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. Author manuscript; available in PMC: 2017 Jul 25.
Published in final edited form as: Reprod Toxicol. 2016 Jun 25;65:448–456. doi: 10.1016/j.reprotox.2016.06.020

Table 5.

Overview of protocols from developmental immunotoxicity animal studies of BPA

Model Protocol experimental immune model Species BPA: exposure period BPA: exposure route and dose
Host resistance model
Ménard: study 4 (11)		 Parasite Infection: age day 25, day 0 s.c. injection N. brasiliensis. Day 7 Euthanasia, day 14 living larvae counting Wistar female rats GD15 - PND21 Oral Gavage, 0 or 5 μg/kg BW/day
Respiratory allergy model
Bauer: mucosal sensitization model (12)		 sensitization: age 6–10 weeks
i.t. on days 0, 1, and 2 with 100 μg OVA, with, or without, 100 ng LPS.
challenge: twice per day on days 14, 15, and 16 with aerosolized 1% OVA, 48 h later AHR assessment and euthanasia		 C57Bl/6 mice GD6 - PND21 Gavage, 0; 0.5; 5; 50 or 500 μg BPA/kg/day.
Respiratory allergy model
Bauer: systemic sensitization model (12)		 sensitization: age 6–10 weeks
ip sensitized days 0 and 4 with PBS or 100 μg OVA in PBS + Alum
challenged: once (1 h), on day 11, with aerosolized 1% OVA, 48h later AHR assessment and euthanasia		 C57Bl/6 mice GD6 - PND21 Gavage, 0; 0.5; 5; 50 or 500 μg BPA/kg/day.
Food allergy model
Nygaard et al., 2015 (13)		 immunization: age 4 weeks: intergastric gavage of 5.7 mg lupin extract (LE) + 10 μg cholera toxin (CT) as adjuvant on days 0, 1, 2, 7, 21 and 28.
challenge: day 35 the mice were challenged with either a single dose of 5 mg LE i.p. or 25 mg LE divided on two i.g. administrations given 30 min apart. Anaphylaxis assessment, day 35 euthanasia		 C3H/HeJ Mating - end experiment Drinking water: 0; 1; 10 or 100 μg/ml
Calculated BPA: GD8: 180 μg/kg BW/day; 1.81 or 18.8 mg/kg BW/day; PGW2: 340 μg/kg BW/day; 3.46; 35 mg/kg BW/day; PGW 4: 230 μg/kg BW/day, 2.27, 22.17 mg/kg BW/day)**
Oral tolerance model
Nygaard et al., 2015 (13)		 tolerance: age 3 weeks lupin i.g. gavage (5 mg) age 4 weeks: i.g. of 5.7 mg lupin extract (LE) + 10 μg cholera toxin (CT) as adjuvant on days 0, 1, 2, 7, 21 and 28.
challenge: day 35 the mice were challenged with either a single dose of 5 mg LE i.p. or 25 mg LE divided on two i.g. administrations given 30 min apart. Anaphylaxis assessment, day 35 euthanasia		 C3H/HeJ Mating - end experiment Drinking water: 0; 1; 10 or 100 μg/ml
Calculated BPA: GD8: 180 μg/kg BW/day; 1.81 or 18.8 mg/kg BW/day; PGW2: 340 μg/kg BW/day; 3.46; 35 mg/kg BW/day; PGW 4: 230 μg/kg BW/day, 2.270, 22.17 mg/kg BW/day)**
Host resistance model
Roy et al., 2012 (14)		 Infection: age 6–8 weeks i.n. infected with Influenza A virus. Lung tissue harvested: day 3,7 and 10 after infection C57BL/6 mice GD6 - PND 21 Oral gavage, 0 or 50 μg/kg BW/day
Respiratory Allergy model
Petzold et al., 2014 (15)		 sensitization: age: 6-week old offspring were immunized i.p. with OVA, 20 mg + ALUM day 1 and 14
challenge: 20 mg OVA intranasally (i.n.) on days 14–16 and 21–23, AHR assessment and euthanasia.		 BALB/c mice Exposure all groups one week before mating, (discontinued during the mating period of 1 week) then:
1. GD0 - PND0
2. GD0 - PND21
3. GD0 - lifelong exoposure		 Drinking water, 0 or 5 μg/ml (+/− 450 μg/kg BW/day)*
Respiratory Allergy model
O’Brien et al., 2014 (16)		 sensitization: twelve-week-old mice OVA + Alum i.p. injection.
challenge: One week after sensitization, challenged twice, with 24 h in between, by exposure to an aerosol of 3% OVA in PBS for 20 min, 24 h after the second sensitization euthanasia.		 BALB/c mice two weeks before mating - PND21 Diet: 0; 50 ng; 50 μg or 50 mg BPA/kg of rodent chow (+/− 7.5 ng, 7.5 μg, or 7.5 mg BPA/kg BW/day).
Respiratory allergy model
Nygaard et al., 2015 (13)		 sensitisation: 10 mg OVA i.p. without adjuvant at postnatal day (PND) 4 and 18.
challenge: PND 25 with 10 mg OVA intranasally (i.n.). PND 30 euthanasia.		 BALB/c mice Mating - end lactation period Drinking water: 0; 10 or 100 μg/ml
Calculated BPA: GD8: 1.41 or 13.7 mg/kg BW/day and PGW2: 4.50 or 43.7 mg/kg BW/day)**
Respiratory Allergy model
Nakajima et al. (2012) (17)		 sensitization: age PND 4 ip injection 5 μg OVA + alum on PND 4.
challenge: aerosolized 3% OVA for 10 min on PNDs 18, 19, 20 and AHR assessment day 22 and euthanasia		 BALB/c mice 1: one week prior to gestation - PND25;
2: PND2 - PND25;
3: one week prior to gestation - PND2		 Drinking water, 0 or 10 μg/ml (+/− 900 μg/kg bw/day)*
Respiratory Allergy model
Midoro-Horiuti et al., 2010 (18)		 sensitization: age PND4: ip injection 5 μg OVA + alum on PND 4.
challenge: aerosolized 3% OVA for 10 min on PNDs 13, 14, and 15. AHR assessment PND 17 and euthanasia.		 BALB/c mice one week before mating - lactation Drinking water, 0 or 10 μg/ml (+/− 900 μg/kg bw/day)*
*

For chronic studies, a default factor of 0.05 for rats and 0.09 for mice should be used, e.g. 1 mg/L in water is equivalent to a dose of 0.09 mg/kg bw per day in mice (EFSA, Administration of test substances in drinking water).

**

calculated BPA reported in the study at GD8 (Gestational Day); PGW2 or PGW 4 (Post Gestational week 2 or 4, respectively).