Consideration of the variability in control tumor incidence data at the Ramazzini Institute in evaluating treatment-related effects following chemical exposure

Figures & data

Table 1a. Published Ramazzini Institute (RI) studies in SD rats.

Study conduct timeframe	Reference study	Test substance
2005	Falcioni et al. (2018)	Mobile phone radiofrequency
2005	Soffritti et al. (2013)	World Trade Center (WTC) dust
2005	Soffritti and Giuliani (2019)	S-50 Hz MF and 1.8 GHz GSM radiofrequency radiation
2005	Soffritti et al. (2016a)	Sinusoidal-50 Hz magnetic field and formaldehyde
2005	Bua et al. (2018)	ELFEMF
2004	Vornoli et al. (2022)	Aflatoxin B1 alone or with ELFEMF
2003	Soffritti, Belpoggi, Esposti, Lambertini (2006)	Sodium arsenite
2002	Soffritti et al. (2016b)	Sinusoidal-50 Hz Magnetic Field and γ radiation
2002	Belpoggi et al. (2011); Soffritti, Minardi, et al. (2004)	Fluoro-edenitic fibers
2001	Einbond et al. (2012)	Black cohosh
1997	Tibaldi et al. (2020); Chiozzotto et al. (2011); Soffritti et al. (2007)	Aspartame
1997	Belpoggi et al. (2006); Soffritti, Belpoggi, Esposti, Lambertini, Tibaldi, et al. (2006); Soffritti et al. (2005)	Aspartame
1995	Belpoggi, Soffritti, Minardi, et al. (2002)	Tert-amyl-methyl-ether (TAME) and di-isopropyl-ether (DIPE)
1994	Belpoggi, Soffritti, Guarino, et al. (2002)	Mancozeb
1993	Maltoni et al. (1999)	Ethyl tert-butyl ether (ETBE)
1992	Soffritti et al. (2015)	γ-Radiation
1988, 1989, 1991	Maltoni, Minardi, Pinto, et al. (1997)	Tamoxifen
1991	Soffritti et al. (1997)	Chlorine
1990	Minardi and Maltoni (1998)	Rockwool
1990	Soffritti, Belpoggi, Lambertin, et al. (2002)	Formaldehyde and acetaldehyde
1990	Soffritti, Belpoggi, Cevolani, et al. (2002)	Methyl alcohol
1989	Minardi et al. (2002)	Vinyl acetate monomer
1988–1991	Belpoggi et al. (1995)	MTBE
1986	Soffritti, Belpoggi, Cevolani, et al. (2002)	Ethyl alcohol
1985	Maltoni, Ciliberti, Pinto, et al. (1997)	Gasoline
1984	Soffritti et al. (1989)	Formaldehyde
1984	Soffritti, Belpoggi, et al. (2004)	Toluene
1981–1984	Maltoni and Minardi (1988)	Detergency zeolites
1981	Maltoni et al. (1983)	Benzene
1976, 1979, 1981	Maltoni et al. (1985, 1989)	Benzene
1981	Minardi and Maltoni (1988)	Asbestos
1981	Soffritti, Belpoggi, et al. (2004)	Toluene
1980–1983	Conti et al. (1988)	Para-methylstyrene
1980–1983	Cotti et al. (1988)	Vinylidene chloride
1980–1983	Maltoni et al. (1982)	Benzene
1980–1983	Maltoni and Cotti (1988)	Vinyl chloride
1980–1984	Perino et al. (1988)	Olive oil
1979	Maltoni et al. (1983)	Benzene
1979–1983	Maltoni, Lefemine, Cotti, et al. (1988)	Trichloroethylene
1979–1983	Maltoni, Cotti, Perino (1988)	Methylene chloride
1978	Maltoni and Cotti (1986)	Tetrachloroethylene
1977–1980	Ciliberti et al. (1988)	Propylene
1977	Maltoni, Lefemine, Tovoli, et al. (1988)	Chlorofluorocarbons
1976–1983	Maltoni et al. (1986)	Trichloroethylene
1976–1979	Conti et al. (1988)	Styrene oxide
1976–1979	Maltoni et al. (1983)	Benzene
1975–1979	Maltoni, Lefemine, Tovoli, et al. (1988)	Chlorofluorocarbons
1975–1983	Maltoni, Ciliberti, Cotti, et al. (1988)	Acrylonitrile
1974–1977	Conti et al. (1988)	Styrene
1971–1973	Maltoni et al. (1977)	Vinyl chloride and vinylidene chloride
1971–1976	Maltoni et al. (1981)	Vinyl chloride
1971	Maltoni and Lefemine (1974)	Vinyl chloride
1971	Maltoni and Lefemine (1975)	Vinyl chloride

Table 1b. Published Ramazzini Institute (RI) studies in Swiss mice.

Study conduct timeframe	Reference study	Test substance
1997	Soffritti, Padovani, et al. (2016)	Sucralose
1997	Soffritti et al. (2010)	Aspartame
1989	Maltoni, Ciliberti, Lefemine, et al. (1997)	Vinyl acetate monomer
1983–1985	Maltoni, Conti, Perino, et al. (1988)	Benzene
1983–1985	Maltoni et al. (1989)	Benzene
1981	Minardi and Maltoni (1988)	Asbestos
1980–1983	Conti et al. (1988)	Para-methylstyrene
1979–1983	Maltoni, Cotti, Perino (1988)	Methylene chloride
1979–1983	Maltoni, Lefemine, Cotti, et al. (1988)	Trichloroethylene
1977–1980	Ciliberti et al. (1988)	Propylene
1977	Maltoni, Lefemine, Tovoli, et al. (1988)	Chlorofluorocarbons
1976	Maltoni et al. (1986)	Trichloroethylene
1975	Maltoni, Lefemine, Tovoli, et al. (1988)	Chlorofluorocarbons
1971–1976	Maltoni et al. (1981)	Vinyl chloride

Table 2. Variability of tumor incidence from SD rats dietary and drinking water studies.

