Table 2.
Summary of the NOAELs and LOAELs in mg/kg/d as well as the direction of change for each outcome, respectively, found in animal studies for each individual phthalate.
| Phthalate | Maternal Weight Gain | Infertility | Resorptions | Litter Size | Pup Weights | Irregular Estrous Cycle | Sexual Maturation† | Circulating Progesterone | Circulating Estradiol | Ovarian Weight | Ovarian Histology | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DMP | NR* | 2 ml/kg | 2 ml/kg | 2 ml/kg | NR | NR | NR | NR | NR | NR | NR | Peters & Cook (1973) |
| – | – | – | ||||||||||
| NC** | NC | NC | ||||||||||
| DEP | 600 ppm | 15 000 ppm | 15 000 ppm | 1.25% | 2.5% | 15 000 ppm | – | NR | NR | 15 000 ppm | 15 000 ppm | Fujii et al. (2005); Anonymous (1997b) |
| – | – | – | 2.5% | – | – | 15 000 ppm | – | – | ||||
| ↑ | NC | NC | NC | NC | NC | ↑ | NC | NC | ||||
| DPrP | 1000 | 1.25% | 1500 | 1.25% | 500 | 5% | NR | NR | NR | NR | 5% | Heindel et al. (1989); Saillenfait et al. (2011b) |
| 1500 | 2.5% | – | 2.5% | 1000 | – | – | ||||||
| ↓ | ↑ | NC | ↓ | ↓ | NC | NC | ||||||
| DBP | 12 | 12 | 250 | 250 | – | 1000 | – | 250 | 1500 | 1000 | 1500‡ | Ema et al. (1996c, 2000); Gray Jr. et al. (2006); Salazar et al. (2004); Wine et al. (1997) |
| 50 | 50 | 500 | 500 | 12 | – | 12 | 500 | – | 1250 | – | ||
| ↓ | ↑ | ↑ | ↓ | ↓ | NC | ↑ | ↓ | NC | ↓ | NC | ||
| DiBP | 250 | 1000 | 500 | 500 | 250 | NR | NR | NR | NR | NR | NR | Saillenfait et al. (2006) |
| 500 | – | 750 | 750 | 500 | ||||||||
| ↓ | NC | ↑ | ↓ | ↓ | ||||||||
| BBP | 167 | 250 | 375 | 500 | 250 | 500 | 120 | – | 500 | 100 | 1000‡ | Ema et al. 1994; Ema et al. 1996a; Ema et al. 1998; Ema & Miyawaki (2002); Ema et al. (2003); Moral et al. (2011); Nagao et al. (2000) |
| 250§ | 500 | 500 | 625 | 375 | – | 500 | 2% | – | 500 | – | ||
| ↓ | ↑ | ↑ | ↓ | ↓ | NC | ↑ | ↓ | NC | ↓ | NC | ||
| DPP | 100 | – | NR | – | 300 | 2.5% | NR | NR | NR | NR | 2.5% | Hannas et al. (2011); Heindel et al. (1989) |
| 300 | 0.5% | 0.5% | – | – | – | |||||||
| ↓ | ↑ | ↓ | NC | NC | NC | |||||||
| DnHP | 500 | 0.6% | 500 | – | 250 | NR | NR | NR | NR | NR | NR | Anonymous (1997a); Saillenfait et al. (2009a,b) |
| 750 | 1.2% | 625 | 0.3% | 500 | ||||||||
| ↓ | ↑ | ↑ | ↓ | ↓ | ||||||||
| DcHP | 240 ppm | 6000 ppm | 6000 ppm | 6000 ppm | 1200 ppm | 1200 ppm | 500 | NR | 6000 ppm | 500 | NR | Hoshino et al. (2005); Yamasaki et al. (2009) |
| 1200 ppm | – | – | – | 6000 ppm | 6000 ppm | – | – | – | ||||
| ↓ | NC | NC | NC | ↓ | ↑ | NC | NC | NC | ||||
