PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Mirex”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1995

Lack of effect of retinoic acid and fluocinolone acetonide on mirex tumor promotion indicates a novel mirex mechanism.

Mirex, a halogenated hydrocarbon, is a potent skin tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. In the present study retinoic acid (RA) and fluocinolone acetonide (FA), classical inhibitors of phorbol ester- and non-phorbol ester-type skin tumor promoters, were examined for their ability to inhibit mirex tumor promotion. Female CD-1 mice were initiated with 200 nmol DMBA and promoted with equipotent promoting doses of either 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) or 200 nmol mirex twice weekly for 25 weeks and RA (2(1 or 5 nmol), FA (0.5 or 2 nmol) or acetone were applied 30 min prior to each TPA or mirex dose. TPA-promoted papilloma formation was strongly inhibited by > 70% with both doses of RA and by > 90% with both doses of FA. In contrast, mirex-promoted papilloma formation was not inhibited by either dose of RA or 0.5 nmol FA and 2 nmol FA weakly inhibited mirex-promoted papillomas by only 32%. TPA- and mirex-promoted papillomas that were refractory to RA and FA demonstrated the same incidence of Ha-ras mutation as TPA- or mirex-promoted papillomas without RA and FA treatment, further indicating that the inhibitory activity of RA and FA is promoter-dependent and not solely dependent on mutant Ha-ras. FA (2 nmol) treatment completely abolished TPA-induced epidermal hyperplasia and proliferating cell nuclear antigen (PCNA) S phase-positive cells, however, FA had no inhibitory effect on the weak proliferative response induced by mirex. Collectively, these results indicate that the promotional activity of mirex, as well as its weak proliferative response, result from a distinct promoter mechanism and/or that mirex promotes a unique population of epidermal cells that are insensitive to FA and RA and cannot be distinguished by their mutant Ha-ras genotype.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Effect of mirex, dechlorinated mirex derivatives and chlordecone on microsomal mixed-function oxidase activity and other hepatic parameters.

The effects of mirex, two monohydrogen and two dihydrogen mirex derivatives, and chlordecone on several hepatic parameters were studied 2 days following a single oral dose of 100 mg/kg in female rats. All compounds increased microsomal cytochrome P-450 content, NADPH-cytochrome c reductase activity, and hepatic ascorbic acid concentration. Microsomal protein concentration was generally increased. All compounds except chlordecone increased relative liver weight and the activities of aminopyrine N-demethylase and p-nitroanisole O-demethylase. Hepatic concentration of protein and glutathione were unaltered. The dechlorinated mirex derivatives caused effects of a magnitude similar to that of mirex, whereas chlordecone was considerably less potent.

Animals↗
PubMedDate not supplied

Toxicosis of mirex for chick embryos and chickens hatched from eggs inoculated with mirex.

Mirex, a hydrocarbon, was mixed with corn oil and injected into chick embryos to test its toxic effect. At a concentration of 0 05 mg mirex/egg, embryo mortality was 40%, at 0.5 mg/egg, mortality was 49%, and at 5.0 mg/egg, mortality reached 81%. Mortality of control eggs injected with corn oil alone was 36%. The body weights of newly hatched chickens and of 4-week-old chicks were not different from those of controls. No clinical signs of disease were seen during the 4 weeks of observation. However, liver weights were increased at all 3 dosages when the birds were killed at 4 weeks, but spleen and bursal weights were not. The results support the decision to discontinue the use of mirex as a pesticide in the environment for controlling the fire ant (Solenopsis sp.) until a better means of presenting it can be found.

Animals↗
PubMed1994

Synergistic interaction between the non-phorbol ester-type promoter mirex and 12-O-tetradecanoylphorbol-13-acetate in mouse skin tumor promotion.

