Table 2.
Comparison of toxic effects and carcinogenesis of TCDD and PCBs in rodent NTP studies and human epidemiology.
| TCDD
|
PCBs
|
|||||
|---|---|---|---|---|---|---|
| Findings | Human | Rat | Mouse | PCBs Human | PCB126Rat | PeCDF Rat |
| Alimentary System Liver | ||||||
| Hepatocecellular adenoma/carcinoma/neoplastic nodules/liver cancer | Bertazzi et al., 2001 | HSDa (TR521b) OMc (TR209) Walker et al., 2005, 2006 | BCFd (TR209) | ATSDR, 2000; Golden et al., 2003; Kimbrough, 1985; McGregor et al., 1998 | HSD (TR520) Walker et al., 2005 | HSD (TR525) Walker et al., 2005 |
| Cholangioma | —f | HSD (TR521) Walker et al., 2006 | — | — | HSD (TR520) | HSD (TR525) |
| Cholangiocarcinoma/biliary duct cancer | Pesatori et al., 2003 | HSD (TR521) Walker et al., 2005, 2006 | — | ATSDR, 2000; Brown, 1987; Golden et al., 2003 | HSD (TR520) Walker et al., 2005 | HSD (TR525) Walker et al., 2005 |
| Hepatocholangioma | — | HSD (TR521) Walker et al., 2006 | — | — | HSD (TR520) | — |
| Toxic hepatopathy/toxic hepatitis/Chronic liver disease./fatal liver disease | Watanabe et al., 1999; Zober et al., 1994 | HSD (TR521) OM (TR209) Walker et al., 2006 | BCF(TR209) | ATSDR, 2000; McGregor et al., 1998; Yu et al., 1997 | HSD (TR520) | HSD (TR525) |
| Hepatocytic change (hypertrophy, multinucleated hepatocytes, fatty change, necrosis, altered foci) | ATSDR, 1998 | HSD (TR521) Walker et al., 2006 | SWe (TR201) | — | HSD (TR520) | HSD (TR525) |
| Nodular hyperplasia | — | HSD (TR521) Walker et al., 2006 | — | — | HSD (TR520) | HSD (TR525) |
| Inflammation/pigmentation/portal fibrosis | ATSDR, 1998 | HSD (TR521) Walker et al., 2006 | SW (TR201) | — | HSD (TR520) | HSD (TR525) |
| Oval cell hyperplasia/bile-duct hyperplasia/cysts | — | HSD (TR521) Walker et al., 2006 | — | — | HSD (TR520) | HSD (TR525) |
| Cholangiofibrosis | — | HSD (TR521) Walker et al., 2006 | — | — | HSD (TR520) | HSD (TR525) |
| Alimentary System Oral Cavity (gingiva), tooth | ||||||
| Squamous-cell carcinoma | —c | HSDa(TR521b) Walker et al., 2005, 2006; Yoshizawa et al., 2005a | — | — | HSD (TR520) Walker et al., 2005; Yoshizawa et al., 2005a | — |
| Squamous hyperplasia/gum swelling/gum pigmentation | — | HSD (TR521) Yoshizawa et al., 2005a | — | Asahi, 1993 ATSDR, 1998; Brouwer et al., 1998; Guo et al., 1999, 2004; Hashiguchi et al., 1995, 1997; Miller, 1985; Shimizu et al., 1992; Urabe and Asahi, 1985; Wang et al., 2003 | HSD (TR520) Yoshizawa et al., 2005a | — |
| Developmental dental aberration/broken teeth/periodontitis | Alaluusua et al., 2004 | — | — | Asahi, 1993; Brouwer et al., 1998; Guo et al., 1999, 2004; Hashiguchi et al., 1997; Miller, 1985; Shimizu et al., 1992; Wang et al., 2003 | — | — |
| Exocrine pancreas | ||||||
| Acinar adenoma/carcinoma/pancreatic cancer | — | HSD (TR521) Nyska et al 2004; Yoshizawa et al., 2005b; Walker et al., 2006 | — | ATSDR, 2000 Golden et al., 2003; Yassi et al., 1994 | — | HSD (TR525) Nyska et al., 2004 |
| Acinal changes (vacuolization, atropy)/inflammation | — | HSD (TR521) Nyska et al., 2004; Yoshizawa et al., 2005b; Walker et al., 2006 | — | — | HSD (TR520) Nyska et al., 2004 | HSD (TR525) Nyska et al., 2004 |
| Intestine | ||||||
| Gastrointestinal cancer/rectal cancer | Bertazzi et al., 2001 Pesatori et al., 2003 | — | — | ATSDR, 2000 Brown, 1987; Kimbrough, 1985 | — | — |
| Gastrointestinal signs | Geusau et al., 2001 | — | — | ATSDR, 2000 | — | — |
| Appendicitis | Zober et al., 1994 | — | — | — | — | — |
