Biomedical subjects

J C Lamb

Publications and source records attributed to J C Lamb.

At least 55 records · Page 3Linked to original sources

PubMed1986

Carcinogenesis studies of 4,4'-methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F1 mice.

Carcinogenesis studies of 4,4'-methylenedianiline dihydrochloride (98.6% pure) were conducted by administering this chemical in the drinking water of F344/N rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex received drinking water containing 150 or 300 ppm 4,4'-methylenedianiline dihydrochloride (dosage expressed as the free base) for 103 wk. Groups of 50 rats and 50 mice of each sex, given drinking water adjusted with 0.1 N HCl to the pH (3.7) of the 300-ppm formulation, served as controls. Survival was comparable among groups except for male mice receiving the 300-ppm dose of 4,4'-methylenedianiline dihydrochloride; survival in that group was lower than that in controls. Mean body weight was reduced in 300-ppm-dose female rats and 300-ppm-dose male and female mice compared to controls. Water consumption was reduced in a dose-related manner in both sexes of rats. No compound-related clinical effects were observed. Under the conditions of these studies, there was clear evidence of carcinogenicity for F344/N rats and for B6C3F1 mice in that 4,4'-methylenedianiline dihydrochloride caused increased incidences of (1) follicular-cell carcinomas of the thyroid gland (controls, 0/49; low dose, 0/47; high dose, 7/48, 15%; p less than or equal to 0.012) and neoplastic nodules of the liver (controls, 1/50, 2%; low dose, 12/50, 24%; high dose, 25/50, 50%; p less than or equal to 0.001) in male rats, (2) follicular-cell adenomas (controls, 0/47; low dose, 2/47, 4%; high dose, 17/48, 35%; p less than or equal to 0.001) and C-cell adenomas (controls, 0/47; low dose, 3/47, 6%; high dose, 6/48, 13% p less than or equal to 0.029) of the thyroid gland in female rats, (3) follicular-cell adenomas of the thyroid gland (controls, 0/47; low dose, 3/49, 6%; high dose, 16/49, 33%; p less than or equal to 0.001), carcinomas of the liver (controls, 10/49, 20%; low dose, 33/50, 66%; high dose, 29/50, 58%; p less than or equal to 0.001), and pheochromocytomas of the adrenal gland in male mice (controls, 2/48, 4%; low dose, 12/49, 24%; high dose, 14/49, 29%; p less than or equal to 0.001), and (4) follicular-cell adenomas of the thyroid gland (controls, 0/50; low dose, 1/47, 2%; high dose, 13/50, 26%; p less than or equal to 0.001), carcinomas (controls, 1/50, 2%; low dose, 6/50, 12%; high dose, 11/50, 22%; p less than or equal to 0.002) and adenomas (controls, 3/50, 6%; low dose, 9/50, 18%; high dose, 12/50, 24%.(ABSTRACT TRUNCATED AT 400 WORDS)

Aniline Compounds↗

PubMed1986

Effects of di(2-ethylhexyl) phthalate on the gonadal pathophysiology, sperm morphology, and reproductive performance of male rats.

Dietary exposure of adult male F344 rats to 0, 320, 1250, 5000, or 20,000 ppm DEHP for 60 consecutive days resulted in a dose-dependent reduction in total body, testis, epididymis, and prostate weights at 5000 and 20,000 ppm. Degenerative changes were observed in testis, along with decreased testicular zinc content, reduced epididymal sperm density and motility, and increased occurrence of abnormal sperm at 20,000 ppm. There was a trend towards reduced testosterone and increased luteinizing hormone and follicle stimulating hormone in serum at 5000 and 20,000 ppm. The mean percentage of fertile animals was unchanged and reduction in fertility parameters, although not marked in severity, were correlated with gonadal effects. Average litter size was reduced at 20,000 ppm, but initial pup weights and growth were unaffected. There were no grossly observed abnormalities in the offspring and the rate of neonatal deaths was similar in control and DEHP treated groups. Characteristic toxicity manifestations of DEHP included dose-dependent enlargement of liver and reduced sperm triglycerides and cholesterol. Additionally, serum albumin and total proteins were dose dependently increased upon treatment with DEHP. Cessation of exposure to DEHP initiated partial to complete recovery from toxicity in most cases. The magnitude of recovery were variable with that of the gonads being slower than other systems. These data suggest a lack of reproductive dysfunction in F344 male rats at DEHP doses below 20,000 ppm which produced measurable testicular degeneration and afflicted epididymal sperm morphology under the present experimental conditions.

