Inhaled adverse effects

Terbutaline is the N-f-butyl analogue of metaproterenol and, as such, would be expected to have a more potent p2-selectivity. When compared to metaproterenol, terbutaline has a threefold greater potency at the p2-receptor. Like metaproterenol, it is resistant to COMT and slowly metabolized by MAO, therefore having good oral bioavailability with similar onset and duration. Terbutaline is available as tablets and solutions for injection and inhalation. Adverse effects are similar to other... 

Health and Safety Factors. The following toxicides for acetonitrile have been reported oral LD q (lats), 3030—6500 mg/kg skin LD q (rabbits), 3884—7850 mg/kg and inhalation LC q (i ts), 7500—17,000 ppm (29). Humans can detect the odor of acetonitrile at 40 ppm. Exposure for 4 h at up to 80 ppm has not produced adverse effects. However, exposure for 4 h at 160 ppm results in reddening of the face and some temporary bronchial tightness. 

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

In additional EPA studies, subchronic inhalation was evaluated ia the rat for 4 and 13 weeks, respectively, and no adverse effects other than nasal irritation were noted. In the above-mentioned NTP chronic toxicity study ia mice, no chronic toxic effects other than those resulting from bronchial irritation were noted. There was no treatment-related increase ia tumors ia male mice, but female mice had a slight increase in bronchial tumors. Neither species had an increase in cancer. Naphthalene showed no biological activity in other chemical carcinogen tests, indicating Htde cancer risk (44). No incidents of chronic effects have been reported as a result of industrial exposure to naphthalene (28,41). 

Poly(tetramethylene ether) glycols were found to have low oral toxicity in animal tests. The approximate lethal oral dose, LD q, for Terathane 1000 has been found to be greater than 11,000 mg/kg (272). No adverse effects on inhalation have been observed. The polymer glycols are mild skin and eye irritants, and contact with skin, eyes, and clothing should be avoided. Goggles and gloves are recommended. In case of contact with the skin, wash thoroughly with water and soap. If swallowed, no specific intervention is indicated, because the compounds are not hazardous. However, a physician should be consulted (260). 

Vapor Toxicity. Laboratory exposure data indicate that vapor inhalation of alkan olamines presents low hazards at ordinary temperatures (generally, alkan olamines have low vapor pressures). Heated material may cause generation of sufficient vapors to cause adverse effects, including eye and nose irritation. If inhalation exposure is likely, approved respirators are suggested. Monoethan olamine and diethanolamine have OSHA TLVs of 3 ppm. 

Overexposure to tetrachloroethylene by inhalation affects the central nervous system and the Hver. Dizziness, headache, confusion, nausea, and eye and mucous tissue irritation occur during prolonged exposure to vapor concentrations of 200 ppm (15). These effects are intensified and include incoordination and dmnkenness at concentrations in excess of 600 ppm. At concentrations in excess of 1000 ppm the anesthetic and respiratory depression effects can cause unconsciousness and death. A single, brief exposure to concentrations above 6000 ppm can be immediately dangerous to life. Reversible changes to the Hver have been reported foUowing prolonged exposures to concentrations in excess of 200 ppm (16—22). Alcohol consumed before or after exposure may increase adverse effects. 

Inhalation of other general anesthetics susceptible to abuse, such as ether and chloroform, appears to be limited to health professionals who have easy access to these compounds and who tend to use these dtugs in isolation. Recreational and social use of these substances has been somewhat limited by their high flammability and by frequent and intense undesirable adverse effects at moderate doses. It has been suggested that the abuse of ether or chloroform alone is a rare phenomenon (Delteil et al. 1974 Deniker et al. 1972), occurring usually in the context of dependence on othet substances, particularly alcohol (Krenz et al. 2003). 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for methyl parathion. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur. 

Limited information is available regarding the effects of endosulfan in humans and animals after inhalation exposure. The reports of effects in humans are limited to case reports of adverse effects noted in workers exposed to large quantities of endosulfan during its manufacture. Exposures in these reports are likely to be a combination of inhalahon and dermal exposures. Therefore, the findings from these case reports are also presented in the section on dermal exposures (Section 2.2.3). 

No studies were located that examined reproductive function in animals after inhalation exposure to endosulfan. However, routine gross and histopathological examination of the reproductive organs (testes, epididymides, seminal vesicles, prostate, ovaries, and uterus) of rats exposed (nose-only) to concentrations of endosulfan of up to 2 mg/m for 6 hours/day, 5 days/week for a total of 21 out of 29 days revealed no adverse effects (Hoechst 1984c). 

Musculoskeletal Effects. Very limited data were available regarding the effects of endosulfan on the musculoskeletal system. However, the available animal data did not indicate that this system is adversely affected following either inhalation or oral exposure to endosulfan (FMC 1965, 1967 Hoechst 1984b, 1984c, 1988b, 1989a, 1989c). Thus, persons exposed to endosulfan would not be expected to experience adverse effects on the musculoskeletal system. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. 

NO ALL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see footnote "b"). 

A metered dose inhaler with spacer is equivalent to nebulized therapy, may have a more rapid onset, and fewer adverse effects ° 4-8 puff doses... 

Direct airway administration of asthma medications through inhalation is the most efficient route and minimizes systemic adverse effects. 

---