SUMMARY OF LESIONS IN MALE Tg.AC HEMIZYGOUS MICE IN THE 6-MONTH DERMAL STUDY OF PENTAERYTHRITOL TRIACRYLATE

R.S. Chhabra; J. Mahler; D.W. Bristol; J.R. Bucher; J.E. French; J.R. Hailey; J.K. Haseman; R.A. Herbert; R.R. Maronpot; S.D. Peddada; G.N. Rao; C.S. Smith; G.S. Travlos; M.K. Vallant; K.L. Witt; M.R. Hejtmancik; J.D. Toft, II; J.T. Yarrington; J.F. Hardisty; J.C. Peckham; S. Brecher; P.W. Crockett; L.J. Betz; W. Jones; K.P. McGowan; J.T. Scott; P.B. Little; J. Mahler; G.A. Parker; J.R. Hailey; R.A. Herbert; J. Mahler; R.R. Maronpot; A. Nyska; G. Pearse; J.C. Peckham; S.R. Gunnels; P.A. Gideon; L.M. Harper; E.S. Paal; D.C. Serbus

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Chhabra RS, Mahler J, Bristol DW, et al. NTP Genetically Modified Model Report on the Toxicology Studies of Pentaerythritol Triacrylate (Technical Grade) (CASRN 3524-68-3) in F344/N Rats, B6C3F1 Mice, and Genetically Modified (FVB Tg.AC Hemizygous) Mice (Dermal Studies): NTP GMM 04 [Internet]. Research Triangle Park (NC): National Toxicology Program; 2005 Oct.

APPENDIX ASUMMARY OF LESIONS IN MALE Tg.AC HEMIZYGOUS MICE IN THE 6-MONTH DERMAL STUDY OF PENTAERYTHRITOL TRIACRYLATE

Table A1Summary of the Incidence of Neoplasms in Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate^a

	Vehicle Control	0.75 mg/kg	1.5 mg/kg	3 mg/kg	6 mg/kg	12 mg/kg
Disposition Summary
Animals initially in study	15	15	15	15	15	15
Early deaths
Moribund		1			1
Natural deaths	3				2	5
Survivors
Terminal sacrifice	12	14	15	15	12	10
Animals examined microscopically	15	15	15	15	15	15
Alimentary System
Liver	(15)	(15)	(15)	(15)	(15)	(15)
Salivary glands	(1)	(1)		(1)		(2)
Carcinoma	1 (100%)	1 (100%)		1 (100%)		1 (50%)
Stomach, forestomach	(15)	(15)	(15)	(15)	(15)	(15)
Squamous cell papilloma	2 (13%)	3 (20%)	5 (33%)	5 (33%)	5 (33%)	3 (20%)
Squamous cell papilloma, multiple	4 (27%)	1 (7%)		3 (20%)		2 (13%)
Tooth	(2)		(3)	(1)	(3)	(2)
Odontogenic tumor	2 (100%)		3 (100%)	1 (100%)	3 (100%)	2 (100%)
Cardiovascular System
None
Endocrine System
None
General Body System
None
Genital System
None
Hematopoietic System
Spleen	(15)	(15)	(15)	(15)	(15)	(15)
Integumentary System
Skin	(15)	(15)	(15)	(15)	(15)	(15)
Squamous cell papilloma, multiple						1 (7%)
Site of application, squamous cell carcinoma				2 (13%)		2 (13%)
Site of application, squamous cell carcinoma, multiple						1 (7%)
Site of application, squamous cell papilloma	1 (7%)		4 (27%)	4 (27%)
Site of application, squamous cell papilloma, multiple				11 (73%)	15 (100%)	13 (87%)
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	(15)	(15)	(15)	(15)	(15)	(15)
Alveolar/bronchiolar adenoma	2 (13%)	1 (7%)
Carcinoma, metastatic, salivary glands		1 (7%)
Special Senses System
None
Urinary System
Kidney	(15)	(15)	(15)	(15)	(15)	(15)
Systemic Lesions
Multiple organs^b	(15)	(15)	(15)	(15)	(15)	(15)
Leukemia erythrocytic						1 (7%)
Neoplasm Summary
Total animals with primary neoplasms^c	9	5	9	15	15	13
Total primary neoplasms	12	6	12	27	23	26
Total animals with benign neoplasms	7	5	8	15	15	13
Total benign neoplasms	9	5	9	23	20	19
Total animals with malignant neoplasms	1	1		3		5
Total malignant neoplasms	1	1		3		5
Total animals with metastatic neoplasms		1
Total metastatic neoplasms		1
Total animals with uncertain neoplasms-benign or malignant	2		3	1	3	2
Total uncertain neoplasms	2		3	1	3	2

a: Number of animals examined microscopically at the site and the number of animals with neoplasm
b: Number of animals with any tissue examined microscopically
c: Primary neoplasms: all neoplasms except metastatic neoplasms

