Infiltration Irritant

Pulmonary edema with some mucosal irritation (greater water solubility of agent is equal to greater mucosal irritation) leading to ARDS or non-cardiogenic pulmonary edema. Pulmonary infiltrate. 

In some patients believed to suffer from the irritable bowel syndrome, an underlying enteric neuromuscular disorder has later been identified [133]. The bridge to infectious diseases is also of interest, with several entero-tropic viruses in focus, and reports of lymphocytic infiltration of enteric neural structures in patients with unexplained intestinal dysmotility require further studies. 

A number of studies of the toxicity of zinc oxide/hexachloroethane smoke have been conducted (Brown et al. 1990 Karlsson et al. 1986 Marrs et al. 1983). These studies demonstrate that smoke exposure results in pulmonary inflammation and irritation. When male Porton Wistar rats were exposed to hexachloroethane/zinc oxide smoke for 60 minutes, the lungs showed pulmonary edema, alveolitis, and areas of macrophage infiltration 3 days later. At 14 days, there was interstitial fibrosis and macrophage infiltration. At 28 days, increased fibrosis and macrophage infiltration were noted. However, these same symptoms occurred when the animals inhaled zinc chloride there was no apparent synergism between the zinc chloride and residual hexachloroethane (Brown et al. 1990 Richard et al. 1989). This is consistent with the fact that smoke contains little hexachloroethane and the observation that acute exposure to 260 ppm hexachloroethane had no effects on the lungs of rats (Weeks et al. 1979). 

Clinically unaffected skin in atopic dermatitis differs from normal skin the underlying barrier defect associated in more than 30% with filaggrin loss of function mutations first published in 2006 [4] leads to dry skin associated with a greater irritant skin response than in normal healthy skin. Microscopic studies revealed a sparse perivascular T cell infiltrate in unaffected atopic dermatitis skin that is not seen in normal healthy skin. 

Respiratory Effects. Pleural effusions and alveolar infiltrations were noted in a man who had washed his hair with an unknown amount of diesel fuel (Barrientos et al. 1977). The relative contributions from inhalation and dermal exposure could not be distinguished in this case. There was no throat irritation in six volunteers following a 15-minute exposure to a concentration reported to be 140 mg/m of deodorized kerosene vapor (Carpenter et al. 1976). The authors used a hot nichrome wire for the volatilization of their test material and reported that the concentration was probably the "highest attainable concentration at which vapor analysis is representative of liquid analysis." The air saturating concentration of kerosene is considered to approximate 100 mg/m (room temperature and 760 mmHg) and is dependent on the constituents of the mixture. 

Examination of 13 individuals 5 years after they were occupationally exposed to a chlorine dioxide leak revealed sensitivity to respiratory irritants and nasal abnormalities. Delayed deaths occurred in animals after exposure to 15 0-2 00 ppm for less than 1 hour. Rats exposed daily to 10 ppm died after 10-13 days of exposure effects were nasal and ocular discharge and dyspnea autopsy revealed purulent bronchitis. Another study reported that two to four 15-minute exposures to 5 ppm for 1 month did not alter the blood composition or lung histology of rats similar exposures to 10-15 ppm caused bronchitis, bronchiolitis, catarrhal alveolar lesions, and peribronchial infiltration. Lesions healed within 15 days after treatment. Rats and rabbits exposed for 30 days to 5 or 10 ppm (2 hours/day) had localized bronchopneumonia with elevated leukocyte counts slight reversible pulmonary lesions were found after exposures of 2.5ppm for 4-7 hours/day. No adverse reactions were... 

Rabbits died from exposure to 5000 ppm for 3 hours, but 10,000 ppm for 1 hour was not lethal. Effects were conjunctival irritation, lacrimation, slow respiration with some rales, incoordination, ataxia, and weakness. Autopsy of animals exposed to lethal concentrations revealed severe fatty infiltration of the liver and moderate kidney damage. ... 

Extravascular infiltration If local irritation and inflammation caused by extravascular infiltration of the infusion occurs, discontinue the infusion and restart at another site. Benzyl alcohol Benzyl alcohol, contained in some of these products as a preservative, has been associated with a fatal gasping syndrome in premature infants. 

