S.P. Srivastava

Male reproductive toxicity of sodium arsenite in mice

The effect of chronic oral exposure to arsenic on male mouse testicular and accessory sex organ weights, sperm parameters and testicular marker enzymes was studied. In addition, the distribution of arsenic in reproductive organs was measured using atomic absorption spectrophotometry. Sodium arsenite administered to mice (Mus musculus) via drinking water at a dose of 53.39 βmol/L (4 ppm As) for 365 days caused a decrease in the absolute and relative testicular weight. However, epididymal and accessory sex organ weight was similar to control. The activities of marker testicular enzymes such as sorbitol dehydrogenase, acid phosphatase and 17β-hydroxysteroid dehydrogenase (17β-HSD) were significantly decreased, but those of lactate dehydrogenase and γ-glutamyl transpeptidase (γ-GT) were significantly increased. A decrease in sperm count and sperm motility, along with an increase in abnormal sperm, was observed in arsenite-exposed mice. A significant accumulation of arsenic in testes, epididymis, seminal vesicle and prostate gland was observed in treated animals. Thus long term exposure (365 days) at the dose level of 53.39 μmol/L sodium arsenite (4 ppm As), to which human beings are likely to be exposed via drinking water, may cause testicular and spermatotoxic effect.

Effect of dermal application of hexachlorocyclohexane (HCH) on male reproductive system of rat

1 The toxic manifestations of dermally applied hexa chlorocyclohexane (50 mg or 100 mg kg-1 body weight day -1, 5 days in a week for 120 days) on testes and sperm of rat have been investigated. 2 The results indicate that exposure of HCH through the dermal route could lead to an alteration in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH), γ-glutamyl transpeptidase (γ-GT) and β-glucuronidase (βGluc.) associ ated with specific cell types. 3 Significant quantities of HCH and its isomers accumu lated in testes as well as sperm of treated rats. 4 HCH exposure also led to a decrease in serum testos terone levels, epididymal sperm count, sperm motility and an increase in the percentage of abnormal sperm. 5 These observations indicate the possibility of adverse effects of HCH on the male reproductive functions of men exposed dermally to this pesticide in industry or during spraying in the field.

Effect of oral administration of carbofuran on male reproductive system of rat

1 Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg -1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg -1 body weight 2 A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3 Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormali ties in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbo furan kg-1 body weight. 4 In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) (increased) depending on dose. 5 Histologically, the results indicated the toxicity of carbo furan on testes depending on dose. The changes pre dominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6 These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemi cal and morphological indices studied for male repro ductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.

Testicular effects of di-n-butyl phthalate (DBP): Biochemical and histopathological alterations

Di-n-butyl phthalate (DBP) was administered to young male rats by gavage at the doses of 250, 500 and 1000 mg/kg body weight/day for 15 days. A significant decrease in testes weight was observed at 500 and 1000 mg/kg doses of DBP. Histopathological examination revealed marked degeneration of seminiferous tubules. The activities of testicular enzymes associated with postmeiotic spermatogenic cells, such as sorbitol dehydrogenase and acid phosphatase, were decreased significantly, while that of lactate dehydrogenase was significantly increased, coincident with degeneration of spermatogenic cells. The activities of enzymes associated with premeiotic spermatogenic cells, Sertoli cells or interstitial cells, β-glucuronidase, γ-glutamyl transpeptidase and glucose-6-phosphate dehydrogenase were significantly increased. Thus the alterations in activity of these testicular cell specific enzymes suggest that DBP exposure during early life could affect the testicular functions.

Effect of di-2-ethylhexyl phthalate (DEHP) on rat gonads.

Abstract Activity of succinic dehydrogenase and adenosine triphosphatase was significantly reduced and that of β-glucuronidase was increased in rat gonads after treatment with di-2-ethylhexyl phthalate (DEHP). Histopathological studies revealed focal degeneration of seminiferous tubules and edema of interstitium in testis but no detectable alterations in ovary of treated animals as compared to controls. Such alterations may perhaps be responsible for the reported reproductive dysfunction in experimental animals after exposure to this and other phthalate plasticizers.