Sex	Tumor type	Fisher’s exact probability
Tumor incidence significantly greater in dietary studies compared to drinking water studies
Female	Bone head osteosarcoma	0.016
Female	Ear duct carcinoma	0.0025
Female	Intestine adenocarcinoma	0.04
Female	Mammary gland fibroma and fibroadenoma	0.0275
Female	Oral cavity lips and tongue acanthoma	0.0327
Female	Ovaries cystadenoma	0.0263
Female	Thymus benign thymoma	0.0001
Female	Thyroid gland C-cell adenoma	0.0045
Female	Thyroid gland C-cell carcinoma	0.0058
Female	Thyroid gland follicular adenoma	0.0002
Female	Thyroid gland follicular carcinoma	<0.0001
Female	Total benign tumor bearing animals	<0.0001
Female	Uterus leiomyosarcoma	0.0199
Female	Uterus malignant schwannoma	0.0001
Female	Uterus polyp	<0.0001
Female	Zymbal gland carcinoma	0.0075
Male	Ear duct carcinoma	0.0162
Male	Pancreas islet cell carcinoma	0.0385
Male	Pituitary gland adenoma	<0.0001
Male	Subcutaneous tissue lipoma and fibrolipoma	0.0126
Male	Thyroid gland follicular adenoma	0.0001
Male	Thyroid gland follicular carcinoma	<0.0001
Male	Total benign tumor bearing animals	<0.0001
Male	Zymbal gland carcinoma	<0.0001
Tumor incidence significantly greater in drinking water studies compared to dietary studies
Female	Adrenal gland cortical adenoma	0.0091
Female	Adrenal gland pheochromoblastoma	0.0117
Female	Adrenal gland pheochromocytoma	0.0011
Female	CNS brain oligodendroglioma	0.03
Female	Mammary gland adenocarcinoma	0.0184
Female	Pancreas islet cell adenoma	0.011
Female	Pituitary gland adenoma	0.007
Female	Uterus squamous cell carcinoma	0.0401
Male	Adrenal gland pheochromoblastoma	0.0059
Male	Adrenal gland pheochromocytoma	<0.0001
Male	CNS brain oligodendroglioma	0.0222
Male	Testes interstitial cell adenoma	0.0034
Male	Total malignant tumor bearing animals	0.0047

Table 3. Summary statistics for tumors of interest across RI control groups in SD rats for studies conducted between 1987 and 2006 (oral route of administration).

Tumor type	Number of studies	Mean (%)	Standard deviation (%)	Minimum percent incidence (%)	Maximum percent incidence (%)	Total number of animals considered across all controls
Female rats
Intestine leiomyosarcomas	8	0.2%	0.47%	0.00%	1.33%	1538
Ear duct carcinoma	15	4.9%	3.93%	0.00%	14.67%	2030
Intestine leiomyoma	9	0.4%	0.44%	0.00%	1.05%	1594
Lymphoimmunoblastic lymphoma	4	5.0%	7.00%	0.00%	15.33%	370
Lymphomas and leukemias	21	9.5%	5.85%	0.00%	21.62%	2528
Mammary gland adenocarcinoma	20	8.6%	4.30%	1.03%	18.92%	3012
Mammary gland adenocarcinoma	20	8.6%	4.30%	1.03%	18.92%	3012
Pancreas exocrine adenoma	15	0.8%	0.77%	0.00%	2.00%	1989
Pancreas islet cell carcinoma	11	0.02%	0.06%	0.00%	0.20%	2206
Pelvis transitional cell carcinoma	3	0.0%	0.00%	0.00%	0.00%	310
Renal pelvis and ureter dysplastic carcinomas	1	0.0%	NA	0.00%	0.00%	150
Renal pelvis and ureter dysplastic hyperplasia	1	1.3%	NA	1.33%	1.33%	2
Total malignant tumor bearing animals	22	35.7%	11.21%	15.00%	59.46%	3006
Uterus polyp	18	13.5%	6.51%	5.41%	25.33%	2378
Zymbal gland sebaceous adenoma	9	0.6%	0.9%	0.0%	2.7%	1073
Male rats
Intestine leiomyosarcomas	8	0.1%	0.2%	0.0%	0.7%	1551
Adrenal gland pheochromoblastoma	18	23.1%	10.9%	6.7%	48.3%	2378
Adrenal gland pheochromocytoma	16	30.1%	16.3%	6.0%	58.9%	2087
Bone head osteosarcoma	12	3.4%	1.1%	0.0%	10.7%	1817
Ear duct carcinoma	14	4.6%	4.1%	0.0%	13.3%	1856
Glandular stomach adenomatous polyp	3	0.0%	0.00%	0.0%	0.0%	650
Intestine adenocarcinoma	11	0.1%	0.2%	0.0%	0.4%	1722
Intestine leiomyoma	9	0.1%	0.3%	0.0%	1.0%	1192
Lymphomas and leukemias	19	14.6%	9.3%	0.0%	40.0%	2237
Pancreas exocrine adenoma	14	0.9%	1.9%	0.0%	7.1%	1927
PNS other peripheral nerve malignant schwannoma	8	0.6%	0.9%	0.0%	2.0%	997
Spleen fibroangioma	12	0.3%	0.5%	0.0%	1.7%	1757
Testes interstitial cell adenoma	10	5.1%	4.6%	0.0%	12.0%	1706
Total malignant tumor bearing animals	20	32.4%	9.1%	18.3%	50.0%	2684
Zymbal gland sebaceous adenoma	10	0.1%	0.3%	0.0%	1.0%	1572

Figure 1. Incidence of lymphomas and leukemias in control SD male rats.

Figure 2. Incidence of lymphomas and leukemias in control female SD rats.

Figure 3. Incidence of total malignant tumor in female SD rats.

Table 4. Comparative analyses of tumor incidence reported in RI control groups of SD rats.

