Acute toxicity additives

Environmental Considerations. The phosphate flame retardants, plasticizers, and functional fluids have come under intense environmental scmtiny. Results pubUshed to date on acute toxicity to aquatic algae, invertebrates, and fish indicate substantial differences between the various aryl phosphates (159—162). The EPA has summarized this data as well as the apparent need for additional testing (147). 

Cyasin, a component of the nut of the cycad tree, a native of tropical environs, produces an acute toxicity in addition to drastically increasing the incidence of Lou Gerhig s disease (amyotropic lateral sclerosis). Cyasin is carcinogenic (102). 

Acute Toxicity. Plasticizers possess an extremely low order of acute toxicity LD q values are mostiy in excess of 20,000 mg/kg body weight for oral, dermal, or intraperitoneal routes of exposure. In addition to thek low acute toxicity, many years of practical use coupled with animal tests show that plasticizers do not kritate the skin or mucous membranes and do not cause sensitization. 

Although poloxamers show poor biodegradability, they exhibit very low acute toxicity [92] and are reported as having low potential for causing irritation and skin sensitization [26]. Toxicity decreases as ethylene oxide content increases, and the least toxic poloxamers are approved as food additives [80]. 

Toxicity Bioassay. Ninety-six hour acute toxicity tests were conducted on the effluent streams of major industries. A static renewal procedure was used in which waste waters of various dilutions were renewed at 24 hour intervals over a 96 hour period. Rainbow trout was used as the test organism. Tests were conducted at 13°C in 20 liter aquaria according to standard procedures (22), Results are summarized in Table 8. Chemical and toxicity test results indicate that the trace element quantities identified in Table 8 are not acutely toxic under the prevailing conditions and unlikely to pose an acute threat to aquatic life. In this case a chronic toxicity assessment would require additional research. 

Isshiki K, Miyata K, Martsui S, et al. 1983. [Effects of post-harvest fungicides and piperonyl butoxide on the acute toxicity of pesticides in mice. Safety evaluation for intake of food additives. III]. 

Mineral oils have very low acute toxicities, i.e. oral LD50 values of around lOg/kg. They are not absorbed via the skin and are insufficiently volatile to produce harmful vapours at room temperature. Additives are used in small quantities for specific properties but these do not normally affect the health and safety characteristics. Dermatitis may be caused by repeated or prolonged contact of mineral oils with the skin. Such contact with higher boiling fractions over many years can result in warty growths which may become... 

REDUCED Additional acute toxicity Acute daphnia toxicity Biodegradability Physico-chemical properties 100 kg/annum or 500 kg cumulative... 

In many cases, there is difficulty in preserving residues in samples after collection and prior to pesticide analysis which coincides with a rapid further degradation and mineralization of the pesticide residues under most environmental conditions. Storage stability studies and studies on the reactivity of sample collection equipment in addition to field quality assurance procedures can help address some of these questions. Concerns are accentuated for compounds that have short half-lives in the environment but still have high acute toxicity. 

As mentioned previously (and discussed in detail in Sec. IX), contact lens products have specific guidelines that focus on compatibility with the contact lens and biocompatibility with the cornea and conjunctiva [75], These solutions are viewed as new medical devices and require testing with the contact lenses with which they are to be used. Tests include a 21-day ocular study in rabbits and employ the appropriate types of contact lenses with which they are to be used and may include the other solutions that might be used with the lens. Additional tests to evaluate cytotoxicity potential, acute toxicity, sensitization potential (allergenicity), and risks specific to the preparation are also required [75-77], These tests are sufficient to meet requirements in the majority of countries, though testing requirements for Japan are currently much more extensive. 

Also, the test procedure (protocol) is fundamental because it allows comparing results from different laboratories and from different experimental sets. Moreover, selected test protocol could affect the interpretation of the results, the information content and its application in the safety evaluation process, as stated by Frazer if the biological system is exposed to a test chemical for 24 h and the endpoint assay is immediately conducted, the data produced would be most relevant to the acute toxicity of the test material. If, on the other hand, the system is exposed to material for 24 h and the system is cultured in the absence of the test material for additional 48 h before the endpoint assay is conducted, the data would be more relevant to recovery from toxicity rather than acute toxicity [7]. 

