Biomedical subjects

R W Chadwick

Publications and source records attributed to R W Chadwick.

39 records · Page 3Linked to original sources

PubMedDate not supplied

Chlorobenzene-impaired lindane metabolism and the effect of pretreatment with chlorobenzene, lindane, or chlorobenzene plus lindane.

The storage and metabolism of lindane (gamma-HCH) was studied in the female rat after the administration of a hepatotoxic dose of chlorobenzene. Impaired lindane metabolism was observed following a challenge dose of 1.12 g chlorobenzene/kg. The data indicated that a hepatotoxic dose of chlorobenzene (CB) selectively impaired certain pathways, such as dehydrochlorination and the direct hydroxylation of lindane, to a greater extent than others, such as the dehydrogenation and dechlorination of lindane. Pretreatment with a subtoxic level of chlorobenzene produced: (1) significant increases in the dehydrogenation of lindane, (2) significant increase in the excretion of conjugated metabolites, (3) significant increases in the excretion of metabolites derived from the dehydrogenation of lindane through hexachlorocylohexene, gamma-HCCH, (4) significant improvement in the excretion of metabolites derived from CB-impaired dehydrochlorination of lindane as well as from the CB-impaired hydroxylation of lindane, and (5) significant reduction in the level of unaltered lindane stored in the adipose tissue. Repeated pretreatment with a subtoxic level of chlorobenzene offered significant protection against the reduction in lindane metabolism produced by the single hepatotoxic dose of chlorobenzene. Pretreatment with gamma-HCH alone was not as effective against the hepatotoxic effect of CB on lindane metabolism.

Animals↗

PubMedDate not supplied

Investigation of HCB as a metabolite from female rats treated daily for six days with lindane.

The biotransformation of lindane to hexachlorobenzene (HCB) by male rats was recently reported. Since HCB has been widely detected in human milk samples, and since the transplacental transfer of HCB to the fetus has been demonstrated in several species, the metabolism of lindane to HCB in female rats was investigated. Young adult female Fischer 344 rats were dosed p.o. with either 20 mg lindane/kg/day or an equivalent volume of the peanut oil vehicle. Feces samples were collected daily for two consecutive 4-hr intervals and a 16-hr interval. Twenty-four hours after the final treatment, all rats were sacrificed and adipose tissue samples were excised at necropsy. Extracts of fat and feces samples were analyzed by gas-liquid chromatography (GLC) on column packings of different polarity. Results of this study indicated that no significant biotransformation of lindane to HCB occurred in the female Fischer 344 rat.

Adipose Tissue↗

PubMedDate not supplied

Bioisomerization of lindane in rats.

The major environmental problem associated with the use of gamma-hexachlorocyclohexane (gamma-HCH, lindane) has been the appearance of the more oncogenic alpha- and beta- isomers as terminal residues in nature. To account for these residues it was suggested that gamma-hexachlorocyclohexane had been bioisomerized to the more stable alpha- and beta- isomers. In this study the effect of dose and duration of treatment on the proposed bioisomerization of gamma-hexachlorocyclohexane in the rat was investigated. Weanling female Sprague-Dawley rats were randomly assigned to one of four groups receiving Purina Lab Chow fortified with 0, 130, 215, or 350 ppm gamma-HCH. Six animals from each group were sacrificed after 1, 2, 4, 8, 16, and 24 weeks of treatment. Twenty-four hours prior to sacrifice all rats received a single oral dose of gamma-HCH in peanut oil. There were no significant differences in food consumption or body weights, and no deaths occurred throughout the study. The in vitro dechlorinase activity of the treated rats was significantly higher after 1, 4, and 24 weeks of treatment. Except at 4 weeks after treatment began, the liver/body weight ratios of the rats fed diets containing 350 ppm and 215 ppm lindane were significantly greater than the controls; while those receiving 130 ppm lindane were significantly greater than the controls after 1 and 2 weeks of treatment. No beta-HCH was detected in any of the samples analyzed throughout the study. The levels of alpha-HCH found in the adipose tissue after 24 weeks of treatment could be accounted for by trace contamination of the lindane used in this study. There was a negative correlation between the hepatic content of alpha-, gamma-, and sigma-HCH and duration of treatment. It was concluded that bioisomerization does not play a significant role in the metabolism of lindane by rats.

Animals↗