Table A2

Individual Animal Tumor Pathology of Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: Vehicle Control

Number of Days on Study	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
	3	4	5	8	8	8	8	8	8	8	8	8	8	8	8
	2	5	5	5	5	5	5	5	5	5	5	6	6	6	6
Carcass ID Number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Total Tissues/Tumors
	0	1	1	0	0	0	0	0	1	1	1	0	0	0	1
	6	2	5	1	2	3	5	7	0	3	4	4	8	9	1
Alimentary System
Liver	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Salivary glands							+									1
Carcinoma							X									1
Stomach, forestomach	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Squamous cell papilloma										X				X		2
Squamous cell papilloma, multiple		X			X			X					X			4
Tooth			+		+											2
Odontogenic tumor			X		X											2
Cardiovascular System
Heart	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Endocrine System
Adrenal cortex	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Adrenal medulla	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Pituitary gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thyroid gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
General Body System
None
Genital System
Epididymis	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Testes	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Hematopoietic System
Lymph node	M	+	+	+	+	+	+	+	+	+	+	+	+	+	+	14
Lymph node, mandibular	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mesenteric	M	M	+	+	+	+	M	+	+	+	+	+	+	+	+	12
Spleen	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thymus	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Integumentary System
Skin	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Site of application, squamous cell papilloma													X			1
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Alveolar/bronchiolar adenoma		X		X												2
Special Senses System
None
Urinary System
Kidney	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Systemic Lesions
Multiple organs	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15

Individual Animal Tumor Pathology of Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 0.75 mg/kg

Number of Days on Study	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
	2	8	8	8	8	8	8	8	8	8	8	8	8	8	8
	9	5	5	5	5	5	5	5	6	6	6	6	6	6	6
Carcass ID Number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Total Tissues/Tumors
	2	1	1	2	2	2	2	3	1	1	2	2	2	2	2
	5	8	9	0	3	4	6	0	6	7	1	2	7	8	9
Alimentary System
Liver	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Salivary glands	+															1
Carcinoma	X															1
Stomach, forestomach	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Squamous cell papilloma	X	X												X		3
Squamous cell papilloma, multiple										X						1
Cardiovascular System
Heart	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Endocrine System
Adrenal cortex	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Adrenal medulla	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Pituitary gland	+	+	+	+	+	+	+	I	+	+	+	+	+	+	+	14
Thyroid gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
General Body System
None
Genital System
Epididymis	+	+	+	+	+	+	+	+	+	+	+	+	+	+		14
Testes	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Hematopoietic System
Lymph node	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mandibular	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mesenteric	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Spleen	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thymus	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Integumentary System
Skin	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Alveolar/bronchiolar adenoma															X	1
Carcinoma, metastatic, salivary glands	X															1
Special Senses System
None
Urinary System
Kidney	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Urinary bladder	+															1
Systemic Lesions
Multiple organs	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15

Individual Animal Tumor Pathology of Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 1.5 mg/kg

Number of Days on Study	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
	8	8	8	8	8	8	8	8	8	8	8	8	8	8	8
	5	5	5	5	5	5	5	5	5	5	6	6	6	6	6
Carcass ID Number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Total Tissues/Tumors
	3	3	3	3	3	3	4	4	4	4	3	3	3	4	4
	1	2	3	4	8	9	0	3	4	5	5	6	7	1	2
Alimentary System
Liver	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Stomach, forestomach	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Squamous cell papilloma	X	X						X				X		X		5
Tooth		+							+						+	3
Odontogenic tumor		X							X						X	3
Cardiovascular System
Heart	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Endocrine System
Adrenal cortex	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Adrenal medulla	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Pituitary gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thyroid gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
General Body System
None
Genital System
Epididymis	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Testes	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Hematopoietic System
Lymph node	+	+	+	+	+	+	+	+	+	M	+	+	+	+	+	14
Lymph node, mandibular	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mesenteric	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Spleen	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thymus	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Integumentary System
Skin	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Site of application, squamous cell papilloma		X	X			X			X							4
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Special Senses System
None
Urinary System
Kidney	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Systemic Lesions
Multiple organs	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15