Mirex, an organochlorine pesticide and non-genotoxic rodent hepatocarcinogen, is also a potent non-phorbol ester-type promoter of mouse skin tumors. Mirex, unlike most other skin tumor promoters, is not a significant epidermal hyperplasiogen even at a maximally promoting dose (200 nmol). Experiments described here examined whether tumor promotion by mirex and 12-O-tetradecanoylphorbol-13-acetate (TPA) are mediated through different mechanisms as indicated by their additivity when co-applied to 7,12-dimethyl-benz[a]anthracene (DMBA, 200 nmol)-initiated female CD-1 mouse skin. Instead of the additive response of 14 plus 5 tumors/mouse predicted from mice promoted for 20 weeks (2x/week) with either mirex (200 nmol) or TPA (2 nmol) respectively, their co-application yielded 35 tumors/mouse. This synergy with TPA was specific to mirex since a structurally related compound, chlordecone (Kepone) was inactive. Mirex plus TPA-promoted papillomas contained a c-Ha-ras A182-->T mutation as frequently (13/14) as those promoted by mirex or TPA alone, suggesting that these DMBA-initiated/co-promoted papillomas were not atypical in this genotypic marker. Promotional synergy with mirex was only observed with a submaximal promoting dose of 2 nmol TPA; 5 or 8 nmol TPA plus mirex gave additive or less tumor multiplicities. This synergistic multiplicity with mirex plus 2 nmol TPA (35 tumors/mouse) approximated the sum of individual responses to 200 nmol mirex (14 tumors/mouse) and the maximally promoting dose of TPA (12 nmol), 24 tumors/mouse, suggesting that mirex potentiated the promotional activity of TPA, as well as promoted through a mirex-specific mechanism. Epidermal DNA synthesis induced by 2 nmol TPA was potentiated by mirex, further supporting a role for mirex in potentiation of epidermal TPA activity. Collectively, these studies suggest that mirex affects two possibly related responses: (i) promotion through a distinct mirex-specific mechanism, and (ii) potentiation of a mechanism mediating the promotional activity of TPA.

Adenine↗
PubMed1990

NTP Toxicology and Carcinogenesis Studies of Mirex (1,1a,2,2,3,3a,4,5,5,5a,5b,6-Dodecachlorooctahydro-1,3,4- metheno-1H-cyclouta[cd]pentalene) (CAS No. 2385-85-5) in F344/N Rats (Feed Studies).

