Indirect food additives and polymers : migration and toxicology PDF
Preview Indirect food additives and polymers : migration and toxicology
INDIRECT FOOD ADDITNES POLYMERS and Migration and Toxicology INDIRECT FOOD · ADDITIVES POLYMERS and Migration and Toxicology VICTOR 0. SHEFTEL, M.D., PH.D., D.Sc. 2002 PREFACE Substances which in the U.S. have generally been called Indirect Food Additives are in fact Food Contact Substances. Predominantly, they are polymeric materials but also rubber, cellulose, metal, glass, paper and paperboard, etc. Plastics or Polymeric Materials (PM) appear to be an important source of chemical contamination of food and the environment, along with industrial wastes and pesticides. Because of their unique characteristics, plastics are becoming the most important packaging material for food products. The packaging industry is the largest user of plastics; more than 90% of flexible packaging is made of plastics. For the last several decades, the safety assessment of plastics intended for use in contact with foodstuffs or drinking water has continued to present a serious challenge for industry and regulatory agencies. Toxicology of Plastics studies potential hazards of the materials and their ingredients for human health and develops recommendations for manufacture and safe use of such materials. Since it is a comparatively new and insufficiently investigated branch of applied toxicology, the expe rimental data obtained in this field hitherto have not been collected and generalized. One cannot find a large body of migration data in the current literature. Incomplete and fragmentary information on the subject can be found in the following sources: Practical Toxicology ofP lastics, CRC Press, 1968; Les Matieres Plastiques dans l'lndustrie Alimentaire, Paris, 1972, by R. Lefaux; Industrial Hazards of Plastics and Synth£tic Elas tomers, J. Jarvisalo, P. Pkaffii, and H. Vainio, Eds., Alan R. Liss, Inc. (1984). Unfortunately all these books are out-of-date. This handbook is an attempt to provide comprehensive information on the toxic effects of plastics and their ingredients that enter the body mainly by the oral route and thus it may serve as a sort of encyclopedia for specialists and practitioners in this field. Basic toxicological and other scientific data necessary to identify, characterize, measure, and predict hazards of plastic-like materials use have been assembled from the scientific literature and from regulatory national and international documents. The contents of this handbook factually overstep the limits of toxicology of plastics because they com prise information concerning many of the widespread food and water contaminants: heavy metals, solvents, monomers, plasticizers, etc. Because toxic properties of PM depend on toxic properties of the substances released by them, this book will be of use when assessing toxic properties not only of the existing plastics but also of future materials containing ingredients that have already undergone toxicological evaluation. The handbook includes the thoroughly reviewed American and European toxicology literature as well as the screened Russian toxicology data, often unknown in the West but reasonably fit to interpretation. Since the toxic properties of PM are determined by the toxic properties of the substances released by them, toxic hazard assessment of ingredients migrating into food and water is the essential part either of new material development or of the regulatory decision-making process. It should be borne in mind that assessment of toxic potential is an extremely complicated task even for those who have many years of experience in toxicology testing. Such assessment requires examining and scrutinizing of complex data that describe the toxicology of a substance, selecting the appropriate valid information from often conflicting or incomplete data, and arriving at a com:lusion on the relevance of the information to human health risk. For these and other reasons, it has not been possible to assess exactly a relative validity either of data obtained before GLP implementation or of Russian toxicology data. On the other hand, a toxicology profile will be incomplete today if only findings of the last decade are taken into account. Since Russian toxicology developed separately from that of the West, a lot of data collected in Russia are unique, and cannot be ignored, even if they do not completely confonn to GLP requirements. In every case, references should enable easy identification of the place and year of each research cited. The following remarks concerning presentation of the data in this handbook are to be made: 1. For each chemical, the following data are provided when available: • Substance Prime Name • Molecular or Structural Fonnula • Molecular Mass • Synonyms • CASnumber • RTECS number • Properties (sometimes also Composition) • Applications and Exposure • Migration Data • Acute Toxicity • Repeated Exposure • Short-tenn Toxicity • Long-tenn Toxicity • Immunotoxicity or Allergeni~; Effect • Reproductive Toxicity (Embryotoxicity, Teratogenicity, and Gonadotoxicity) • Mutagenicity (In vivo cytogenicity and In vitro genotoxicity) • Carcinogenicity (including IARC, U.S. EPA, NTP and other cancer classifications) • Chemobiokinetics • Standards, Guidelines, Regulations, Recommendations • References 2. The oral route of administration is intended throughout the book unless otherwise specified. In the absence of oral toxicity data, infonnation from inhalation or dennal toxicity studies, as well as from admi nistration via i/p, ilv, or other routes, is presented. 