Individual Animal Tumor Pathology of Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 3 mg/kg

Number of Days on Study	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
	8	8	8	8	8	8	8	8	8	8	8	8	8	8	8
	5	5	5	5	5	5	5	5	6	6	6	6	6	6	6
Carcass ID Number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Total Tissues/Tumors
	4	4	4	5	5	5	5	5	4	5	5	5	5	5	6
	6	7	8	2	3	6	7	8	9	0	1	4	5	9	0
Alimentary System
Liver	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Salivary glands											+					1
Carcinoma											X					1
Stomach, forestomach	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Squamous cell papilloma			X				X				X	X			X	5
Squamous cell papilloma, multiple									X	X			X			3
Tooth						+										1
Odontogenic tumor						X										1
Cardiovascular System
Heart	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Endocrine System
Adrenal cortex	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Adrenal medulla	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Pituitary gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thyroid gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
General Body System
None
Genital System
Epididymis	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Testes	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Hematopoietic System
Lymph node	+	+	+	+	+	+	+	+	+	+	+	M	M	+	+	13
Lymph node, mandibular	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mesenteric	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Spleen	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thymus	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Integumentary System
Skin	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Site of application, squamous cell carcinoma					X			X								2
Site of application, squamous cell papilloma		X		X									X		X	4
Site of application, squamous cell papilloma, multiple	X		X		X	X	X	X	X	X	X	X		X		11
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Special Senses System
None
Urinary System
Kidney	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Systemic Lesions
Multiple organs	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15

Individual Animal Tumor Pathology of Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 6 mg/kg

Number of Days on Study	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
	6	6	8	8	8	8	8	8	8	8	8	8	8	8	8
	3	6	4	5	5	5	5	5	5	5	6	6	6	6	6
Carcass ID Number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Total Tissues/Tumors
	6	6	6	6	6	6	6	6	7	7	6	7	7	7	7
	3	1	2	4	6	7	8	9	0	1	5	2	3	4	5
Alimentary System
Liver	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Stomach, forestomach	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Squamous cell papilloma						X					X	X	X	X		5
Tooth			+				+								+	3
Odontogenic tumor			X				X								X	3
Cardiovascular System
Heart	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Endocrine System
Adrenal cortex	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Adrenal medulla	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Pituitary gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thyroid gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
General Body System
None
Genital System
Epididymis	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Testes	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Hematopoietic System
Lymph node	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mandibular	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mesenteric	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Spleen	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thymus	+	+	+	+	+	+	+	+	+	+	M	+	+	+	+	14
Integumentary System
Skin	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Site of application, squamous cell papilloma, multiple	X	X	X	X	X	X	X	X	X	X	X	X	X	X	X	15
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Special Senses System
None
Urinary System
Kidney	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Systemic Lesions
Multiple organs	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15

Individual Animal Tumor Pathology of Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 12 mg/kg

Number of Days on Study	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
	3	6	6	7	8	8	8	8	8	8	8	8	8	8	8
	8	0	7	0	2	5	5	5	5	5	5	5	5	6	6
Carcass ID Number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Total Tissues/Tumors
	8	9	8	8	7	7	7	8	8	8	8	8	8	7	8
	8	0	9	7	9	6	7	0	1	3	4	5	6	8	2
Alimentary System
Liver	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Salivary glands			+													1
Carcinoma			X													1
Stomach, forestomach	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Squamous cell papilloma							X			X		X				3
Squamous cell papilloma, multiple								X	X							2
Tooth				+							+					2
Odontogenic tumor				X							X					2
Cardiovascular System
Heart	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Endocrine System
Adrenal cortex	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Adrenal medulla	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Pituitary gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thyroid gland	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
General Body System
None
Genital System
Epididymis	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Preputial gland							+									1
Testes	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Hematopoietic System
Lymph node	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mandibular	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Lymph node, mesenteric	+	+	+	+	M	+	+	+	+	+	+	+	+	+	+	14
Spleen	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Thymus	+	+	+	M	+	+	+	+	+	+	+	+	+	+	+	14
Integumentary System
Skin	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Squamous cell papilloma, multiple									X							1
Site of application, squamous cell carcinoma						X						X				2
Site of application, squamous cell carcinoma, multiple					X											1
Site of application, squamous cell papilloma, multiple	X	X	X	X	X	X	X	X	X	X	X	X	X			13
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Special Senses System
None
Urinary System
Kidney	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Systemic Lesions
Multiple organs	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	15
Leukemia erythrocytic	X															1

