Direct irritants

Ozone Reaction product of VOC and nitrogen oxides Not produced directly Irritant to eyes and respiratory system... 

Direct irritation of the mucosal lining by NSAIDs occurs because NSAIDs are weak acids. Topical irritation is therefore most pronounced with more acidic NSAIDs such as aspirin. While the direct irritant effects of NSAIDs play a contributory role in the development of NSAID-induced gastritis, this mechanism generally plays a minor role in the evolution of NSAID-induced PUD. 

A skin redness reported in experimental animals (rats, rabbits, cats and monkeys) after inhalation exposure to acrylonitrile may be due to a vasodilatory effect, rather than a direct irritant action (Ahmed and Patel 1981). Guinea pigs, which do not exhibit the cyanide-type effects of acrylonitrile poisoning (see Section 2.2.1.4), were observed to have nose and eye irritation from the acrylonitrile vapors (Dudley and Neal 1942). 

Workers exposed to acrylonitrile vapors at 16 to 100 ppm for 20 to 45 minutes complained of intolerable itching of the skin, but no dermatitis was observed (Wilson et al. 1948). This is presumably a direct irritant effect of acrylonitrile on the skin. 

Avoid foods that have a direct irritant effect on the esophageal mucosa (spicy foods, orange juice, tomato juice, and coffee). 

Rats exposed for 7 hours/day for 50 days to about 10 ppm showed no overt signs of toxicity and no deaths, although a few animals, when euthanized, had mild pulmonary inflammation and nonspecific cellular changes in the liver. Exposure to 5 and 12 ppm PGE 30 hours/week for 13 weeks caused hair loss in rats attributed to direct irritation of the skin rather than to systemic toxicity. ... 

Sulfuric acid is a direct irritant that results in adverse effects at the site of contact. The concentration of acid is the determinant of... 

In humans, four clinical syndromes (three of which are associated with immunologic reactions) are induced by inhalation of TMAN dust and furne. The first is a direct irritant syndrome characterized by cough and upper airway irritation related to the irritant properties of the anhydride at high-dose exposures. 

For the plant, another good way to stop consumption by an animal is to affect the animal s gastrointestinal system. This approach is used by a number of plants, but the mechanism of action varies. The first approach is direct irritation of the stomach lining to induce nausea and vomiting. The induction of mild vomiting is useful in some situations. The sacred bark of the California buckthorn produces cascara that is used to induce mild vomiting (a purgative). 

Because inhalation exposure is unlikely to be directly irritating to the gastrointestinal tract, it is probable that these effects are secondary to effects on the autonomic nervous system (Stewart and Witts 1944). 

To demonstrate the ability of HDI to be a direct irritant to the skin, HDI was applied to the non-oeeluded intaet skin of adult male albino guinea pigs either undiluted (100%) or in solutions of 0.05, 0.5, 5, or 25% in 1 1 aeetone-dioxane eontaining 13% guinea pig fat. HDI was demonstrated to produce severe-eiythema and edema when applied to the skin at concentrations of 5, 25, and 100%. Applieation of undiluted material resulted in frank skin necrosis. Moderate irritation to intaet skin was noted at the 0.5% HDI dose, while a 0.05% solution failed to produce any perceptible eutaneous irritation response (Haskell Laboratory 1961). 

HDI also induces an allergic contact dermatitis in guinea pigs (Haskell Laboratory 1961). Neither direct irritant or allergic contact dermatitis effects of HDI have been documented in humans. 

Acute, Intermediate and Chronic-Duration Exposures. Inhalation exposures in both humans and laboratory animals predominate in the available information on acute, intermediate, and chronic effects of HDl, and will be considered here as a group. Information on laboratory animals describes the direct irritant effects of HDl, which was usually inhaled in large doses (>4 ppm) however, no information on the allergic component of HDl toxicity at low doses, the type of dose most commonly encountered in humans, was provided. Information on acute inhalation exposure of humans may be misleading. In most cases of acute exposure, the workers had been exposed to HDl and HDl prepolymers in their workplace for several months or several years (doses often not available). These workers were then tested with a small dose of either HDl or a product containing HDl with the HDl prepolymers and other organics. 