| Alimentary System Stomach | —e | — | — | — | — | — |
| Squamous hyperplasia (forestomach) | — | HSDa (TR521b) Walker et al., 2006 | — | — | — | HSD (TR525) |
| Cardiovascular System Heart | ||||||
| Cardiomyopathy/chronic circulatory diseases/ischemic heart disease/hypertension | ATSDR, 1998; Bertazzi et al., 2001; Pesatori et al., 2003; Steenland et al., 1999; Watanabe et al., 1999 | HSD (TR521) Walker et al., 2006 | — | ATSDR, 2000 | HSD (TR520) | HSD (TR525) |
| Endocrine System Adrenal cortex | ||||||
| Adenoma/carcinoma | — | — | — | — | HSD (TR520) | — |
| Hyperplasia | — | HSD (TR521) Walker et al., 2006 | — | — | — | — |
| Vacuolization | — | — | — | — | HSD (TR520) | — |
| Atrophy | — | HSD (TR521) Walker et al., 2006 | — | — | HSD (TR520) | — |
| Cystic degeneration | — | — | — | — | — | HSD (TR525) |
| Thyroid | ||||||
| Follicular-cell adenoma/carcinoma | Pesatori et al., 2003 | OMc (TR 209) | BCFd (TR209) | — | — | — |
| Follicular-cell hypertrophy/thyroid-related hormone changes (T4, T3, TSH)/thyroid disease/goiter/hyperthyroidism | ATSDR, 1998; Zober et al., 1994 | HSD (TR521) Tani et al., 2004; Walker et al., 2006 | — | ATSDR, 2000; Guo et al., 1999 | HSD (TR520) | HSD (TR525) |
| Endocrine pancreas (islets) | ||||||
| Diabetes/glucose intolerance | ATSDR, 1998; Bertazzi et al., 2001; Pesatori et al., 2003 | — | — | McGregor et al., 1998 | — | — |
| Genital System (Female) Clitoral gland | ||||||
| Cystic ducts | —d | HSDa (TR521b) Walker et al., 2006 | — | — | HSD (TR520) | — |
| Uterus Squamous-cell carcinoma | — | HSD (TR521) Walker et al., 2006 | — | — | HSD (TR520) | HSD (TR525) |
| Endometrial cyctic hyperplasia | — | — | — | — | — | HSD (TR525) |
| Inflammation | — | — | — | — | — | HSD (TR525) |
| Squamous metaplasia | — | — | — | — | — | HSD (TR525) |
| Endometriosis | Eskenazi et al., 2002; Mayani et al., 1997 | — | — | Arisawa et al., 2005; Gerhard et al., 1999; Louis et al., 2005 | — | — |
| Menstrual cycle changes | — | — | — | ATSDR, 2000 | — | — |
| Genital System (Male) | ||||||
| Hormonal changes (testosterone, FSH, LH) | ATSDR, 1998; Egeland et al., 1994 | — | — | — | — | — |
| Alterations in sexual development/shorter penis length (infant) | — | — | — | Brouwer et al., 1998; Guo et al., 2004 | — | — |
| Immune and Hematopoietic System | ||||||
| Hodgkin’s disease/non-Hodgkin’s Lymphoma/acute leukemia/myeloid leukemia/multiple myeloma/lymphaemopoietic cancer/lymphoma/leukemia | ATSDR, 1998; Bertazzi et al., 2001; Buckley et al., 1989; Huff et al., 1994; Mannetje et al., 2004; Pesatori et al., 2003; Rix et al., 1998; Viel et al., 2000 | — | BCF c (TR209) | ATSDR, 2000 Golden et al., 2003 Kimbrough et al., 1985 | — | — |
| Immunosuppressant effects | ATSDR, 1998; Halperin et al., 1998; Watanabe et al., 1999 | — | — | ATSDR, 2000 McGregor et al., 1998; Weisglas-Kuperus et al., 2000, 2004 | — | — |
| Infectious diseases/parasitic diseases/otitis media due to immunosuppression | Zober et al., 1994 | — | — | Weisglas-Kuperus et al., 2004 ATSDR, 2000 Guo et al., 2004 | — | — |
| Immune and Hematopoietic System Thymus | ||||||
| Atrophy | —d | HSDa (TR521b) Walker et al., 2006 | — | — | HSD (TR520) | HSD (TR525) |
| Spleen | ||||||
| Lymphoid follicular atrophy | — | — | — | — | HSD (TR520) | — |
| Integumentary System Skin, mammary gland | ||||||
| Fibrosarcoma | — | — | SW c(TR201) | — | — | |
| Malignant melanoma | Akhtar et al., 2005 | — | — | ATSDR, 2000; Golden et al., 2003 | — | — |