+: Tissue examined microscopically	M: Missing tissue	X: Lesion present
A: Autolysis precludes examination	I: Insufficient tissue	Blank: Not examined

Table A3Statistical Analysis of Primary Neoplasms in Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate

	Vehicle Control	0.75 mg/kg	1.5 mg/kg	3 mg/kg	6 mg/kg	12 mg/kg
Lung: Alveolar/bronchiolar Adenoma
Overall rate^a	2/15 (13%)	1/15 (7%)	0/15 (0%)	0/15 (0%)	0/15 (0%)	0/15 (0%)
Adjusted rate^b	14.3%	7.0%	0.0%	0.0%	0.0%	0.0%
Terminal rate^c	1/12 (8%)	1/14 (7%)	0/15 (0%)	0/15 (0%)	0/12 (0%)	0/10 (0%)
First incidence (days)	145	185 (T)	–^e	–	–	–
Poly-3 test^d	P=0.133N	P=0.490N	P=0.215N	P=0.215N	P=0.224N	P=0.238N
Skin: Squamous Cell Papilloma
Overall rate	1/15 (7%)	0/15 (0%)	4/15 (27%)	15/15 (100%)	15/15 (100%)	13/15 (87%)
Adjusted rate	7.4%	0.0%	26.7%	100.0%	100.0%	86.7%
Terminal rate	1/12 (8%)	0/14 (0%)	4/15 (27%)	15/15 (100%)	12/12 (100%)	8/10 (80%)
First incidence (days)	185 (T)	–	185 (T)	185 (T)	163	138
Poly-3 test	P<0.001	P=0.487N	P=0.198	P<0.001	P<0.001	P<0.001
Skin: Squamous Cell Carcinoma
Overall rate	0/15 (0%)	0/15 (0%)	0/15 (0%)	2/15 (13%)	0/15 (0%)	3/15 (20%)
Adjusted rate	0.0%	0.0%	0.0%	13.3%	0.0%	22.1%
Terminal rate	0/12 (0%)	0/14 (0%)	0/15 (0%)	2/15 (13%)	0/12 (0%)	2/10 (20%)
First incidence (days)	–	–	–	185 (T)	–	182
Poly-3 test	P=0.011	–^f	–	P=0.257	–	P=0.106
Skin: Squamous Cell Papilloma or Squamous Cell Carcinoma
Overall rate	1/15 (7%)	0/15 (0%)	4/15 (27%)	15/15 (100%)	15/15 (100%)	13/15 (87%)
Adjusted rate	7.4%	0.0%	26.7%	100.0%	100.0%	86.7%
Terminal rate	1/12 (8%)	0/14 (0%)	4/15 (27%)	15/15 (100%)	12/12 (100%)	8/10 (80%)
First incidence (days)	185 (T)	–	185 (T)	185 (T)	163	138
Poly-3 test	P<0.001	P=0.487N	P=0.198	P<0.001	P<0.001	P<0.001
Stomach (Forestomach): Squamous Cell Papilloma
Overall rate	6/15 (40%)	4/15 (27%)	5/15 (33%)	8/15 (53%)	5/15 (33%)	5/15 (33%)
Adjusted rate	43.0%	26.7%	33.3%	53.3%	34.8%	37.0%
Terminal rate	5/12 (42%)	3/14 (21%)	5/15 (33%)	8/15 (53%)	5/12 (42%)	5/10 (50%)
First incidence (days)	145	129	185 (T)	185 (T)	185 (T)	185 (T)
Poly-3 test	P=0.550	P=0.300N	P=0.441N	P=0.429	P=0.474N	P=0.526N
Tooth: Odontogenic Tumor
Overall rate	2/15 (13%)	0/15 (0%)	3/15 (20%)	1/15 (7%)	3/15 (20%)	2/15 (13%)
Adjusted rate	14.5%	0.0%	20.0%	6.7%	20.8%	14.6%
Terminal rate	1/12 (8%)	0/14 (0%)	3/15 (20%)	1/15 (7%)	2/12 (17%)	1/10 (10%)
First incidence (days)	155	–	185 (T)	185 (T)	184	170
Poly-3 test	P=0.358	P=0.223N	P=0.538	P=0.472N	P=0.519	P=0.697
All Organs: Benign Neoplasms
Overall rate	7/15 (47%)	5/15 (33%)	8/15 (53%)	15/15 (100%)	15/15 (100%)	13/15 (87%)
Adjusted rate	50.2%	33.3%	53.3%	100.0%	100.0%	86.7%
Terminal rate	6/12 (50%)	4/14 (29%)	8/15 (53%)	15/15 (100%)	12/12 (100%)	8/10 (80%)
First incidence (days)	145	129	185 (T)	185 (T)	163	138
Poly-3 test	P<0.001	P=0.297N	P=0.578	P<0.001	P<0.001	P=0.033
All Organs: Malignant Neoplasms
Overall rate	1/15 (7%)	1/15 (7%)	0/15 (0%)	3/15 (20%)	0/15 (0%)	5/15 (33%)
Adjusted rate	7.4%	6.7%	0.0%	20.0%	0.0%	34.7%
Terminal rate	1/12 (8%)	0/14 (0%)	0/15 (0%)	3/15 (20%)	0/12 (0%)	2/10 (20%)
First incidence (days)	185 (T)	129	–	185 (T)	–	138
Poly-3 test	P=0.008	P=0.736N	P=0.478N	P=0.340	P=0.486N	P=0.094
All Organs: Benign or Malignant Neoplasms
Overall rate	9/15 (60%)	5/15 (33%)	9/15 (60%)	15/15 (100%)	15/15 (100%)	13/15 (87%)
Adjusted rate	62.7%	33.3%	60.0%	100.0%	100.0%	86.7%
Terminal rate	7/12 (58%)	4/14 (29%)	9/15 (60%)	15/15 (100%)	12/12 (100%)	8/10 (80%)
First incidence (days)	145	129	185 (T)	185 (T)	163	138
Poly-3 test	P<0.001	P=0.108N	P=0.589N	P=0.008	P=0.008	P=0.137

