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[Toxicity of dichloropropanols].

A rare outbreak of acute hepatic damage in workers exposed to dichloropropanols was reported in 1992. As there are no detailed reports of dichloropropanols (DCPs) toxicity and its mechanism, we reviewed the toxicity of dichloropropanols using our results. 1) A marked elevation of serum AST and ALT with massive necrosis of the liver was noted in the 1/2 x, the 1 x and 2 x LD50 (0.149 mg/kg) of 1, 3-dichloro-2-propanol(DC 2 P). Hepatic malondialdehyde level was significantly increased, and associated with a decrease in liver glutathione S-transferase activity and reduced glutathione content. It is suggested that the free radical is associated with DCPs. 2) A reduction of leukocytes, platelets and fibrinogen, and prolonged prothrombin time were observed in the 1 x LD50 of DC 2 P. 3) In the CA1 area of the hippocampus, inhibition of population spikes was reduced by the 1 x LD50 of DC 2 P. This research was completed with the assistance of several other papers concerning dichloropropanols toxicity.

Animals↗

Conformational features of reduced and disulfide intact forms of hen egg white lysozyme in aqueous solution in presence of 3-chloro-1, 2-propanediol and dioxane: implications for protein folding intermediates.

Conformational features of reduced and disulfide intact hen egg white lysozyme in aqueous 1,4-dioxane and 3-chloro-1, 2-propanediol solutions have been examined using circular dichroism and fluorescence spectroscopy. We find that in presence of 1, 4-dioxane, reduced lysozyme assumes a relatively compact conformational form with secondary structure closer to native state and no tertiary structure as judged by peptide and aromatic CD spectra and ANS binding studies monitored by fluorescence. Further, in presence of 40% (v/v) 3-chloro-1, 2-propanediol, disulfide intact lysozyme (DI-lysozyme) assumes a conformational form with native like secondary structure and no tertiary structure akin to a molten globule state. We correlate our results to kinetic hydrogen- deuterium exchange NMR results of the refolding of lysozyme available in literature and suggest that the conformational forms observed in our study could be models for kinetic intermediates in the refolding of lysozyme.

Animals↗

[Survey of 3-monochloropropane-1,2-diol in soy sauce and similar products].

A survey of 3-monochloropropane-1,2-diol (3-MCPD) in soy sauce and other similar products available in China has been completed. Thirty samples of soy, oyster sauce and other sauces were purchased from six supermarkets in Beijing during March and April 2000 and analysed using a validated method of analysis by capillary gas chromatography with mass spectrometric detection. The UK Food Advisory Committee (FAC) has advised a level of 0.01 mg/kg for 3-MCPD. Following reports that high levels had been detected in some brands of soy sauce in China. 3-MCPD was undetectable with a detection limit of 0.01 mg/kg in 15 of the 30 samples analyzed in the survey, with a further 4 samples (13.3%) containing very low levels of between 0.01 and 0.02 mg/kg. However, 5 samples (16.7%) contained 3-MCPD levels above 1 mg/kg.

Chemosterilants↗

Determination of 3-chloro-1,2-propanediol in foods and food ingredients by gas chromatography with mass spectrometric detection: collaborative study.

The results of a collaborative study are reported for the determination of 3-chloro-1,2-propanediol (3-monochloropropane-1,2-diol; 3-MCPD) in a wide range of foods and food ingredients, using gas chromatography with mass spectrometric detection and incorporating the use of a deuterated internal standard. After a pretrial study, 12 laboratories (6 United Kingdom, 1 Switzerland, 1 Japan, 2 United States, 1 The Netherlands, and 1 from the European Commission) were asked to analyze 12 test materials (as known duplicates or split-level samples) by using a prescribed procedure. The test materials consisted of duplicate samples of acid-hydrolyzed vegetable protein (containing 3-MCPD at 0.029 mg/kg), malt extract (0.055 mg/kg), wholemeal bread crumbs (0.030 mg/kg), salami (0.016 mg/kg), cheese alternative (0.043 mg/kg), and soup powder (split levels at 0.045 and 0.041 mg/kg). Repeatability ranged from 0.005 to 0.013 mg/kg and reproducibility, from 0.010 to 0.027 mg/kg, for the samples tested. Precision values were well within statistically predicted levels (HORRAT values of <1 for 5 of the 6 matrixes tested) and within method criteria prepared by a joint working group composed of the United Kingdom Ministry of Agriculture, Fisheries and Food and industry representatives. The study demonstrated the satisfactory validation of the method for quantifying 3-MCPD at levels of > or = 0.010 mg/kg. The limit of detection derived from separate in-house studies was estimated to be 0.005 mg/kg. The method was adopted First Action by AOAC INTERNATIONAL.

Animal Feed↗

[Study on the toxicological effect of chloropropanols on rats].

