Reproductive and developmental effects of phthalate diesters in females

Figures & data

Figure 1. The general chemical structure of a phthalate diester (alkyl chains designated by R) in addition to the chemical structures of the more commonly researched phthalates and major metabolites of the diester.

Table 1. Summary of the epidemiological literature exploring the link between phthalate exposure and adverse reproductive health outcomes in women.

Outcome	Associations	References
Puberty	96.5 ± 134 ng/ml MMP in cases of premature thelarche versus 26.4 ± 30 ng/ml MMP in controls 68% of premature thelarche cases associated with high levels of phthalates in serum Association with delayed pubic hair growth (mean age 11.4 years [11.1–11.7] in the fourth quartile of exposure compared to 10.7 years [10.4–11.0] in the first), no association with breast development No association with precocious puberty No association between exposure to extracorporeal membrane oxygenation in infancy and onset of puberty DBP and DEHP detected in the serum of more girls with precocious puberty (27.3% and 22.7% of cases with DBP and DEHP respectively compared to 4% and 3% of controls) High molecular weight phthalates associated with decreased development of pubic hair (prevalence ratio = 0.94 [0.88–1.00] p = 0.04); Low-molecular weight phthalates non-significantly associated with more rapid breast development (first to fifth quintile: prevalence ratio = 1.06 [0.99–1.14], p = 0.087)	Chou et al. (2009) Colon et al. (2000) Frederiksen et al. (2012) Lomenick et al. (2010) Rais-Bahrami et al. (2004) Qiao et al. (2007) Wolff et al (2010)
Endometriosis	Higher plasma DEHP in cases compared to controls (p = 0.0047), no difference in plasma MEHP No significant association, MBP and MEHP non-significantly higher in endometriosis (MBP: OR = 2.77 [0.68–11.3], MEHP: OR = 2.03 [0.62–6.69]) No association (p = 0.23–0.90) Plasma MEHP associated with endometriosis (OR = 1.020 [1.003–1.038] p = 0.020); plasma DEHP was not associated with endometriosis (OR = 1.001 [1.000–1.002] p = 0.161) Plasma DBP, BBP, DEHP and DnOP associated with endometriosis (p < 0.01) and with severity of endometriosis (p < 0.01) Plasma DBP, BBP, DEHP and DnOP associated with endometriosis (p < 0.05) MBP non-significantly associated with endometriosis (OR = 1.36 [0.77–2.41]), MEHP higher in controls (OR = 0.44 [0.19–1.02])	Cobellis et al. (2003) Huang et al. (2010) Itoh et al. (2009) Kim et al. (2011) Reddy (2006a,b) Weuve et al. (2010)
Leiomyomas	MEHP associated with leiomyomas (OR = 2.90 [1.05–7.97]; p = 0.04), no association with other metabolites MBP non-significantly higher in cases (OR = 1.56 [0.93–2.61); MEHP non-significantly higher in controls (OR = 0.63 [0.35–1.12])	Huang et al. (2010) Weuve et al. (2010)
Time to Pregnancy	Probable occupational exposure associated with increased time to pregnancy (OR = 2.16 [1.02–4.57])	Burdorf et al. (2011)
Pregnancy Loss	Phthalate exposure associated with increased risk of spontaneous abortion MEHP associated with early pregnancy loss (third to first tertile: OR = 2.87 [1.09–7.57]), MEHP associated with reduced late pregnancy loss (third to first tertile OR = 0.25 [0.05–1.8])	Tabacova et al. (1999) Toft et al. (2012)
Gestational Age	MEHP, MEOHP, MEHHP associated with increased gestational age at birth (MEHP: OR = 2.0 [1.1–3.5], MEOHP: OR = 2.2 [1.3–4.0], MEHHP: OR = 2.1 [1.3–3.7]) Absence of MEHP associated with increased gestational age at birth (OR = 1.50 [1.013–2.21]) MEHP associated with decreased gestational age at birth (5 d shorter [2.1–8 d], p = 0.001 between fourth and first quartiles) Low-molecular-weight phthalates (β = 0.14 week [0.01–0.27 week]) and MEHP (β = 0.15 weeks [0.02–0.29]) associated with increased gestational age at birth	Adibi et al. (2009) Latini et al. (2003) Whyatt et al. (2009) Wolff et al. (2008)
Preterm Birth	No association (OR = 1.28 [0.39–4.20]) MBP associated with preterm birth (OR = 5.4 [1.5–19.3])	Burdorf et al. (2011) Meeker et al. (2009)
Birth Size	Occupational exposure to phthalates associated with low birth weight (OR = 2.42 [1.10–5.34]) DBP associated with increased birth weight and length (birth weight p = 0.031; length p = 0.018 between first and fourth quartiles) No association with birth weight, length or head circumference No association with birth weight, length or head circumference Low-molecular-weight phthalates associated with increased head circumference (β = 0.13 cm [0.01–0.24 cm] with increases in concentration), MBzP associated with increased length (β = 0.20 cm [0.00–0.40]), MEP associated with increased head circumference (β = 0.12 cm [0.01–0.23]) DBP and MEHP associated with low birth weight (DBP: OR = 3.54 [1.54–6.15], p = 0.008; MEHP: OR = 2.05 [1.17–3.70], p = 0.05), no associations with DEP or DEHP	Burdorf et al. (2011) Huang et al. (2009) Philippat et al. (2012) Suzuki et al. (2010) Wolff et al. (2008) Zhang et al. (2009)
Breast Cancer	No association with occupational exposure to BBP MEP and MECPP associated with breast cancer (MEP OR = 2.20 [1.33–3.63], p = 0.003], MECPP: OR = 1.68 [1.01–2.78], p = 0.047); MBP and MCPP associated with decreased risk of breast cancer (MBzP: OR = 0.46 [0.27–0.79], p = 0.008, MCPP OR = 0.44 (0.24–0.80)	Aschengrau et al. (1998) Lopez-Carrillo et al. (2010)

