Oral Modified One-Generation Reproductive Study with Prenatal, Reproductive Performance, and Subchronic Cohorts

Select 'Reproductive' as study type. Animal groups to create - with exposure duration text and doses to use for each group:

P0 Female Sprague Dawley Rats - GD6-LD28 (extract multiple dose representations: ppm in diet, mg/kg-day (gestation) shown in Table 10, mg/kg-day (lactation) shown in Table I08: Mean Test Compound Consumption for BSA only (https://doi.org/10.22427/NTP-DATA-002-03263-0010-0000-7), and mg/kg-day which are time weighted average doses calculated by extractor.

F1 Male and Female Sprague Dawley Rat Pups - GD6-PND28 (select P0 females as dosed animals)

F1 Male Sprague Dawley Rat Pups - GD6-PND28 (select P0 females as dosed animals)

F1 Female Sprague Dawley Rat Pups - GD6-PND28 (select P0 females as dosed animals)

F1 Male Sprague Dawley Rats (all cohorts) - GD6-PND98 (for doses use chemical intake in Table 15 for PND28-98 and also enter ppm in diet)

F1 Female Sprague Dawley Rats (all cohorts) - GD6-PND98 (for doses use chemical intake in Table 16 for PND28-98 and also enter ppm in diet)

F1 Male Sprague Dawley Rats (Subchronic cohort) - GD6-~PND115 (for doses use mean compound consumption in Table I08 for PND28-112 and also enter ppm in diet)

F1 Female Sprague Dawley Rats (Subchronic cohort) - GD6-~PND116 (for doses use mean compound consumption in Table I08 for PND28-112 and also enter ppm in diet)

P1 Male Sprague Dawley Rats (Reproductive cohort) - GD6-~PND152 (for doses use chemical intake in Table 15 for PND28-98 and also enter ppm in diet)

P1 Female Sprague Dawley Rats (Reproductive cohort) - GD6-~PND161(PND28 of F2) (for doses use chemical intake in Table 16 for PND28-98, doses during gestation and lactation from I08, and also enter ppm in diet)

F2 Male and Female Sprague Dawley Rat Pups - GD0-PND28 (for doses use time weighted average doses for gestation and lactation GD0-21 and LD1-13 calculated by extractor: 0, 36.3, 117.9 mg/kg-day and also enter ppm in diet)

F2 Male Sprague Dawley Rat Pups - GD0-PND28 (for doses use time weighted average doses for gestation and lactation GD0-21 and LD1-13 calculated by extractor: 0, 36.3, 117.9 mg/kg-day and also enter ppm in diet)

F2 Female Sprague Dawley Rat Pups - GD0-PND28 (for doses use time weighted average doses for gestation and lactation GD0-21 and LD1-13 calculated by extractor: 0, 36.3, 117.9 mg/kg-day and also enter ppm in diet)

F2 Male Sprague Dawley Rats - GD0-~PND91 (for doses use chemical intake for PND28-91 in Table 33 and also enter ppm in diet)

F2 Female Sprague Dawley Rats - GD0-~PND91 (for doses use chemical intake for PND28-91 in Table 33 and also enter ppm in diet)

F1 Male Sprague Dawley Rats (Prenatal cohort) - GD6-~PND119 (for doses use chemical intake in Table 15 for PND28-98 and also enter ppm in diet)

F1 Female Sprague Dawley Rats (Prenatal cohort) - GD6-~PND123(GD21 of F2) (for doses use chemical intake in Table 16 for PND28-98 and also enter ppm in diet and mg/kg-d gestation from Table I08)

F2 Male and Female Sprague Dawley Rat Fetuses - GD0-21 (mean test compound consumption for F1 females in Table I08 for GD0-21 and also enter ppm in diet)

F2 Male Sprague Dawley Rat Fetuses - GD0-21 (mean test compound consumption for F1 females in Table I08 for GD0-21 and also enter ppm in diet)

F2 Female Sprague Dawley Rat Fetuses - GD0-21 (mean test compound consumption for F1 females in Table I08 for GD0-21 and also enter ppm in diet)

Results to extract:

P0 clinical observation and mortality - use dummy variables ("BPAF exposure did not affect survival of the F0 females (Appendix E). No clinical observations were attributed to BPAF exposure during gestation or lactation (Appendix E)."

Table 9: maternal body weight GD21 and weigh gain GD6-21

Table 10: GD6-21

Table 11: Dams not delivering with evidence of pregnancy, dams with litters on LD0, gestation length, LD1 pup weight, percent live male pups per litter

Table 12: maternal body weight LD1, LD28, weight gain LD4-28, feed consumption LD1-13

Yellow stained fur (clinical observation) for F1 male and female rat pups group: extract pup incidence quantitatively from I05P: Pup Clinical Observations Summary and indicate treament-related increase in 3750 ppm group

Table 13: PND0 total litter size; live litter size on PND0, 4, 28; dead/litter PND0, 1-4, 5-28; survival ratio PND1-4, 5-28

Table 14: body weight PND1, 28, weight gain 4-28 for both sexes

'Necropsy appeared normal' endpoint for P0 females - use dummy variables ("There were no BPAF-related gross or microscopic findings in the F0 females.")