In utero and lactational exposure of carbofuran to rats: Effect on testes and sperm

1 Male offspring of adult females treated with 0.2 or 0.4 mg/kg during either the whole of pregnancy or the whole of the lactation period did not induce general ised toxic effects. 2 A significant alteration in enzymatic activities i.e. SDH (decreased), LDH and Y-GT (increased) were observed in testes only at 0.4 mg/kg. 3 A decrease in sperm motility, sperm count along with increase in percent abnormal sperm was observed at 0.4 mg/kg dose level. 4 Histopathological examination revealed loss of sper mato-genesis, degenerative changes in Sertoli cells which are well supported with biochemical studies indicating that carbofuran interferes with the matura tion process of testis. 5 No such effects were observed at 0.2 mg/kg. 6 The testicular and spermatotoxic effects observed in rats given in utero or lactational exposure may be due to transfer of carbofuran or its metabolites through placenta or mothers milk.

Testicular effects of acrylonitrile in mice

Daily oral administration of acrylonitrile (10 mg/kg body weight) to mice for a period of 60 days caused a significant decrease in the activity of testicular sorbitol dehydrogenase and acid phosphatase, and an increase in that of lactate dehydrogenase and beta-glucuronidase. Histopathological studies revealed degeneration of the seminiferous tubules. A decrease in the sperm counts of the epididymal spermatozoa was also observed in the animals of the acrylonitrile-exposed group. These observations suggest that acrylonitrile may affect the male reproductive function by causing testicular injury.

Effect of di-2-ethylhexyl phthalate (DEHP) on glycogen metabolism in rat liver

Effect of di-2-ethylhexyl phthalate (DEHP) on glycogen contents and certain enzymes of carbohydrate metabolism of rat liver was investigated. A significant decrease in glycogen content of unfasted and an increase in fasted animals was observed. Blood glucose tolerance was reduced and the rate of both glycogenesis and glycogenolysis, as judged by measuring glycogen contents after feeding labelled and unlabelled glucose, was also decreased. Activities of glucose-6-phosphate dehydrogenase, phosphorylase and glucose-6-phosphatase were significantly decreased while activities of fructose-1-6-diphosphatase and aldolase remained unaltered. The present results suggest that DEHP affects both glycogenesis and glycogenolysis in rat liver.

Spirometric abnormalities among welders

A group of manual welders (N = 57) engaged in gas welding joint faces of moulded brasswares, age group 13-60 years (mean: 29.2 +/- 1.37 years), having a mean exposure period of 12.4 +/- 1.12 years (range: 1-35 years) were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The findings were compared with those obtained from a reference group (N = 131) (mean age: 31.2 +/- 1.35 years) engaged in nonwelding jobs such as packing, labelling, and transportation of the finished brassware articles. The welders showed a significantly higher prevalence of respiratory impairment (28.0%) than that observed among the unexposed controls (6.1%) (P less than 0.001), as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the exposed group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders (40.0 vs 18.7%) (P less than 0.10). A similar trend was observed in the control group indicating that smoking had a deteriorating effect on spirometric tests. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment (12.3%) followed by a mixed ventilatory defect (8.7%) among the welders. The effect of age on pulmonary impairment was not discernible either in the exposed or unexposed group. The analysis of data in relation to duration of exposure showed significant correlation between the prevalence of respiratory abnormalities and length of exposure. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years (44.4 vs 13.3%) (P less than 0.01) thereby showing that occupational exposure to welding fumes resulted in increased prevalence of pulmonary impairment in the welders. Smoking also had a contributory role thereby suggesting an interaction between smoking and welding exposure on the prevalence of pulmonary impairment in the welders engaged in brassware industries.

Effect of Di-(2-ethylhexyl) phthalate (DEHP) on chemical constituents and enzymatic activity of rat liver.

Effect of Di(2-ethylhexyl) phthalate (DEHP), was investigated on chemical constituents and activity of certain enzymes of rat liver. A significant increase in liver weight; total and relative to body weight; decrease in total, free and esterified cholesterol; and no change in dry weight, moisture; RNA, DNA, total lipids, phospholipids, pyruvic acid and lactic acid contents was observed in liver of DEHP-treated rats as compared to controls. Activity of 3 mitochondrial enzymes, malic dehydrogenase, cytochrome-c-oxidase and diaphorase were significantly decreased while that of NADH-cytochrome c reductase, RNAase and DNAase remained unaltered upon treatment. The results suggest that DEHP exerts its hepatotoxic effects by interfering with bioenergetics of the cell.