Comparative Toxicokinetics. Little information is present on the comparative toxicokinetics of HDl, both between laboratory animal species and between humans and laboratory animals. As discussed earlier in this chapter, the majority of the laboratory animal studies have focused on the direct irritant effects of HDl after inhalation exposure (E.l. Dupont de Nemours 1978 Haskell Laboratory 1961 Karol... 

Stimulant laxatives Bisacodyl, 5-15 mg daily. Senna, dosage varies, consult product labeling Correctol, Dulcolax, Ex-Lax, Senokot, various generic Stimulant laxative actions include direct irritation of intestinal mucosa or stimulation of the myenteric plexus, resulting in peristalsis. These agents may also cause alteration of fluid and electrolyte absorption, resulting in luminal fluid accumulation and bowel evacuation. 

Dermal/Ocular Effects. Because BCME is highly reactive, it is directly irritating to skin and other epithelial tissues. Chronic (lifetime) application of BCME (1 mg/dose) to the skin of mice produced a strong corrosive response, including hair loss, hemorrhagic rash and edema of subcutaneous tissue (Van Duuren et al. 1968). In rabbits, a single application of undiluted BCME lead to moderate erythema and marked necrosis, and a primary dermal irritation score of 6 was assigned (Union Carbide 1968). A dose of 5 / L (7 mg) applied to the eye of rabbits produced severe corneal necrosis (Union Carbide 1968). 

Nicolazzo et al. [52] considered the use of the lipophilic skin penetration enhancers, octisalate and padimate (both used in sunscreens), in comparison to Azone on the buccal absorption of various drugs in vitro. They were found to have limited effect in enhancing the permeation of triamcinolone acetonide (although some increase in tissue uptake was proposed in some cases) relative to Azone, while reducing the penetration of estradiol and caffeine. One interesting report is that of the effect of capsaicin from capsicum, a commonly used food ingredient, which has been reported to enhance the permeability of sulfathiazole in human volunteers [53] presumably by a direct irritation effect on the mucosa. This raised an interesting issue of the effect of diet on oral mucosal permeability. 

Stimulant Laxatives. The precise mechanism of stimulant laxatives is not known. They may activate peristalsis by a direct irritant effect on the intestinal mucosa or by stimulating the nerve plexus within the... 

No information was located regarding the mechanism by which tetryl enters the blood stream from the lungs, skin, or gastrointestinal tract, the mechanism by which tetryl is transported in the blood stream, or the mechanism of toxicity for tetryl. Earlier studies suggested that the cause of tetryl-induced dermatitis, which is the most common and widely studied adverse effect, may be both physical (direct irritation by sharp tetryl crystals) and chemical (by reacting with components of the skin) (Ruxton 1917). The chemical hypothesis was later advanced by others as well (Bain and Thompson 1954 Brownlie and Cumming 1946). Bain and Thompson (1954) specifically suggested that histamine release may result from a tetryl-induced sensitization reaction or from direct tetryl-induced release from mast cells. 

DNOC is generally not irritating to the eyes of animals. DNOC did not cause any signs of ocular irritation <24 hours after 5 drops of 0.9% DNOC as the sodium salt was instilled into the conjunctival sac of 6 rabbits (Ambrose 1942). Blepharospasm and excessive lacrimation were observed in cats exposed to 36 or 60 mg/m DNOC dust for 4 hours (Burkatskaya 1965a). Since these effects were not reported in the cats similarly exposed to a mist of DNOC in solution, they were probably due to a direct irritating effect of the dust particles on the eyes, rather than to DNOC. 

Direct irritation may thus be dehned as an adverse effect of chemicals directly applied to the skin that does not involve prior sensitization and thus initiation by an immune mechanism. Irritation is usually assessed by a local inflammatory response characterized by erythema (redness) and/or edema (swelling). Other responses may be present that do not elicit inflammation such as an increase in skin thickness. Irritant reactions may be classified as acute, cumulative, traumatic, or pustular. However, two classifications are generally used by toxicologists. Acute irritation is a local response of the skin usually caused by a single agent that induces a reversible inflammatory response. Cumulative irritation occurs after repeated exposures to the same compound and is the most common type of irritant dermatitis. 

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