Basic considerations in evaluating health hazards of food-packaging materials and insect repellents by Industrial Hygiene Foundation H. H. Schrenk, Research Director
REVENTION of injurious effects
P during manufacture and use of industrial chemicals depends on a
knowledge of the toxicity and physiological effects of the compounds. However, it has been repeatedly emphasized that toxicity and hazard are not synonymous. Toxicity is a fundamental property of a, substance which determines its capacity to produce injury. Whether or not injury is produced depends upon the magnitude of contact with the compound, and hence hazard is measured in terms of toxicity and exposure, Thus, to evaluate the potential hazard of a substance, one must know not only the toxicity but also the conditions of usage and the type of contact likely to be incurred. The kind and scope of toxicity data also vary, depending upon the anticipated exposure or contact with the material. For example, in evaluating exposures in industry, particular attention is paid to inhalation of gases, vapors, and dusts. A basic tool of industrial hygienists is the list of maximum acceptable concentrations which serve as standards of good practice and engineering guides for design and operation. The validity and efficacy of the engineering controls are continually checked by medical controls through preplacement and periodic physical examinations. However, when contamination of foods is involved, the viewpoint is somewhat different, although there is considerable similarity. The ingestion of a chemical may continue over the entire life span rather than just the working life span. Consideration must also be given to various degrees of pre-existing impaired health and hypersensitivity or allergic reactions. There may be sources of contact with the particular substance other than in food. Food-packaging materials
The discussion in a recent article (2) October 1955
of basic considerations in determining safety of chemicals used in foodpackaging materials is pertinent. The contamination of food, whether directly by addition or indirectly through processing or packaging, is a primary concern of the Food and Drug Administration. Within recent years a wide variety of packaging materials has been developed to protect products not only to the point of purchase but also after they reach the ultimate consumer. I n addition to accomplishing the objectives of convenience, better keeping qualities, and reduced wastage, the packaging material must not adversely affect or contaminate the food. Consideration must be given to additives or Contaminants in the packaging material as well as in the basic material itself. For example, the plasticizer may be more important than the plastic; its solubility in water or fat is significant and its use may be restricted to fatty foods or foods with a high water content, based on the solubility characteristics. Thus, as in the case of industrial exposures, the potential hazard depends on the magnitude of exposurethat is, the extent to which the food is contaminated. Hence, before instituting detailed toxicity studies, it is advisable to conduct extractability tests to determine the degree of potential contamination. A prerequisite of the extractability tests is an analytical method with sensitivity of 0.1 p.p.m. or better for each ingredient except those known to be nontoxic. The use of radioactive tracers may be more efficient and less expensive than conventional analytical procedures in some instances. The first step in the extractability tests is proof of the adequacy of the analytical method, which is based on the analysis of blanks (food before contact with packaging materials) and recovery of known quantities of chemical added t o the unpackaged
food. Recoveries should cover the range 0.01 to 1p.p.m. and, a t the upper limit, recovery should be 90% or better. If the recovery is less than SO%, the results are considered to have only qualitative significance and recoveries less than 70% have limited value in the interpretation of the data. At least five blanks and five recoveries are considered necessary for each food involved to give a satisfactory evaluation of extractability. Ideally, the extractability tests should be conducted with the foods that may come in contact with the packaging material. Occasionally such a program of tests may become so extensive and complex as to be impractical owing to analytical difficulties. Under such circumstances extractability tests may be conducted with a series of solvents simulating various types of food. Such solvents include pickle juice, meat juice, Locke-Ringer’s solution, 3% sodium chloride, 3% sodium bicarbonate, 3% acetic acid, 3% lactic acid, 20% sugar solution, and liquid fat as lard oil or a vegetable oil. Other facts to be considered are temperature, length of contact, and area of packaging material in relation to the amount of solvent. Chemical tests should provide information on the complete composition of the package material, its constancy of composition, and the extractability of each significant component by each food or special type of substituted solvent. The results of these tests should establish whether toxicity studies are required; unless toxic materials are extracted in significant amounts, such studies are not indicated. However, if toxic substances are extracted, toxicological studies are needed for those substances. The toxicity studies required include acute toxicity by oral administration to several species of animals with careful observations for indications of mechanism of action, sensi-
INDUSTRIAL AND ENGINEERING CHEMISTRY
