"No adverse maternal effects were seen in physical in-life examination data, liver weight data or gross post-mortem examination data. Likewise, corpora lutea and uterine implantation

data, fetal weight and sexing data and ossi􀂠cation variation data did not appear to be adversely affected by treatment."

"Fetal body weight and sex distribution data Mean fetal body weight were considered comparable between the control and treated groups. No stunted fetuses were recovered either in the control or treated groups. Likewise, no fetuses were calculated as being stunted in respects to littermates in these same groups. Fetal sex distribution data revealed a preponderance of males in each of the treated groups with an increase in the number of females in the control group. The differences in sex distribution are attributed to normal biological variability noted with this parameter and the relatively small group sizes involved. No treatment related effect was evident in fetal body weight or fetal sexing data.

Fetal external examination data No external malformations were seen in the 84 low-dose fetuses (seven litters), or 85 high-dose fetuses (seven litters). In the control group, one fetus had a darkened, raised area on its back (thoracic region). No other external malformations were seen in the 90 remaining fetuses for the control group (seven litters).

Fetal soft tissue examination data The most common observations noted during the soft tissue evaluations involved distention and/or the tortuous condition of the ureter (s). These types of observation were seen in 2/48 controls (4.2%), 6/43 low-dose fetuses, and 2/44 high-dose fetuses (4.5%). The significance of these types of observations is unclear. In these same fetuses with ureter observations, the bladders were noted as filled (indicating a patency between urteter and bladder) and no kidney malformations (e.g. severely distended renal pelvis, absence of renal papillae) were seen. These types of ureter observations (i.e. distended , tortuous condition) are seen frequently in the term rat fetuses; historically, the incidence of such ureter observations is 8.7% (representing 1067 fetuses from 100 litters). Since no dose relationship was apparent in the incidence of these ureter observations, no treatment-related effect was indicated. With the exception of the ureter observations, the only other observation noted during the soft tissue evaluations was a small, dark, discolored area on the medium lobe of the liver. This observation was seen in one low-dose fetus. Thus, no treatment-related effect on the fetus was evident from data collected during the soft tissue evaluation. Ossication variation data Ossication variations were seen in 87/91 control fetuses, 75/84 low-dose fetuses and 77/85 high-dose fetuses, and incidence of 95.6%, 89.3% and 90.6% respectively. These data were comparable between control and each treated group. The types and incidences of ossication variations seen were similar between the control and treated groups. No treatment-related effect was evident in these data.

Fetal skeletal examination data The incidence of skeletal malformations, both on a per fetus and a per litter basis, was comparable between the control and treated groups. In the control group, one fetus had an angulated/shortened rib defect. No other skeletal malformations were seen in this group. Fused sternebrae were seen in two treated group fetuses. In the low-dose group, one fetus from the litter of female No. 2580 had a fusion between the first and second sternebrae. The fused sternebrae seen in one-high dose fetus from the litter of female No. 3578, involved the second through the fth sternebrae. A mid-line cleft was also evident through this fused segment of the sternum. The sternebral fusion defects seen in a single fetus from each of the treated groups were dissimilar in respects to the sternebrae involved and were not considered to represent a treatment-related effect.

During the external, soft tissue and skeletal evaluations, malformations were seen in 4/91 control fetuses (4.4%), 8/84 low-dose fetuses (9.5%) and 3/85 high-dose fetuses (3.5%). The mean percentages of malformed fetuses per litter for the control, low- and high-dose groups were 4.3%, 9.8% and 3.3% respectively. Though these values are increased in the low-dose group, differences from control were not statistically signicant. Likewise, no dose-relationship was evident in these values. It was concluded that exposure to PFBE by whole-body inhalation at levels of 1000 and 70,000 ppm during the Days 6 through 15 of gestation did not appear to be embryotoxic or teratogenic in the seven pregnant rats evaluated per dose level. Applicant's summary and conclusion / Conclusions: No evidence of embryotoxicity or treatment-related malformations were seen in the offspring of rats exposed during days 6-15 of gestation to levels of PFBE (3,3,4,4,5,5,6,6,6- nonauorohexene) of 1,000 or 70,000 ppm"

"For exposure-response array data display purposes, the following results were coded (control and no effect findings were coded as "0", treatment-related increases were coded as "1", and treatment-related decreases were coded as "-1"."

F1 Sprague-Dawley Rats