Appendix 3 Key Reproduction Studies with DEHP in – Laboratory Animals (Adapted from FDA, 2002; ECB, 2006) Study Design/ Route NOAEL LOAEL References Species (mg/kg bw/d) (mg/kg bw/d) (mg/kg bw/d) & Endpoint ORAL Two-generation studies 17 males/group 1000, 7500, 10000 Fert: 46 2003) Fert: 592, nb live pups (F1); ↓ Rat, Sprague-Dawley Diet 1.5, 10, 30, 100, 300, Sys: 14-23 (Wolfe & Layton, Sys: 46, kidney wt ↑ ppm (F0/F1/F2: 0.1, Devp: 4.8 Devp: 14, testes, epididymis atrophy (F1,2) 0.5-0.8, 1.4-2.4, 4.8- 7.9, 14-23, 46-77, 359- 592, 543-775) Rat, Wistar; Diet 0, 1000, 3000, 9000 Mat: 340 (Schilling et al., Mat: 1088, bw & food consumption ↓ 25/group ppm Fert: NE 2001) Fert: 113, minimal testes atrophy (F2); (0, 113, 340, 1088) Devp: NE Devp: 113, testes atrophy (described above) Repeat dose studies Mouse, CD-1 Diet 0, 0.01, 0.1, 0.3 % Sys: 140 Sys: 425 (Lamb et al., 1987) 11-week-old (0, 14, 140, 425) Fert: 14 Fert: 140, reduced fertility; Live pups per litter ↓ 20 pairs of mice 98 days Rat, Long-Evans Gavage 0, 10, 100 Sys: NE Sys: NE (Akingbemi et al., 10/group Fert: NE 2004) Fert: 10, serum LH and testosterone, nb Leydig ↑ ↑ 70 or 100 days cells
Appendix 3 – Key Reproduction Studies with DEHP in Laboratory Animals (Adapted from FDA, 2002; ECB, 2006) Study Design/ Species Route (mg/kg bw/d) NOAEL (mg/kg bw/d) LOAEL (mg/kg bw/d) & Endpoint References ORAL Two-generation studies Rat, Sprague-Dawley Diet 1.5, 10, 30, 100, 300, Sys: 14-23 Sys: 46, ↑ kidney wt (Wolfe & Layton, 17 males/group 1000, 7500, 10000 ppm (F0/F1/F2: 0.1, 0.5-0.8, 1.4-2.4, 4.8- Fert: 46 Devp: 4.8 Fert: 592, ↓ nb live pups (F1); Devp: 14, testes, epididymis atrophy (F1,2) 2003) 7.9, 14-23, 46-77, 359- 592, 543-775) Rat, Wistar; Diet 0, 1000, 3000, 9000 Mat: 340 Mat: 1088, ↓ bw & food consumption (Schilling et al., 25/group ppm Fert: NE Fert: 113, minimal testes atrophy (F2); 2001) (0, 113, 340, 1088) Devp: NE Devp: 113, testes atrophy (described above) Repeat dose studies Mouse, CD-1 Diet 0, 0.01, 0.1, 0.3 % Sys: 140 Sys: 425 (Lamb et al., 1987) 11-week-old (0, 14, 140, 425) Fert: 14 Fert: 140, reduced fertility; ↓ Live pups per litter 20 pairs of mice 98 days Rat, Long-Evans Gavage 0, 10, 100 Sys: NE Sys: NE (Akingbemi et al., 10/group Fert: NE Fert: 10, ↑ serum LH and testosterone, ↑ nb Leydig 2004) 70 or 100 days cells
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