Irritancy definitions

Toxicology. The acute oral and dermal toxicity of naphthalene is low with LD q values for rats from 1780—2500 mg/kg orally (41) and greater than 2000 mg/kg dermally. The inhalation of naphthalene vapors may cause headache, nausea, confusion, and profuse perspiration, and if exposure is severe, vomiting, optic neuritis, and hematuria may occur (28). Chronic exposure studies conducted by the NTP ia mice for two years showed that naphthalene caused irritation to the nasal passages, but no other overt toxicity was noted. Rabbits that received 1—2 g/d of naphthalene either orally or hypodermically developed changes ia the lens of the eye after a few days, foUowed by definite opacity of the lens after several days (41). Rare cases of such corneal epithelium damage ia humans have been reported (28). Naphthalene can be irritating to the skin, and hypersensitivity does occur. 

TABLE 21 Skin Irritation Scores and Verbal Definitions... 

Early diagnosis of skin cancer is the key to improved prognosis. Diagnostic accuracy and clinical skills are two essential factors in the appropriate management of skin cancer. On presentation to a clinician s office, patients may offer a history of a new growth or an area of irritation. Conversely, the skin cancer may have been present for years undetected by the patient. The definitive diagnosis of any suspected cutaneous malignancy should be confirmed by a biopsy prior to treatment. 

FMC. 1991b. Durad 125. Non-definite primary skin irritation study in rabbits. FMC Corporation, Princeton, NJ. 

Data on acute exposures of humans to both isomers of dimethylhydrazine are limited to case reports of accidental exposures. Signs and symptoms of exposure include respiratory irritation, pulmonary edema, nausea, vomiting, and neurologic effects. However, definitive exposure data (concentration and duration) were unavailable for these accidents. The limited data in humans suggest that the nonlethal toxic response to acute inhalation of dimethylhydrazine is qualitatively similar to that observed in animals. No information was available regarding lethal responses in humans. In the absence of quantitative data in humans, the use of animal data is considered a credible approach for developing AEGL values. 

In general, no matter what the route, certain characteristics will predispose a material to have local effects (and, by definition, if not present, tend to limit the possibility of local effects). These factors include pH, redox potential, high molar concentration, and the low flexibility and sharp edges of certain solids. These characteristics will increase the potential for irritation by any route and, subsequent... 

The correlation (or lack of correlation) of other physiochemical characteristics has not yet been established. For instance, are all surfactants irritants Can one classify severity by the size of the molecule Can octanol water partition coefficients predict irritation potential does a propensity to partition out of the ocular fluid mean that a compound presents more of an irritation hazard than one which is more water soluble Theoretically, these data should reflect the ability of a compound to penetrate the eye and cause an irreversible lesion. However, until definitive data are available, physical and chemical parameters will probably have limited utility in an overall assessment of irritation. 

To summarize the utility of nonexperimental methods, it is obvious that the more available information there is about a compound, the more likely one will be able to substantially reduce the amount of testing involved in prediction of ocular irritation potential. However, at this point in time, none of the individual methods, alone or in combination, are sufficiently predictive to provide a definitive assessment of in vivo ocular irritation. There is definitely a place, however, for consideration of the above factors in a battery of tests, as well as for prioritizing compounds to be tested further. 

All studies - - - - reported an association between symptoms and changes in lung function. In general, people who noticed cough and substantial tightness first were the ones who developed the greatest defect in function. Ozone-induced defects in function were not usually found in the absence of definite symptoms of ozone-induced respiratory irritation. 

These two definitions reflect two sides of the same situation. In this book, the term critical effect(s) will be used for the hazard/effect considered as being the essential one(s) for the purpose of the risk characterization, e.g., for the establishment of a health-based guidance value, permissible exposure level, or Reference Dose. It should be noted that the critical effect could be a local as well as a systemic effect. It should also be recognized that the critical effect for the establishment of a tolerable exposure level is not necessarily the most severe effect of the chemical substance. For example, although a substance may cause a serious effect such as liver necrosis, the critical effect for the establishment of, e.g., an occupational exposure limit could be a less serious effect such as respiratory tract irritation, because the irritation occurs at a lower exposure level. 

A general definition of the term acute toxicity is The adverse effects occurring within a given time, following a single exposure to a substance. The term usually excludes local irritant or corrosive effects arising from a single application of a substance to the skin or eye (Section 4.5) (EC 2003). 

A general definition of an irritant substance is A noncorrosive substance, which, through immediate contact with the tissue under consideration, may cause inflammation. 

In the OECD test guideline for acute dermal irritation/corrosion (OECD TG 404), the following definitions are provided ... 

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