Mirex (95% pure), formerly used a systemic insecticide and as a fire retardant, was studied for toxicologic and carcinogenic effects by administering diets containing 0, 0.1, 1.0, 10, 25, or 50 ppm mirex to groups of 52 F344/N rats of each sex for 104 weeks. Doses selected for the 2-year studies were based primarily on the effects on body weights and survival of rats in a 26-week study. During the first 6 months of the 2-year study, because of good survival and the absence of observable toxic effects in female rats, additional groups (termed second study) of 52 F344/N female rats were started at higher dietary concentrations of 0, 50, and 100 ppm mirex. Based on feed consumption data, the estimated average intake per day was 0, 0.007, 0.075, 0.75, 1.95, and 3.85 mg mirex/kg body weight for male rats and female rats in the first study, and 0, 3.9, and 7.7 mg/kg for female rats in the additional study. Body Weights, Feed Consumption, and Survival in Two-Year Studies: Mean body weights of male rats that received 25 or 50 ppm mirex were 5%-18% lower than those of the controls throughout most of the study; mean body weights of female rats that received 50 or 100 ppm mirex were 4%-18% lower than those of the controls after week 40; mean body weights of groups receiving 0.1, 1.0, or 10 ppm were similar to those of controls. Feed consumption by dosed male rats was 83%-91% that by controls, and that by dosed female rats was 86%-99% that by controls. The top dietary exposure groups of rats received the equivalent of 3.85 mg mirex/kg body weight, whereas the 100-ppm group of female rats (second study) averaged 7.7 mg/kg. At the end of the study, survival of male rats that received 25 or 50 ppm of mirex was lower than that of controls, whereas survival of all dosed groups of female rats was similar to that of controls (male: control, 44/52; 0.1 ppm, 37/52; 1 ppm, 36/52; 10 ppm, 37/52; 25 ppm, 19/52; 50 ppm, 15/52; female-- first study: 38/52; 38/52; 35/52; 41/52; 35/52; female-- second study: control, 44/52; 50 ppm, 44/52; 100 ppm, 39/52). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: The most notable compound-related effects were observed in the liver of male and female rats. Fatty metamorphosis, cytomegaly, angiectasis (males only), and necrosis of the liver were observed at increased incidences in dosed rats. The incidences of of neoplastic nodules of the liver were dose related, and in the 10-, 25-, and 50-ppm groups of males and the 50- and 100-ppm groups of females (second study), they were markedly greater than those in controls (52/group-- male: control, 3; 0.1 ppm, 5; 1 ppm, 5;10 ppm, 14; 25 ppm, 15; 50 ppm, 26; female (second study): control, 2; 50 ppm, 23; 100 ppm, 30). In the first study in female rats, the incidences of neoplastic nodules were not significantly different between control and dosed groups (10; 5; 4; 5; 9; 7). The 10 neoplastic nodules of the liver seen in the control group (19%) was significantly greater than the mean incidence observed historically (57/2,015; 2.8%). The incidences of hepatocellular carcinomas in control and dosed groups were relatively low and were not significantly different between groups. The incidences of pheochromocytomas of the adrenal gland occurred with a positive trend in male rats (8/51; 7/52; 13/52; 11/52; 18/51, 19/51); the incidences in the 25- and 50-ppm male rats were greater than that in controls; malignant pheochromocytomas were observed in 2 controls and in 2 mirex-exposed male rats. The incidence of pheochromocytomas in 50-ppm female rats in the first study was marginally greater than that in controls (control, 1/51; 50 ppm, 6/52); this borderline increase was not observed in the second female rat study and thus is not considered to be due to the dietary administration of mirex. Nephropathy occurred at similar incidences in control and mirex-exposed groups of male and female rats; however, the severity of this nonneoplastic lesion was judged to be slightly greater in the groups given 25, 50, or 100 ppm mirex (male: severe vs. moderate in controls; femas given 25, 50, or 100 ppm mirex (male: severe vs. moderate in controls; female: moderate to severe vs. moderate). Hyperplasia of the transitional epithelium of the kidney pelvis was observed in dosed male rats (0/51; 2/51; 2/52; 5/52; 14/51; 9/52). Transitional cell papillomas of the renal pelvis in male rats occurred with a positive trend (P<0.02) (0/51; 0/51; 0/52; 1/51; 3/52). The highest incidence previously observed in untreated male F344/N rats in NTP studies is 1/48, and the mean historical incidence is 5/1,968 (0.3&percnt;). In both the first and second studies in female rats, the incidence of mononuclear cell leukemia showed dosed-related increases (first study: 8/52; 8/52; 11/52; 14/52; 18/52; 18/52; second study: 6/52; 9/52; 14/52). When the data from both studies are combined, the incidences are significantly increased in the 10-, 25-, 50-, and 100-ppm groups. The mean historical incidence is 19&percnt; (375/2,021). For the thyroid gland, there was a positive trend for follicular cell neoplasms in male rats (0/51; 1/50; 0/47; 1/47; 0/35; 4/49) and a negative trend for C-cell neoplasms in male rats (8/51; 6/50; 4/47; 7/47; 3/35; 0/49) and infemale rats in the first study (12/50; 13/50; 7/48; 9/47; 6/48; 2/46). Neither observation is considered to be associated with the dietary administration of mirex. Genetic Toxicology: Mirex was not mutagenic in the Salmonella typhimurium-microsome assay when tested in a preincubation protocol in the presence or absence of exogenous metabolic activation in strains TA98, TA100, TA1535, or TA1537. Mirex did not induce either sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells in the presence or absence of S9. Conclusions: Under the conditions of these 2-year feed studies of mirex, there is clear evidence of carcinogenic activity for male and female F344/N rats, as primarily indicated by marked increased incidences of benign neoplastic nodules of the liver, as well as by increased incidences of pheochromocytomas of the adrenal gland and transitional cell papillomas of the kidney in males and by increased incidences of mononuclear cell leukemia in females. Nonneoplastic effects induced by mirex include cytomegaly, fatty metamorphosis, angiectasis (males only), and cellular necrosis in the liver. Synonyms and Trade Names: 1,1a,2,2,3,3a,4,5,5,5a,5b,6-dodecachlorooctahydro-1,3,4-metheno-1H-cyclobta[cd]pentalene; hexachloropentadiene dimer; dodecachloropentacyclodecane; perchloropentacyclodecane; hexachlorocyclopentadiene dimer; Dechloranereg.; Ferriamicidereg.