Tumor	Time period	Total studies	Total with tumor	Total examined	Mean percent incidence (%)	STD (%)	Minimum percent incidence (%)	Maximum percent incidence (%)
Female rats
Intestine leiomyoma	1987–1992	3	1	236	0.3%	0.6%	0.0%	1.0%
	1993–1996	1	0	100	0.0%	NA	0.0%	0.0%
	1997–2001	4	3	757	0.5%	0.5%	0.0%	1.1%
	2001–2006	1	1	501	0.2%	NA	0.2%	0.2%
Lymphoimmunoblastic lymphoma	1987–1992	1	1	60	1.7%	NA	1.7%	1.7%
	1993–1996	2	4	160	2.3%	0.9%	1.7%	3.0%
	1997–2001	1	58	150	38.7%^*,†	NA	38.7%	38.7%
Lymphomas and leukemias	1987–1992	13	84	1035	7.7%	5.5%	0.0%	21.6%
	1993–1996	3	26	235	11.1%	8.9%	5.0%	21.3%
	1997–2001	4	106	757	13.3%*	3.5%	8.7%	16.6%
	2001–2006	1	68	501	13.6%*	NA	13.67%	13.6%
Mammary gland adenocarcinoma	1987–1992	11	162	1422	10.7%	4.4%	6.0%	18.9%
	1993–1996	3	18	235	7.2%	2.6%	5.0%	10.0%
	1997–2001	5	52	854	5.3%*	2.7%	1.0%	8.7%
	2001–2006	1	32	501	6.4%*	NA	6.4%	6.4%
Pancreas exocrine adenoma	1987–1992	7	5	496	1.0%	0.8%	0.0%	2.0%
	1993–1996	3	3	235	1.2%	1.1%	0.0%	2.0%
	1997–2001	4	2	757	0.2%^†	0.2%	0.0%	0.4%
	2001–2006	1	1	501	0.2%	NA	0.2%	0.2%
Pelvis transitional cell carcinoma	1987–1992	1	0	100	0.0%	NA	0.0%	0.0%
	1993–1996	1	0	60	0.0%	NA	0.0%	0.0%
	1997–2001	1	0	150	0.0%	NA	0.0%	0.0%
Renal pelvis and ureter dysplastic carcinomas	1997–2001	1	0	150	0.0%	NA	0.0%	0.0%
	1997–2001	1	2	150	1.3%	NA	1.3%	1.3%
Total malignant tumor bearing animals	1987–1992	13	552	1463	34.1%	12.4%	20.0%	59.5%
	1993–1996	3	77	235	31.1%	14.1%	15.0%	41.3%
	1997–2001	4	328	757	42.7%^*,†	4.8%	36.7%	48.0%
	2001–2006	2	231	551	39.3%^*,†	4.6%	36.0%	42.5%
Uterus polyp	1987–1992	10	96	885	11.0%	4.7%	5.4%	21.7%
	1993–1996	3	35	235	16.0%	6.8%	10.0%	23.3%
	1997–2001	4	105	757	16.8%*	9.8%	7.7%	25.3%
	2001–2006	1	90	501	18.0%*	NA	18.0%	18.0%
Zymbal gland sebaceous adenoma	1987–1992	5	2	386	0.7%	1.2%	0.0%	2.7%
	1993–1996	2	1	175	0.5%	0.7%	0.0%	1.0%
	1997–2001	2	2	512	0.4%	0.5%	0.0%	0.7%
Male rats
Adrenal gland pheochromoblastoma	1987–1992	8	25	581	5.3%	7.5%	0.0%	21.4%
	1993–1996	3	3	235	1.4%*	1.4%	0.0%	2.7%
	1997–2001	4	17	771	1.9%*	1.4%	0.0%	3.1%
	2001–2006	1	1	500	0.2%^*,†,‡	NA	0.20	0.2%
Adrenal gland pheochromocytoma	1987–1992	8	217	581	38.2%	16.1%	19.0%	58.9%
	1993–1996	3	36	235	17.0%*	9.9%	6.0%	25.0%
	1997–2001	4	247	771	27.4%^*,†	15.1%	12.0%	44.7%
	2001–2006	1	77	500	15.4%^*,‡	NA	15.4%	15.4%
Bone head osteosarcoma	1987–1992	5	10	371	2.00%	2.8%	0.0%	6.0%
	1993–1996	2	10	175	6.3%*	6.1%	2.0%	10.7%
	1997–2001	4	20	771	2.3%^†	1.6%	0.9%	4.1%
	2001–2006	1	42	500	8.4%^*,‡	NA	8.4%	8.4%
Glandular stomach adenomatous polyp	1987–1992	1	0	100	0.0%	NA	0.0%	0.0%
	2001–2006	1	1	500	0.2%	NA	0.2%	0.2%
Intestine adenocarcinoma	1987–1992	5	0	371	0.0%	0.0%	0.0%	0.0%
	1993–1996	2	0	175	0.0%	0.0%	0.0%	0.0%
	1997–2001	3	1	676	0.1%	0.3%	0.0%	0.4%
	2001–2006	1	2	500	0.4%	NA	0.4%	0.4%
Lymphomas and leukemias	1987–1992	11	96	731	11.4%	7.1%	0.0%	28.0%
	1993–1996	3	50	235	20.7%*	17.8%	5.0%	40.0%
	1997–2001	4	151	771	18.3%*	7.1%	9.5%	26.4%
	2001–2006	1	83	500	16.6%*	NA	16.6%	16.6%
Pancreas exocrine adenoma	1987–1992	6	3	421	1.7%	2.8%	0.0%	7.1%
	1993–1996	3	1	235	0.6%	1.0%	0.0%	1.7%
	1997–2001	4	2	771	0.2%*	0.2%	0.0%	0.4%
	2001–2006	1	0	500	0.0%*	NA	0.0%	0.0%
Spleen fibroangioma	1987–1992	6	1	421	0.2%	0.4%	0.0%	1.0%
	1993–1996	2	0	160	0.0%	0.0%	0.0%	0.0%
	1997–2001	3	5	676	0.7%	0.9%	0.0%	1.7%
	2001–2006	1	2	500	0.4%	NA	0.4%	0.4%
Testes interstitial cell adenoma	1987–1992	2	22	200	11.0%	1.4%	10.0%	12.0%
	1993–1996	3	7	235	3.1%*	5.4%	0.0%	9.3%
	1997–2001	4	44	771	4.9%*	3.2%	1.3%	8.1%
	2001–2006	1	3	500	0.6%^*,†,‡	NA	0.6%	0.6%
Total malignant tumor bearing animals	1987–1992	11	433	1128	31.3%	9.8%	24.0%	50.0%
	1993–1996	3	70	235	29.0%	10.2%	18.3%	38.7%
	1997–2001	4	306	771	36.9%*^,^†	9.5%	24.2%	46.0%
	2001–2006	2	192	550	34.5%^†	0.7%	34.0%	35.0%
Zymbal gland sebaceous adenoma	1987–1992	5	0	371	0.0%	0.0%	0.0%	0.0%
	1993–1996	2	1	175	0.5%	0.7%	0.00%	1.0%
	1997–2001	2	0	526	0.0%	0.0%	0.0%	0.0%
	2001–2006	1	0	500	0.0%	NA	0.0%	0.0%

NA: not applicable.

* Significantly different from those collected between 1987 and 1992.

^† Significantly different from those collected between 1993 and 1996.

^‡ Significantly different from those collected between 1997 and 2001.

Table 5a. Comparative analyses of percent tumor incidence in SD rats between RI aspartame-treated groups and RI control dataset.

Tumor type	RI control dataset minimum and maximum percent incidence		Aspartame treated group percent incidence (%)
	Minimum	Maximum	0 ppm	80 ppm	400 ppm	2000 ppm	10,000 ppm	50,000 ppm	100,000 ppm
Female rats
Lymphomas and leukemias*	0.0%	21.6%	12.6%^‡	NA	17.1%	31.4%^¶	NA	NA	NA
Lymphomas and leukemias^†	0.0%	21.6%	8.7%^‡	14.7%a	20.0%^¶	18.7%^¶	19.0%^¶	25.0%^¶	25.0%^¶
Mammary gland adenocarcinoma*	1.0%	18.9%	5.3%^‡	NA	7.1%	15.7%^¶	NA	NA	NA
Renal pelvis and ureter dysplastic carcinomas^†	0.0%	0.0%	0.0%	0.7%	2.0%	2.0%	3.0%	3.0%	4.0%^¶
Renal pelvis and ureter dysplastic hyperplasia^†	1.3%	1.3%	1.3%^‡	2.7%	3.3%	4.0%	6.0%	6.1%	8.0%
Total malignant tumor bearing animals^†	15.0%	59.5%	36.7%^‡	42.7%	46.7%	44.7%	40.0%	58.0%^¶	51.0%
Male rats
Lymphomas and leukemias^†	0.0%	40.0%	20.7%^‡	15.3%	16.7%	22.0%	15.0%	20.0%	29.0%
Lymphomas and leukemias*	0.0%	40.0%	9.5%	NA	15.7%	17.1%^¶	NA	NA	NA
Total malignant tumor bearing animals*	18.3%	50.0%	24.2%^‡	NA	25.7%	40.0%^¶	NA	NA	NA

NA: not applicable.

