). In a study in which pregnant rats were treated by gavage with trichloroethylene in com oil on gestation days 6-15, 2 of 13 died at 1,125 mg/kg/day, while all survived at 844 mg/kg/day (Narotsky etal. 1995). The lethality of trichloroethylene may be related to the delivery vehicle. Administration of trichloroethylene in an aqueous Emulphor vehicle proved to be more lethal but less hepatotoxic than similar administration of trichloroethylene in com oil during a 4-week exposure period (Merrick et al. 1989). Further... 

Rales and dyspnea were observed in pregnant rats treated by gavage with 1,500 mg/kg/day trichloroethylene in com oil on gestation days 6-19 (Narotsky and Kavlock 1995). Respiratory effects were not observed at 1,125 mg/kg/day. Pulmonary vasculitis was observed in 6 of 10 female rats treated with 1,000 mg/kg/day (by gavage) and 6 of 10 male rats treated with 2,000 mg/kg/day (in com oil) for 13 weeks (NTP 1990). This effect was also observed in 1 of 10 male and 1 of 10 female control rats. Histopathological examinations were not completed at the other doses in this study. Therefore, it is not possible to determine if this is a dose-related effect. 

II. 7%, and 30% of pups from dams treated at 0, 475, 633, 844, and 1,125 mg/kg/day, respectively (Narotsky et al. 1995). In a study in mice that did not use maternally toxic doses, no developmental effects were observed in the offspring of B6C3Fj mice treated by gavage with 240 mg/kg/day trichloroethylene in com oil on gestation days 1-5, 6-10, or 1-15 (Cosby and Dukelow 1992). 

Other additional studies or pertinent information which lend support to this MRL Additional studies have reported developmental effects in rodents exposed to trichloroethylene. Following exposure of rats on gestation days 6-19, decreased litter size (Narotsky and Kavlock 1995), and increased micro- or anophthalmia (Narotsky and Kavlock 1995 Narotsky et al. 1995) were observed in the offspring at 1,125 mg/kg/day, but not at 844 mg/kg/day (Narotsky et al. 1995). 

Decreased fetal weight and increased fetal death were reported following single intravenous injection of pregnant rats with 241Am (activity level 90 pCi/kg or 3,330 kBq/kg) on gestation day 9 (Rommerein and Sikov 1986). The investigators indicated a tendency toward increased incidences of fetuses with anomalous ribs. 

Gd gestational day (Gl) = gastric intubation (GO) = gavage in oil Hemato - hematological incr. = increased IPTPP = isopropyl triphenyl phosphate LD = lethal dose, 50% kill LOAEL = lowest-observed-adverse-effect level M = male MCV = mean corpuscular volume MCHC = mean corpuscular hemoglobin concentration mo = month(s) Musc/skel = musculoskeletal NOAEL = no-observed-adverse-effect level NS = not specified NTE = neurotoxic esterase RBC red blood cell Resp = respiratory TBEP = tributoxyethyl phosphate TBP = tributyl phosphate TMP = trimethyl phosphate TNBP = tri-n-butyl phosphate TOP = trioctyl phosphate wk = week(s) x = times yr = year(s). 

The actual composition of the Cellulube 220 was not reported in either the Dollahite or Carpenter studies, so the large difference in doses causing death can not be explained. Deaths were also reported in 5 of 5 pregnant Wistar rats after 5-6 daily doses of 800 mg/kg tributyl phosphate beginning on gestation day 7 (Nodaetal. 1994). 

In Sprague-Dawley rat dams exposed to 20, 50, or 75 ppm of hydrogen sulfide for 7 hours/day from gestation day 1 through postnatal day 21, blood glucose levels were increased about 50% at all exposure concentrations (Hayden et al. 1990a). 

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