Industrial Hygiene tivity or allergic response, and subacute and chronic toxicity. The subacute or pilot tests are designed to give preliminary information, with a minimum of time and expenditure, on the magnitude of toxicity, to indicate if more exhaustive studies are warranted, and to serve as a basis for selecting dosage for the chronic feeding studies. I n the chronic feeding experiments, animals are fed for their normal life span a t several dosages to cover ranges of no measurable response to little to moderate response. In addition to mortality rates, weight changes, orThe most reliable method of purifying water containing dissolved solids such as calcium gan weight changes, and histopathcarbonate, magnesium sulphate, sodium ological examination of tissues, parchloride, silica, or many other common con- ticular attention is paid to the absorptaminants, is ILLCO-WAY i o n x c h a n g e tion, metabolic rate, and elimination (also known as de-ionization). Many adap- of the chemical under study. Infortations of the basic methods are available mation on metabolism of a compound including the new mixed-bed de-ionizers is extremely important in evaluating which produce water described by one user potential harmful effects. as of “fantastic purity” It is not practical to give a set of detailed which will be appliPRACTICAL EQUIPMENT cable to criteria all chemicals. Hence, each M A D E BY I ‘ ILLCO=W A Y ” substance must be treated individually Illinois Water Treatment Company has and evaluated on the basis of all availpioneered in the design and manufacture of able information. I n some instances pr~cticalequipmentforionxchange processes sufficient data may be available, ever since the first year that the de-ionization whereas in other instances a compreidea came out of the laboratories. A wealtl-. hensive toxicological and biochemical of experience has been accumulated so tha: study may be required to provide the “ILLCO-WAY” is today recognized as the necessary information. leader in the development of commerciallj The report under discussion lists successfEl1 instaZlations. resins, plasticizers, stabilizers, reADAPTED FOR PURIFYING lease agents, antioxidants, accelerators, colorants, antimycotics, protectants against insects, and proRADIOACTIVE WASTES With the rapid expansion of the field of tectants against rodents, with comnuclear science, various needs have de- ments regarding acceptability or unveloped for ionxchange, particularly in the acceptability. In some instances adepurification of wastes contaminated by quate information is not available on radioactivity. ILLCO-WAY equipment has n-hich to base a final decision at this been designed and built for this and other time. purposes i n several plants employing atomic Tin has a low order of toxicity and energy. Forfurther information on the uses of no public health hazard is considered ILLCO-WAY ionxchange, w r i t e . . . to exist in the use of tin plate or foil as a packaging material. Aluminum is relatively unreactive and its comILLINOIS WATER TREATMENT CO. pounds are considered harmless, hence it is a satisfactory packaging material. Steel drums do not present a problem, but consideration must be given to possible contamination by heavy metal 840 CEDAR ST. impurities as zinc, cadmium, and chroROCKFORD, mium, if bonderizing is used for rustILLINOIS proofing. Lead is toxic and unsuitNEW YORK OFFICE: 141 E. 44TH ST., NEW VORK 17. N. Y. able for many applications. However, CANADIAN DIST. PUMPS B SOFTENERS, LTD. LONDON. ONT. the lead-tin solder along the seams of metal containers and the solder pellets which may escape detection in the Circle No. 96 A on Readers’ Service Card, page 123 A
PURIFIES W A T E R BY R E M O V I N G DISSQLVED SOLID
finished product have been shown by extensive analytical studies to be dissolved in quantities too small to be of any health significance. Various substances are used in conjunction with cellulose materials to protect them from mold or repel insects or rodents. While glass containers present no problem, closures for them may be cause for concern. Chemicals that are used in formulations of plastic packaging materials are given in the list mentioned. Insect repellents
Another article ( I ) deals with toxicity studies of insect repellents. An approximate 50% mortality dose by oral administration in several species of animals in excess of 1.0 ml. per kg. of body weight is considered to satisfy the first of the criteria of safety. A second criteria consists of topical application of a single dose to the clipped skin of a rabbit. Repellent is held in contact with the skin for 24 hours by means of a rubber cuff. A 50% mortality value of 6.0 ml. per kg. is considered satisfactory. Other tests include exposure of the clipped trunk of a rabbit for 21 days to a twill impregnated with the repellent, topical application of doses of 0.5 ml. per kg. daily for 90 days, and application to intact and abraded skin, to evaluate primary irritation. Histopathological and hematological data were obtained in the 90-day experiment s . Among the compounds tested and considered acceptable for use as insect repellents or in certain formulations are: dimethyl phthalate, 2ethyl-l,3-hexanediol, dimethyl carbate, indalone, undecylenic acid, pyrethrins, piperonyl butoxide, and n-dibutyl phthalate. The following substances were considered satisfactory for impregnating clothing : Z-ethyl-2-butyl-l,3-propanediol, n-isopropyl acetanilide, and npropyl acetanilide. Literature cited (1) Lehman, A. J., Assoc. Food & Drug Oi9icials U . S.,Quart.Bull., 19,87 (1955).
(2) Lehman, A. J., and Patterson, W. L., Modern Packaging,28, 115 (1955). Correspondence concerning this column will be forwarded if addressed to the author, %/o Editor, CHEMISTRY, ISDUSTRIALAND ENQINEERIXQ 1155-16th St., N.W., Washington 6, D. C .
INDUSTRIAL A N D ENGINEERING CHEMISTRY
Vol. 47, No. 10