Inhalation toxicity tests, acute

A Guidance Document on Acute Inhalation Toxicity Testing is being developed and presently exists as a draft (OECD 2004b). The document recommends the Acute Toxic Class (ATC) Method with a group size of three animals per sex, if the objective of the test is solely related to hazard classification. Limits for particle-size distribution of aerosolized test substances are suggested. The preferred mode of exposure is the nose-only, head-only, or head/nose-only exposure technique, because this mode of exposure minimizes exposure or uptake by noninhalation routes. 

OECD. 2004h. Draft guidance document on acute inhalation toxicity testing. OECD Series on Testing and Assessment No. 39B. Environment Directorate, Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology. December 8, 2004 (1st version). Paris OECD. 

Determination of LC50 value provides an estimate of a chemical s relative toxicity by inhalation. Extrapolation of the LC50 values and the results of acute toxicity studies from animals to humans is valid only to limited degrees. The results of acute inhalation toxicity tests may be summarized in tabular form. They should include all important aspects of the test, as in the case of acute oral toxicity studies. 

Acute inhalation exposure of rats to 200,000 ppm VF for 30 minutes or more produced weak anaesthesia and no deaths (90). In rats VF is only slightly metabolized at a rate of one-fifth that of vinyl chloride (91—95). An extensive program of toxicity testing of vinyl fluoride is ia progress (96,97). 

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. 

No animal or human data were available for inhalation exposure. There are no data regarding effects in humans after oral exposure. Information is available in animals regarding health effects following acute, intermediate, and chronic oral ingestion of diisopropyl methylphosphonate. The animal data obtained after oral exposure indicate that diisopropyl methylphosphonate is moderately toxic after acute bolus exposure but has a lower order of toxicity after intermediate and chronic exposures in food. No data were found on the toxicity of diisopropyl methylphosphonate after exposure in drinking water. Further, diisopropyl methylphosphonate is rapidly metabolized and excreted and does not accumulate. It does not appear to have reproductive or developmental effects. At the doses tested, it does not appear to be an acetylcholinesterase inhibitor, although this issue has not been resolved yet. Limited data are available for dermal exposure in humans and animals. Diisopropyl methylphosphonate does not appear to be a... 

Levin, B.C. Fowell, A.J. Birky, M.M. Paabo, M. Stolte, A. Malek, D. Further Development of a Test Method for the Assessment of the Acute Inhalation Toxicity of Combustion Products, NBSIR 82-2532. National Institute of Standards and Technology, Gaithersburg, MD, 1982. 

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. 

Toxicity indicators, 23 112-114 Toxicity inhalation tests, 10 660 Toxicity studies acute, 25 217 chronic, 25 218 short-term repeated, 25 217 subchronic, 25 217-218 Toxicity units (TU), 25 887 Toxic materials, 21 833-836... 

Acute inhalation toxicity To determine the potential acute toxicity-lethality following a single 4-h inhalation exposure to a test atmosphere containing the new pharmaceutical excipient (aerosol, vapor or particles)... 

Testing on animals may provide initial information on the effect of a possible shortterm exposure on human health. Acute toxicity is defined as the toxic effect of a substance after a single oral, dermal, or inhalative application. For acute oral toxicity, for instance, LD50 is defined as the amount of substance expressed in mg per kg body weight which has a lethal effect on 50% of the test animals after a single oral application. Such tests are useful in that they assess the toxicity of a material relative to that of other known compounds. 

Acute Inhalation Toxicity - Acute Toxic Class (ATC) Method, Draft New Guideline (December 2004) 487 In Vitro Micronucleus Test, Draft New Guideline (June 2004)... 

Acute inhalation toxicity is the total of adverse effects caused by a substance following a single, uninterrupted exposure by inhalation over a short period of time to an airborne substance. Eor testing, a fixed duration of exposure of 4h is generally recommended in the OECD TG 403. 

Several experimental studies have described the respiratory effects of HDI after acute inhalation exposures in laboratory animals. The acute inhalation toxicity of the aerosols of HDI and various prepolymer products were tested on male and female Wistar rats exposed to 105, 143, 259, 341, 383, 443, 575, 589, or 719 mg HDI/m (15.3, 20.7, 37.6, 49.4, 55.5, 64.2, 83.4, 85.4, 104.3 ppm) in inhalation chambers for 4 hours. All HDI-exposed rats exhibited signs of labored breathing at all exposure concentrations. Lung edema and pneumonia were observed upon necropsy (Kimmerle 1976). 

LCS0 Concentration of an active ingredient in the air which, when inhaled, kills half of the test animals exposed to it expression of a compound s toxicity when present in the air as a gas, vapor, dust, or mist generally expressed in ppm when a gas or vapor, and in micrograms per liter when a dust or mist often used as the measure of acute inhalation toxicity. The lower the LC50 number value the more poisonous die pesticide. 

A comparison of some of the above-mentioned preliminary prescreening results with those of a regular 4-hour test of acute inhalation toxicity (see Section 5.1.2.1.) demonstrates the reliability of this inexpensive and rapid method for orientation purposes in most cases (Table 18). 

IBT. 1972a. Acute dust inhalation toxicity study with biomet (tri-n-butyltin fluoride) in albino rats. Report to M and T Chemicals, Inc., Rahway, NJ, by Industrial Bio-Test Laboratories, Inc.,... 

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