Survival for F1 male, F1 female groups for period PND28-98 - use dummy variables to indicate no effects ("There was no effect of BPAF exposure on the survival of F1 males or females, with the exception of two females in the 3,750 ppm group that were euthanized due to malformations of the vagina (no apparent vaginal opening) (Appendix E). Three additional unscheduled deaths were recorded but were not deemed related to BPAF exposure..."

Clinical observation for F1 female groups for period PND28-98 - use dummy variables to indicate no treatment-related effects

Small testis, missing testis - both endpoints for F1 male group for period PND28-98 - use dummy variables and indicate increase in 3750 ppm group for both endpoints

Table 15: body weight PND98, weight gain PND28-91, feed consumption PND28-98 in g/kg/day

Table 16: body weight PND98, weight gain PND28-91, feed consumption PND28-98 in g/kg/day

Table 17: extract all (F2 data are from the reproductive performance cohort)

R14 Developmental Markers Summary: No. of male pups with areolae/nipples

Table 18: No. not attaining testicular descent, mean day of descent

Table 19: Day of VO litter mean and adjusted litter mean, mean body weight at acquisition

Table 20: No. not attaining BPS, Day of BPS litter mean and adjusted litter mean, body weight at acquisition

Mortality for all F1 parental groups (in reproductive and prenatal cohorts) - use dummy variables to indicate no effects (p. 67 "There were no exposure-related deaths")

Table 21: all - put F1 results under the F1 Female Sprague Dawley Rats (all cohorts) group

Table 22: all endpoints beginning with "percent of..." as well as precoital interval for both cohorts (the first 2 rows will be used as sample sizes for the endpoints to extract).

Table 23: all

Table 24: maternal body weight GD21 and weight gain GD0-21 for both cohorts

Table 25: maternal feed consumption in g/kg/day for GD0-21 for both cohorts

Prenatal cohort specific tables and findings

Table 26: from Pregnancy Summary section only mated females and pregnant females; all endpoints in rest of table

Placental abnormalities - extract for F1 females (prenatal cohort) - use dummy variables to indicate no effects

R11 Fetal Defect Summary: External Malformations, Total (fetal incidence); Visceral Malformations, Total (fetal incidences); Visceral Variations, Total (fetal incidences); Skeletal Malformations, Total (fetal incidences); Skeletal Variations, Total (fetal incidences)

Table 27: fetal incidences of both brain variations; Authors concluded these are treatment-related so LOAEL is 1125 ppm even though not significant.

Table 28: fetal incidences of both skeletal findings

Reproductive cohort specific tables and findings

Table 29: all the "Percent of..." endpoints, precoital interval, gestation length

Table 30: maternal body weight LD1, LD28, weight gain LD4-28, feed consumption LD1-13 in g/kg/day

Table 31: total litter size PND0; live litter size PND0, PND4, PND28; dead per litter for each interval; survival ratio for each interval

Table 32: pup body weight on PND1, PND28, weight gain for PND4-28

Table 33: body weight day 91, weight gain 28-91, feed consumption in g/kg/day

Necropsy, hematology, and clinical chemistry (extracted under the relevant cohort)

Table 34: all

Table 35: all, except only need Total incidence for Cowper's Gland Missing and Reduced and Seminal Vesicles Reduced; also, you don't need to extract a finding for a cohort if there is a dash (–) for all concentrations indicating that it was not noted in any groups of that cohort

Table 36: all

Table 37: all

Table 38: all

Table 39: all except only need Total for reduced ovaries

Table 40: all

Table 41: all

Table 42: all

PA43 Hematology Summary: Male hematology endpoints hemoglobin, erythrocytes, reticulocytes, mean cell volume, mean cell hemoglobin concentration, white blood cells, neutrophils, lymphocytes, monocytes, basophils

PA41 Clinical Chemistry Summary: all

For all histopathology: only extract incidence (do not need to extract average severity grade of lesions)

Table 44: all

Table 45: all

Table 46: all

Table 47: all

Table 48: all

Table 49: all, except only extract total for Cowper's Gland Size Reduced

Table 50: all

Table 51: all

For other organs examined for histopathology in the reproductive and subchronic cohorts not included in the above tables: create general histopathology endpoints and use dummy variables based on any information provided in the text. Lack of discussion can be considered no effect.

Reproductive cohort: pituitary gland (both sexes), preputial gland (males)
Subchronic cohort: see full list of organs examined in Table 3 (p. 25 of the report)

F2 Female Sprague Dawley Rats (Reproductive cohort)