Gray shading indicates tumor incidence that was statistically significantly increased compared to concurrent controls and the percent incidence was outside of the RI control dataset range.

* Soffritti et al. (2007) and Chiozzotto et al. (2011).

^† Belpoggi et al. (2006) and Soffritti, Belpoggi, Esposti, Lambertini, Tibaldi, et al. (2006).

^‡ Statistically significant trend as reported by the study authors.

^¶ Statistically significantly different compared to concurrent controls as reported by the study authors.

Table 5b. Comparative analyses of percentage of SD rats between RI aspartame treated groups and RI control dataset for studies conducted from 1992 to 1997.

Tumor type	RI control minimum and maximum percent incidence (1992–1997)			Aspartame treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	80 ppm	400 ppm	2000 ppm	10,000 ppm	50,000 ppm	100,000 ppm
Female rats
Lymphomas and leukemias*	10.6%^¶	5.0%	21.3%	NA	17.1%^‡	31.4%^‡	NA	NA	NA
Lymphomas and leukemias^†	10.6%^¶	5.0%	21.3%	14.7%	20.0%^‡	18.7%^‡	19.0%^‡	25.0%^‡	25.0%^‡
Mammary gland adenocarcinoma^†	6.5%^¶	5.0%	10.0%	NA	7.1%	15.7%^‡	NA	NA	NA
Renal pelvis and ureter dysplastic carcinomas^†	0.0%^¶	0.0%	0.0%	0.7%	2.0%	2.0%	3.0%	3.0%	4.0%^‡
Renal pelvis and ureter dysplastic hyperplasia^†	1.3%^¶	1.3%	1.3%	2.7%	3.3%	4.0%	6.0%^‡	6.1%^‡	8.0%^‡
Total malignant tumor bearing animals*	36.3%	15.0%	44.2%	NA	38.6%	32.9%	NA	NA	NA
Male rats
Lymphomas and leukemias^†	18.8%^¶	5.0%	40.0%	15.3%	16.7%	22.0%	15.0%	20.0%	29.0%^‡
Lymphomas and leukemias*	18.8%	5.0%	40.0%	NA	15.7%	17.1%	NA	NA	NA
Total malignant tumor bearing animals*	30.4%	18.3%	38.7%	NA	25.7%	40.0%	NA	NA	NA

NA: not applicable.

Gray shading indicates tumor incidence from treated groups was significantly different from tumor incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Soffritti et al. (2007) and Chiozzotto et al. (2011).

^† Belpoggi et al. (2006) and Soffritti, Belpoggi, Esposti, Lambertini, Tibaldi, et al. (2006).

^‡ Significantly different from mean tumor incidence from RI control dataset range.

^¶ Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 5c. Comparative analyses of percentage of SD rats between RI aspartame treated groups and RI control dataset for studies conducted from 1997 to 2006.

Tumor type	RI control mean, minimum and maximum percent incidence (1997–2006)			Aspartame treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	80 ppm	400 ppm	2000 ppm	10,000 ppm	50,000 ppm	100,000 ppm
Female rats
Lymphomas and leukemias*	14.0%^¶	8.7%	16.6%	NA	17.1%^‡	31.4%^‡	NA	NA	NA
Lymphomas and leukemias^†	14.0%^¶	8.7%	16.6%	14.7%	20.0%^‡	18.7%^‡	19.0%^‡	25.0%^‡	25.0%^‡
Mammary gland adenocarcinoma^†	6.1%^¶	1.0%	8.7%	NA	7.1%	15.7%^‡	NA	NA	NA
Renal pelvis and ureter dysplastic carcinomas^†	0.0%^¶	0.0%	0.0%	0.7%	2.0%	2.0%	3.0%	3.0%	4.0%^‡
Renal pelvis and ureter dysplastic hyperplasia^†	1.3%^¶	1.3%	1.3%	2.7%	3.3%	4.0%	6.0%^‡	6.1%^‡	8.0%^‡
Total malignant tumor bearing animals*	42.9%	36.0%	48.0%	NA	38.6%	32.9%	NA	NA	NA
Male rats
Lymphomas and leukemias^†	19.6%^¶	9.5%	26.4%	15.3%	16.7%	22.0%	15.0%	20.0%	29.00%^‡
Lymphomas and leukemias*	19.6%	9.5%	26.4%	NA	15.7%	17.1%	NA	NA	NA
Total malignant tumor bearing animals*	39.34%	24.21%	45.96%	NA	25.70%	40.00%	NA	NA	NA

NA: not applicable.

Gray shading indicates tumor incidence from treated groups was significantly different from tumor incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Soffritti et al. (2007) and Chiozzotto et al. (2011).

^† Belpoggi et al. (2006) and Soffritti, Belpoggi, Esposti, Lambertini, Tibaldi, et al. (2006).

^‡ Significantly different from mean tumor incidence from RI control dataset range.

^¶ Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 5d. Comparative analyses of percentage of SD rats between RI aspartame treated groups and RI control dataset for studies conducted from 1992 to 2006.

Tumor type	RI control mean, minimum and maximum percent incidence (1992–2006)				Aspartame treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	80 ppm		400 ppm	2000 ppm	10,000 ppm	50,000 ppm	100,000 ppm
Female rats
Lymphomas and leukemias*	13.3%^¶	5.0%	21.3%	NA		17.1%^‡	31.4%^‡	NA	NA	NA
Lymphomas and leukemias^†	13.3%^¶	5.0%	21.3%	14.7%		20.0%^‡	18.7%	19.0%	25.0%^‡	25.0%^‡
Mammary gland adenocarcinoma^†	6.4%^¶	1.0%	10.0%	NA		7.1%	15.7%^‡	NA	NA	NA
Renal pelvis and ureter dysplastic carcinomas^†	0.0%^¶	0.0%	0.0%	0.7%		2.0%	2.0%	3.0%	3.0%	4.0%^‡
Renal pelvis and ureter dysplastic hyperplasia^†	1.3%^¶	1.3%	1.3%	2.7%		3.3%	4.0%	6.0%^‡	6.1%^‡	8.0%^‡
Total malignant tumor bearing animals*	40.6%	15.0%	48.0%	NA		38.6%	32.9%	NA	NA	NA
Male rats
Lymphomas and leukemias^†	19.3%^¶	5.0%	40.0%	15.3%		16.7%	22.0%	15.0%	20.0%	29.0%^‡
Lymphomas and leukemias*	19.3%	5.0%	40.0%	NA		15.7%	17.1%	NA	NA	NA
Total malignant tumor bearing animals*	33.6%	18.3%	46.0%	NA		25.7%	40.0%	NA	NA	NA

NA: not applicable.

Gray shading indicates tumor incidence from treated groups was significantly different from tumor incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Soffritti et al. (2007) and Chiozzotto et al. (2011).

^† Belpoggi et al. (2006) and Soffritti, Belpoggi, Esposti, Lambertini, Tibaldi, et al. (2006).

^‡ Significantly different from mean tumor incidence from RI control dataset range.

^¶ Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 6a. Comparative analyses of percent tumor incidence in SD rats between RI formaldehyde-treated groups and RI control dataset.

