Effect of Carboxymethyl Cellulose (CMC) as Emulsifier on the Onset of Chinoform-Induced SMON

Abstract

A previous study made it clear that SMON was an iatrogenic disease caused by the abuse of chinoform, however, reasons for the absence of SMON before 1955 remain unsolved. From the fact that the disease began to appear almost in the same years as the commencement of domestic production of the emulsified chinoform, the authors supposed that surface active agents and emulsives contained in the drug might have enhanced the occurrence of SMON. An experimental study was carried out on dogs to prove this supposition by using carboxymethyl cellulose (CMC) as an emulsive.1. Symptoms clinically similar to SMON appeared in 4 of the 5 dogs given chinoform with CMC, whereas only one of the 5 given chinoform alone showed the symptoms. The disease appeared earlier and the total amounts of chinoform required for giving rise to the disease were markedly lesser in dogs given chinoform with CMC.2. Electromyographic examinations revealed the existence of degeneration in the nerves innervated to M. tibialis anterior and M. adductor of dogs with the disease.3. Degenerative changes were detected also light and electron microscopically in the central and peripheral nervous tissues of dogs with the disease, but the changes were less severe as compared to those of human cases.4. The effect of CMC on the intestinal absorption of chinoform was studied by examining the nonconjugated chinoform (NC) in the blood of dogs. The concentration of blood NC reached the highest levels earlier and maintained its levels higher thereafter when chinoform was given with CMC. However, such effects of CMC were reduced greatly by repeating the administration of the same drugs.5. These results suggest strongly that the abuse of emulsified chinoform, which did not come into common use before 1955 in Japan, played a great role in the occurrence of SMON in man.