PPAR𝛼- and DEHP-Induced Cancers

Table 1

Primary studies on DEHP-induced carcinogenesis in mice and rats (modifying the paper reported by Huber et al. [2]).

Author	Sex	Route	Duration	Dosage	Type of tumor	Tumor frequency (%)
Species, strain
[39] Rat F344	M	Feed	103 w	0.00%	Hepatic tumors	6
				0.60%		12
				1.20%		24
	F	Feed	103 w	0.00%	Hepatic tumors	0
				0.60%		12
				1.20%		26
[41] Rat F344	F	Feed	2 y	0.00%	Hepatic tumors	0
				0.03%		6
				0.10%		5
				1.20%		30
[42] Rat F344	M	Oral	24 m	0 (water)	Liver carcinoma	4
				0 (vehicle)		12
				2EH 50 mg/kg		6
				2EH 150		6
				2EH 500		2
	M	Oral	24 m	0 (water)	Liver adenoma	0
				0 (vehicle)		0
				2EH 50 mg/kg		0
				2EH 150		2
				2EH 500		0
	F	Oral	24 m	0 (water)	Liver carcinoma	0
				0 (vehicle)		2
				2EH 50 mg/kg		2
				2EH 150		4
				2EH 500		0
[42] Mouse B6C3F1	M	Oral	18 m	0 (water)	Liver carcinoma	8
				0 (vehicle)		12
				2EH 50 mg/kg		12
				2EH 200		14
				2EH 750		18
	M	Oral	18 m	0 (water)	Liver adenoma	0
				0 (vehicle)		0
				2EH 50 mg/kg		0
				2EH 200		0
				2EH 750		2
	F	Oral	18 m	0 (water)	Liver carcinoma	2
				0 (vehicle)		0
				2EH 50 mg/kg		2
				2EH 200		6
				2EH 750		10
[43] Rat F344	M	Feed	2 y	0 ppm	Hepatocellular carcinoma	2
				6000 ppm		2
				12000 ppm		10
	M	Feed	2 y	0 ppm	Hepatocellular neoplastic nodule	4
				6000 ppm		10
				12000 ppm		14
≻	F	Feed	2 y	0 ppm	Hepatocellular carcinoma	0
				6000 ppm		4
				12000 ppm		16
				0 ppm	Hepatocellular neoplastic nodule	0
				6000 ppm		8
				12000 ppm		10
[43] Mouse B6C3F1	M	Feed	2 y	0 ppm	Hepatocellular carcinoma	18
				3000 ppm		29
				6000 ppm		38
				0 ppm	Hepatocellular adenoma	10
				3000 ppm		23
				6000 ppm		20
	F	Feed	2 y	0 ppm	Hepatocellular carcinoma	0
				3000 ppm		14
				6000 ppm		34
				0 ppm	Hepatocellular adenoma	2
				3000 ppm		10
				6000 ppm		2
[40] Rat F344	M	Diet	79 w	0 ppm	Hepatocellular carcinoma	10
				2500 ppm		0
				12500 ppm		40
				0 ppm	Hepatocellular adenoma	10
				2500 ppm		10
				12500 ppm		10
	F	Diet	79 w	0 ppm	Hepatocellular carcinoma	0
				2500 ppm		0
				12500 ppm		20
				0 ppm	Hepatocellular adenoma	0
				2500 ppm		0
				12500 ppm		10
	M	Diet	105 w	0 ppm	Hepatocellular carcinoma	1
				100 ppm		0
				500 ppm		2
				2500 ppm		5
				12500 ppm		30
				Recovery		13
				0 ppm	Hepatocellular adenoma	5
				100 ppm		10
				500 ppm		5
				2500 ppm		12
				12500 ppm		26
				Recovery		22
				0 ppm	Hepatocellular carcinoma	0
				100 ppm		2
				500 ppm		0
				2500 ppm		2
				12500 ppm		18
				Recovery		7
≻	F	Diet	105 w	0 ppm	Hepatocellular adenoma	0
				100 ppm		6
				500 ppm		2
				2500 ppm		3
				12500 ppm		10
[40] Mouse B6C3F1	M	Diet	79 w	0 ppm	Hepatocellular carcinoma	0
				100 ppm		0
				500 ppm		10
				1500 ppm		0