Tumor type	RI control minimum and maximum percent incidence		Formaldehyde treated group percent incidence (%)
	Minimum	Maximum	0 mg/L	10 mg/L	50 mg/L	100 mg/L	500 mg/L	1000 mg/L	1500 mg/L
Female rats
Intestine leiomyoma	0.0%	1.1%	0%	4%	2%	0%	0%	0%	6%
Lymphomas and leukemias	0.0%	21.6%	7%	10%	14%	16%	14%	22%*	20%*
Male rats
Intestine adenocarcinoma	0.0%	0.4%	0%	2%	0%	0%	0%	0%	6%
Intestine leiomyosarcomas	0.0%	0.7%	0%	0%	0%	0%	0%	0%	4%
Lymphomas and leukemias	0.0%	40.0%	8%	8%	20%	26%*	24%*	22%*	46%*
Testes interstitial cell adenoma	0.0%	12.0%	10%	6%	12%	12%	20%	24%*	18%
Total malignant tumor bearing animals	18.3%	50.0%	38%	28%	24%	44%	48%	46%	72%*

Gray shading indicates tumor incidence that was statistically significantly increased compared to concurrent controls and the percent incidence was outside of the RI control dataset range.

* Statistically significantly different compared to controls as reported by the study authors.

Table 6b. Comparative analyses of percent tumor incidence in SD rats between RI formaldehyde-treated groups and RI control dataset from 1992 to 1997.

Tumor type	RI control minimum and maximum percent incidence (1992–1997)			Formaldehyde treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	10 mg/L	50 mg/L	100 mg/L	500 mg/L	1000 mg/L	1500 mg/L
Female rats
Intestine leiomyoma	0.6%^†	0.0%	1.1%	4%	2%	0%	0%	0%	6%*
Lymphomas and leukemias	10.6%^†	5.0%	21.3%	10%	14%	16%	14%	22%	20%*
Male rats
Intestine adenocarcinoma	0.0%^†	0.0%	0.0%	2%	0%	0%	0%	0%	6%
Intestine leiomyosarcomas	0.3%^†	0.0%	0.7%	0%	0%	0%	0%	0%	4%*
Lymphomas and leukemias	18.8%^†	5.0%	40.0%	8%	20%	26%	24%	22%	46%
Testes interstitial cell adenoma	2.5%^†	0.0%	9.3%	6%	12%*	12%*	20%*	24%*	18%*
Total malignant tumor bearing animals	30.4%^†	18.3%	38.7%	28%	24%	44%*	48%*	46%*	72%*

Gray shading indicates percent tumor incidence from treated groups was significantly different from mean percent incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Significantly different from tumor incidence from RI control dataset range.

^† Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 6c. Comparative analyses of percent tumor incidence in SD rats between RI formaldehyde-treated groups and RI control dataset from 1997 to 2006.

Tumor type	RI control minimum and maximum percent incidence (1997–2006)			Formaldehyde treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	10 mg/L	50 mg/L	100 mg/L	500 mg/L	1000 mg/L	1500 mg/L
Female rats
Intestine leiomyoma	0.4%^†	0.0%	1.1%	4%	2%	0%	0%	0%	6%*
Lymphomas and leukemias	14.0%	8.7%	16.6%	10%	14%	16%	14%	22%	20%*
Male rats
Intestine adenocarcinoma	0.0%^†	0.0%	0.0%	2%	0%	0%	0%	0%	6%
Intestine leiomyosarcomas	0.2%^†	0.0%	0.7%	0%	0%	0%	0%	0%	4%*
Lymphomas and leukemias	19.6%^†	9.5%	26.4%	8%	20%	26%	24%	22%	46%
Testes interstitial cell adenoma	5.7%^†	1.3%	8.1%	6%	12%	12%	20%*	24%*	18%*
Total malignant tumor bearing animals	39.3%^†	24.2%	46.0%	28%	24%	44%	48%	46%	72%*

Gray shading indicates percent tumor incidence from treated groups was significantly different from mean percent incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Significantly different from tumor incidence from RI control dataset range.

^† Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 6d. Comparative analyses of percent tumor incidence in SD rats between RI formaldehyde-treated groups and RI control dataset from 1992 to 2006.

Tumor type	RI control minimum and maximum percent incidence (1992–2006)			Formaldehyde treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	10 mg/L	50 mg/L	100 mg/L	500 mg/L	1000 mg/L	1500 mg/L
Female rats
Intestine leiomyoma	0.4%^†	0.0%	1.1%	4%	2%	0%	0%	0%	6%*
Lymphomas and leukemias	13.3%^†	5.0%	21.3%	10%	14%	16%	14%	22%	20%*
Male rats
Intestine adenocarcinoma	0.0%^†	0.0%	0.0%	2%	0%	0%	0%	0%	6%
Intestine leiomyosarcomas	0.1%^†	0.0%	0.7%	0%	0%	0%	0%	0%	4%*
Lymphomas and leukemias	20.0%^†	5.0%	40.0%	8%	20%	26%	24%	22%	46%
Testes interstitial cell adenoma	5.17%^†	0.0%	9.3%	6%	12%*	12%*	20%*	24%*	18%*
Total malignant tumor bearing animals	37.2%^†	18.3%	46.0%	28%	24%	44%	48%	46%	72%*

Gray shading indicates percent tumor incidence from treated groups was significantly different from mean percent incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Significantly different from tumor incidence from RI control dataset range.

^† Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 7a. Comparative analyses of percent tumor incidence in SD rats between RI methyl alcohol-treated groups and RI control dataset.

Tumor type	RI control minimum and maximum percent incidence		Methyl alcohol treated group percent incidence (%)
	Minimum	Maximum	0 ppm	500 ppm	5000 ppm	20,000 ppm
Female rats
Ear duct carcinoma	0.0%	14.7%	9.0%^†	8.0%*	16.0%*	19.0%*
Lymphomas and leukemias	0.0%	21.6%	13.0%	24.0%*	24.0%*	28.0%*
Total malignant tumor bearing animals	15.0%	59.5%	43.0%^†	48.0%*	48.0%*	63.0%*
Male rats
Ear duct carcinoma	0.0%	13.3%	13.0%^†	13.0%*	17.0%*	24.0%*
Total malignant tumor bearing animals	18.3%	50.0%	55.0%^†	55.0%*	64.0%*	70.0%*

Gray shading indicates tumor incidence that was statistically significantly increased compared to concurrent controls and the percent incidence was outside of the RI control dataset range.

* Statistically significantly different compared to controls as reported by the study authors.

^† Statistically significant trend as reported by the study authors.

Table 7b. Comparative analyses of percent tumor incidence in SD rats between RI methyl alcohol-treated groups and RI control dataset from 1992 to 1997.