Journal Article↗
PubMed1997

Evidence that mirex promotes a unique population of epidermal cells that cannot be distinguished by their mutant Ha-ras genotype.

Mirex is a potent tumor promoter in 7,1 2-dimethylbenz[a]anthracene (DMBA)-initiated female CD-1 mouse skin. Like 12-O-tetradecanoylphorbol-13-acetate (TPA), mirex promotes papillomas that have a Ha-ras mutation; however, unlike TPA promotion, mirex promotion does not involve a general hyperplastic response. We used proliferating cell nuclear antigen (PCNA) and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemical staining to further examine the proliferative capacity of mirex. The numbers of PCNA- and BrdU-positive epidermal S-phase cells were highly concordant in all treatment groups. Unlike a single application of TPA, a single application of mirex had little or no effect on the number of S-phase epidermal cells, and chronic application of mirex to mouse skin produced only minimal increases in S-phase cells. Moreover, mirex did not significantly alter the growth of BALB/MK-2 keratinocytes in media containing either 0.05 or 1.2 mM Ca++. These results suggest that mirex may have highly specific effects on the proliferation of initiated cells and support the existence of a unique mirex mechanism and/or distinct population of mirex-promotable mutant Ha-ras epidermal cells. To begin to address this issue of a distinct population of mirex-promotable mutant Ha-ras cells, we conducted a tandem experiment in which DMBA-initiated mice were treated twice weekly with a maximal promoting dose of mirex. Then, when the number of papillomas reached a plateau, these same mice were treated twice weekly with a maximal promoting dose of TPA. Mice treated with mirex developed a maximum of 6.4 papillomas/mouse. These mice were then promoted with TPA, which produced 8.9 additional papillomas/mouse for a total of 15.3 papillomas/mouse. The maximum tumor yields from other groups of mice treated with only TPA or mirex were 9.8 and 7.3 papillomas/mouse, respectively. Therefore, under these tandem conditions, tumor yields were additive, indicating that there are at least two distinct populations of mutant Ha-ras cells: one promoted by mirex and the other by TPA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2002

17beta-estradiol is a hormonal regulator of mirex tumor promotion sensitivity in mice.

Mirex, an organochlorine pesticide, is a potent non-phorbol ester tumor promoter in mouse skin. Previous studies have shown that female mice are 3 times more sensitive to mirex tumor promotion than male mice and that ovariectomized (OVX) female mice are resistant to mirex promotion, suggesting a role for ovarian hormones in mirex promotion. To determine whether the ovarian hormone 17-beta estradiol (E2) is responsible for the sensitivity of female mice to mirex promotion, female mice were initiated with DMBA; 2 weeks later groups of mice were OVX and implants, with or without E2, were surgically implanted subcutaneously. These mice were treated topically twice weekly with mirex for 26 weeks. E2 implanted OVX mice demonstrated high normal physiologic levels of serum E2 throughout the tumor promotion experiment. E2 implants restored by 80% the intact mirex-sensitive phenotype to the OVX mice. Consistent with a role for E2 and ERalpha and ERbeta, treatment of DMBA-initiated female mice with topical ICI 182,780, an estrogen-receptor antagonist, reduced mirex tumor multiplicity by 30%. However, in cells co-transfected with ERalpha or ERbeta and estrogen-responsive promoter reporter, mirex did not stimulate promoter reporter activity, suggesting that the promotion effect of mirex is downstream of ERalpha/beta. Finally, a tumor promotion study was conducted to determine whether E2 implants could increase the sensitivity of male mice to mirex promotion. E2 implants in male mice did increase sensitivity to mirex promotion; however, the implants did not produce the full female sensitivity to mirex tumor promotion. Collectively, these studies indicate that E2 is a major ovarian hormone responsible for mirex tumor promotion sensitivity in female mice.

Animals↗
PubMed1988

Alterations in the hepatic glucocorticoid response to mirex treatment.