3. Descriptions of the common toxic effects are subdivided into acute, repeated, short-term, and long tenn (chronic) toxicity: acute toxicity refers to the result of a single oral exposure; repeated exposure refers to a length of exposure of about 2 weeks to 2 months; short-term toxicity refers to a period of treatment not less than 3 to 4 months; long-term toxicity refers to a length of exposure not Jess than 6 months. 4. A quantitative assessment of functional accumulation is given. Coefficient of accumulation (on the lethal level) has been detennined by one of the following three methods: the method ofYu. S. Kagan and V. V. Stankevich (designated as "by Kagan") stipulates administration of the agent to experimental animals at equal daily doses of 115 to 1150 LD for 2 to 4 months; the method of R. K. Lim et al. 50 (designated as "by Lim") stipulates administration of the substance at gradually increasing doses, beginning with 111 0 LD for no more than 4 weeks; the method of S. N. Cherkinsky et al. (designated as 50 "by Cherkinsky") stipulates administration of 115 LD for 20 days. 50 5. Data on certain Jong-tenn or delayed effects, in particular carcinogenicity, may not present appro priate information about safe levels. These data are usually obtained at high dose levels, and recommen dations for carcinogenicity evaluation have been computed from hypothetical mathematical models that cannot be verified experimentally. 6. There are three usually acknowledged carcinogenicity classifications: IARC, U.S. EPA, and NTP. All substances tested could be subdivided according to IARC weight of evidence for carcinogenicity: 1 -Human carcinogens 2A -Probable carcinogens 2B-Possible carcinogens 3-Not classified 4 -Probably not carcinogenic to humans. According to the U.S. EPA weight of evidence for carcinogenicity the classification is as follows: A -Human carcinogens Bl and 82-Probable human carcinogens C -Possible human carcinogens D -Not classified E -No evidence ofc arcinogenicity in humans. NTP categorization according to the weight of experimental evidence is presented by the following groups: CE -Clear evidence ofc arcinogenic activity . SE -Some evidence ofc arcinogenic activity EE -Equivocal evidence ofc arcinogenic activity NE -No evidence ofc arcinogenic activity IS -Inadequate study ofc arcinogenic activity. Earlier NfP designations are as follows: P-Positive E -Equivocal N -Negative. Designations of this categorization are displayed in the following order: Male Rats-Female Rats -Male Mice -Female Mice. Absence of the data is designated as XX. Rodent carcinogens with significantly elevated tumor rate at some dose(s) below MTD are marked with * (according to J. K. Haseman and A. Lockhart, 1993 ). It is now clear that tumor induction can arise in a variety of ways including not only a DNA-reactive genotoxic mode of action, but also non-DNA-reactive non genotoxic cytotoxic and non-genotoxic-mitogenic modes of action. Initial risk assessment approaches that recognized this distinction identified a chemical carcinogen as either genotoxic or non-genotoxic, with no middle ground (B. E. Butterworth and M. S. Bogdanffy, 1999). 7. Within chapters, ingredients are placed in the English alphabetical order of their prime names, ignoring special characters such as Greek letters or numerals. Abbreviation of a substance described in an entry consists predominantly of its first letter. If abbreviation consists of two or more letters, it is specified. Toxicity data are transformed into a special, newly developed format to facilitate the use of available toxicology information to evaluate potential migration levels of plastic ingredients into food or drinking water. 8. WHO, EU, U.S., and some other available national standards, guidelines, and recommen dations, taken from the following sources are presented: WHO Guidelines for Drinking-Water Quality, 1996; Council Directive of 15 July 1980, Official Journal of European Communities, 30, 8, August 1980; Drinking Water Regulations and Health Advisories by the U.S. EPA, 1998; Commission Directive 90/128/EEC of 23 February 1990 relating to plastics materials and articles intended to come in contact with foodstuffs, Official Journal ofE uropean Communities, 33 (L7 5), 19, 1990; Commission Directive 96111/EC of March 5, 1996 (amending Directive 90/128/EEC), Official Journal ofE uropean Communities, L61, 12.03.1996; Code ofF ederal Regulations, Food and Drugs, 21 CFR Part 175-179, 1998; Sanitary Standards of Maximum Allowable Concentrations of Harmful Chemicals in Water Bodies set by Ministry of Health, Russia, Appendix 2, Sanitary Rules and Standards, No 4630-88, 1988 (revised in 1994 and 1995). References to the U.S. FDA are cited according to CFR. 9. Definitions of abbreviations: ADI - Acceptable Daily Intake (an estimate of the amount of a substance in food that can be ingested daily over a lifetime by humans without appreciable risk) BW-Body Weight CFR-U.S. Code of Federal Regulations DNA -Deoxyribonucleic acid DWEL-Drinking Water Equivalent Level (a lifetime exposure concentration in drinking water protective of adverse, non-cancer