Litter size

The progeny, mated within the experimental group, had a decreased number of pregnancies and reduced litter size at the 0.5 )u.g/kg while no effect was observed in 0.25 /xg/kg progeny. 

Studies in animals indicate that trichloroethylene can act as a developmental toxicant, especially at doses also resulting in maternal toxicity. Significant decreases in litter size have been reported in rats treated by gavage... 

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). 

Increased litter size and weight Bulky diets have appeared to increase litter size and the birth weight of piglets. 

No differences were noted in the litter sizes among those treated and the controls. No differences were noted in the number of stillborn pups or in pup weights. The study authors concluded that there was no evidence of adverse diisopropyl methylphosphonate-induced reproductive effects. However, as discussed in Section 2.2.2.1, there is some confusion regarding the actual doses to which the animals were exposed in the Hardisty et al. (1977) study. Therefore, results from this study are considered inappropriate for human health risk assessment. 

With acute-duration exposure to tricresyl phosphate and dibutyl phenyl phosphate, decreased litter size and pup survivability were found at 400 mg/kg/day (Carleton et al. 1987) and 50 mg/kg/day (Healy et al. 

However, significant decreases in the number of females delivering live young, litter size, and pup viability were observed in the high-dose group (Carlton et al. 1987). 

At 2000 mg/kg BW, most pups born dead at 800 and 1000 mg/kg BW, litter size reduced 50-100% (Peters and Cook 1973)... 

Decreased incidence of females showing sperm in vaginal smears, decreased litter size, and thyroid histopathology in rats fed 5 mg mirex/kg diet since weaning (Chu et al. 1981)... 

PCB diets were associated with reproductive impairment including anovulation, fetal resorption, delayed ovulation, increased gestation, and decreased litter size. Hepatic estrogen binding site concentrations decreased with increasing dietary PCB concentrations but not uterine estrogen receptor sites... 

PCB 126 dams given 0.01 or 0.02 mg/kg BW by gavage every second day from days 9-19 of gestation Reduction in litter size, body weight, and survival of sucklings delayed spontaneous movement and neuromuscular maturation. Dams and pups had reduced body weight, and increased cytochrome P-4501 A1 activity 25... 

No teratogenesis observed in 7 generations at dietary level of 17.5 mg/kg positive effect on litter size and survival... 

Dibutyl sebacate was tested for reproductive toxicity in a dietary study with Sprague-Dawley rats 6.25% (approximately 5.6 g/kg/d) in the diet for 10 wk prior to breeding (Smith 1953). No effect on fertility, litter size, or pup survival was found. However, pups from treated dams weighed less than pups from the control group. 

Not only is it difficult to detect effects on male fertility because of group-size considerations, effects on male fertility mediated by decreased sperm production are also difficult to detect because of the normally huge excess of sperm included in a rat ejaculate. Sperm production can be decreased by up to 90% without effect on fertility (either pregnancy rate or litter size) in the rat. This is not the case for men, so the sperm excess in the rat represents a serious flaw in the rat model (see Working, 1988). To address this deficiency and improve the sensitivity of the model, it is advisable to determine the effects of the test agent on testes weights, testicular spermatid counts, and histopathology of the testes (preferably plastic sections) in the male fertility study and/or the 14-week toxicity study. In some cases, these parameters may be more predictive of possible effects on male fertility in humans than the fertility rate in rats. 

FIGURE 8.4. Effect of litter size on mean percentage preimplantation loss in 1035 control rat litters. Between 1970 and 1988, 1035 control rats were cesarean sectioned on Day 20 of gestation and the numbers of resorptions and implants were counted. Numbers within the bars indicate number of litters. 

FIGURE 8.6. Effect of litter size (live fetuses per litter) on incidence of supernumerary rib in 1379 control rat litters. Between 1978 and 1988, fetal skeletons from 1379 litters of control rats were stained with alizarin red and examined for supernumerary rib. 

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