				6000 ppm		7
				0 ppm	Hepatocellular adenoma	7
				100 ppm		10
				500 ppm		20
				1500 ppm		10
				6000 ppm		7
	F	Diet	79 w	0 ppm	Hepatocellular carcinoma	0
				100 ppm		0
				500 ppm		0
				1500 ppm		0
				6000 ppm		13
				0 ppm	Hepatocellular adenoma	0
				100 ppm		10
				500 ppm		10
				1500 ppm		10
				6000 ppm		27
	M	Diet	105 w	0 ppm	Hepatocellular carcinoma	6
				100 ppm		8
				500 ppm		14
				1500 ppm		22
				6000 ppm		31
				Recovery		22
				0 ppm	Hepatocellular adenoma	6
				100 ppm		17
				500 ppm		20
				1500 ppm		22
				6000 ppm		27
				Recovery		5
	F	Diet	105 w	0 ppm	Hepatocellular carcinoma	4
				100 ppm		3
				500 ppm		5
				1500 ppm		15
				6000 ppm		23
				Recovery		42
				0 ppm	Hepatocellular adenoma	0
				100 ppm		3
				500 ppm		6
				1500 ppm		14
				6000 ppm		49
				Recovery		24
[43] Rat F344	M	Feed	2 y	0, 6000, 12000 ppm	Pituitary adenoma or carcinoma	Decrease in highest dose
	F	Feed	2 y	0, 6000, 12000 ppm	Pituitary adenoma or carcinoma	Decrease in lower dose
	M	Feed	2 y	0, 6000, 12000 ppm	Thyroid C-cell adenoma or carcinoma	Decrease in highest dose (unclear)
	M	Feed	2 y	0, 6000, 12000 ppm	Testis interstitial cells tumor	Decrease in highest dose
	F	Feed	2 y	0, 6000, 12000 ppm	Mammary gland	Decrease in highest dose
[36] Rat F344	M	Diet	78 w	0 ppm	Interstitial cells tumor or testes	90
				2500 ppm		100
				12500 ppm		30
	M	Diet	104 w	0 ppm	Interstitial cells tumor or testes	92
				100 ppm		90
				500 ppm		91
				2500 ppm		92
				12500 ppm		31
				0 ppm	Mononuclear cell leukemia	23
				100 ppm		26
				500 ppm		29
				2500 ppm		49
				12500 ppm		42
				0 ppm	Pancreatic acinar cell adenoma	0
				100 ppm		0
				500 ppm		0
				2500 ppm		0
				12500 ppm		8
	F	Diet	104 w	0 ppm	Mononuclear cell leukemia	22
				100 ppm		34
				500 ppm		20
				2500 ppm		25
				12500 ppm		26
				0 ppm	Pancreatic acinar cell adenoma	0
				100 ppm		0
				500 ppm		0
				2500 ppm		0
				12500 ppm		3
[44] Rat F344	M	Diet	79 w	0 ppm	Interstitial cells tumor or testes	90
				12500 ppm		30
				0 ppm	Mononuclear cell leukemia	0
				12500 ppm		10
≻	M	Diet	105 w	0 ppm	Interstitial cells tumor or testes	92
				12500 ppm		31
				Recovery		32
				0 ppm	Mononuclear cell leukemia	23
				12500 ppm		42
				Recovery		53
[35] Mouse B6C3F1	M,	Diet	78 w,	0, 100, 500, 1500,	No data about tumors
				6000 ppm
[44] Rat F344	F	Diet	79 w	0 ppm, 12500 ppm	No data about tumors
[44] Mouse B6C3F1	M,	Diet	79 w	0 ppm, 6000 ppm,	No data about tumors
	M,	Diet	105 w	0 ppm, 6000 ppm,	No data about tumors
[45] Mouse 129/Sv, PPARα-null	M	Diet	21 m		Liver tumors (hepatocellular adenoma, hepatocellular carcinoma, cholangiocellular carcinoma)	Wild-type	PPAR𝛼-null
				0%		0	4
				0.01%		9	4
				0.05%		10	25.8