Unless otherwise noted, phthalate exposure was estimated by measurement of phthalate metabolites in urine.

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/m^3	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/m^3	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).

Chou YY, Huang PC, Lee CC, et al. (2009). Phthalate exposure in girls during early puberty. J Pediatr Endocrinol Metab, 22, 69–77

 PubMed Web of Science ®Google Scholar

Colon I, Caro D, Bourdony CJ, Rosario O. (2000). Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect, 108, 895–900

 PubMed Web of Science ®Google Scholar

Frederiksen H, Sorensen K, Mouritsen A, et al. (2012). High urinary phthalate concentration associated with delayed pubarche in girls. Int J Androl, 35, 216–26

 PubMedGoogle Scholar

Lomenick JP, Calafat AM, Melguizo Castro MS, et al. (2010). Phthalate exposure and precocious puberty in females. J Pediatr, 156, 221–5

 PubMed Web of Science ®Google Scholar

Rais-Bahrami K, Nunez S, Revenis ME, et al. (2004). Follow-up study of adolescents exposed to di(2-ethylhexyl) phthalate (DEHP) as neonates on extracorporeal membrane oxygenation (ECMO) support. Environ Health Perspect, 112, 1339–40

 PubMed Web of Science ®Google Scholar

Qiao L, Zheng L, Cai D. (2007). Study on the di-n-butyl phthalate and di-2-ethylhexyl phthalate level of girl serum related with precocious puberty in Shanghai. Wei Sheng Yan Jiu, 36, 93–95

 Google Scholar

Wolff MS, Teitelbaum SL, Pinney SM, et al. (2010). Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls. Environ Health Perspect, 118, 1039–46

 PubMed Web of Science ®Google Scholar

Cobellis L, Latini G, De FC, et al. (2003). High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis. Hum Reprod, 18, 1512–15

 PubMed Web of Science ®Google Scholar

Huang PC, Tsai EM, Li WF, et al. (2010). Association between phthalate exposure and glutathione S-transferase M1 polymorphism in adenomyosis, leiomyoma and endometriosis. Hum Reprod, 25, 986–94

 PubMed Web of Science ®Google Scholar

Itoh H, Iwasaki M, Hanaoka T, et al. (2009). Urinary phthalate monoesters and endometriosis in infertile Japanese women. Sci Total Environ, 408, 37–42