| Breast cancer | Birnbaum and Fenton, 2003; Huff et al., 1994 | — | — | ATSDR, 2000; Kimbrough, 1985 | — | — |
| Porphyria/cutanea tarda/hypertrichosis/hirsutism/hyperpigmentation | ATSDR, 1998; Wantanabe et al., 1999 | — | — | Asahi, 1993; ATSDR, 2000; Guo et al., 1999, 2004; Kimbrough, 1985; Miller, 1985; Urabe et al, 1985 | — | — |
| Choloracne/squamous metaplasia & keratinization of sebaceous glands & hair follicles/hypertrophy of Meibomian gland | ATSDR, 1998; Geusau et al., 2001; Pesatori et al., 2003; Zober et al., 1994, 1997/1998; Wantanabe et al., 1999 | — | — | Asahi, 1993; ATSDR, 2000; Guo et al., 1999, 2004; McGregor et al., 1998; Miller, 1985; Urabe et al, 1985 | — | — |
| Nervous System | ||||||
| Neurological disorders (peripheral nervous signs, lower limb weakness, muscle pains, sleepiness, headaches, dizziness, nausea) | ATSDR, 1998; Zober et al., 1994, 1997/1998; Wantanabe et al., 1999 | — | — | — | — | — |
| Delay in neurodevelopment/neurobehavioral changes (hypotony, hyperactivity, lower mean intelligence quotients, altered latencies and amplitudes of auditory event-related potentials)/mental disorders (infant/in utero exposure) | — | — | — | ATSDR, 2000; Brouwer et al., 1998; Carpenter, 2006; Guo et al., 2004 | — | — |
| Respiratory System Lung | ||||||
| Cystic keratinizing epithelioma of lung/lung cancer | ATSDR, 1998; Bertazzi et al., 2001; Fingerhut et al., 1991; Huff et al., 1994; McGregor et al., 1998; Pesatori et al., 2003 | HSDa (TR 521b) Walker et al., 2005, 2006 | — | Pavuk et al., 2004 | Brix et al., 2004 HSD (TR 520) Walker et al., 2005, 2006 | HSD (TR 525) Walker et al., 2005, 2006 |
| Metaplasia of lung alveolar epithelium (bronchiolar, squamous) | —c | HSD (TR521) | — | — | Brix et al., 2004 HSD (TR520) Walker et al., 2006 | HSD (TR525) Walker et al., 2006 |
| Chronic (obstructive) respiratory diseases/upper respiratory tract infections/bronchitis, laryngitis/hemorrhagic pleuritis | ATSDR, 1998; Bertazzi et al., 2001; Wantanabe et al., 1999; Zober et al., 1994 | — | — | Asahi, 1993; ATSDR, 2000; Brouwer et al., 1998; Guo et al., 2004 | — | — |
| Urinary System Kidney | ||||||
| Nephropathy Skeletal System | — | HSD (TR521) | — | — | HSD (TR520) | HSD (TR525) |
| Bone & Joint | ||||||
| Arthritis/herniated disks | — | — | — | Guo et al., 1999 Kuratsune, 1980 | — | — |
| Others | ||||||
| Soft-tissue sarcomas | ATSDR, 1998; Fingerhut et al., 1991; Huff et al., 1994; McGregor et al., 1998; Pesatori et al., 2003; Rix et al., 1998; Viel et al., 2000 | — | — | — | — | — |
a
Harlan Sprague-Dawley rats.
b
National Toxicology Program (NTP) study report number.
c
Osborne Mendel rats.
d
B6C3F1 mice,
e
Swiss-Webster mice.
f
No available information published.
a
Harlan Sprague Dawley rats.
b
National Toxicology Program (NTP) study report number.
c
No available information published.
a
Harlan Sprague-Dawley rats.
b
National Toxicology Program (NTP) study report number.
c
Osborne Mendel rats.
d
B6C3F1 mice.
e
No available information published.
a
Harlan Sprague-Dawley rats.
b
National Toxicology Program (NTP) study report number.
c
B6C3F1 mice.
d
No available information published.
a
Harlan Sprague-Dawley rats.
b
National Toxicology Program (NTP) study report number.
c
Swiss-Webster mice.
d
No available information published.
a
Harlan Sprague Dawley rats.
b
National Toxicology Program (NTP) study report number.
c
No available information published.