A 6-month multispecies inhalation study with maleic anhydride

Area of Science:

• Toxicology
• Occupational Health

Background:

• Maleic anhydride (MA) is an industrial chemical with potential respiratory and ocular irritant properties.
• Establishing safe exposure limits is crucial for worker protection in industries using MA.

Purpose of the Study:

• To evaluate the systemic toxicity and local irritant effects of chronic inhalation exposure to maleic anhydride in animal models.
• To inform occupational exposure limits for maleic anhydride.

Main Methods:

• Rats, hamsters, and monkeys were exposed to varying concentrations of maleic anhydride (0-9.8 mg/m3) for 6 months.
• Atmosphere monitoring used Tenax columns and gas chromatography for total maleic (MA and maleic acid).
• Safety assessments included clinical observations, body weight, hematology, clinical chemistry, urinalysis, pulmonary function tests, and histopathology.

Main Results:

• Dose-dependent nasal and ocular irritation (discharge, sneezing, gasping, coughing) occurred in all species.
• No significant treatment-related mortality or systemic toxicity was observed.
• Reduced weight gain in rats at higher doses, but terminal body weights remained above 90% of controls.
• Microscopic analysis confirmed nasal irritation but no systemic effects attributed to maleic anhydride.

Conclusions:

• Maleic anhydride inhalation causes local irritation but not systemic toxicity at the tested concentrations.
• Study findings support the current ACGIH Threshold Limit Value (TLV) and OSHA Permissible Exposure Limit (PEL) of 1 mg/m3 for systemic toxicity.
• Continuous exposure at 1 mg/m3 may still cause some irritant signs.