Inhalation toxicity testing

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

B.29 Sub-Chronic Inhalation Toxicity Test 90-Day Repeated Inhalation Dose Study Using Rodent Species (1988) B.30 Chronic Toxicity Test (1988)... 

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. 

B.26 Sub-chronic oral toxicity test. Repeated dose 90-day toxicity study in rodents B.27 Sub-chronic oral toxicity test Repeated dose 90-day toxicity study in non-rodents B.28 Sub-chronic dermal toxicity test 90-Day repeated dermal dose study using rodent species B.29 Sub-chronic inhalation toxicity test 90-Day repeated inhalation dose study using rodent species B.30 Chronic toxicity test... 

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 Draft guidance document on acute inhalation toxicity testing.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. 

Tansy MF, Werley M, Landin W Subacute inhalation toxicity testing with iodoform vapor. Toxicol Environ Health 8 59-70, 1981... 

There are no studies showing that n-pentane alone, without hexane, affects the peripheral nervous system. When tested in a 90-day inhalation toxicity test at levels up to 7000 ppm -pentane did not influence mortality or weight loss, nor did it produce any microscopic effects suggestive of target organ toxicity. ... 

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. 

The results of the subchronic inhalation toxicity study may be summarized in tabular form. These results may be based on the same lines as subchronic oral toxicity test in addition to experimental conditions used for the inhalation toxicity test. 

Because findings from several studies indicate the potential for adverse health effects from exposure to JP-8 aerosols at concentrations below the interim PEL of 350 mg/m3 and because the JP-8 vapor concentrations tested were approximately 1,000 mg/m3 (that is, less than three times the interim PEL), the subcommittee strongly recommends that a battery of inhalation-toxicity tests in experimental animals be conducted with JP-8 vapors and mixtures of vapors and aerosols. The animal studies should include evalua-... 

One of the two nanoparticles that was the subject of the November 2008 SNUR is a siloxane modified silica nanoparticle, and the other is a siloxane modified alumina nanoparticle. EPA explained in the SNUR that it was concerned about dermal and inhalation exposures for new uses that were not described in the PMNs filed for those substances. It suggested that a ninety-day inhalation toxicity test would help characterize the human health effects for each substance. The SNURs for these two substances say that it would be a significant new use to use either substance without specified personal protective equipment, for any use other than the uses specified in the PMNs for those substances, and to manufacture, process or use them in powder form. The preamble to the SNUR says that the PMNs do not claim confidentiality for use of these substances as additives, but the PMN for one of these substance clearly limits the kind of additive for which it was intended, but everything except the word additive is claimed as confidential. Therefore, any other entity that intends to manufacture, import, or process any nanoparticles described by the generic names for these substances should submit a bona fide letter to determine their exact chemical compositions and the specifics of what uses are significant new uses. 

Toxicological studies revealed that gellan is relatively nontoxic to animals when administered as a single large dose (LD = 5000 mg/kg) in the diet (Table 1.3), while an inhalation toxicity test formd it caused no deaths in a group of 10 animals [6]. An eye irritation test described in the above study confirmed the safety of gellan in the case of contact with eyes. Gellan formulations received their first approval for food applications in Japan in 1988. It is now acceptable for food, non-food, cosmetic and pharmaceutical use in the United States, Canada, Australia, Latin America, South America, Asia, and in the European Union [12]. 

---