Tumor type	RI control minimum and maximum percent incidence (1992–1997)			Methyl alcohol treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	500 ppm	5000 ppm	20,000 ppm
Female rats
Ear duct carcinoma	6.0%^†	1.7%	14.7%	8.0%	16.0%*	19.0%*
Lymphomas and leukemias	10.6%^†	5.0%	21.3%	24.0%*	24.0%*	28.0%*
Total malignant tumor bearing animals	36.3%^†	15.0%	44.2%	48.0%*	48.0%*	63.0%*
Male rats
Ear duct carcinoma	4.7%^†	0.0%	13.3%	13.0%*	17.0%*	24.0%*
Total malignant tumor bearing animals	30.4%^†	18.3%	38.7%	55.0%*	64.0%*	70.0%*

Gray shading indicates percent tumor incidence from treated groups was significantly different from mean percent incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Significantly different from tumor incidence from RI control dataset range.

^† Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 7c. Comparative analyses of percent tumor incidence in SD rats between RI methyl alcohol-treated groups and RI control dataset from 1997 to 2006.

Tumor type	RI control minimum and maximum percent incidence (1997–2006)			Methyl alcohol treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	500 ppm	5000 ppm	20,000 ppm
Female rats
Ear duct carcinoma	6.1%^†	5.8%	6.4%	8.0%	16.0%*	19.0%*
Lymphomas and leukemias	14.0%^†	8.7%	16.6%	24.0%*	24.0%*	28.0%*
Total malignant tumor bearing animals	42.9%^†	36.0%	48.0%	48.0%	48.0%	63.0%*
Male rats
Ear duct carcinoma	6.5%^†	6.0%	6.9%	13.0%*	17.0%*	24.0%*
Total malignant tumor bearing animals	39.3%^†	24.2%	46.0%	55.0%*	64.0%*	70.0%*

Gray shading indicates percent tumor incidence from treated groups was significantly different from mean percent incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Significantly different from tumor incidence from RI control dataset range.

^† Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 7d. Comparative analyses of percent tumor incidence in SD rats between RI methyl alcohol-treated groups and RI control dataset from 1992 to 2006.

Tumor type	RI control minimum and maximum percent incidence (1992–2006)			Methyl alcohol treated group percent incidence (%)
	Percent incidence	Minimum	Maximum	500 ppm	5000 ppm	20,000 ppm
Female rats
Ear duct carcinoma	6.0%^†	1.7%	14.7%	8.0%	16.0%*	19.0%*
Lymphomas and leukemias	2.9%^†	1.7%	3.3%	24.0%*	24.0%*	28.0%*
Total malignant tumor bearing animals	40.6%^†	15.0%	48.0%	48.0%	48.0%	63.0%*
Male rats
Ear duct carcinoma	5.9%^†	0.0%	13.3%	13.0%*	17.0%*	24.0%*
Total malignant tumor bearing animals	37.2%^†	18.3%	46.0%	55.0%*	64.0%*	70.0%*

Gray shading indicates percent tumor incidence from treated groups was significantly different from mean percent incidence from the RI control dataset and the percent incidence was outside of the RI control dataset range.

* Significantly different from tumor incidence from RI control dataset range.

^† Statistically significant trend when compared to mean tumor incidence from RI control dataset.

Table 8. Summary statistics for relevant tumor incidence across RI control groups in Swiss mice.

Tumor type	Number of studies	Mean (%)	Standard deviation (%)	Min. (%)	Max. (%)	Total number of animals considered across all controls
Male mice
Liver hepatocellular carcinoma	2	23.87%	3.46%	21.43%	26.32%	52
Lymphomas and leukemias	2	34.02%	7.71%	28.57%	39.47%	52
Total malignant tumor bearing animals	2	75.07%	30.02%	53.85%	96.30%	40

Table 9. Comparative analyses of percent tumor incidence in Swiss mice between RI aspartame-treated groups and RI control dataset.

Tumor type	RI control minimum and maximum percent incidence		Aspartame treated group percent incidence (%)
	Minimum	Maximum	0 ppm	2000 ppm	8000 ppm	16,000 ppm	32,000 ppm
Male mice
Liver hepatocellular carcinoma	21.4%	26.3%	5.1%	11.7%	14.5%	15.6%*	18.1%*
Lung alveolar/bronchiolar carcinoma	NA	NA	6.0%^†	5.8%	11.3%	12.5%	13.3%*
Total malignant tumor bearing animals	53.9%	96.3%	56.4%	56.3%	72.6%	60.9%	68.7%

* Statistically significantly greater than the concurrent control reported by authors.

^† Significant dose related trend reported by authors.

Table 10. Comparative analyses of percent tumor incidence in Swiss mice between RI sucralose-treated groups and RI control dataset.

Tumor type	RI control minimum and maximum percent incidence		Sucralose treated group percent incidence (%)
	Minimum	Maximum	0 ppm	500 ppm	2000 ppm	8000 ppm	16,000 ppm
Male mice
Leukemias	NA	NA	1.7%^†	5.3%	17.5%*	10.6%*	15.7%*
Histiocytic sarcoma	NA	NA	0.9%^†	0.9%	0.0%	1.5%	4.3%
Total hematopoietic tumors	NA	NA	8.5%^†	9.6%	20.0%*	15.2%	25.7%*
Total malignant tumor bearing animals	53.9%	96.3%	56.4%^†	58.8%	58.8%	53.0%	62.9%*

NA: not applicable.

* Statistically significantly greater than the concurrent control reported by authors.

^† Significant dose related trend reported by authors.

Falcioni L, Bua L, Tibaldi E, Lauriola M, De Angelis L, Gnudi F, Mandrioli D, Manservigi M, Manservisi F, Manzoli I, et al. 2018. Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission. Environ Res. 165:496–503. doi: 10.1016/j.envres.2018.01.037.

 PubMed Web of Science ®Google Scholar

Soffritti M, Falcioni L, Bua L, Tibaldi E, Manservigi M, Belpoggi F. 2013. Potential carcinogenic effects of World Trade Center dust after intratracheal instillation to Sprague-Dawley rats: first observation. Am J Ind Med. 56(2):155–162. doi: 10.1002/ajim.22109.

 PubMed Web of Science ®Google Scholar

Soffritti M, Giuliani L. 2019. The carcinogenic potential of non-ionizing radiations: the cases of S-50 Hz MF and 1.8 GHz GSM radiofrequency radiation. Basic Clin Pharmacol Toxicol. 125(Suppl. 3):58–69. doi: 10.1111/bcpt.13215.

 PubMedGoogle Scholar

Soffritti M, Padovani M, Tibaldi E, Falcioni L, Manservisi F, Lauriola M, Bua L, Manservigi M, Belpoggi F. 2016. Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male Swiss mice. Int J Occup Environ Health. 22(1):7–17. doi: 10.1080/10773525.2015.1106075.

 PubMed Web of Science ®Google Scholar

Bua L, Tibaldi E, Falcioni L, Lauriola M, De Angelis L, Gnudi F, Manservigi M, Manservisi F, Manzoli I, Menghetti I, et al. 2018. Results of lifespan exposure to continuous and intermittent extremely low frequency electromagnetic fields (ELFEMF) administered alone to Sprague Dawley rats. Environ Res. 164:271–279. doi: 10.1016/j.envres.2018.02.036.