Animals↗

PubMed1985

Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats.

A 14-day dietary study was conducted in adult, male, Fischer 344 rats at levels of 0.0, 0.625, 1.25, 2.5 and 5.0% butyl benzyl phthalate (BBP) to evaluate potential effects of this plasticizer on the male reproductive and hematopoietic systems. Total body, thymus, testis, epididymis, prostate and seminal vesicle weights were reduced in the 2.5% and 5% BBP dose groups, while pituitary weight was unaffected. Histological evaluations revealed dose-dependent atrophy of the testis, prostate and seminal vesicles at 2.5% and 5%, atrophy of the thymus and epididymis at 5%, and the presence of immature sperm cells in the tubular lumens and necrosis of the tubular epithelium in the epididymis at 2.5% and 5% BBP. Plasma testosterone concentration was decreased at 5%, while follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were increased at 2.5% and 5.0% BBP. The circulating components of blood, and clotting times (prothrombin time, activated partial thromboplastin time), were unaffected although bone marrow cellularity was reduced at 2.5% and 5%. Changes in non-reproductive organs included enlargement of liver and kidneys, thymic atrophy and associated morphological abnormalities in these organs. These data indicate a direct toxic effect of BBP on the testis with secondary effects on other reproductive organs. Pituitary and hypothalamic responses did not appear to be affected. The reduced bone marrow cellularities suggest that prolonged exposures to BBP could affect circulating blood components or compromise clotting ability.

Animals↗

PubMed1985

Reproductive and developmental toxicity of ethylene glycol in the mouse.

The effects of ethylene glycol on reproduction of CD-1 mice were tested in a protocol which permitted continuous breeding during a specified interval. The dosage amounts of 0, 0.25, 0.5, or 1% ethylene glycol by continuous administration in drinking water for male and female mice were selected from the general toxic responses observed in a 14-day pilot study. After the first week of administration, begun at 11 weeks of age, the animals were housed one male and one female per cage for 14 weeks during which time any offspring were examined, sexed, weighted, and killed to allow continuous mating of the first generation. At the end of the 14-week cohabitation period, the males and females were separated and any litters delivered after that time were kept until weaning. Those second-generation animals were mated at about 70 days of age. Slight, but statistically significant, decreases were found in the numbers of litters per fertile pair and live pups per litter in the 1% dose group and live pup weight at the 1% dose groups compared to control F0 mice. Facial anomalies were noted in a number of offspring of high-dose-treated mice and an examination for skeletal defects demonstrated a pattern including reduction in the size of bones in the skull, fused ribs, and abnormally shaped sternebrae and vertebrae in the high-dose-treated, but not the untreated, mice. Neither the 0.25 nor 0.5% dose groups were significantly affected. No clinical signs of toxicity or significant adverse effects on body weight or water consumption were seen at the doses used, but two deaths occurred at the 0.5% quantity which may have been related to oxalate crystal deposition in the kidney.

Animals↗

PubMed1985

Toxic interaction of specific polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin: increased incidence of cleft palate in mice.

The induction of cleft palate in C57BL/6N mice is an extremely reproducible and sensitive indicator of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity. This endpoint was used to look for potential interactions between two polychlorinated biphenyl (PCB) congeners and TCDD. Both 2,3,4,5,3',4'-hexachlorobiphenyl (HCB) and 2,4,5,2',4',5'-HCB are of relatively low toxic potency, but their biological properties differ. Pregnant mice were treated with TCDD and either HCB on gestation Days 10 through 13, and the fetuses examined for the presence of cleft palate and renal abnormalities on gestation Day 18. At a dose of TCDD which caused a low level of cleft palate, moderate hydronephrosis was observed. No renal or palatal anomalies were detected after 2,4,5,2',4',5'-HCB treatment, and the combination of this isomer with TCDD had no effect on the incidence of TCDD-induced cleft palate. 2,3,4,5,3',4'-HCB caused mild renal toxicity, but no cleft palate. However, treatment of pregnant mice with a combination of TCDD and 2,3,4,5,3',4'-HCB resulted in a 10-fold increase in the incidence of cleft palate. Thus, the toxicity of compounds such as TCDD may be enhanced by compounds of relatively low acute toxicity such as selected PCBs. The widespread environmental occurrence of such combinations suggests a need for further evaluation of the mechanism of this interaction.

