Subchronic Inhalation Toxicity 90-Day Study

Subchronic inhalation toxicity is the study of adverse effects that follow repeated daily exposure via inhalation to environmental chemicals for a part (not exceeding 10%) of the life span of the species. 

In the evaluation of the toxic characteristics of a gas, volatile chemical, aerosol, or particulate matter, determination of subchronic inhalation toxicity may be performed after initial toxicity information has been obtained via acute testing. It provides information on health hazards likely to arise from repeated exposure by the inhalation route over a limited period of time. Hazards of inhaled chemicals are influenced by the inherent toxicity and by physical factors such as volatility and particle size. The housing and feeding conditions, before and after exposure to environmental chemicals, should be planned according to the standard animal husbandry conditions described for acute oral toxicity study. 

Test System At least 20 animals (10 female, 10 male) should be used for each test group. Females should be nulliparous and nonpregnant. If interim animal sacrifices are planned, the number should be increased by the number scheduled to be sacrificed before the completion of study. In addition, a satellite group of 20 animals (10 per gender) may be treated with the high-concentration level for 90 days and observed for reversibility, persistence, or delayed occurrence of toxic effects for a posttreatment of appropriate length, not less than 28 days. 

Healthy, young adult animals—preferably rats—are acclimated to laboratory conditions for at least 5 days prior to the test. Before the test, animals are randomized and assigned to the required groups. When necessary, a suitable vehicle may be added to the test chemical in the atmosphere. If a vehicle is used, it should not influence the absorption of the test chemical or produce toxic effects in test animals. 

The subchronic inhalation toxicity should be studied with at least three concentrations of the test chemical with a control (and where appropriate, a vehicle control corresponding to the concentration of the vehicle at the highest exposure level). The remaining details of exposure are similar to those described for acute oral and acute inhalation toxicity. The duration of daily exposure should be 6 hours after equilibrium of the chamber concentrations. Other durations may be used to meet specific requirements. 

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Subchronic Inhalation Toxicity 90-Day Study (Original Guideline, adopted 12 May 1981)... 

OECD, 1981c, Test Guideline 412, Repeated Dose Inhalation Toxicity 28-Day or 14-Day Study. OECD, 1981d, Test Guideline 413, Subchronic Inhalation Toxicity 90-Day Study. 

Biodegradation By a Shake-Flask Die-Away Method Conducting a 90-Day Oral Toxicity Study in Rats Conducting a Subchronic Inhalation Toxicity Study in Rats Conducting Aqueous Direct Photolysis Tests... 

Subchronic Oral Dosing Studies Subchronic 21-Day Dermal Toxicity Study Subchronic 90-Day Dermal Toxicity Study Subchronic Inhalation Toxicity Study Subchronic Neurotoxicity Studies... 

These so-called subacute or subchronic toxicity studies involve the repeated application of a test substance to animals, typically for a period of 30 or 90 days. The time pattern is thus an intermediate one between acute and chronic toxicity. To test a substance for subacute or subchronic toxicity, it is mainly applied by ingestion or inhalation. Not one out of the large number of organic pigments which have thus been tested has demonstrated any irreversible toxic effect. No toxic response was observed in rats which were fed either Pigment Yellow 1 or Pigment Yellow 57 1 for 30 days [22],... 

In the test guidelines for 90-day dermal (OECD TG 411) and inhalation (OECD TG 413) toxicity studies, the following definition in relation to the term subchronic is provided Subchronic dermal/inhalation toxicity is the adverse effects, which follow repeated daily dermal application/ inhalation of a chemical for part (not exceeding 10%) of a life span. ... 

The subchronic toxicity of EGBE has been examined in animals via oral, inhalation, and dermal routes of exposure. The lowest no-observed-effect level (NOEL) in an oral subchronic study was 80 mg kg for rats administered EGBE in feed over a 90 day period. Inhalation exposure of rats for 13 weeks, 6h day , 5 days week to EGBE vapors at 25-77 ppm indicated an NOEL of 25 ppm. In a 90 day dermal study of rabbits, EGBE was applied 6 h day, 5 days week at doses up to 150 mg kg There was no evidence of systemic toxicity or skin irritation at the site of application at any of the dose levels tested. 

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