 PubMed Web of Science ®Google Scholar

Kim SH, Chun S, Jang JY, et al. (2011). Increased plasma levels of phthalate esters in women with advanced-stage endometriosis: a prospective case-control study. Fertil Steril, 95, 357–9

 PubMed Web of Science ®Google Scholar

Reddy BS, Rozati R, Reddy BV, Raman NV. (2006a). Association of phthalate esters with endometriosis in Indian women. BJOG, 113, 515–20

 PubMed Web of Science ®Google Scholar

Weuve J, Hauser R, Calafat AM, et al. (2010). Association of exposure to phthalates with endometriosis and uterine leiomyomata: findings from NHANES, 1999–2004. Environ Health Perspect, 118, 825–32

 PubMed Web of Science ®Google Scholar

Burdorf A, Brand T, Jaddoe VW, et al. (2011). The effects of work-related maternal risk factors on time to pregnancy, preterm birth and birth weight: the Generation R Study. Occup Environ Med, 68, 197–204

 PubMed Web of Science ®Google Scholar

Tabacova S, Little R, Balabaeva L. (1999). Maternal exposure to phthalates and complications of pregnancy. Epidemiology, 10, S127

 Google Scholar

Toft G, Jonsson BA, Lindh CH, et al. (2012). Association between pregnancy loss and urinary phthalate levels around the time of conception. Environ Health Perspect, 120, 458–63

 PubMed Web of Science ®Google Scholar

Adibi JJ, Hauser R, Williams PL, et al. (2009). Maternal urinary metabolites of Di-(2-Ethylhexyl) phthalate in relation to the timing of labor in a US multicenter pregnancy cohort study. Am J Epidemiol, 169, 1015–24

 PubMed Web of Science ®Google Scholar

Latini G, De FC, Presta G, et al. (2003). In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environ Health Perspect, 111, 1783–5

 PubMed Web of Science ®Google Scholar

Whyatt RM, Adibi JJ, Calafat AM, et al. (2009). Prenatal di(2-ethylhexyl)phthalate exposure and length of gestation among an inner-city cohort. Pediatrics, 124, e1213–20

 PubMed Web of Science ®Google Scholar

Wolff MS, Engel SM, Berkowitz GS, et al. (2008). Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect, 116, 1092–7

 PubMed Web of Science ®Google Scholar

Meeker JD, Hu H, Cantonwine DE, et al. (2009). Urinary phthalate metabolites in relation to preterm birth in Mexico city. Environ Health Perspect, 117, 1587–92

 PubMed Web of Science ®Google Scholar

Huang PC, Kuo PL, Chou YY, et al. (2009). Association between prenatal exposure to phthalates and the health of newborns. Environ Int, 35, 14–20

 PubMed Web of Science ®Google Scholar

Philippat C, Mortamais M, Chevrier C, et al. (2012). Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ Health Perspect, 120, 464–70

 PubMed Web of Science ®Google Scholar

Suzuki Y, Niwa M, Yoshinaga J, et al. (2010). Prenatal exposure to phthalate esters and PAHs and birth outcomes. Environ Int, 36, 699–704

 PubMed Web of Science ®Google Scholar

Zhang Y, Lin L, Cao Y, et al. (2009). Phthalate levels and low birth weight: a nested case-control study of Chinese newborns. J Pediatr, 155, 500–4

 PubMed Web of Science ®Google Scholar

Aschengrau A, Coogan PF, Quinn M, Cashins LJ. (1998). Occupational exposure to estrogenic chemicals and the occurrence of breast cancer: an exploratory analysis. Am J Ind Med, 34, 6–14

 PubMed Web of Science ®Google Scholar

Lopez-Carrillo L, Hernandez-Ramirez RU, Calafat AM, et al. (2010). Exposure to phthalates and breast cancer risk in northern Mexico. Environ Health Perspect, 118, 539–44

 PubMed Web of Science ®Google Scholar

Peters JW, Cook RM. (1973). Effect of phthalate esters on reproduction in rats. Environ Health Perspect, 3, 91–4