Corticosterone has been shown to be involved in the regulation of mirex-induced adaptive liver growth. To further investigate the role of corticosterone in this response, plasma corticosterone, hepatic tyrosine aminotransferase (TAT) activity, and hepatic cytosolic binding of glucocorticoids were determined in male Sprague-Dawley rats following a single oral dose of mirex (100 mg/kg body wt). Mirex stimulated a significant elevation in plasma corticosterone levels 12 and 24 hr after dosing; however, hepatic tyrosine aminotransferase activity was not induced above control levels 6, 12, or 24 hr after mirex dosing. Mirex does not appear to directly inhibit the enzyme because tyrosine aminotransferase activity was increased in a dose-dependent manner in both intact and adrenalectomized rats when corticosterone supplements (1-50 mg/kg body wt) were given after mirex dosing. In an effort to explain the lack of hepatic TAT induction, the concentration of cytosolic binding sites for [3H]dexamethasone in intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats was measured 12, 24, and 48 hr after mirex dosing. There was a significant decrease in the total concentration of cytosolic binding sites for [3H]dexamethasone 12 and 48 hr after mirex dosing in intact rats, 12 and 48 hr after mirex dosing in adrenalectomized rats, and 12 and 24 hr after mirex dosing in adrenalectomized corticosterone-supplemented rats. There was a significant increase in the apparent dissociation constant (Kd) in intact rats dosed with mirex as compared to the oil controls, but there was no difference in Kd after mirex dosing in the adrenalectomized (ADX) rats when compared to the Kd for the oil-dosed control rats. The maximal binding capacity (Bmax) was not significantly different from oil controls after mirex dosing in either intact or ADX rats. The lack of hepatic TAT induction in the presence of increased plasma levels of corticosterone appears to be related to glucocorticoid receptor alterations in the liver of intact rats.

Adrenalectomy↗
PubMed2003

Trend analysis reveals a recent reduction in mirex concentrations in coho (Oncorhynchus kisutch) and chinook (O. tshawytscha) salmon from Lake Ontario.

Lake Ontario, bordering both Canada and the United States, is the only Great Lake with persistent, significant levels of mirex in its biota. Some models suggested that it would take hundreds of years before mirex disappeared from the ecosystem. From 1977 to 1996 the mirex concentrations in coho and chinook salmon greater than 2 kg in weight exceeded the 0.1 mg/kg Food and Drug Administration (FDA) action level for mirex. To determine temporal trends in salmonine mirex levels, slopes and elevations of the regression lines of mirex concentration versus fish weight were compared for each of the six sampling years (1977, 1982, 1986, 1992, 1996, and 1999) by ANCOVA with weight as a covariate. Within 24 years of mirex being banned, mirex least-squares mean concentrations in salmon fillets had decreased significantly. ANCOVA revealed that the slope of the 1999 regression line was significantly flatter (P < or = 0.014) than the slopes of all other regression lines except 1996 (P = 0.966). A Tukey test revealed that the elevation of the 1999 regression line was also significantly lower than all other years (P < 0.001). Based on our results, mirex concentrations in the fillets of most salmon under the size of 12 kg are now below the 0.1 mg/kg United States FDA action level for human consumption. Models suggest that mirex reductions in biota are most likely due to the settling of mirex-contaminated organisms to the sediments and the loss of mirex from the lake through the St Lawrence River. A third mechanism is suggested as the cause of the higher rate of reduction observed in the mid to late 1990s--the control and removal of contaminated groundwater at the former Hooker Chemical site on the Niagara River, the major source of mirex in the watershed of Lake Ontario.

Animals↗
PubMed1992

The chlorinated pesticide mirex is a novel nonphorbol ester-type tumor promoter in mouse skin.

