Instillation studies

Warheit, D.B., Brock, W.J., Lee, K.P., Webb, T.R., and Reed, K.L. (2005) Comparative pulmonary toxicity inhalation and instillation studies with different Ti02 particle formulations impact of surface treatments on partide toxicity. Toxicological Sciences, 88 (2), 514-524. 

Acetaldehyde was tested for carcinogenicity in rats by inhalation exposure and in hamsters by inhalation exposure and intratracheal instillation. Following inhalation exposure, an increased incidence of carcinomas was induced in the nasal mucosa of rats, and laryngeal carcinomas were induced in hamsters. In another inhalation study in hamsters, using a lower exposure level, and in an intratracheal instillation study, no increased incidence of tumours was observed. In hamsters, inhalation of acetaldehyde enhanced the incidence of respiratory-tract tumours produced by intratracheal instillation of benzo a -pyrene (lARC, 1985). 

Ketkar M, Resnick G, Scheider P, et al. 1978. Investigations on the carcinogenic burden by air pollution in man Intratracheal instillation studies with benzo[a]pyrene in bovine serum albumin. Cancer Lett 4 235-239. 

Warheit, D. B., Webb, T. R., Sayes, C. M., Colvin, V. L., and Reed, K. L. (2006). Pulmonary instillation studies with nanoscale Ti02 rods and dots in rats Toxicity is not dependent upon particle size and surface area. Toxicol Sci 91, 227-236. 

Intratracheal instillation studies in rabbits indicate that single high doses of manganese (158 mg/kg, as Mn02) can cause severe degenerative changes in the seminiferous tubules and lead to sterility (Chandra et al. 1973 Seth et al. 1973). This effect did not occur immediately but developed slowly over the course of... 

Available information from human exposures indicates that airborne americium-containing particles are deposited in the respiratory tract, cleared to some extent via mucociliary action, and swallowed or expelled (Edvardsson and Lindgren 1976 Fry 1976 Newton et al. 1983 Sanders 1974 Toohey and Essling 1980). Descriptions of human respiratory tract models that can be used for radiation protection also include relevant information regarding biokinetics of inhaled particles (ICRP 1994b, 1995 NCRP 1997). Quantitative data are not available, however. Supporting animal studies include inhalation exposure to aerosols of americium (Buldakov et al. 1972 DOE 1978 Gillett et al. 1985 Sanders and Mahaffey 1983 Talbot et al. 1989 Thomas et al. 1972) or intratracheal instillation of americium compounds (Moushatova et al. 1996). 

In summary, intratracheal instillation of CNTs has shown that their potential in eliciting adverse pulmonary effects is influenced by exposure time, CNT dose, CNT biopersistence, surface defects, and metal contamination [71, 72]. Despite the use of surfactants, all studies showed that intratracheal instillation caused major difficulties due to the agglomerative nature of CNTs in a biological environment. More realistic exposure methods, namely inhalation rather than intratracheal administration, are therefore needed for determining the pulmonary toxicity [59, 65, 73]. Several investigations have been performed by using administration different from intra-... 

Li, J.G. et al. (2007) Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs ofmice by intratracheal instillation andinhalation. Environmental Toxicology, 22 (4), 415-421. 

In critical evaluation of the effect of a gas, vapor, or aerosol inhaled in to the respiratory tract of an animal, the dosimetric method has been recommended (Oberst, 1961). However, due to the complexity of measuring the various parameters simultaneously, only a few studies on gaseous drugs or chemicals have employed the dosimetric method (Weston and Karel, 1946 Adams et al., 1952 Leong and MacFarland, 1965 Landy et al., 1983 Stott and McKenna, 1984 Dallas et al., 1986, 1989). For studies on liquid or powdery aerosols, modified techniques such as intratracheal instillation (Brain et al., 1976) or endotracheal nebulization (Leong et al., 1988) were used to deliver an exact dose of the test material into the lower respiratory tract (LRT) while bypassing the URT and ignoring the ventilatory parameters. 

The design of vaginal, rectal, and nasal irritation studies is less formalized, but follows the same basic pattern as the primary dermal irritation test. The rabbit is the preferred species for vaginal and rectal irritation studies, but the monkey and dog have also been used for these (Eckstein et al., 1969). Both the rabbit and rat have commonly seen use for nasal irritation evaluations. Defined quantities (typically 1.0 ml) of test solutions or suspensions are instilled into the orifice in question. For the vagina or rectum inert bungs are usually installed immediately thereafter to continue exposure for a defined period of time (usually the same period of hours as future human exposure). The orifice is then flushed clean, and 24 h after exposure it is examined and evaluated (graded) for irritation using the scale in Table 11.1. 

Leopold and Comroe2 studied the use of 0 05, 01 and 0-2 per cent D.F.P. in arachis oil in glaucoma, and found that cases unrelieved by eserine responded readily to 01 per cent D.F.P. instilled into the conjunctival sac. However, the action of D.F.P. in the glaucomatous eye lasts for about 12 hr. compared to an action of about 12 days in the normal eye. The short-lived action of D.F.P. in cases of raised intra-ocular tension lends evidence to the suggestion that there may be an upset of the acetylcholine-cholinesterase mechanism in glaucoma. There are certain side effects such as ciliary spasm and headache which may prove troublesome during treatment. 

Li JG, Li WX, Xu JY, Cai XQ, Liu RL, Li YJ, Zhao QF, Li QN (2007a) Comparative study of pathological lesions induced by multiwalled carbon nanotabes in lungs of mice by intratracheal instillation and inhalation. Environ Toxicol 22 415—421. 

Liquid instillation and nebulised aerosols are the most common methods for pulmonary administration to experimental animals [22, 54, 109, 134], The use of pressurised metered dose inhaler (pMDIs) and dry powder inhaler (DPIs) in preclinical studies is limited by the need for formulation development, which often cannot be performed in early drug discovery due to short supply of test materials. A number of alternative techniques for intra-tracheal administration of coarse sprays and powder formulations have been described [9, 15, 21, 36, 71, 80, 99, 138],... 

A variety of automatic voltage clamp devices with special modifications have been extensively utilized in electrophysiological studies of /sc in several ocular tissues including the amphibian corneal epithelium [42] and human fetal retinal pigment epithelium [43, 44], as well as non-ocular tissues like the rat tracheal epithelium [45], A strong temperature dependency and inhibitory effect of serosally instilled ouabain on the rabbit conjunctival /sc are characteristic of active ion transport driven by Na+/K+-ATPases in the conjunctiva [6, 7],... 

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