| DEHP | 375 | 5 | 100 | 100 | – | 5 mg/m3 | 5 | – | – | – | – | Grande et al. (2006), Ma et al. (2006); Moore et al. (2001); Pocar et al. (2012); Schmidt et al. (2012); Svechnikova et al. (2007); Takai et al. (2009) |
| 750 | 500 | 500 | 500 | 0.05 | 25 mg/m3 | 15 | 500 | 500 | 0.05 | 300 | ||
| ↓ | ↑ | ↑ | ↓ | ↓ | ↑ | ↑¶ | ↓ | ↓⊥ | ↑ | ↓∥ | ||
| DHPP | 1000 | 1000 | 1000 | 1000 | 1000$ | NR | NR | NR | NR | NR | NR | Saillenfait et al. (2011a) |
| – | – | – | – | – | ||||||||
| NC | NC | NC | NC | NC | ||||||||
| DiHP | 300 | 4500 ppm | 300 | 300 | 300 | 8000 ppm | 8000 ppm | NR | NR | 4500 ppm | 8000 ppm | McKee et al. (2006) |
| 750 | 8000 ppm | 750 | 750 | 750 | – | – | 8000 ppm | – | ||||
| ↓ | ↑ | ↑ | ↓ | ↓ | NC | NC | ↓ | NC | ||||
| DnOP | 5% | 5% | 1000 | 5% | 5% | 5% | NR | NR | NR | NR | NR | Heindel et al. (1989); Saillenfait et al. (2011a) |
| – | – | – | – | – | – | |||||||
| NC | NC | NC | NC | NC | NC | |||||||
| DiNP | 0.5% | 900 | 900 | – | 600¥ | NR | 900 | NR | NR | 1% | NR | Boberg et al. (2011); Waterman et al. (2000) |
| 1% | – | – | 0.2% | 750 | – | 1.5% | ||||||
| ↓ | NC | NC | ↑ | ↓ | NC | ↓ | ||||||
| DiDP | 0.4% | 0.8% | NR | 0.8% | 0.4% | 0.8% | 0.2% | NR | NR | 0.4% | 0.8% | Hushka et al. 2001 |
| 0.8% | – | – | 0.8% | – | 0.4% | 0.8% | – | |||||
| ↓ | NC | NC | ↓ | NC | ↑ | ↓ | NC | |||||
| D79P | 1000 | 1000 | 1000 | 1000 | 0.5% | 1% | NR | NR | NR | 0.5% | 1% | Fulcher et al. (2001); Willoughby et al. (2000) |
| – | – | – | – | 1% | – | 1% | – | |||||
| NC | NC | NC | NC | ↓ | NC | ↓ | NC | |||||
| D911P | 1000 | 1000 | 1000 | 1000 | 0.5% | 1% | 1% | NR | NR | 1% | 1% | Fulcher et al. (2001); Willoughby et al. (2000) |
| – | – | – | – | 1% | – | – | – | – | ||||
| NC | NC | NC | NC | ↓ | NC | NC | NC | NC | ||||
| DAP | 150 | 405 | 405 | 405 | 150 | NR | NR | NR | NR | NR | NR | Saillenfait et al. (2008a) |
| 200 | – | – | – | 200 | ||||||||
| ↓ | NC | NC | NC | ↓ |
*Not Reported.
**No Change.
†Where ↑ is a delay in the onset of vaginal opening.
‡Based on the number of corpora lutea.
§MBzP, the metabolite of BBP.
¶Another study reported earlier vaginal opening after inhalation of 5 and 25 mg/m3 (Ma et al., 2006).
⊥Another study reported increased estradiol after inhalation of 5 and 25 mg/m3 (Ma et al., 2006).
∥Vacuolization of stromal cells.
$A trend for decreased pup weight at 1000 mg/kg/d.
¥Another study reported an increase in male pup weights at a dose of 250 mg/kg/d (Adamsson et al., 2009).