: (T)Terminal sacrifice
a: Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for lung and skin; for other tissues, denominator is number of animals necropsied.
b: Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality
c: Observed incidence at terminal kill
d: Beneath the vehicle control incidence is the P value associated with the trend test. Beneath the dosed group incidence are the P values corresponding to pairwise comparisons between the vehicle controls and that dosed group. The Poly-3 test accounts for the differential mortality in animals that do not reach terminal sacrifice. A negative trend or a lower incidence in a dosed group is indicated by N.
e: Not applicable; no neoplasms in animal group
f: Value of statistic cannot be computed.

Table A4Summary of the Incidence of Nonneoplastic Lesions in Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate^a

	Vehicle Control	0.75 mg/kg	1.5 mg/kg	3 mg/kg	6 mg/kg	12 mg/kg
Disposition Summary
Animals initially in study	15	15	15	15	15	15
Early deaths
Moribund		1			1
Natural deaths	3				2	5
Survivors
Terminal sacrifice	12	14	15	15	12	10
Animals examined microscopically	15	15	15	15	15	15
Alimentary System
Liver	(15)	(15)	(15)	(15)	(15)	(15)
Atrophy	1 (7%)
Hematopoietic cell proliferation					2 (13%)
Infiltration cellular					5 (33%)	3 (20%)
Inflammation, chronic active	5 (33%)	11 (73%)	10 (67%)	13 (87%)	13 (87%)	5 (33%)
Mineralization	1 (7%)
Myelodysplasia						5 (33%)
Pigmentation		1 (7%)	1 (7%)
Hepatocyte, necrosis	1 (7%)		1 (7%)		1 (7%)	1 (7%)
Hepatocyte, vacuolization cytoplasmic			1 (7%)
Salivary glands	(1)	(1)		(1)		(2)
Parotid gland, infiltration cellular						1 (50%)
Stomach, forestomach	(15)	(15)	(15)	(15)	(15)	(15)
Hyperkeratosis	2 (13%)		1 (7%)		3 (20%)	4 (27%)
Epithelium, hyperplasia			1 (7%)
Cardiovascular System
Heart	(15)	(15)	(15)	(15)	(15)	(15)
Infiltration cellular						3 (20%)
Inflammation, chronic active		3 (20%)			1 (7%)
Myelodysplasia						3 (20%)
Endocrine System
Adrenal cortex	(15)	(15)	(15)	(15)	(15)	(15)
Hypertrophy	7 (47%)	10 (67%)	3 (20%)	5 (33%)	1 (7%)	3 (20%)
Myelodysplasia						2 (13%)
Adrenal medulla	(15)	(15)	(15)	(15)	(15)	(15)
Infiltration cellular						2 (13%)
Myelodysplasia						2 (13%)
Pituitary gland	(15)	(14)	(15)	(15)	(15)	(15)
Pars distalis, cyst	1 (7%)				3 (20%)
Thyroid gland	(15)	(15)	(15)	(15)	(15)	(15)
Inflammation, chronic active					1 (7%)
Myelodysplasia						1 (7%)
General Body System
None
Genital System
Epididymis	(15)	(14)	(15)	(15)	(15)	(15)
Infiltration cellular					5 (33%)	5 (33%)
Inflammation, chronic active		1 (7%)				4 (27%)
Myelodysplasia						5 (33%)
Bilateral, hypospermia						1 (7%)
Unilateral, hypospermia	1 (7%)	1 (7%)				2 (13%)
Preputial gland						(1)
Duct, ectasia						1 (100%)
Testes	(15)	(15)	(15)	(15)	(15)	(15)
Cyst	2 (13%)	1 (7%)		1 (7%)	1 (7%)
Bilateral, germinal epithelium, degeneration					1 (7%)
