N is the number of pregnant P0 females; could not determine total pup size.

"Five groups (F0) of 32 male and 32 female Sprague Dawley rats were exposed to vapours of HCFC 123 starting at 6 weeks of age and continuing on through weaning of all litters (approximately 23 weeks of treatment). The target exposure levels were 0 (control), 30, 100, 300, and 1000 ppm. Exposure levels for this phase of the study were 0, 30 (±2), 100 (±8), 299 (±14), and 1010 (±17) ppm, respectively. Exposures for the F0 generation were conducted 6 hr per day, 7 days per week, from 6 weeks of age through weaning of all litters (a total of 23 weeks of treatment). Exposure levels (±SD) for this phase of the study were 0, 30 (±2), 100 (±4), 298 (±13), and 1008 (±23) ppm. For the F1 generation, exposures were conducted from 4 weeks of age to weaning of their offspring (a total of approximately 26 weeks). Throughout the study, temperatures in the chambers were within the range of 18.6 to 22.9°C. The humidity ranged from 41 to 71%.

There was no effect on mating performance. No differences were seen in the copulation, fertility, or gestation indices or pregnancy rate (Table 4) for either the F0 or F1 animals. In the F0 males, body weight gain for groups exposed to 100 ppm HCFC 123 and above were reduced compared to controls, starting around the 14th week of treatment. In the F0 females, a similar effect was seen starting around Week 8 (Fig. 1). In the F1 animals a similar effect was seen starting in Week 48 for the males and the females (Fig. 2).

In both F0 and F1 males, total cholesterol levels were higher in all exposure level groups except for the F1 high exposure level. However, at 1000 ppm, in F0 males the effect was not as pronounced as in most lower-level-exposure groups, and in F1 males it was even lower than controls. The reason for this is unknown. In the F0 and F1 females, dose-related decreases in cholesterol were seen, primarily in the highest-exposure-level group. Decreased serum triglyceride levels were seen in F0 and F1 animals in the 100, 300, and 1000 ppm exposure level groups. Triglyceride levels in the 30 ppm exposure level group were similar to controls. While a few other differences in biochemical parameters were seen, these tended not to be reproducible and appeared spurious in nature (Tables 5, 6, and 7). Specifically, while cholesterol levels tended to be lower in HCFC 123-exposed females, in F0 males they tended to be higher and in F1 males they tended to be lower.

F0 and F1 pup viability at birth and weaning was unaffected by treatment. Likewise, sex ratios (data not shown) were unaffected. There were no significant differences in litter size for the F1 generation. Although the litter size was significantly smaller for the F2 group exposed to 1000 ppm compared to the controls (Table 9), both were within the normal range for this strain of rat (Charles River, 1995). At birth, and through Day 4, pup weights in both F0 and F1 litters were comparable. During the period when the mothers were exposed to the vapours of HCFC 123, and nursing the pups (Day 5 through weaning) there was a marked treatment related retardation in body weight gains in the pups. In the F1 generation, this effect was seen in all four exposure F0 generation litters, this effect was significant in the 100, groups, 30, 100, 300, and 1000 ppm (Table 9). As prior 300, and 1000 ppm exposure level groups (Table 8). In the studies (Rusch et at, 1994; Malley et al, 1995) as well as this study had shown that exposure to HCFC 123 can cause a reduction in serum triglyceride levels, the possibility that this could also occur in the milk was considered. Unfortunately, analysis of the fat content of the milk from the mothers in this study gave results that were highly variable and not useful.

Liver weights were increased in F0 and F1 HCFC 123- exposed adult animals in the 300 and 1000 ppm exposure level groups and occasionally at 30 and 100 ppm (Table 10). Microscopic changes included hepatocyte enlargement and vacuolation at 300 and 1000 ppm, but at 100 ppm microscopic changes were limited to hepatocyte enlargement in the F1 animals. No microscopic changes were seen in the 30 ppm exposure level group. There were no significant differences seen on reproductive organ weights and no microscopic changes were seen on reproductive organs."

F1 Male and Female Pups