Tables 5a and 5b. Bisphenol A: Reproduction and Fertility Assessment in CD-1 Mice When Administered in the Feed ( Reel et al. 1985).

Table 5a - TASK 1. Two-Week Dose-Range Finding Study for Continuous Breeding Study. (a) Clinical signs of toxicity consisted of dehydration, dyspnea, lethargy, tremors, ptosis, piloerection, diarrhea and moribundity.

Dietary Feed (%)

(8/Sex/Group)

0

0.31

0.62

1.25

2.5

5.0

Clinical Signs

No

No

No

No

Yes (a)

Yes (a)

Mortality (%)

0

0

0

0

0

75.0 (a)

Final Male Body Wt. (g)

33.3

34.2

32.9

30.8

28.5

23.5

Final Female Body Wt. (g)

27.0

27.6

27.6

25.7

24.0

17.8


Table 5b - TASK 2. Continuous Breeding Phase, Consisting of a 7-Day Premating Exposure, 98-Day Cohabitation Period and a 21-Day Segregation Period.

Dose Level (mg)

(#/Sex/Group)

(mg/kg/day)

0

(40)

(0)

0.25

(20)

(438)

0.50

(20)

(875)

1.0

(20)

(1750)

  M F M F M F M F
Body Weight (Week 1) (g) 34.3 27.1 34.6 27.2 34.3 27.0 33.3 26.8
Body Weight (Week 18) (g) 39.0 45.1 - 46.7 - 41.7 35.8 38.2
No. Fertile/No. Cohabited 37/37 19/19 18/19 20/20
Fertility Index (%) 100 100 95 100
# Litters/pair 4.97 4.89 4.72 4.50
# Live Pups/Litter (Comb. M/F) 12.07 11.20 9.67 (b) 6.30 (b)
Sex of Pups Born Alive (M/Total) 0.50 0.48 0.49 0.54
% Pups Born Alive 99 99 99 95 (b)
Live Pup Weight (g) 1.56 1.57 1.64 (b) 1.65 (a)
Postpartum F0 Dam Wt. Litter 1 35.13 35.27 24.59 32.31 (b)
Postpartum F0 Dam Wt. Litter 2 38.15 38.99 37.0 35.67 (b)
Postpartum F0 Dam Wt. Litter 3 38.86 38.68 39.16 36.68 (b)
Postpartum F0 Dam Wt. Litter 4 41.06 41.09 40.55 38.01 (b)
Postpartum F0 Dam Wt. Litter 5 41.26 42.13 40.02 37.50 (b)

(a) Significantly different (p <0.05) (b) Significantly different (p < 0.01)

(b) Significantly different (p <0.05) (b) Significantly different (p < 0.01)

Notes: Indications of non-estrogenicity included no significant changes in fertility index, # litters/pair and sex ratio. Significant changes in # live pups/litter, % pups born alive, live pup weight and postpartum dam weights may be attributed to generalized maternal toxicity. The maternal and fetal NOEL for this study is 0.25% BPA in dietary feed (438 mg/kg/day).


Table 5c. Bisphenol A: Reproduction and Fertility Assessment in CD-1 Mice When Administered in the Feed ( Reel et al. 1985).

Dietary Feed (%)

(#/Sex/Group)

(mg/kg/day)

0

(40)

(0)

0.25

(20)

(438)

0.50

(20)

(875)

1.0

(20)

(1750)

  M F M F M F M F
Body Weight at Birth (g) 1.64 1.57 1.61 1.56 1.82 1.72 1.78 1.70
Body Weight at Day 74 (g) 33.93 27.22 33.75 27.04 34.13 28.61 32.62 26.87
Liver Wt. (g) 1.92 1.87 2.07 1.95 2.10 2.18(b) 2.52(b) 2.22(b)
Kidneys/ Adrenals Wt. (g) 0.70 0.48 0.81(b) 0.53(b) 0.85(b) 0.56(b) 0.84(b) 0.54(b)
# Copulatory Plugs/ # Cohabited 19/20 19/19 20/20 10/11
Mating and Fertility Index (%) 95 100 100 91
# Live Pups/ Litter (Comb. M/F) 11.00 10.74 12.35 10.90
% Pups Born Alive 95 95 100 99
Live Pup Weight (g) 1.46 1.49 1.47 1.43
Postpartum F1 Dam Wt. Litter 1 34.33 33.94 34.84 32.68
Left Testis/ Epididymis (mg) 196 194 178 (b) 179 (a)
Right Testis (mg) 141 136 126 (b) 133
Right Epididymis (mg) 55 49 (a) 46 (b) 45 (b)
Prostate (mg) 42 45 46 48
Seminal Vesicles (mg) 341 304 314 248
% Motile Sperm 75.32 63.85 51.75 (b) 69.55
Sperm Concentration ( No.

