Tests subacute

Subacute or subchronic toxicity Three doses, two species. 2 weeks to 3 months of testing may be necessary before clinical trial. The longer the duration of expected clinical use, the longer the subacute test. Determine biochemical, physiologic effects. 

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. 

Subacute tests require the feeding of a range of doses below the LD50 to at least two species for 2-3 months. A threshold or no observable effect level (NOEL) is determined from the highest dose that produces no harm in the most sensitive species. 

Neilson, A.H., A.S. Allard, S. Fischer, M. Malmberg and T. Viktor. Incorporation of a subacute test with zebra fish into a hierarchical system for evaluating the effect of toxicants in the aquatic environment. 

Stage 1 Acute tests using for example, algae, crustaceans, and fish Stage 2 Subacute tests including, for example ... 

In a 90-day subacute test the no-effect level of the active substance for rats and dogs was 660 ppm. 

Benazolin is a slightly toxic compound. Its acute oral ld,q for mice, rats and dogs is 1000-3000 mg/kg. Subacute tests on rats showed that the no-effect level lies between 300 and 1000 mg/kg/day. The same value was found in chronic toxicity tests. Its aqueous solution is a slight irritant to the mucous membranes and the skin. 

Fig. 10.1 Concentration of organic fluorine in rat blood as a function of the dose in a 10-dose oral subacute test. ( ) 4-h recovery (O) 14-day recovery. (From Ref. 12.)...

PVDE is a nontoxic resin and may be safely used in articles intended for repeated contact with food (190). Based on studies under controked conditions, including acute oral, systemic, subchronic, and subacute contact implantation and tissue culture tests, no adverse toxicological or biological response has been found in test animals (191,192). PVDE is acceptable for use in processing and storage areas in contact with meat or poultry products prepared under federal inspection and it complies with the 3-A sanitary standards for dairy equipment. 

All the PMBs are Hsted on the U.S. EPA s Toxic Substances Control Act NonConfidential Chemical Substances Inventory (Table 8). In the early to mid-1980s, pseudocumene, mesitylene, hemimellitene, and trimethylbenzene were coveted by TSCA Section 8(a) Preliminary Assessment Information Rule (PAIR) reporting requirements (22) and by TSCA Section 8(d) for health and safety data (23). Mesitylene is the subject of a test rule subacute oral toxicity and subchtonic oral toxicity in tats were underway in 1994 (24). The Safe Drinking Water Act (SDWA) allows monitoring for pseudocumene and mesitylene at the discretion of the State (25). Of the PMBs, only pseudocumene is subject to SARA Tide III section 313 annual release reporting (26). 

The health effects of sorbic acid and sorbates have been reviewed (165—167). The extremely low toxicity of sorbic acid enhances its desirabiHty as a food preservative. The oral LD q for sorbic acid in rats is 7—10 g/kg body weight compared to 5 g/kg for sodium chloride (165—169). In subacute and chronic toxicity tests in rats, 5% sorbic acid in the diet results in no abnormal effects after 90 days or lifetime feeding studies. A level of 10% in rat diets results in a slight enlargement of the Hver, kidneys, and thyroid gland (170). This same dietary level fed to mice also resulted in an increase in Hver and kidney weight... 

Short-term repeated exposures involve consecutive daily exposures to the test chemical which are continued over a period of a few days to a few weeks but usually not more than 5% of the lifespan of the animal. These test conditions are sometimes referred to as subacute, but this is a misleading term which should be avoided in order to prevent confusion between single and repetitive exposure toxicity. 

Physicochemical properties requked include melting/boiling point, vapor pressure, solubiUty, and flammabiUty/explosion characteristics. The toxicological studies include acute toxicity tests, oral, inhalation, and dermal skin and eye kritation skin sensiti2ation subacute toxicity, oral, inhalation, and dermal and mutagenicity tests. In vitro reverse mutation assay (Ames test) on Salmonella typhimurium and/or E.scherichia coli and mammalian cytogenic test. In vivo mouse micronucleus test. 

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). 

Subacute and chronic toxicity of alcohol and alcohol ether sulfates has been extensively tested in several animals and sometimes humans. The duration of the tests was in some cases as long as 2 years. When administered below the toxic amount no specific damages were observed in any of the species tested [333]. No severe side effects were observed in the study by Swisher, carried out with volunteers who ingested considerable amounts of anionic and nonionic surfactants over long periods [348]. Similarly, the effects produced by the intake of daily doses of 1 g of alcohol sulfate per person over 8 weeks [349],... 

For disodium undecyleneamido MEA-sulfosuccinate (DUMS) a test report [97] indicates that the subacute toxicity, measured as 30% of LD50 during 5 days, allowed all test animals to survive. 

Ecotoxicological Prolonged fish toxicity (including reproduction) Avian acute/subacute toxicity Accumulation, degradation and mobility tests... 

In toxicity studies, acute toxicity tests are usually carried out in the rat, mouse, cat, and dog. Subacute toxicity studies for IM products are performed by giving SC injections to rats and IM injections to dogs. In IV studies the rat tail vein or a front leg is used. Deliberate overdosing usually washes out metabolism differences between species. In dogs it is common to give an IV dose five times that intended for humans. In rats this is increased to 10 times. 

Major organ function tests Acute and subacute toxicity studies... 

Toxicological properties Acute toxicity (by two routes of admission) Skin irritation Eye irritation Skin sensitization 28 days subacute toxicity Ames test In vitro metaphase analysis (or mouse micronucleus test)... 

Hill, E.F. and M.B. Camardese. 1982. Subacute toxicity testing with young birds response in relation to age and intertest variability of LC50 estimates. Pages 41-65 in D.W. Lamb, and E.E. Kenaga (eds.). Avian and Mammalian Wildlife Toxicology Second Conference. Am. Soc. Testing Mater. ASTM STP 757. 

In subacute thyroiditis, thyroid function tests typically run a triphasic course in this self-limited disease. Initially, serum T4 levels are elevated due to release of preformed thyroid hormone from disrupted follicles. The 24-hour RAIU during this time is less than 2% because of thyroid inflammation and TSH suppression by the elevated T4 level. As the disease progresses, intrathyroidal hormone stores are depleted, and the patient may become mildly hypothyroid with an appropriately elevated TSH level. During the recovery phase, thyroid hormone stores are replenished and serum TSH elevation gradually returns to normal. 

AALAC certified laboratory. In-housing testing included acute, subacute, and subchronic oral, dermal and inhalation studies and specialty reproductive, behavioural, haematological and renal function toxicity studies. Preparation of risk assessment, submissions and presentations to regulatory agencies and trade association. 

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],... 

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