Unilateral, germinal epithelium, degeneration	1 (7%)	1 (7%)		2 (13%)	1 (7%)	4 (27%)
Hematopoietic System
Bone marrow						(1)
Myeloid cell, hyperplasia						1 (100%)
Lymph node	(14)	(15)	(14)	(13)	(15)	(14)
Hyperplasia					1 (7%)
Infiltration cellular, plasma cell					1 (7%)
Inflammation, chronic active					1 (7%)
Myelodysplasia						1 (7%)
Axillary, hyperplasia, lymphoid						1 (7%)
Axillary, infiltration cellular					1 (7%)	1 (7%)
Axillary, infiltration cellular, plasma cell					1 (7%)	1 (7%)
Axillary, infiltration cellular, histiocyte						1 (7%)
Inguinal, myelodysplasia						1 (7%)
Mediastinal, hyperplasia					1 (7%)
Mediastinal, infiltration cellular					4 (27%)	2 (14%)
Mediastinal, myelodysplasia						1 (7%)
Lymph node, mandibular	(15)	(15)	(15)	(15)	(15)	(15)
Hematopoietic cell proliferation					3 (20%)
Hyperplasia			2 (13%)	1 (7%)	2 (13%)
Hyperplasia, plasma cell						1 (7%)
Infiltration cellular					5 (33%)	6 (40%)
Infiltration cellular, plasma cell					1 (7%)	6 (40%)
Myelodysplasia						2 (13%)
Necrosis, lymphoid					2 (13%)
Lymph node, mesenteric	(12)	(15)	(15)	(15)	(15)	(14)
Hematopoietic cell proliferation					1 (7%)	1 (7%)
Infiltration cellular					4 (27%)	2 (14%)
Myelodysplasia						3 (21%)
Necrosis, lymphoid					1 (7%)
Spleen	(15)	(15)	(15)	(15)	(15)	(15)
Atrophy	1 (7%)
Depletion cellular					2 (13%)	2 (13%)
Hematopoietic cell proliferation	1 (7%)	2 (13%)	1 (7%)	2 (13%)	9 (60%)	8 (53%)
Infiltration cellular					1 (7%)	4 (27%)
Myelodysplasia						4 (27%)
Necrosis, lymphoid					2 (13%)	1 (7%)
Thymus	(15)	(15)	(15)	(15)	(14)	(14)
Atrophy	4 (27%)	1 (7%)	2 (13%)		4 (29%)	5 (36%)
Myelodysplasia						3 (21%)
Thymocyte, necrosis					2 (14%)
Integumentary System
Skin	(15)	(15)	(15)	(15)	(15)	(15)
Dermis, site of application, necrosis						1 (7%)
Epidermis, site of application, hyperplasia			3 (20%)	8 (53%)	10 (67%)	14 (93%)
Epidermis, site of application, ulcer					1 (7%)
Site of application, cyst epithelial inclusion						1 (7%)
Site of application, hyperkeratosis	1 (7%)		2 (13%)	6 (40%)	10 (67%)	13 (87%)
Site of application, inflammation, chronic active				2 (13%)	5 (33%)	12 (80%)
Musculoskeletal System
None
Nervous System
None
Respiratory System
Lung	(15)	(15)	(15)	(15)	(15)	(15)
Infiltration cellular					1 (7%)	3 (20%)
Inflammation, chronic active					1 (7%)	2 (13%)
Myelodysplasia						3 (20%)
Alveolar epithelium, hyperplasia			1 (7%)
Mediastinum, infiltration cellular						1 (7%)
Special Senses System
None
Urinary System
Kidney	(15)	(15)	(15)	(15)	(15)	(15)
Hydronephrosis						1 (7%)
Infarct			1 (7%)	2 (13%)
Infiltration cellular					2 (13%)	3 (20%)
Inflammation, chronic active	1 (7%)		4 (27%)	4 (27%)	3 (20%)
Mineralization					1 (7%)
Myelodysplasia						4 (27%)
Nephropathy	6 (40%)	1 (7%)
Pigmentation	1 (7%)
Cortex, cyst		1 (7%)		1 (7%)	1 (7%)	1 (7%)
Renal tubule, dilatation				1 (7%)
Renal tubule, regeneration	1 (7%)	2 (13%)		3 (20%)

