National Toxicology Program Toxicity Report Series Number 17 NTP Technical Report on Toxicity Studies of Black Newsprint Inks Administered Topically to F344/N Rats and C3H Mice Joel F. Mahler, DVM, Study Scientist National Toxicology Program Post Office Box 12233 Research Triangle Park, NC 27709 NIH Publication 92­3340 July 1992 United States Department of Health and Human Services Public Health Service National Institutes of Health NOTE TO THE READER The National Toxicology Program (NTP) is made up of four charter agencies of the U.S. Department of Health and Human Services (DHHS): the National Cancer Institute (NCI), National Institutes of Health; the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health; the National Center for Toxicological Research (NCTR), Food and Drug Administration; and the National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control. In July, 1981, the Carcinogenesis Bioassay Testing Program, NCI, was transferred to the NIEHS. The NTP coordinates the relevant programs, staff, and resources from the Public Health Service agencies relating to basic and applied research and to biological assay development and validation. The NTP develops, evaluates, and disseminates scientific information about potentially toxic and hazardous chemicals. This knowledge is used for protecting the health of the American people and for the primary prevention of disease. The studies described in this toxicity study report were performed under the direction of the NIEHS and were conducted in compliance with NTP chemical health and safety requirements and must meet or exceed all applicable federal, state, and local health and safety regulations. Animal care and use were in accordance with the Public Health Service Policy on Humane Care and Use of Animals. These studies are designed and conducted to characterize and evaluate the toxicologic potential of selected chemicals in laboratory animals (usually two species, rats and mice). Chemicals selected for NTP toxicology studies are chosen primarily on the bases of human exposure, level of production, and chemical structure. Selection per se is not an indicator of a chemical's toxic potential. Single copies of this Report are available without charge while supplies last from the NTP Public Information Office, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709 (919­ 541­3991). National Toxicology Program Toxicity Report Series Number 17 NTP Technical Report on Toxicity Studies of Black Newsprint Inks Administered Topically to F344/N Rats and C3H Mice Joel F. Mahler, DVM, Study Scientist National Toxicology Program Post Office Box 12233 Research Triangle Park, NC 27709 NIH Publication 92­3340 July 1992 United States Department of Health and Human Services Public Health Service National Institutes of Health 2 BLACK NEWSPRINT INK, NTP TOXICITY REPORT NUMBER 17 CONTRIBUTORS The NTP report on the toxicity studies of black newsprint ink is based primarily on 30­day and 13­ week studies performed over the period of December, 1987, to September, 1988, at Battelle Memorial Laboratories, Columbus Division, Columbus, Ohio. National Toxicology Program NTP Pathology Working Group Evaluated experiment, interpreted results, Evaluated slides and prepared pathology report and reported findings John Seely, DVM Joel F. Mahler, DVM Chairperson Study Scientist Pathco, Inc. John R. Bucher, PhD Michael R. Elwell, DVM, PhD Leo T. Burka, PhD National Toxicology Program Rajendra S. Chhabra, PhD Michael P. Dieter, PhD Michael R. Elwell, DVM, PhD Experimental Pathology Laboratories, Inc. Provided pathology quality assessment H.B. Matthews, PhD Morrow Thompson, DVM, PhD Cynthia Shackelford, PhD Errol Zeiger, PhD William MacKenzie, DVM, MS Coordinated report preparation Jane M. Lambert, BS Environmental Health Research and Kristine Witt, MS Testing Inc. Oak Ridge Associated Universities Sperm morphology and vaginal cytology evaluation Dushant K. Gulati, PhD Battelle Memorial Laboratories, Teresa Cocanougher, BA Columbus, OH Susan Russell, BA Principal contributors Arthur C. Peters, DVM Principal Investigator Analytical Sciences, Inc. Milton Hejtmancik, PhD Statistical analysis Study Director, Toxicologist Ming Chang, PhD Steven Seilkop, MS Chemistry Janet Teague, MS Peter Jepsen, DVM, MS Study Veterinarian Ronald Pershing, DVM Study Pathologist Michael Ryan, DVM Clinical Pathology 3 BLACK NEWSPRINT INK, NTP TOXICITY REPORT NUMBER 17 TABLE OF CONTENTS CONTRIBUTORS ....................................................................................................................................2 TABLE OF CONTENTS ...........................................................................................................................3 ABSTRACT .............................................................................................................................................5 PEER REVIEW PANEL ...........................................................................................................................7 SUMMARY OF PEER REVIEW COMMENTS .............................................................................................8 INTRODUCTION .....................................................................................................................................9 Physical Properties, Production, and Exposure................................................................................9 Epidemiology..................................................................................................................................9 Animal Studies .............................................................................................................................10 Mutagenicity ................................................................................................................................10 Study Rationale and Design..........................................................................................................11 MATERIALS AND METHODS ................................................................................................................12 Procurement and Characterization of Samples ..............................................................................12 30­Day Study Design....................................................................................................................13 13­Week Study Design .................................................................................................................13 Reproductive Toxicity....................................................................................................................14 Genetic Toxicology ........................................................................................................................15 Statistical Methods .......................................................................................................................15 Quality Assurance ........................................................................................................................16 RESULTS .............................................................................................................................................18 30­Day Studies in F344/N Rats ....................................................................................................18 13­Week Studies in F344/N Rats..................................................................................................18 30­Day Studies in C3H Mice .........................................................................................................21 13­Week Studies in C3H Mice.......................................................................................................22 Genetic Toxicology ........................................................................................................................31 DISCUSSION ........................................................................................................................................32 REFERENCES ......................................................................................................................................34 TABLES Table 1 Experimental Design and Materials and Methods in the 30­Day and 13­Week Dermal Studies of Black Newsprint Inks ...................................................17 Table 2 Survival and Weight Gain of F344/N Rats in the 30­Day Dermal Studies of Black Newsprint Inks.................................................................................................19 Table 3 Survival and Weight Gain of F344/N Rats in the 13­Week Dermal Studies of Black Newsprint Inks.................................................................................................19 Table 4 Selected Organ Weights of F344/N Rats in the 13­Week Dermal Studies of Black Newsprint Inks.................................................................................................21 Table 5 Survival and Weight Gain of C3H Mice in the 30­Day Dermal Studies of Black Newsprint Inks.................................................................................................22 4 BLACK NEWSPRINT INK, NTP TOXICITY REPORT NUMBER 17 Table 6 Survival and Weight Gain of C3H Mice in the 13­Week Dermal Studies of Black Newsprint Inks.................................................................................................23 Table 7 Liver Weights of C3H Mice in the 13­Week Dermal Studies of Black