Although most patch testing is done with nickel sulfate because it is less irritating than nickel chloride, exposure of the skin to nickel alloys results in the release of nickel chloride from the influence of human sweat. Therefore, nickel chloride is the more relevant form of nickel for examining threshold concentrations (Menne 1994). Menne and Calvin (1993) examined skin reactions to various concentrations of nickel chloride in 51 sensitive and 16 nonsensitive individuals. Although inflammatory reactions in the sweat ducts and hair follicles were observed at 0.01% and lower, positive reactions to nickel were not observed. To be scored as a positive reaction, the test area had to have both redness and infiltration, while the appearance of vesicles and/or a bullous reaction were scored as a more severe reaction. At 0.1%, 4/51 and 1/51 tested positive with and without 4% sodium lauryl sulfate. Menne et al. (1987) examined the reactivity to different nickel alloys in 173 nickel-sensitive individuals. With one exception (Inconel 600), alloys that released nickel into synthetic sweat at a rate of <0.5 pg/cmVweek showed weak reactivity, while alloys that released nickel at a rate of >1 pg/cm /week produced strong reactions. 

Retinotoxic effects associated with iontophoresis have been evaluated by slit lamp microscopy, indirect ophthalmoscopy, light and electron microscopy. Commonly reported toxic effects include slight retinal and choroidal bums and retinal pigment epithelial and choroidal necrosis, comeal epithelial edema, persistent corneal opacities and polymorphonuclear cell infiltration. Disadvantages of iontophoresis include side-effects such as itching, erythema and general irritation. Although the technique is found to be suitable for a... 

Dermal/Ocular Effects. Schonning (1966) described a case of a 57- year-old man who accidentally spilled acrolein over his genital area. Swelling of the penis and scrotum occurred, and after 15 days the genital area was deeply ulcerated and gangrenous. No follow-up information was provided. Lacroix et al. (1976) applied a solution of 10% acrolein in ethanol to 12 volunteers the skin was biopsied 48 hours later. All subjects exhibited irritation and had papillary edema, and 11 had polymorphonuclear infiltrates. In addition, five cases of epidermal necrosis occurred. No further information was provided. 

Various tissue constructs have been reassembled from isolated constituents, including resident cell types whose numbers have been amplified or modified in culture. A three-dimensional co-culture system for human skin keratinocytes layered upon a synthetic mesh infiltrated with dermal fibroblasts, when floated to allow contact of the uppermost keratinocytes with air, exhibits stratification and cornification remarkably similar to in vivo squamous epithelia. This reconstructed epithelial model has been recommended as an in vitro replacement for dermal corrosivity testing. It has been anticipated that this and a similar noncomified model will have application in dermal and ocular irritation testing, but thus far validation studies have yielded mixed results. Reconstructed tissues can also provide context for basic toxicological research on aberrant cellular interactions with cellular and acellular constituents, as illustrated by invasion of cancerous epithelial cells into underlying dermis of a skin equivalent model. 

All subjects exhibited dyspnea, cough, bronchospasm. Other effects included irritation of the eyes and throat, headache, abdominal pain, vomiting, giddiness. 5 subjects had cyanosis, X rays showed cases of patchy infiltrates, hilar congestion. Pulmonary function was affected in most subjects bronchoscopy revealed tracheobronchial mucosal irritation. Some subjects had hemorrhagic spots, erosions, ulcers. In a follow-up of 16 patients for 1 yr, 4 reported... 

Rate of drug absorption controlled by infusion pump May use drugs with poor lipid solubility and/or irritating drugs Tissue damage at site of injection (infiltration, necrosis, or sterile abscess)... 

Transient vestibular irritation without hearing loss after infiltration of the auditory canal has been incidentally attributed to diffusion of the local anesthetic from the site of injection (342). 

Nasal formulations containing benzalkonium chloride and disodium edetate, both known to be local irritants, were shown to produce an inflammatory reaction, and microscopic examination showed an extended infiltration of the mucosa by eosinophils, and pronounced atrophy and disorganization of the epithelium, although these effects were subsequently shown to be reversible. ... 

In acute irritation tests in rabbits, diesel fuel was only mildly irritating to the eyes but severely irritating to the skin. Male and female mice dosed dermally with 2000-40 000 mg kg of marine diesel fuel for 14 consecutive days demonstrated skin lesions and acanthosis, parakeratosis, hyperkeratosis, and inflammatory infiltrates of the dermis. Mice receiving > 20 000 mg kg displayed 100% mortality. 

Effects from oral exposure to the soluble lanthanides include eosinophil infiltration of the submucosa, hyperkerotosis of the stomach, and gastric hemorrhages. As with the irritation that occurs after skin or eye exposure, the hyperkerotosis and gastric hemorrhages seen in the stomach appears to be the result of the acidic environment produced by the anion. 

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