a: Number of animals examined microscopically at the site and the number of animals with lesion

Table A5

In-Life Observation of Skin Papilloma at the Site of Application in Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 3 mg/kg^a

Carcass ID Number	4	4	4	4	5	5	5	5	5	5	5	5	5	5	6	Total Tumors	Animals with Tumors
Carcass ID Number	6	7	8	9	0	1	2	3	4	5	6	7	8	9	0	Total Tumors	Animals with Tumors
Week
14	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	1
15	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	2	2
16	0	0	0	0	0	0	0	2	0	0	0	2	3	1	0	8	4
17	0	0	0	0	0	0	0	1	0	0	0	2	2	1	0	6	4
18	0	0	0	0	0	0	0	1	0	0	4	2	2	1	0	10	5
19	0	0	0	0	0	0	0	0	0	0	3	2	2	1	1	9	5
20	0	0	1	4	0	0	0	0	0	0	3	2	2	1	1	14	7
21	0	0	2	5	2	0	0	0	3	0	2	4	1	1	1	21	9
22	0	0	2	6	9	3	0	0	3	0	3	4	1	1	1	33	10
23	0	0	2	6	9	3	0	0	2	0	4	5	1	1	1	34	10
24	0	0	1	7	11	4	0	0	5	0	5	8	1	1	1	44	10
25	2	0	2	6	11	4	0	0	5	0	9	7	1	2	1	50	11
26	2	0	3	8	12	3	1	0	5	0	10	9	1	3	1	58	12
27	2	0	3	7	10	6	1	0	5	0	11	11	2	3	1	62	12
Necropsy	2	1	3	8	14	8	1	6	7	2	10	13	3	3	1	89	15

In-Life Observation of Skin Papilloma at the Site of Application in Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 6 mg/kg