health effects) ET5 0- Median Time from ingestion up to death of animals after LD50 administration EU - European Union FAO-Food and Agricultural Organization of the United Nations GLP -Good Laboratory Practice GRAS -Generally Recognized As Safe IARC -International Agency for Research on Cancer IPCS -International Program of Chemical Safety JECFA -Joint FA O/WHO Expert Committee on Food Additives K.cc -Coefficient of Accumulation (a quantitative assessment of functional accumulation) LOAEL - Lowest-Observed-Adverse-Effect-Level (the lowest level of exposure at which an adverse effect was observed) LOEL - Lowest-Observed-Effect-Level (the lowest level of exposure at which any biological effect was observed) MAC - Maximum Allowable Concentration in water bodies (maximum permissible level of a contaminant protective of adverse, non-cancer health effects) MCL -Maximum Contaminant Level in drinking water MCLG -Maximum Contaminant Level Goal in drinking water MPC - Maximum Permissible Concentration in food (maximum permissible level of a contaminant in food, Russia) MTD-Maximum Tolerable Dose, see ADI n/m -not monitored NOAEL -No-Observed~Adverse-Effect-Level (the greatest concentration or amount of chemical found by experiment or observation that causes no detectable adverse alteration of morphology, functional capacity, growth, development, or lifespan of the target organism) NOEL -No-Observed-Effect-Level (the greatest concentration or amount of chemical found by experiment or observation that causes no detectable change in morphology, functional capacity, growth, development, or lifespan of the target organism) NTP-U.S. National Toxicology Program organolept. -organoleptic criterion PML -Permissible Migration Level from polymeric materials to food or water (Russia) PTWI-Provisional Tolerable Weekly Intake [a provisional estimate of the amount of a substance (contaminant) in food or drinking water that can be ingested weekly over a lifetime without appreciable health risk] QM -Maximum Permitted Quantity of the residual substance in the material or article RID -Reference Dose (an estimate of a daily exposure to the human population that is likely to be without appreciable risk of deleterious effects over lifetime) RNA-Ribonucleic acid RTECS-Registry ofToxic Effects of Chemical Substances SML -Specific Migration Limit in food or food simulant TDI-Tolerable Daily Intake [an estimate of the amount of a substance (contaminant) in food or drinking water that can be ingested daily over a lifetime without appreciable health risk] UF-Uncertainty factor (a factor applied to the NOEL to derive ADI) WHO-World Health Organization AL T -alanine aminotransferase AST -aspartate aminotransferase BW -body weight CA -chromosome aberrations CNS -central nervous system DLM -dominant lethal mutations DNA -deoxyribonucleic acid ECG -electrocardiogram EEG -electroencephalogram GC -gas chromatography GI-gastro-intestinal Hb -hemoglobin HPLC -high-performance liquid chromatography Vg -intragastric administration Vm -intramuscular injection Vp -intraperitoneal injection Vv-intravenous injection LDH -lactate dehydrogenase MetHb -methemoglobin MS -mass spectrometry NS -nervous system ppm -parts per million ppb -parts per billion RNA -ribonucleic acid sic -subcutaneous injection SCE -sister chromatid exchanges STI -summation threshold index 10. The following reference numbers relate to the most repeatedly used literature sources: • 01 - Alexander, H. C., McCarty, W. A., and Bartlett, E. A., Aqueous odor and taste threshold values of industrial chemicals, J. Am. Water Work Assoc., 74, 595, 1982. • 02 - Amoore, J. E., and Hautala, E., Odor as an aid to chemical safety: Odor threshold compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution, J. Appl. Toxicol., 3, 272, 1983. • 03 -Patty, F. A., Ed., Industrial Hygiene and Toxicology, 3'd ed., John Wiley & Sons, New York, 1982. • 04 -Lefaux, R., Chimie et Toxicologie des Matieres Plastiques, Paris, 1964. • 05-Lefaux, R., Les Matieres Plastiques dlJns l'Industrie Alimentaire, Paris, 1972. • 06-Registry ofTo xic Effects of Chemical Substances, 1985-86 ed., User's Guide, D. V. Sweet, Ed., U.S. Dept. Health and Human Services, WliShington, D.C., 1987. • 07-Sheftel, V. 0., Toxic Properties ofM onomers and Additives, E. Inglis, and S. Dunstall, Eds., Rapra Technology Ltd., UK, 1990. • 08-Broitrnan, A. Ya, Basic Problems oft he Toxicology ofS ynthetic AntioxidlJnts Intended for Stabilizing Plastics, Author's abstract of thesis, Leningrad, 1972, 48 (in Russian). • 09-Gold, L. S., Manley, N. B., Slone, T. H., Garfinkel, G. B., Rohrbach, L., and Ames, B. N., The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989, Environ. Health Perspect., 100, 65, 1993. • 010-Identification and Treatment ofTastes and Odors in Drinking Water, Mallevialle, J. and Suffet, I. H., Eds., AWWA Research Foundation, Lyonnaise des Eaux-Dumez, 1987, 292. • Oil-Industrial Hygiene and Toxicology; Patty, F. A., Ed., 2nd ed., Volume II, Toxicology, lnterscience Publishers, New York, 1963. • 012 - Sax, N. 1., Dangerous Properties of Industrial Materials, 6 th ed., Van Nostrand Reinold, New York, 1984. • 013 - Mortelmans, K., Haworth, S., Lawlor, T., Speck, W., Tainer, B., and Zeiger, E., Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals, Environ. Mutagen., 8 (Suppl. 7), 1, 1986.
The list of books you might like