Abnormalities, Drug-Induced↗

PubMed1985

Effects of ethylene glycol monomethyl ether (EGME) on mating performance and epididymal sperm parameters in F344 rats.

Previous histologic studies on the effects of EGME identified dividing spermatocytes as a primary target cell type in the testis. The following studies were undertaken to assess possible effects of EGME on late-stage and epididymal spermatids, and spermatogonia. Adult male F344 rats (n = 20/group) of proven fertility were dosed po with 0, 50, 100, or 200 mg EGME/kg/day for 5 days. Each male was then mated with two females/week for 8 weeks. Females were sacrificed ca. 2 weeks after removal from the male, and number of live and dead fetuses, resorption sites, and corpora lutea were noted. Additional males were treated similarly, sacrificed at weekly intervals, and measures of epididymal sperm count, motility, and morphology were made. The fertility of males treated with 200 mg EGME/kg declined at Week 4, and remained low for the rest of the study. There was a modest but significant increase in the number of resorption sites at Weeks 5 and 6 in the high dose group. There was a decrease in the number of litters sired at Week 5 after dosing in the 100-mg EGME/kg group. There were time- and dose-related decreases in sperm concentration and motility, primarily in the 100- and 200-mg/kg groups, as well as concurrent elevations in the number of abnormal sperm forms in the epididymis. These studies show that EGME is a very weak inducer of dominant-lethal mutations, and produces previously undescribed effects on late-stage spermatids and spermatogonia.

Animals↗

PubMed1985

The recovery of the testis over 8 weeks after short-term dosing with ethylene glycol monomethyl ether: histology, cell-specific enzymes, and rete testis fluid protein.

Ethylene glycol monomethyl ether (EGME) has been found to affect meiotic spermatocytes, spermatids, other stages of spermatocytes, and spermatogonia, depending on the dose used. These studies, which examine testicular recovery from EGME treatment, analyzed tissues from rats treated for 5 days with 0, 50, 100, or 200 mg EGME/kg/day and sacrificed at eight subsequent weekly intervals; some epididymal sperm parameters of these animals have been described. Histologically, the testes of the low-dose group showed very mild changes, while the 100- and 200-mg/kg groups showed widespread damage and cell death which recovered somewhat during the course of the study. There was no treatment-related effect on seminal vesicle or prostate weights. Rete testis fluid protein levels were changed only in the high-dose group, when protein levels rose to a maximum of sixfold the control values at Week 4; by Week 6, there was no difference between groups. Changes in cell-specific enzyme activities were dose dependent and generally mirrored changes in the number of germ cells in the testis.

Acid Phosphatase↗

PubMed1984

Reproductive toxicity of dimethyl methyl phosphonate (DMMP) in the male Fischer 344 rat.

Dimethyl methyl phosphonate (DMMP) has been considered for use by the U.S. Armed Forces as a nerve gas simulant in a variety of experimental situations to simulate the physical properties of nerve gases, but not the neurotoxic properties. Dimethyl methyl phosphonate is also used as a flame retardant for urethane foams and polyester resins. This study was conducted to determine the reproductive toxicity of DMMP after subchronic dosing. DMMP was administered to male Fischer 344 rats by gavage 5 days/week for 90 days at dosages of 0, 250, 500, 1000, and 2000 mg/kg, and all animals survived this dosing schedule. At Day 84, the rats were mated to untreated female Fischer 344 rats. There was a dose-related decrease in sperm count, sperm motility, and the male fertility index. The male fertility index was 70, 75, 60, 40, and 0% in the 0, 250, 500, 1000, and 2000 mg/kg dose groups. DMMP acted as a dominant lethal mutagen as demonstrated by an increase in the number of resorptions with increasing doses of the drug. The percentage of resorptions in the control group was 6.1% and increased to 14.9, 37.8, and 79.1% in the 250, 500, and 1000 mg/kg groups, respectively. The testes of the male rats were examined histologically to determine the relationship between reproductive function and pathologic abnormalities. DMMP altered reproductive function at all dose levels, while histologic abnormalities of the testis were seen only in the high-dose group. Changes in the testes of the high-dose animals were characterized by lack of spermatogenesis or by degeneration, vacuolization, and necrosis of cells in the spermatogenic tubules. Histopathologic abnormalities of the kidney were seen in some animals from each of the dosed groups and microscopic changes of the prostate were seen in some of the high-dose animals.

