THE CHRONIC TOXICITIES OF TECHNICAL BENZENE HEXACHLORIDE AND ITS ALPHA, BETA AND GAMMA ISOMERS

¹ Division of Pharmacology, Food & Drug Administration, Federal Security Agency, Washington, D. C.

In a total of 420 rats fed for a lifetime diets containing the technical benzene hexachloride or the alpha, beta or gamma isomer in dosage levels ranging from 5 to 1600 p.p.m. the following effects were observed:

1. Beta isomer retarded growth rate at 100 p.p.m., the alpha isomer and the technical benzene hexachloride at 800 p.p.m. and the gamma isomer at 1600 p.p.m. Lower dosages had no effect on growth.

2. All isomers, except dry gamma and the technical benzene hexachloride, increased the mortality rate at 800 p.p.m.

3. All isomers and the technical benzene hexachloride increased the size of the liver. The lowest dosage of each substance which produced a significant effect was 10 p.p.m. beta, 100 p.p.m. alpha, gamma and technical, and 800 p.p.m. dry gamma.

4. Tissue storage was marked with the beta isomer and somewhat less for the alpha and gamma isomers. In a decreasing order these substances were found in fat, kidney, brain, muscle and liver tissues.

5. In a total of 238 animals microscopically sectioned, the chief organ affected was the liver; the kidney was affected to a lesser degree.

6. Grossly, the chief alteration of the liver consisted of enlargement, but changes such as off color and small foci of necrosis also appeared.

7. The microscopic alterations in the liver were of two types, namely, the specific one of certain hepatic cell changes as generally seen in rodents fed various chlorinated compounds and the less specific but sometimes more damaging ones such as diffuse hepatic cell enlargement, hepatic cell atrophy, fatty degeneration and focal necrosis.

8. In descending order of total damage to the liver the dosage levels of the compounds were: 800 p.p.m. beta, 800 p.p.m. technical, 800 p.p.m. alpha, 1600 p.p.m. gamma, 800 p.p.m. dry gamma, 800 p.p.m. gamma, 100 p.p.m. beta, 400 p.p.m. gamma, 100 p.p.m. technical and 100 p.p.m. alpha. Very slight changes only were seen in the groups on 100 p.p.m. gamma, 100 p.p.m. dry gamma, 50 p.p.m. technical, 50 p.p.m. alpha and 10 p.p.m. beta. No effect was observed with 50, 10 and 5 p.p.m. gamma and 10 p.p.m. technical, alpha and dry gamma.

9. Slight to moderate kidney damage occurred in the groups on 800 p.p.m. alpha and 800 p.p.m. dry gamma, and slight damage in the group on 800 p.p.m. technical.

10. A moderate degree of testicular atrophy occurred in the group on 800 p.p.m. technical.

11. In comparison with previous chronic experiments with DDT this experiment indicates that the gamma isomer of benzene hexachloride is about a fourth as toxic as DDT, the beta isomer is two to three times as toxic, and the alpha isomer and the technical benzene hexachloride are of the same order of chronic toxicity as DDT.