TESTING CHRONIC

Data for PCP and terrestrial wildlife are incomplete and — in view of the large interspecies variations in sensitivity — need to be collected. Research is needed on reproductive effects in animals following inhalation exposure to PCP additional acute and intermediate toxicity testing chronic duration exposure studies on cancer induction, genotoxicity, and immunotoxicity and the development of alternate biomarkers of PCP exposure and antidotes (WHO 1987 USPHS 1994). Until the results of these studies become available, it seems reasonable to apply to wildlife the same levels recommended for human health protection. 

In France, industrial effluents are regularly monitored for toxicity with daphnids. The toxicity data are used as a base for discharge taxation [193]. The Microtox test, chronic toxicity test, and a test on mutagenicity to the set of required bio-criteria are also used for wastewater monitoring [12,194]. 

Decreases in the relative weights of the lymph nodes and thymus were noted in male mice following daily dermal exposures for 1 week to 0.1 mL kerosene (Upreti et al. 1989). In addition, thymocyte counts, bone marrow nucleated cell counts, thymic cortical lymphocytes, and the cellularity of the thymic lobules were decreased. Increases in the cellular populations of the popliteal lymph nodes and the axial lymph nodes were also present. This study is limited because females were not tested. Chronic exposure to 500 mg/kg/day JP-5 induced granulocytic hyperplasia in the bone marrow in male and female mice and hyperplasia in the lymph nodes of female mice (NTP/NIH 1986). Plasmacytosis of the lymph nodes was found to be secondary to dermatitis in mice chronically exposed to 250 and 500 mg/kg/day of marine diesel fuel. 

Chronic Toxicity The effect of a chemical (or test substance) in a mammalian species (usually rodent) following prolonged and repeated exposure for the major part of the lifetime of the species used for the test. Chronic exposure studies over two years are often used to assess the carcinogenic potential of chemicals. 

Gaining a broad perspective about the vast number of chemicals to which humans are exposed can be helpful when setting research and regulatory priorities. Rodent cancer tests by themselves provide little information about how a chemical causes cancer or about low-dose risk. The assumption that synthetic chemicals are hazardous has led to a bias in testing, and such chemicals account for 76 percent (451 of 590) of the chemicals tested chronically in both rats and mice (Table 1). The world of natural chemicals has never been tested systematically. 

Melphalan is an antineoplastic drug, listed also as a Class I immunosuppressive agent (effective only when given prior to the immune stimulus) [1]. It is used for the treatment of multiple myeloma, ovarian carcinoma, tumors of the testes, chronic granulocytic leukemia, chronic lymphocytic leukemia, seminoma, Ewing s sarcoma, reticulum cell sarcoma, and thymoma [1,2]. Its use as an adjuvant to surgery in the management of primary breast cancer was one of the first illustrations of the therapeutic potential of combined modalities of treatment [3]. 

Vibrio fischeri - luminescent bacteria test - chronic Test organism Vibrio fischeri (NRRL-B 11177). 

Fig. 47.1 Effect of nicotine on AP-induced deficits in spatial shoit-teim memory and long-term memory performance in the RAWM. On days 6-8 of testing, chronic nicotine treatment (1 mg/ kg s.c. twice/day for 6 weeks prior to and during Ap infusion) prevented the AP-induced cognitive decline. All values are mean S.E.M. (n = 12 rats/group) p < 0.05 compared to all groups...

There are other complications. Detecting an effect (other than death ) requires that you decide what to test. Some organ systems produce chemicals or enzymes that indicate a toxic effect. But, there are many organ systems in the body. Which to test And, many of these tests are conducted (first, at least) on animals, and animals (including humans) show inter-species differences. So, would a liver disease in rats be a useful test for liver disease in humans And, since we are testing chronic toxicity, was the test performed over a long enough period of time to detect the adverse effect ... 

To test chronic oral toxicity, dogs were fed a diet containing 2% of various PEGs (400, 1500, and 4000) for one year. Rats were given 4% PEG 1500 and PEG 4000 for two years [6]. No adverse effects of any kind were recorded the PEGs proved to be inert. 

Current toxicological test methods address the need to evaluate chemicals for both acute and chronic exposure with respect to a variety of effects on humans and organisms in the environment. Laboratory tests begin with acute tests. Chronic tests are performed in cases where high exposure or releases take place and/or where there is an indication from acute studies, chemical structure, or chemical and physicochemical properties indicating that further study is needed. 

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