Animals↗

PubMed1984

Development of reproductive tract lesions in male F344 rats after treatment with dimethyl methylphosphonate.

Dimethyl methylphosphonate (DMMP) is an organophosphorous compound that impairs fertility in male rodents. In previous studies, male rats treated with DMMP had decreased sperm motility and count, and sired fewer litters with fewer pups per litter. The following studies examined the development of the reproductive lesions by light and electron microscopy after treatment with DMMP. Adult male F344 rats were treated po with DMMP, 1750 mg/kg, for up to 12 weeks. Tissues were perfused in situ with Karnovsky's fixative and embedded in glycol methacrylate. After 5 weeks of treatment there were occasional PAS-positive bodies in lumina of tubules in stages XII-III. These were ultrastructurally similar to cytoplasm of step 12-17 spermatids. After 7 weeks of treatment, there was an increase in the number of tubules exhibiting these bodies, as well as an increase in the number of tubules showing delayed or early spermiation, or focal exfoliation of nonnecrotic cap-phase spermatids and some spermatocytes. No multinucleated giant cells were seen. Focal loss of germ cells occurred more frequently as duration of exposure increased, and occupied 5-100% of an affected tubule. Frequently, an area of germ cell exfoliation occurred adjacent to areas of normal tubular epithelium. These lesions were not specific to any particular stages of spermatogenesis. Occasionally, elongating spermatids were without rib elements of the fibrous sheath in the tail; these were not seen in epididymal sections. Animals left to recover for 14 weeks after treatment showed approximately 80% normal tubules; affected tubules varied in their degree of recovery, but all showed the loss of normal epithelial organization, a characteristic of DMMP treatment. Epididymal epithelium was not visibly affected by treatment with DMMP. DMMP produced morphologic alterations in Sertoli cells and elongating spermatids, as well as producing functional defects in spermatozoa.

Animals↗

PubMed1984

Estrogen-like activity of chlordecone (kepone) on the hypothalamo-pituitary axis: effects on the pituitary enkephalin system.

Similarities between the activity of chlordecone and estrogen on the hypothalamo-pituitary axis (HPA) were examined by using the pituitary enkephalin system as a model. A single injection (25 to 75 mg/kg, ip) or repeated injections (2.5 to 10 mg/kg/day for 10 days, ip) of chlordecone caused a time- and dose-related decrease in pituitary [Met5]-enkephalin-like immunoreactivity (ME-LI) in adult rats. Similar to the reported effects of estrogen, chlordecone treatment decreased the levels of ME-LI in the anterior lobe but not in the neurointermediate lobe of male pituitaries. Furthermore, chlordecone failed to alter the pituitary levels of ME-LI in female rats. The level of another pituitary peptide hormone, beta-endorphin, was increased in male rats after chlordecone treatment, indicating some degree of selectivity of this effect. Similarities between chlordecone and estrogen were found with other pituitary hormones, i.e., implantation of diethylstilbestrol or of chlordecone in ovariectomized rats caused qualitatively similar changes in serum prolactin and luteinizing hormone levels. These results suggest that chlordecone qualitatively resembles estrogen in its effect on some HPA peptide systems.

Animals↗

PubMed1984

Teratogenicity of 2.3.7.8-tetrachlorodibenzofuran (TCDF) in mice.

Treatment of pregnant C57BL/6N mice with 2,3,7,8-tetrachlorodibenzofuran (TCDF) (0, 250, 500, and 1000 micrograms/kg on gestation day 10 or 0, 10, 30, 50, and 100 micrograms/kg on gestation days 10-13) results in dose-related increases in isolated cleft palates and hydronephrotic kidneys in the offspring. TCDF is teratogenic in 100% of the fetuses at dose levels that are not maternally toxic. The fetal kidney is the most sensitive target organ but the kidney lesions may be reversible.

Abnormalities, Drug-Induced↗

PubMed1984

Immersion fixation methods for glycol methacrylate-embedded testes.