 PubMedGoogle Scholar

Heindel JJ, Gulati DK, Mounce RC, et al. (1989). Reproductive toxicity of three phthalic acid esters in a continuous breeding protocol. Fundam Appl Toxicol, 12, 508–18

 PubMedGoogle Scholar

Saillenfait AM, Roudot AC, Gallissot F, et al. (2011b). Developmental toxic potential of di-n-propyl phthalate administered orally to rats. J Appl Toxicol, 31, 36–44

 Google Scholar

Ema M, Kurosaka R, Harazono A, et al. (1996c). Phase specificity of developmental toxicity after oral administration of mono-n-butyl phthalate in rats. Arch Environ Contam Toxicol, 31, 170–6

 PubMed Web of Science ®Google Scholar

Gray LEJr, Laskey J, Ostby J. (2006). Chronic di-n-butyl phthalate exposure in rats reduces fertility and alters ovarian function during pregnancy in female Long–Evans hooded rats. Toxicol Sci, 93, 189–95

 PubMed Web of Science ®Google Scholar

Saillenfait AM, Sabate JP, Gallissot F. (2006). Developmental toxic effects of diisobutyl phthalate, the methyl-branched analogue of di-n-butyl phthalate, administered by gavage to rats. Toxicol Lett, 165, 39–46

 PubMed Web of Science ®Google Scholar

Ema M, Kurosaka R, Amano H, Ogawa Y. (1994). Embryolethality of butyl benzyl phthalate during early pregnancy in rats. Reprod Toxicol, 8, 231–6

 PubMedGoogle Scholar

Ema M, Harazono A, Miyawaki E, Ogawa Y. (1996a). Characterization of developmental toxicity of mono-n-benzyl phthalate in rats. Reprod Toxicol, 10, 365–72

 PubMed Web of Science ®Google Scholar

Ema M, Miyawaki E, Kawashima K. (1998). Reproductive effects of butyl benzyl phthalate in pregnant and pseudopregnant rats. Reprod Toxicol, 12, 127–32

 PubMedGoogle Scholar

Ema M, Miyawaki E. (2002). Effects on development of the reproductive system in male offspring of rats given butyl benzyl phthalate during late pregnancy. Reprod Toxicol, 16, 71–6

 PubMed Web of Science ®Google Scholar

Ema M, Miyawaki E, Hirose A, Kamata, E. (2003). Decreased anogenital distance and increased incidence of undescended testes in fetuses of rats given monobenzyl phthalate, a major metabolite of butyl benzyl phthalate. Reprod Toxicol, 17, 407–12

 PubMed Web of Science ®Google Scholar

Moral R, Santucci-Pereira J, Wang R, Russo IH, Lamartiniere CA, Russo J. (2011). In utero exposure to butyl benzyl phthalate induces modifications in the morphology and the gene expression profile of the mammary gland: an experimental study in rats. Environ Health, 10, 5 . doi: 10.1186/1476-069X-10-5

 PubMed Web of Science ®Google Scholar

Nagao T, Ohta R, Marumo H, et al. (2000). Effect of butyl benzyl phthalate in Sprague–Dawley rats after gavage administration: a two-generation reproductive study. Reprod Toxicol, 14, 513–32

 PubMedGoogle Scholar

Hannas BR, Furr J, Lambright CS, et al. (2011). Dipentyl phthalate dosing during sexual differentiation disrupts fetal testis function and postnatal development of the male Sprague–Dawley rat with greater relative potency than other phthalates. Toxicol Sci, 120, 184–93

 Google Scholar

Saillenfait AM, Gallissot F, Sabate JP. (2009a). Differential developmental toxicities of di-n-hexyl phthalate and dicyclohexyl phthalate administered orally to rats. J Appl Toxicol, 29, 510–21

 Google Scholar

Saillenfait AM, Sabate JP, Gallissot F. (2009b). Effects of in utero exposure to di-n-hexyl phthalate on the reproductive development of the male rat. Reprod Toxicol, 28, 468–76

 Google Scholar

Hoshino N, Iwai M, Okazaki Y. (2005). A two-generation reproductive toxicity study of dicyclohexyl phthalate in rats. J Toxicol Sci, 30, 79–96

