Subacute/subchronic/chronic studies

Subacute/Subchronic/Chronic studies 8e Checklist Subacute o Checklist to Determine Whether a Subacute/Subchronic/Chronic Study is 8(e) Reportable... 

Study is reportable based on criteria on Subacute/Subchronic/Chronic Study checklist. ... 

These so-called subacute or subchronic toxicity studies involve the repeated application of a test substance to animals, typically for a period of 30 or 90 days. The time pattern is thus an intermediate one between acute and chronic toxicity. To test a substance for subacute or subchronic toxicity, it is mainly applied by ingestion or inhalation. Not one out of the large number of organic pigments which have thus been tested has demonstrated any irreversible toxic effect. No toxic response was observed in rats which were fed either Pigment Yellow 1 or Pigment Yellow 57 1 for 30 days [22],... 

Vermeire et al. (1999) reviewed several studies comparing NOAELs from chronic and subacute/subchronic studies in order to evaluate the distribution of the extrapolation factor for duration of exposure. The ratios of observed NOAELs from oral studies using historical data for various compounds were calculated. The most likely distribution of the ratios was considered to be lognormal and the parameters of the distributions of the ratios were estimated, see Table 5.8. 

The authors noted that it may be expected that the NOAELs from subacute/subchronic smdies tend to be larger than NOAELs from chronic studies and it was considered that the GM ratios for the NOAELs assessed in the studies most likely overestimated the median of the distribution of the extrapolation factor for duration of exposure. The authors also noted that it is very likely that the databases used in these studies overlap each other significantly. It was also pointed out that the distributions presented in Table 5.8 were based on rather variable exposure periods for the subchronic NOAELs, included interspecies variation (no matching for species) for... 

KEMl (2003) suggested that, if necessary, extrapolation can be performed from subchronic to chronic exposure and that such an extrapolation should be based on the distribution of NOAEL ratios reported by Vermeire et al. (2001). If the 95th percentile is chosen, i.e., covering 95% of the substances compared, the corresponding assessment factor is 16. Extrapolation from subacute to chronic exposure should preferably not be performed, but if it is necessary a similar approach is suggested for this extrapolation, an assessment factor of 39 corresponds to the 95th percentile based on the lognormal distribution of NOAEL ratios from subacute and chronic exposure studies in Vermeire et al. (2001). 

Subacute, subchronic, and chronic studies have been conducted in experimental animals to test the toxicity of HFC-134a (Kennedy 1979 Riley et al. 1979 Silber and Kennedy 1979b Hext and Parr-Dobrzanski 1993 Hext 1989 Alexander and Libretto 1995 Collins et al. 1995). Those studies are summarized in Table A-4. 

It is common practice for toxicologists to differentiate exposure to chemicals based on the dose and the duration of exposure. Lour timeframes have been used to define duration of exposures acute, subacute, subchronic, and chronic. It is useful in light of today s interest in long-term, low-levef exposures to clarify these terms. Acute exposure is defined as exposure to a chemical for less than 24 h. Subacute exposure refers to an exposure of 1 month or less, subchronic for 1 to 3 months, and chronic for more than 3 months. These exposures can be by any route for most chemicals it is the oral route with the chemical given in the diet. However, the limited animal studies using nerve agents have usually employed parenteral administration... 

No review of subacute, subchronic, or chronic toxicity of chemical warfare nerve agents would be complete without discussion of the significant paper by Munro et al. that reviewed both animal and human studies of the nerve agents tabun (GA), sarin (GB), and VX. These studies included subacute, subchronic, and chronic toxicity studies in animals. Special attention was paid to the phenomenon of Organophosphorus-Induced Delayed Neuropathy (OPIDN). Reproductive toxicity and carcinogenicity tests were reviewed as well as in vitro studies of mutagenicity. Munro et al. s findings can be summarized as follows ... 

In the prediction of long-term "no effect" doses there are two important concepts to consider. One is that there are predictable dose relationships between acute, subchronic and chronic toxic effects. Acute toxicity tests refers to studies wherein single or repeated doses are studied 14 days or less. Subchronic (subacute) tests refers to studies wherein the doses are given five-seven days per week for 90 days, Subchronlc studies are also referred to as 13-week, three-month or short-term tests. 

Chronic toxicity tests determine the effects of either single or multiple exposures to medical devices, materials, and/or their extracts during a period of at least 10% of the life span of the test animal, for example, over 90 days in rats. Chronic toxicity tests may be considered an extension of subchronic (subacute) toxicity testing and both may be evaluated in an appropriate experimental protocol or study. 

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