Routine processing of testicular tissue through 10% neutral buffered formalin (NBF) into paraffin produces severe cellular shrinkage which obscures most of the morphologic detail. The following studies were performed to compare different combinations of immersion fixatives and embedding media for optimal cellular detail in the final histologic sections. We examined sections of testes from rats, mice, and rabbits fixed in either NBF, Bouin's, Zenker's, or Helly's fixatives, and embedded in either standard paraffin or glycol methacrylate. The results were similar in all 3 species. In paraffin, Bouin's or Helly's fixatives produced the fewest artifacts, while in glycol methacrylate, NBF-fixed tissue showed the greatest intracellular detail and preservation. The merits and limitations of each method are discussed for the rat, with exceptions for the other species noted where appropriate. The use of glycol methacrylate as the support medium for sectioning makes high-quality tissue sections available from formalin-fixed testes.

Acrylates↗

PubMed1984

Effects of ethylene glycol monomethyl ether on various parameters of testicular function in the F344 rat.

These studies were designed to define the target cell for ethylene glycol monomethyl ether (EGME) action in the rodent testis, and to compare fluid production and protein secretory patterns in the testes of treated and control animals. Adult F344 rats were treated with 150 mg/kg/day, 5 day/week, and sacrificed 1, 2, 4, 7 or 10 days after the first dose. In the testes of treated animals, the most sensitive cells were the premeiotic and meiotic spermatocytes. As length of treatment continued, the younger transitional spermatocytes, and more pachytene spermatocytes, were affected. Early and late stage spermatids did not appear affected, nor was the visual appearance of spermatogonia changed by exposure to EGME. Fluid production, androgen-binding protein secretion and electrophoreograms of proteins found in the ligated rete testis were also unchanged by EGME, showing that these indices of Sertoli cell function were not affected by EGME. The histologic and biochemical data suggest that both early and late spermatocytes are targets for EGME in the testis, and that the Sertoli cells are relatively unaffected.

Androgen-Binding Protein↗

PubMed1984

Reproductive toxicity of ethylene glycol monoethyl ether tested by continuous breeding of CD-1 mice.

The reproductive toxicity of ethylene glycol monoethyl ether (EGEE) was evaluated in the Fertility Assessment by Continuous Breeding protocol. Both male and female CD-1 mice were given 0, 0.5, 1.0 or 2% EGEE in the drinking water and were housed as breeding pairs continuously for 14 weeks. Significant adverse effects on fertility were seen at 1 and 2% but not at 0.5%. After the continuous breeding phase of this test was completed, treated males were housed with control females and treated females with control males and fertility and reproduction were compared to the corresponding pairs of control male and control female mice. Both males and females from the 1 and 2% groups were affected. Testicular atrophy, decreased sperm motility and increased abnormal sperm were noted in the treated males, but no specific anomalies were detected in the females.

Abnormalities, Drug-Induced↗

PubMed1984

Neoplastic response of F344 rats and B6C3F1 mice to the polymer and dyestuff intermediates 4,4'-methylenebis(N,N-dimethyl)-benzenamine, 4,4'-oxydianiline, and 4,4'-methylenedianiline.

Feeding 4,4'-methylenebis(N,N-dimethyl)benzenamine [CAS: 101-61-1; 4,4'-methylenebis(N,N-dimethylaniline)] to inbred F344 rats increased the incidence of thyroid lesions (hyperplasia, adenomas, and carcinomas) in both sexes, especially in the female rats. 4,4'- Oxydianiline (CAS: 101-80-4) in the diet increased adenomas and carcinomas in the thyroid gland and neoplastic nodules and carcinomas in the liver of male and female F344 rats. In addition to increasing thyroid adenomas in females and hepatocellular adenomas or carcinomas in male and female B6C3F1 mice, 4,4'- oxydianiline increased adenomas of the harderian gland in male and female mice. 4,4'- Methylenedianiline (CAS: 101-77-9) in the drinking water increased neoplasms of the thyroid gland and liver in F344 rats and B6C3F1 mice.

Aniline Compounds↗

PubMed1983

The comparative effects of 1,2-dibromo-3-chloropropane (DBCP) and its metabolites, 3-chloro-1,2-propaneoxide (epichlorohydrin), 3-chloro-1,2-propanediol (alphachlorohydrin), and oxalic acid, on the urogenital system of male rats.