 PubMedGoogle Scholar

Yamasaki K, Okuda H, Takeuchi T, Minobe Y. (2009). Effects of in utero through lactational exposure to dicyclohexyl phthalate and p,p′-DDE in Sprague–Dawley rats. Toxicol Lett, 189, 14–20

 PubMed Web of Science ®Google Scholar

Grande SW, Andrade AJ, Talsness CE, et al. (2006). A dose-response study following in utero and lactational exposure to di(2-ethylhexyl)phthalate: effects on female rat reproductive development. Toxicol Sci, 91, 247–54

 PubMed Web of Science ®Google Scholar

Ma M, Kondo T, Ban S, et al. (2006). Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions. Toxicol Sci, 93, 164–71

 Google Scholar

Moore RW, Rudy TA, Lin TM, et al. (2001). Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate. Environ Health Perspect, 109, 229–37

 PubMed Web of Science ®Google Scholar

Pocar P, Fiandanese N, Secchi C, et al. (2012). Exposure to di(2-ethyl-hexyl) phthalate (DEHP) in utero and during lactation causes long-term pituitary-gonadal axis disruption in male and female mouse offspring. Endocrinology, 153, 937–48

 PubMed Web of Science ®Google Scholar

Schmidt JS, Schaedlich K, Fiandanese N, et al. (2012). Di(2-ethylhexyl) Phthalate (DEHP) impairs female fertility and promotes adipogenesis in C3H/N mice. Environ Health Perspect, 120, 1123--9

 PubMed Web of Science ®Google Scholar

Svechnikova I, Svechnikov K, Soder O. (2007). The influence of di-(2-ethylhexyl) phthalate on steroidogenesis by the ovarian granulosa cells of immature female rats. J Endocrinol, 194, 603–9

 Google Scholar

Takai R, Hayashi S, Kiyokawa J, et al. (2009). Collaborative work on evaluation of ovarian toxicity. Two- or four-week repeated dose studies and fertility study of di-(2-ethylhexyl) phthalate (DEHP) in female rats. J Toxicol Sci, 34, SP111–19

 Google Scholar

Saillenfait AM, Roudot AC, Gallissot F, Sabate JP. (2011a). Prenatal developmental toxicity studies on di-n-heptyl and di-n-octyl phthalates in Sprague–Dawley rats. Reprod Toxicol, 32, 268–76

 PubMed Web of Science ®Google Scholar

McKee RH, Pavkov KL, Trimmer GW, et al. (2006). An assessment of the potential developmental and reproductive toxicity of di-isoheptyl phthalate in rodents. Reprod Toxicol, 21, 241–52

 Google Scholar

Boberg J, Christiansen S, Axelstad M, et al. (2011). Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats. Reprod Toxicol, 31, 200–9

 PubMed Web of Science ®Google Scholar

Waterman SJ, Keller LH, Trimmer GW, et al. (2000). Two-generation reproduction study in rats given di-isononyl phthalate in the diet. Reprod Toxicol, 14, 21–36

 PubMed Web of Science ®Google Scholar

Hushka LJ, Waterman SJ, Keller LH, et al. (2001). Two-generation reproduction studies in Rats fed di-isodecyl phthalate. Reprod Toxicol, 15, 153–69

 Google Scholar

Fulcher SM, Willoughby CR, Heath JA, et al. (2001). Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat. Reprod Toxicol, 15, 95–102

 PubMedGoogle Scholar

Willoughby CR, Fulcher SM, Creasy DM, et al. (2000). Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat. Reprod Toxicol, 14, 427–50

 PubMedGoogle Scholar

Saillenfait AM, Gallissot F, Sabate JP. (2008a). Evaluation of the developmental toxicity of diallyl phthalate administered orally to rats. Food Chem Toxicol, 46, 2150–6

 Google Scholar

Adamsson A, Salonen V, Paranko J, Toppari J. (2009). Effects of maternal exposure to di-isononylphthalate (DINP) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) on steroidogenesis in the fetal rat testis and adrenal gland. Reprod Toxicol, 28, 66–74

 Google Scholar