Subacute toxicity from animals

One of the prime concerns, apart from acute and subacute toxicity, is the question of whether a product causes chronic effects. In this context, carcinogenicity studies are of cardinal importance. A possible chronic hazard may be indicated by epi-demological studies. Where such investigations are not available, experiments are performed on animals for the duration of their entire life span. The type of application depends on the exposition (perorally, dermally, per inhalation). 

In subacute toxicity studies lower concentrations are given to determine the so-called NOEL (No Effect Level), i.e. the maximum concentration at which no effect of the applied substance can be seen. This NOEL is important to determine the ADI (acceptable daily intake, see Table 2). This is done by dividing the NOEL by 100 (a factor of 10 to pass from animals to man and a safety factor of lOx). In the subacute toxicity studies... 

Polymers. Studies to determine possible exposure of workers to residual epichl orohydrin and ethylene oxide monomers in the polymers have been done. Tests of warehouse air where Hydrin H and Hydrin C are stored showed epichl orohydrin levels below 0.5 ppm. Air samples taken above laboratory mixing equipment (Banbury mixer and 6" x 12" mill) when compounds of Hydrin H or C were mixed gave epichl orohydrin levels below detectable limits, and ethylene oxide levels less than 0.2 ppm, well below permissible exposure limits (46). A subacute vapor inhalation toxicity study in which animals were exposed to emission products from compounded Parel 58 suggests that no significant health effects would be expected in workers periodically exposed to these vapors (47). 

Scientific information for the process of establishing OELs may come from human or animal data obtained using different methods, from studies of acute, subacute, and chronic toxicity through various routes of entry. Human data, which is usually the best source, is not easily available, and frequently it is incomplete or inadequate due to poor characterization of exposure and clear dose-response relationships. Human data falls into one of the following categories ... 

IPCS Environmental Health Criteria Documents reflect the collective view of an international group of experts and do not necessarily represent the decision or stated policy of UNEP, ILO, or WHO. The reports summarize and interpret the pertinent published literature. Unpublished information is used when published information is absent or when data are pivotal to the risk assessment. Adequate human data are preferred to animal data. Topics include physical chemistry sources of exposure environmental fate and transport concentrations in the environment and in humans pharmacokinetics effects from acute, subacute, and long-term exposure toxic effects on skin, eye, and reproduction mutagenesis and cancer. 

Toxicity test procedure in higher animals (e.g., rats, mice, rabbits, dogs, and monkeys) is different from that in lower animals because the number of available animals usually is limited. As mentioned earlier, it is not economical or practical to use a few hundred mammals for the evaluation of a single toxicity test. The limitation in number has necessitated several adjustments to assure the validity of toxicity determinations in higher animals. Typically, in the pesticide industry, three types of tests are required acute, subacute, and chronic. 

The principal toxicities observed in animals acutely or subacutely exposed to diesel are dermal irritation by the dermal route and renal toxicity, liver toxicity, and CNS depression from all routes of exposure. Application of marine diesel fuel to the skin of mice resulted in ulceration and in diesel fuel-induced chromosomal aberrations on bone marrow cells of rats. 

In May 1980, Notification 698 from the MHW specified the type of data required for the evaluation of safety in animals and Guidelines for Toxicity Studies were subsequently established in 1984. It is necessary to generate data on acute, subacute and chronic toxicity, effect on reproduction, dependence, antigenicity, mutagenicity, carcinogenicity, and local irritation. 

Pb(CH3)4 administered to mice by Intraperitoneal Injection Is converted Into trimethyllead species. The LD50 value In mice is given as 14.3 mg/kg [37]. In the muscle of mice, intoxicated subacutely or chronically with Pb(CH3)4, morphological anomalies concerning mostly the inner part of the blood vessels, sarcoplasmic reticulum, and mitochondria are observed [82]. The effect of microparticles from pyrolysis of Pb(CH3)4 and other antiknock compounds on lungs of mice was Investigated [62]. For studies of intoxication In mice by Pb(CH3)4, see also [8]. The toxicity of Pb(CH3)4 solutions to mice and other animals In combination with other compounds, mainly fuel additives, was studied [20, 25, 26]. 

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