Reported similarities in the acute toxic effects of 1,2-dibromo-3-chloropropane (DBCP), 3-chloro-1,2-propaneoxide (epichlorohydrin, ECH), 3-chloro-1,2-propanediol (alphachlorohydrin, ACH), and oxalic acid (OA) have been suggested as presumptive evidence that the metabolism of DBCP to OA, via ECH and ACH, is the cause of the resulting injuries to the kidney and, perhaps, to the epididymis and testis. To test this hypothesis, the comparative toxicities of these four chemicals were studied in male rats after single subcutaneous (sc) injections of maximally tolerated (nonlethal) doses. Kidney, testicular, and liver functions were monitored, and the occurrences of morphological changes in these and several other organs were evaluated 24 hr, 3, 8, 25, and 75 days post-treatment. DBCP caused renal dysfunction (alterations in urine composition and reduced glomerular filtration rate) and marked necrosis of the proximal tubular epithelium in the outer medulla of the kidney. ACH and OA also elicited renal dysfunction, but ACH produced only a mild swelling of the proximal tubular epithelium in the renal cortex and OA produced a focal necrosis anatomically associated with crystal deposition. ECH caused a swelling of the proximal tubular epithelium in the renal cortex, but not frank kidney dysfunction. DBCP also caused a reversible vacuolization of the tubular epithelium in the caput epididymis, progressive testicular atrophy, and a reduction of cauda epididymal sperm concentration. ACH and ECH produced similar effects, as well as epididymal sperm granulomas, spermatocoeles, and an increase in the number of morphologically abnormal spermatozoa. OA failed to produce discernible epididymal or testicular lesions at any time during the study. The development of similar lesions in the epididymis and testis following DBCP, ECH, or ACH treatments is consistent with the theory of metabolism of these chemicals to a common causative gonadotoxic agent. Oxalic acid (OA), however, would not appear to be the common gonadal toxicant. Differences in the effects, both morphological and functional, of DBCP, ECH, ACH, and OA on the kidney, moreover, indicate that DBCP nephropathy is not mediated through metabolism to OA and suggest, as well, that it differs causally from that induced by ECH or ACH. Therefore, the metabolism of DBCP to ECH or ACH, and of ECH or ACH to OA, is insufficient to explain totally the toxic effects of these agents on the urogenital system in male rats.

Animals↗

PubMed1983

1,2-dibromo-3-chloropropane (DBCP)-induced infertility in male rats mediated by a post-testicular effect.

The potential for the chemosterilant 1,2-dibromo-3-chloropropane (DBCP) to reduce male fertility by acting at a site in the genital tract beyond the testis was evaluated in male, Fischer 344 rats. A single sc treatment with 100 mg/kg DBCP reduced fertility in male rats 2 to 7 days postexposure without affecting mating frequency. Doses of 10, 20, or 40 mg/kg DBCP given sc once daily for 7 days caused a dose-dependent reduction in the metabolism of glucose to CO2 by epididymal sperm, as measured in vitro. Conversion of glucose to lactate was not reduced, indicating inhibition of energy metabolism at a step post-glycolysis. No clinical signs of toxicity were observed in these studies. Direct addition of DBCP to epididymal sperm being incubated in vitro also inhibited the metabolism of glucose to CO2. Inhibition was concentration related, and the minimal inhibitory concentration was 0.316 mM. These data indicate that DBCP may cause a nearly immediate infertility via a direct effect on post-testicular sperm. A possible mechanism of this infertility is inhibition by DBCP of glucose metabolism in the ejaculated sperm.

Animals↗

PubMed1982

Subchronic dietary exposure of rats to chlordecone (Kepone) modifies levels of hypothalamic beta-endorphin.

Rats were exposed for extended times to low doses of chlordecone (1 and 6 ppm in the diet). After 105 days of exposure of female rats to this diet, levels of circulating prolactin and growth hormone were not significantly altered, but at the higher dose of chlordecone, hypothalamic beta-endorphin levels were selectively reduced. Since no changes were seen in pituitary levels of beta-endorphin of treated rats, chlordecone had some regional specificity. Levels of dopamine, serotonin, and their metabolites were unchanged in the caudate nucleus of female rats exposed to chlordecone. Thus, low levels of chlordecone appear to selectively affect hypothalamic beta-endorphin suggesting the hypothalamus may be especially sensitive to this neurotoxicant. The gestationally and lactationally-exposed female offspring of these rats showed a major increase in the levels of growth hormone at 100 days of age. However, other parameters assayed remained unaltered. These consisted of biogenic amines within the caudate nucleus, pituitary and hypothalamic met-enkephalin and circulating prolactin, growth hormone, and estrogen.

Animals↗