The hepatocarcinogenic organochlorine pesticide, mirex, was examined as a tumor promoter in the mouse skin initiation-promotion model. Female CD-1 mice were initiated with 200 nmol 7,12-dimethylbenz[a] anthracene and topically promoted three times weekly for 20 weeks with doses of 25, 50, 100, or 200 nmol mirex. Mirex promoted tumors at all dose levels in a dose-dependent manner. At 20 weeks, mice promoted with 25, 50, 100, and 200 nmol mirex developed an average of 0.2, 4, 10, and 16 tumors per mouse with a 10, 60, 93, and 96% incidence of tumor-bearing mice, respectively. With continued treatment to 34 weeks, mice promoted with 25, 50, and 100 nmol mirex developed an average of 0.7, 7, and 12 tumors per mouse with a 27, 85, and 100% incidence of tumor-bearing mice, respectively. These results demonstrate that mirex is a very effective tumor promoter in mouse skin. The effect of mirex on several biochemical and morphological events associated with tumor promotion was then investigated. Mirex did not stimulate epidermal protein kinase C activity in vitro. Unlike the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, a single topical application of mirex (200 nmol) did not increase [3H]thymidine incorporation into epidermal DNA up to 108 h after application. Furthermore, multiple applications of 200 nmol mirex (3 times weekly for 4 weeks) resulted in only a very weak proliferative response; mirex increased the number of nucleated epidermal cell layers from 1 to 2 in acetone-treated controls to 2 to 3 while 2 nmol 12-O-tetradecanoylphorbol-13-acetate produced 6 to 7 nucleated cell layers. Mirex (200 nmol) did not induce ornithine decarboxylase activity up to 56 h after a single topical application. Collectively, these data indicate that mirex is a novel nonphorbol ester-type tumor promoter in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Mirex-induced adaptive liver growth in rats subjected to thyroidectomy.

The organochlorine compound mirex (dodecachloro-octahydro-1,3,4-metheno-2H-cyclobuta-CD- pentalene) induces an adaptive liver growth dependent on the hormonal status of the experimental animal. In the intact laboratory rat, mirex induces liver growth that is an expression of both cellular hyperplasia and hypertrophy. However, in rats subjected to adrenalectomy, mirex induces liver growth that is essentially hyperplastic. Corticosterone supplements given to rats subjected to adrenalectomy and treated with mirex restore the hypertrophic component of liver growth. Therefore it appears that the expression of the hypertrophic component of mirex-induced liver growth is corticosterone dependent. To further explore the hormonal modulation of the expression of mirex-induced adaptive liver growth, rats subjected to thyroidectomy were studied. In male rats subjected to thyroidectomy, a single oral dose of mirex (100 mg/kg body wt) increased relative liver weight (liver wt/body wt x 100) by 62% within 72-hr after mirex administration. Liver growth occurred in the absence of [3H]thymidine incorporation into liver DNA. Thus the observed liver growth was totally hypertrophic. However, in mirex-dosed rats subjected to thyroidectomy given twice-daily subcutaneous injections of thyroxine (5 mg/kg body wt), relative liver weight was increased by 204% of the control value within 72-hr after mirex administration, and there was a peak of [3H]thymidine incorporation into liver DNA 54 hr after mirex administration. These studies suggest that the expression of hyperplasia in mirex-induced adaptive liver growth is thyroxine dependent.

Animals↗
PubMed1991

Mirex inhibits bile acid secretory function in vivo and in the isolated perfused rat liver.

The insecticides mirex and chlordecone suppress the biliary excretion of a wide variety of non-bile acid organic anions in vivo in the rat, and mirex inhibits the uptake of taurocholate (TC), a common bile acid, in isolated rat hepatocytes. We have therefore investigated the effects of mirex and chlordecone on bile acid secretory function (bile flow, bile acid concentration, bile acid secretory rate) in vivo and in the single-pass isolated perfused liver. Male Sprague-Dawley rats were orally dosed with corn oil, mirex (50 mg/kg), or chlordecone (18.75 mg/kg; in vivo studies only) for 3 consecutive days and experiments performed on Day 6. Mirex significantly increased liver weight from 12.2 +/- 0.8 to 20.8 +/- 1.3 g with no change in body weight whereas chlordecone had no significant effect on liver weight (11.9 +/- 0.7 g) or body weight. Mirex significantly decreased while chlordecone increased bile flow per gram liver in vivo; both compounds, however, increased bile flow when expressed per kilogram of body weight. Mirex and chlordecone significantly decreased the bile acid concentration in bile and the bile acid secretory rate (nmol/min/g liver and mumol/min/kg body weight). Studies in the isolated perfused liver were designed to determine the effect of mirex on the ability of the liver to extract increasing concentrations of [3H]TC from the perfusate and excrete it in the bile. Mirex treatment significantly decreased the TC extraction ratio by 40-89% and the hepatic intrinsic clearance by 85-95%. Mirex also significantly decreased the TC-induced choleresis, the concentration of TC in the bile, and the TC secretory rate. The data indicate that mirex treatment markedly inhibits the ability of the liver to extract TC from the blood/perfusate and concentrate it in the bile.