Studies using radioactivity-labeled acrylonitrile indicate that acrylonitrile or its metabolites form covalent adducts with cellular macromolecules in most tissues. Studies to develop chemical or immunological methods for measuring these adducts would be especially valuable in detecting and perhaps even quantifying human exposure to acrylonitrile. Adverse health effects demonstrated following exposure to acrylonitrile, particularly acute exposures, were characteristic of cyanide toxicity. Because these effects are also indicative of exposure to many other toxicants, additional methods are needed for more specific biomarkers of effects of acrylonitrile exposure. 

The precise mechanism of monomethylhydrazine toxicity is uncertain. In addition to the contact irritant effects, the acute toxicity of dimethylhydrazine exposure probably involves the central nervous system as exemplified by tremors and convulsions (Shaffer and Wands 1973) and behavioral changes at sublethal doses (Streman et al. 1969). Additionally, renal and hepatic toxicity and hemolytic effects imply alternate mechanisms of toxicity. 

In addition to the chemicals included on the other lists, the CDC also included heavy metals such as arsenic, lead, and mercury volatile solvents such as benzene, chloroform, and bromoform decomposition products such as dioxins and furans polychlorinated biphenyls (PCBs) flammable industrial gases and liquids such as gasoline and propane explosives and oxidizers and all persistent and nonpersistent pesticides. Agents included in this volume are limited to those that are most likely to pose an acute toxicity hazard. 

In all cases, the concentrations of malathion and fenitrothion measured in water (up to 5.8 and 1.2 pg/L, respectively) were below the LC50 (lethal concentration 50%) values reported for these compounds in oysters and mussels, which range between 2.7 and 278 mg/L in the case of malathion, and between 10.3 pg/L and 123 mg/L in the case of fenitrothion (http //www.pesticideinfo.org). However, it has to be stressed that these LC50 values express acute toxicity, that both malathion and fenitrothion might be bioaccumulated by molluscs (as their detection in biota suggests), and that aquatic organisms are exposed to a variety of contaminants, some of which could show synergetic or additive effects [40]. Further matters of... 

Pharmacologically, carbofuran inhibits cholinesterase, resulting in stimulation of the central, parasympathetic, and somatic motor systems. Sensitive biochemical tests have been developed to measure cholinesterase inhibition in avian and mammalian brain and plasma samples and are useful in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents (Bal-lantyne and Marrs Hunt and Hooper 1993). Acute toxic clinical effects resulting from carbofuran exposure in animals and humans appear to be completely reversible and have been successfully treated with atropine sulfate. However, treatment should occur as soon as possible after exposure because acute carbofuran toxicosis can be fatal younger age groups of various species are more susceptible than adults (Finlayson et al. 1979). Carbofuran labels indicate that application is forbidden to streams, lakes, or ponds. In addition, manufacturers have stated that carbofuran is poisonous if swallowed, inhaled, or absorbed through the skin. Users are cautioned not to breathe carbofuran dust, fumes, or spray mist and treated areas should be avoided for at least 2 days (Anonymous 1971). Three points are emphasized at this juncture. First, some carbofuran degradation... 

Chlordane interacts with other chemicals to produce additive or more-than-additive toxicity. For example, chlordane increased hepatotoxic effects of carbon tetrachloride in the rat (USEPA 1980 WHO 1984), and in combination with dimethylnitrosamine acts more than additively in producing liver neoplasms in mice (Williams and Numoto 1984). Chlordane in combination with either endrin, methoxychlor, or aldrin is additive or more-than-additive in toxicity to mice (Klaassen et al. 1986). Protein deficiency doubles the acute toxicity of chlordane to rats (WHO 1984). In contrast, chlordane exerts a protective effect against several organophosphorus and carbamate insecticides (WHO 1984), protects mouse embryos against influenza virus infection, and mouse newborns against oxazolone delayed hypersensitivity response (Barnett et al. 1985). More research seems warranted on interactions of chlordane with other agricultural chemicals. 

Most often, response-dose curves are developed using acute toxicity data. Chronic toxicity data are usually considerably different. Furthermore, the data are complicated by differences in group age, sex, and method of delivery. If several chemicals are involved, the toxicants might interact additively (the combined effect is the sum of the individual effects), synergisti-cally (the combined effect is more than the individual effects), potentiately (presence of one increases the effect of the other), or antagonistically (both counteract each other). 

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