 PubMed Web of Science ®Google Scholar

Vornoli A, Tibaldi E, Gnudi F, Sgargi D, Manservisi F, Belpoggi F, Tovoli F, Mandrioli D. 2022. Evaluation of toxicant-associated fatty liver disease and liver neoplastic progress in Sprague-Dawley rats treated with low doses of aflatoxin B1 alone or in combination with extremely low frequency electromagnetic fields. Toxins. 14(5):325. doi: 10.3390/toxins14050325.

 PubMed Web of Science ®Google Scholar

Soffritti M, Belpoggi F, Esposti DD, Lambertini L, Tibaldi E, Rigano A. 2006. First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environ Health Perspect. 114(3):379–385. doi: 10.1289/ehp.8711.

 PubMed Web of Science ®Google Scholar

Belpoggi F, Tibaldi E, Lauriola M, Bua L, Falcioni L, Chiozzotto D, Manservisi F, Manservigi M, Soffritti M. 2011. The efficacy of long-term bioassays in predicting human risks: mesotheliomas induced by fluoro-edenitic fibres present in lava stone from the Etna Volcano in Biancavilla, Italy. Eur J Oncol. 16:185–195.

 Google Scholar

Soffritti M, Minardi F, Bua L, Esposti DD, Belpoggi F. 2004. First experimental evidence of peritoneal and pleural mesotheliomas induced by fluoro-edenite fibres present in Etnean volcanic material from Biancavilla (Sicily, Italy). Eur J Oncol. 9(3):169–175.

 Google Scholar

Einbond LS, Soffritti M, Degli Esposti D, Tibaldi E, Lauriola M, Bua L, He K, Genovese G, Su T, Huggins L, et al. 2012. Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats. Anticancer Res. 32(1):21–30.

 PubMed Web of Science ®Google Scholar

Tibaldi E, Gnudi F, Panzacchi S, Mandrioli D, Vornoli A, Manservigi M, Sgargi D, Falcioni A, Bua L, Belpoggi F. 2020. Identification of aspartame-induced haematopoietic and lymphoid tumours in rats after lifetime treatment. Acta Histochem. 122(5):151548. doi: 10.1016/j.acthis.2020.151548.

 PubMed Web of Science ®Google Scholar

Chiozzotto D, Soffritti M, Falcioni L, Tibaldi E, Manservisi F, Manservigi M, Bua L, Belpoggi F. 2011. Results of life span carcinogenicity bioassay on Sprague-Dawley rats exposed to aspartame since foetal life. Eur J Oncol. 16(2):81–97.

 Google Scholar

Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. 2007. Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environ Health Perspect. 115(9):1293–1297. doi: 10.1289/ehp.10271.

 PubMed Web of Science ®Google Scholar

Belpoggi F, Soffritti M, Padovani M, Degli Esposti D, Lauriola M, Minardi F. 2006. Results of long-term carcinogenicity bioassay on Sprague-Dawley rats exposed to aspartame administered in feed. Ann N Y Acad Sci. 1076(1):559–577. doi: 10.1196/annals.1371.080.

 PubMedGoogle Scholar

Soffritti M, Belpoggi F, Esposti DD, Lambertini L. 2005. Aspartame induces lymphomas and leukaemias in rats L’aspartame Induce Linfomi e Leucemie Nei Ratti. Eur J Oncol. 10(2):107–116.

 Google Scholar

Belpoggi F, Soffritti M, Minardi F, Bua L, Cattin E, Maltoni C. 2002. Results of long-term carcinogenicity bioassays on tert-amyl-methyl-ether (TAME) and di-isopropyl-ether (DIPE) in rats. Ann N Y Acad Sci. 982(1):70–86. doi: 10.1111/j.1749-6632.2002.tb04925.x.

 PubMedGoogle Scholar

Belpoggi F, Soffritti M, Guarino M, Lambertini L, Cevolani D, Maltoni C. 2002. Results of long-term experimental studies on the carcinogenicity of ethylene-bis-dithiocarbamate (mancozeb) in rats. Ann N Y Acad Sci. 982(1):123–136. doi: 10.1111/j.1749-6632.2002.tb04928.x.

 PubMedGoogle Scholar

Maltoni C, Belpoggi F, Soffritti M, Minardi F. 1999. Comprehensive long-term experimental project of carcinogenicity bioassays on gasoline oxygenated additives: plan and first report of results from the study on ethyl-tertiary-butyl ether (ETBE). Eur J Oncol. 4(5):493–508.

 Google Scholar

Soffritti M, Tibaldi E, Bua L, Padovani M, Falcioni L, Lauriola M, Manservigi M, Manservisi F, Belpoggi F. 2015. Life-span carcinogenicity studies on Sprague-Dawley rats exposed to γ-radiation: design of the project and report on the tumor occurrence after post-natal radiation exposure (6 weeks of age) delivered in a single acute exposure. Am J Ind Med. 58(1):46–60. doi: 10.1002/ajim.22391.

 PubMed Web of Science ®Google Scholar

Maltoni C, Minardi F, Pinto C, Belpoggi F, Bua L. 1997. Results of three life-span experimental carcinogenicity and anticarcinogenicity studies on tamoxifen in rats. Ann N Y Acad Sci. 837(1):469–512. doi: 10.1111/j.1749-6632.1997.tb56895.x.

 PubMedGoogle Scholar

Soffritti M, Belpoggi F, Lenzi A, Maltoni C. 1997. Results of long-term carcinogenicity studies of chlorine in rats. Ann N Y Acad Sci. 837(1):189–208. doi: 10.1111/j.1749-6632.1997.tb56875.x.

 PubMedGoogle Scholar

Minardi F, Maltoni C. 1998. Results of long-term carcinogenicity bioassays of rockwool on Sprague-Dawley rats. Eur J Oncol. 3(3):251–260.

 Google Scholar

Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C. 2002. Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats. Ann N Y Acad Sci. 982(1):87–105. doi: 10.1111/j.1749-6632.2002.tb04926.x.

 PubMedGoogle Scholar

Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C. 2002. Results of long-term experimental studies on the carcinogenicity of methyl alcohol and ethyl alcohol in rats. Ann N Y Acad Sci. 982(1):46–69. doi: 10.1111/j.1749-6632.2002.tb04924.x.

 PubMedGoogle Scholar

Minardi F, Belpoggi F, Soffritti M, Ciliberti A, Lauriola M, Cattin E, Maltoni C. 2002. Results of long-term carcinogenicity bioassay on vinyl acetate monomer in Sprague-Dawley rats. Ann N Y Acad Sci. 982(1):106–122. doi: 10.1111/j.1749-6632.2002.tb04927.x.

 PubMedGoogle Scholar

Belpoggi F, Soffritti M, Maltoni C. 1995. Methyl-tertiary-butyl ether (MTBE) – a gasoline additive – causes testicular and lymphohaematopoietic cancers in rats. Toxicol Ind Health. 11(2):119–149. doi: 10.1177/074823379501100202.