Sperm x 1000/mg caudal tissue)

651.03 691.87 583.04 535.15
% Abnormal Sperm 7.89 9.35 6.84 7.47
% Tailless Sperm 12.23 13.86 12.99 16.84

(a) Significantly different (p <0.05) (b) Significantly different (p < 0.01)
(b) Significantly different (p <0.05) (b) Significantly different (p < 0.01)

Notes: Generalized toxicity was evident and included significant effects on the liver, kidneys and adrenals. Indications of non-estrogenicity include no significant changes in fertility and mating indexes, % pups born alive, % abnormal sperm, % tailless sperm and weights of the testis, epididymis and prostate. Possible indications of estrogenicity include decreases in # live pups/litter, seminal vesicle weight, % motile sperm and sperm concentration. All signficant effects may be due to generalized maternal toxicity. A NOEL for this study was not established but only one dose level was administered (1% or 1750 mg/kg/day).


Table 5d. Bisphenol A: Reproduction and Fertility Assessment in CD-1 Mice When Administered in the Feed ( Reed et al. 1985) Table 5d - TASK 4. F1 Offspring Reproductive Assessment. (a) Significantly different (p <0.05) (b) Significantly different (p < 0.01)

Treatment Group

Control Male & Female

Combined Control Males

Combined Control Females

1.0% BPA Male & Control Females

Control Male & 1.0% BPA Female

# Copulatory Plug/# Cohabited

17/19

-

-

18/19

18/19

Mating Index (%)

89

-

-

95

95

# Fertile/# Cohabited

16/19

-

-

17/19

16/19

Fertility Index (%)

84

-

-

89

84

# Live Pups/Litter (Comb. M/F)

11.31

-

-

8.41 (a)

5.50 (b)

% Pups Born Alive

99

-

-

92

94

Sex of Pups Born Alive (M/Total)

0.53

-

-

0.53

0.45

Adjusted Live Pup Weight (g)

1.61

-

-

1.71

1.81 (b)

Postpartum F0 Dam Wt. Litter 1

40.30

-

-

-

38.51

Body Wt. (g)

-

36.55

35.78

35.37

34.19 (a)

Liver Wt. (g)

-

2.00

2.17

2.49 (b)

2.62 (b)

Kidneys/Adrenals Wt. (g)

-

0.80

0.64

0.92 (b)

0.67

Left Testis/Epididymis Wt. (mg)

-

194

-

188

-

Right Testis Wt. (mg)

-

133

-

129

-

Right Epididymis Wt. (mg)

-

53

-

53

-

Prostate (mg)

-

55

-

53

-

Seminal Vesivles (mg)

-

457

-

358 (b)

-

% Motile Sperm

-

64.30

-

39.00 (b)

-

Sperm Concentration

(# Sperm x 1000/mg caudal tissue)

-

258.27

-

182.80

-

% Abnormal Sperm

-

10.85

-

9.29

-

% Tailless Sperm

-

17.38

-

17.14

-

Notes: Generalized toxicity was evident and included significant effects on the liver, kidneys and adrenals. Indications of non-estrogenicity include no significant changes in fertility and mating indexes, % pups born alive, live pup weight, prostate weight, sperm concentration, % abnormal sperm and % tailless sperm. Possible indications of estrogenicity include decreases % motile sperm and decreases in testis, epididymis and seminal vesicle weight. All significant effects may be due to generalized maternal toxicity.

There is not a maternal or fetal NOEL for this study. For risk assessment purposes, this study is superceded by the 90-day reproduction and toxicity studies conducted by Wazeter, 1976 (Table 1) and Goldenthal, 1978 (Table 2), which estimated the maternal and fetal NOEL to be 50 mg/kg/day. A similar value for an estimated NOEL can be derived from this study by dividing the LOEL of 438 mg/kg/day by a factor of 10.