Animals↗
PubMed1985

The human body burden of mirex in the southeastern United States.

Mirex is an organochlorine chemical with pesticidal and other industrial usages. Biologically, mirex was used as an insecticide for the control of imported fire ants in large areas of the southeastern United States. Evidence of mirex exposure in a national survey of chemicals in adipose tissue led to a more intensive survey of the general population in treated counties of the southeastern United States. Forty sites were selected randomly from 8 southeastern states where mirex was used widescale to combat fire ants; a total of 624 adipose tissue specimens were collected from these 40 sites. Tissue specimens were prepared by a modified Mills-Onley-Gather procedure and analyzed for mirex and selected other organochlorine compounds by electron-capture gas chromatography. Positive residue findings were confirmed by combined gas chromatography and mass spectrometry. Weighted statistical analysis of the data was conducted to estimate the level of mirex in the study area. It was estimated that 10.2% of the population of southern United States had quantifiable levels of mirex in adipose tissue. The estimated geometric mean of the quantifiable residue amounts was 0.286 ppm (lipid basis). Statistical tests of association and regression were used to investigate possible relationships between the presence and levels of mirex, and the Census Division or state of tissue-specimen collection, by age, race, and sex. These analyses indicated that region or location of tissue specimen collection (assumed to be area of residence) strongly related to both the presence of mirex residue and the amount of mirex residue detected. This may be correlated with the amount of mirex applied for fire ant control or with some other exposure patterns in different regions.

Adipose Tissue↗
PubMed1987

Regional mirex distribution and its effects on gamma-aminobutyric acid and flunitrazepam binding in mouse brains.

Following ip injection of [14C]mirex, its regional distribution was studied parallel to its in vitro effects on [3H]-gamma-aminobutyric acid (GABA) and [3H]flunitrazepam (FNZ) binding to, and [3H]GABA release from, synaptosomes of various mouse brain regions, in order to determine the relationship between relative mirex distribution and its neurotoxic effects mediated through the GABA receptor-ionophore complex. The pattern of mirex uptake into cerebral cortex (CC), brainstem (BS), and cerebellum (CB) showed an initial linear dose-dependent uptake, followed by a decline at higher concentration. The Vmax and Km values determined for the linear mirex uptake phase indicated varied affinities by brain regions, CB and BS being more susceptible to mirex uptake than CC. Both synaptosomal GABA binding and FNZ binding were significantly reduced by mirex in the order of BS approximately equal to CB greater than CC for GABA, and BS approximately equal to CC greater than CB for FNZ. However, mirex lacked any significant effect on the Ca2+-dependent, K+-stimulated release of GABA from radio-prelabeled synaptosomes. While the data indicate no significant differences between brain regions in mirex uptake, they suggest that regional specificities do exist with respect to the inhibition caused by mirex on GABA and FNZ binding to synaptosomes. Unlike the major effects of chlordecone (an analog of mirex) on the dopaminergic system, mirex seems to be primarily neurotoxic through its more specific interaction with the GABA and FNZ binding sites.

Animals↗
PubMed1975

Movement of mirex from sediment and uptake by the hogchoker, Trinectes maculatus.

Mirex contaminated sediments of the static test retained virtually all of the insecticide over a 4 week period. About 40% of the initial concentration was lost from the sediment under constant flow conditions. Mirex in water was directly related to levels of mirex in sediment. Mirex in water reached an equilibrium during the first week and declined over the following 3 weeks. Uptake of mirex by tissues showed a dose dependent relationship. Accumulation of the insecticide increased over time and did not appear to reach an equilbrium. Residues in the muscle of fish increased significantly with time (pless than.01) and test concentration (pless than.01). Mirex in the liver of fish increased significantly with time (pless than.05) of the flow-through test. Declinging levels of mirex in water indicated mirex was absorbed from the water by the fish. Considerably more mirex, however, was gained by the fish than was lost from the water. Thus the fish probably absorbed a significant amount of mirex from the sediments.

Absorption↗