Carcass ID Number	6	6	6	6	6	6	6	6	6	7	7	7	7	7	7	Total Tumors	Animals with Tumors
Carcass ID Number	1	2	3	4	5	6	7	8	9	0	1	2	3	4	5	Total Tumors	Animals with Tumors
Week
9	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1
10	2	0	0	0	0	0	0	0	0	0	1	0	0	0	0	3	2
11	2	0	2	0	0	0	0	0	0	0	1	0	0	0	0	5	3
12	2	0	2	2	4	0	0	0	0	2	1	0	0	0	0	13	6
13	6	3	3	2	5	0	0	2	0	4	1	2	1	0	0	29	10
14	6	3	5	6	3	2	0	2	3	7	1	3	4	4	0	49	13
15	7	3	6	7	3	3	5	2	2	9	2	5	4	7	5	70	15
16	9	3	7	7	4	4	6	3	3	7	4	8	5	4	8	82	15
17	17	3	13	9	6	8	9	6	2	12	3	6	5	10	10	119	15
18	20	5	15	11	13	10	9	6	5	15	5	16	6	11	20	≥167	15
19	20	5	16	13	14	15	11	7	5	20	6	20	5	13	18	≥188	15
20	20	6	20	17	14	17	12	11	4	20	12	20	9	11	20	≥213	15
21	20	6	20	15	18	20	16	11	4	20	12	20	14	15	20	≥231	15
22	20	8	20	20	17	20	20	12	10	20	15	20	15	20	20	≥257	15
23	20	15	20	20	20	20	20	15	13	20	14	20	14	20	20	≥271	15
24	20	20	20	20	20	20	20	20	16	20	20	20	20	20	20	≥296	15
25	X	20	X	20	20	20	20	17	17	20	20	20	15	20	20	≥249	13
26		20		20	20	20	20	20	20	20	20	20	20	20	20	≥260	13
27		20		20	20	20	20	20	20	20	20	20	20	20	20	≥260	13
Necropsy	20	20	20	20	20	20	20	20	20	20	20	20	20	20	20	≥300	15

In-Life Observation of Skin Papilloma at the Site of Application in Male Tg.AC Hemizygous Mice in the 6-Month Dermal Study of Pentaerythritol Triacrylate: 12 mg/kg

Carcass ID Number	7	7	7	7	8	8	8	8	8	8	8	8	8	8	9	Total Tumors	Animals with Tumors
Carcass ID Number	6	7	8	9	0	1	2	3	4	5	6	7	8	9	0	Total Tumors	Animals with Tumors
Week
9	4	0	0	0	0	3	0	0	4	4	1	2	0	0	0	18	6
10	4	0	0	2	3	5	0	0	8	13	1	2	0	8	0	46	9
11	4	0	0	4	6	4	0	3	9	15	1	2	3	10	0	61	11
12	6	0	0	9	10	10	0	4	14	20	4	2	7	15	13	≥114	12
13	7	7	0	10	11	14	0	6	14	20	5	2	6	20	20	≥142	13
14	7	10	0	11	12	9	0	6	14	20	4	2	7	20	20	≥142	13
15	11	12	0	20	20	10	0	6	15	20	4	3	13	20	20	≥174	13
16	10	13	0	20	16	15	0	6	16	20	6	3	16	20	20	≥181	13
17	18	15	0	18	20	20	0	7	20	20	10	4	20	20	20	≥212	13
18	20	20	0	20	20	20	0	12	20	20	17	4	20	20	20	≥233	13
19	20	20	0	20	20	20	0	15	20	20	12	7	20	20	20	≥234	13
20	20	20	0	20	20	20	0	15	20	20	15	12	20	20	20	≥242	13
21	20	20	0	20	20	20	0	20	20	20	20	14	X	20	20	≥234	12
22	20	20	0	20	20	20	0	20	20	20	20	20		20	20	≥240	12
23	20	20	0	20	20	20	0	20	20	20	20	20		20	20	≥240	12
24	20	20	0	20	20	20	0	20	20	20	20	20		20	X	≥220	11
25	20	20	0	20	20	20	0	20	20	20	20	20		X		≥200	10
26	20	20	0	20	20	20	0	20	20	20	20	X				≥180	9
27	20	20	0	X	20	20	0	20	20	20	20					≥160	8
Necropsy	20	20	0	20	20	20	0	20	20	20	20	20	20	20	20	≥260	13

: X=Animal died
a: Animal 8 in the vehicle control group had a single papilloma first observed at necropsy. No papillomas occurred in the 0.75 mg/kg group. In the 1.5 mg/kg group, animal 32 had a single papilloma observed only at week 21, and animal 39 had a single papilloma observed from week 20 through necropsy. The maximum number of papillomas reported in the 6 and 12 mg/kg groups was 20, although some mice in these groups had more than 20 papillomas. Animal 62 in the 6 mg/kg group was sacrificed one day before study termination.

This is a work of the US government and distributed under the terms of the Public Domain

Bookshelf ID: NBK576070

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