 PubMed Web of Science ®Google Scholar

Maltoni C, Ciliberti A, Pinto C, Soffritti M, Belpoggi F, Menarini L. 1997. Results of long-term experimental carcinogenicity studies of the effects of gasoline, correlated fuels, and major gasoline aromatics on rats. Ann N Y Acad Sci. 837(1):15–52. doi: 10.1111/j.1749-6632.1997.tb56863.x.

 PubMedGoogle Scholar

Soffritti M, Maltoni C, Maffei F, Biagi R. 1989. Formaldehyde: an experimental multipotential carcinogen. Toxicol Ind Health. 5(5):699–730. doi: 10.1177/074823378900500510.

 PubMed Web of Science ®Google Scholar

Soffritti M, Belpoggi F, Padovani M, Lauriola M, Esposti DD, Minardi F. 2004. Life-time carcinogenicity bioassays of toluene given by stomach tube to Sprague-Dawley rats. Eur J Oncol. 9(2):91–102.

 Google Scholar

Maltoni C, Minardi F. 1988. First available results of long-term carcinogenicity bioassay on detergency zeolites (MS 4A and MS 5A). Ann N Y Acad Sci. 534:978–985. doi: 10.1111/j.1749-6632.1988.tb30189.x.

 PubMed Web of Science ®Google Scholar

Maltoni C, Conti B, Cotti G. 1983. Benzene: a multipotential carcinogen. Results of long-term bioassays performed at the Bologna Institute of Oncology. Am J Ind Med. 4(5):589–630. doi: 10.1002/ajim.4700040503.

 PubMed Web of Science ®Google Scholar

Maltoni C, Conti B, Cotti G, Belpoggi F. 1985. Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: current results and ongoing research. Am J Ind Med. 7(5–6):415–446. doi: 10.1002/ajim.4700070508.

 PubMed Web of Science ®Google Scholar

Maltoni C, Ciliberti A, Cotti G, Conti B, Belpoggi F. 1989. Benzene, an experimental multipotential carcinogen: results of the long-term bioassays performed at the Bologna Institute of Oncology. Environ Health Perspect. 82:109–124. doi: 10.1289/ehp.8982109.

 PubMed Web of Science ®Google Scholar

Minardi F, Maltoni C. 1988. Results of recent experimental research on the carcinogenicity of natural and modified asbestos. Ann N Y Acad Sci. 534(1):754–761. doi: 10.1111/j.1749-6632.1988.tb30164.x.

 PubMedGoogle Scholar

Conti B, Maltoni C, Perino G, Ciliberti A. 1988. Long-term carcinogenicity bioassays on styrene administered by inhalation, ingestion and injection and styrene oxide administered by ingestion in Sprague-Dawley rats, and para-methylstyrene administered by ingestion in Sprague-Dawley rats and Swiss mice. Ann N Y Acad Sci. 534(1):203–234. doi: 10.1111/j.1749-6632.1988.tb30112.x.

 PubMedGoogle Scholar

Cotti G, Maltoni C, Lefemine G. 1988. Long-term carcinogenicity bioassay on vinylidene chloride administered by inhalation to Sprague-Dawley rats. New results. Ann N Y Acad Sci. 534(1):160–168. doi: 10.1111/j.1749-6632.1988.tb30109.x.

 PubMedGoogle Scholar

Maltoni C, Cotti G, Valgimigli L, Mandrioli A. 1982. Zymbal gland carcinomas in rats following exposure to benzene by inhalation. Am J Ind Med. 3(1):11–16. doi: 10.1002/ajim.4700030104.

 PubMedGoogle Scholar

Maltoni C, Cotti G. 1988. Carcinogenicity of vinyl chloride in Sprague-Dawley rats after prenatal and postnatal exposure. Ann N Y Acad Sci. 534(1):145–159. doi: 10.1111/j.1749-6632.1988.tb30108.x.

 PubMedGoogle Scholar

Perino G, Conti B, Ciliberti A, Maltoni C. 1988. Incidence of pancreatic tumors and tumor precursors in Sprague-Dawley rats after administration of olive oil. Ann N Y Acad Sci. 534(1):604–617. doi: 10.1111/j.1749-6632.1988.tb30151.x.

 PubMedGoogle Scholar

Maltoni C, Cotti G, Perino G. 1988. Long-term carcinogenicity bioassays on methylene chloride administered by ingestion to Sprague-Dawley rats and Swiss mice and by inhalation to Sprague-Dawley rats. Ann N Y Acad Sci. 534(1):352–366. doi: 10.1111/j.1749-6632.1988.tb30122.x.

 PubMedGoogle Scholar

Maltoni C, Cotti G. 1986. Results of long-term carcinogenicity bioassays of tetrachloroethylene on Sprague-Dawley rats administered by Ingestion. Acta Oncol. 7(1):11–26.

 Google Scholar

Ciliberti A, Maltoni C, Perino G. 1988. Long-term carcinogenicity bioassays on propylene administered by inhalation to Sprague-Dawley rats and Swiss mice. Ann N Y Acad Sci. 534(1):235–245. doi: 10.1111/j.1749-6632.1988.tb30113.x.

 PubMedGoogle Scholar

Maltoni C, Lefemine G, Tovoli D, Perino G. 1988. Long-term carcinogenicity bioassays on three chlorofluorocarbons (trichlorofluoromethane, FC11; dichlorodifluoromethane, FC12; chlorodifluoromethane, FC22) administered by inhalation to Sprague-Dawley rats and Swiss mice. Ann N Y Acad Sci. 534(1):261–282. doi: 10.1111/j.1749-6632.1988.tb30116.x.

 PubMedGoogle Scholar

Maltoni C, Lefemine G, Cotti G. 1986. Experimental research on trichloroethylene carcinogenesis. In: Archives of research on industrial carcinogenesis. Princeton (NJ): Scientific Publishing Company, Inc.; p. 45–153.

 Google Scholar

Maltoni C, Cotti G, Morisi L, Chieco P. 1977. Carcinogenicity bioassays of vinylidene chloride. Research plan and early results. Med Lav. 68(4):241–262.

 PubMedGoogle Scholar

Maltoni C, Lefemine G, Ciliberti A, Cotti G, Carretti D. 1981. Carcinogenicity bioassays of vinyl chloride monomer: a model of risk assessment on an experimental basis. Environ Health Perspect. 41:3–29. doi: 10.1289/ehp.81413.

 PubMed Web of Science ®Google Scholar

Maltoni C, Lefemine G. 1974. Carcinogenicity bioassays of vinyl chloride: I. Research plan and early results. Environ Res. 7(3):387–405. doi: 10.1016/0013-9351(74)90040-1.

 Web of Science ®Google Scholar

Maltoni C, Lefemine G. 1975. Carcinogenicity bioassays of vinyl chloride: current results. Ann N Y Acad Sci. 246(1):195–218. doi: 10.1111/j.1749-6632.1975.tb51094.x.

 PubMedGoogle Scholar

Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L, Bua L. 2010. Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. Am J Ind Med. 53(12):1197–1206. doi: 10.1002/ajim.20896.

 PubMed Web of Science ®Google Scholar