Toxicological effect of 3-chloro-1,2-propanediol on rats were studied to provide scientific basis for assessing the effect of Chloropropanols on human health. 170 SD rats were divided randomly into 8 groups and the dose of 0, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0 mg/kg 3-chloro-1,2-propanediol were given to rats for 90 days by gavages per day, respectively. The weight and food efficiency, hematology and clinical chemistry, NAG, GGT and total protein in urine, sperm number, sperm survive rate and sperm aberration rate, the LDH and LDH-X activity in testis, rate of organ/weight and histopathological analysis were measured. The results showed that different dose of 3-chloro-1,2-propanediol did not has adverse effect on body weight, food efficiency, Hb, red cell, white cell, serum AST, ALT, creatine, ALP, LDH, total protein and albumin, urine GGT and total protein, LDH activity in testis. At the dose of 4.0, 8.0 and 16.0 mg/kg group, the activity of NAG in urine and the rate of kidney/weight was significantly increased compared with negative control groups; the pathological changes in kidney were observed in the same groups, and the sperm number was also significantly decreased. At the dose of 8.0 and 16.0 mg/kg group, sperm survive rate and the X-LDH activity were significantly decreased and pathological changes were also observed in testis and caudal epididymis. It was concluded that the activity of NAG in urine and sperm number is the sensitive biological effective marker. Because urine is a kind of convenient available biological material, NAG activity in urine is a good biological effective marker for assessing effect of Chloropropanols on health. If the NAG activity can be used as sensitive marker for assessment on human health need to be tested further in human study.

Acetylglucosaminidase↗

[Study on the absorption, distribution and excretion of 3-chloro-1,2-propandiol in rats].

OBJECTIVE: To explore the absorption, distribution and excretion of 3-Chloro-1,2-propandiol (3-MCPD) in healthy male SD rats after oral administration. METHODS: 3-MCPD was administrated with a single oral dosage of 75 mg/kg BW to each rat. Samples of blood, tissues (including liver, kidney, brain and testicle) and excreta were then collected, and analyzed by the GC-MS method to determine 3-MCPD concentrations. The reported value is the mean value of three rats. RESULTS: At 2 h after the administration, 3-MCPD concentrations in blood, testicle and kidney were (67.46 +/- 7.72), (78.37 +/- 5.15) and (56.21 +/- 3.64) microg/g, respectively. At 24 h, however, the corresponding values changed to (1.07 +/- 0.97) microg/g, (49.43 +/- 28.18) microg/g and (11.41 +/- 2.55) microg/g. During the 24-hour period, 9.74 +/- 3.05% of the given parent compound was excreted in urine, whereas 0.56 +/- 0.22% and 0.28 +/- 0.03% were excreted in feces and bile, respectively, which implies that kidney is a major organ for excretion 3-MCPD. CONCLUSIONS: 3-MCPD was quickly absorbed through the alimentary tract and quickly distributed into a number of tissues, and then accumulated in the target organs, especially in the testicle. The excretion of the parent compound was largely through the kidney. It was inferred that 3-MCPD was mainly metabolized in the liver.

Absorption↗

Malignant transformation of mouse M2-fibroblasts by glycerol chlorohydrines contained in protein hydrolysates and commercial food.

Glycerol chlorohydrines, such as 3-chloro-1,2-propanediol and 1,3-dichloro-2-propanol, are present in commercial protein hydrolysates used for human nutrition. These compounds are genotoxic and 1,3-dichloro-2-propanol induced tumors in rats. Now it is reported that both compounds are active at inducing malignant transformation of mouse fibroblasts. Therefore, the carcinogenic risk to humans by exposure to these compounds contained in food is of concern. The investigation of the in vivo carcinogenic potential of 3-chloro-1,2-propanediol is urgently required to further evaluate the carcinogenic risk to exposed consumers.

Animals↗

Nonhormonal mediation of male reproductive tract damage: data from contraceptive drug research.

Chemicals can interfere with hormonal control of the male reproductive tract and/or directly alter male reproductive tract function. A review is presented of those chemicals developed and tested as male contraceptive agents which have a direct effect on the male reproductive tract with minimal disturbance of the hormonal milieu. Such chemicals can have one or more sites of action: 1) the testis, disturbing spermatogenesis; 2) the epididymis, altering sperm maturation; 3) the vas deferens, affecting sperm transport; and 4) the accessory sex glands, entering the ejaculate and changing the functional activity of the spermatozoa. Examples of each mode of action are presented.

Animals↗

Effects of low doses of alpha chlorohydrin on the lipid metabolism of the rat testis and epididymis--a correlative histochemical and biochemical study.

A biochemical and histochemical study was carried out on the effects of low doses of alpha chlorohydrin on the lipid metabolism of the rat testis and epididymis. Administration of alpha chlorohydrin in low doses (6.5 mg/kg for 9 days) to Wistar strain rats caused an elevation of lipid levels in the testis and epididymis. Actually, an increase in the neutral fat occurred with a corresponding decrease in the phospholipids after treatment with alpha chlorohydrin. We suggest that the rat's total lipid, total cholesterol, cholesterol esters, and triglycerides were increased at the cost of phospholipids. The altered levels of lipid fractions were due to the increased activity of glycerol phosphate dehydrogenase and to the decreased activities of nonspecific esterase and lipase after treatment with the drug. These alterations of lipid metabolism, which were regulated through their enzyme systems, strongly reflect the damage to the metabolism of the testis and epididymis after treatment with low doses of alpha chlorohydrin, although there was no histological damage at this dose level.

Animals↗

The epididymal microenvironment: a site of attack for a male contraceptive?

During their development, spermatozoa are continually bathed in fluid provided by epithelial secretions of the seminiferous tubule and the epididymal duct. This fluid or microenvironment is probably very important for spermatozoal maturation and survival. Micropuncture and microanalytic studies have revealed the occurrence of several biochemical changes of this specialized microenvironment along the epididymal duct; these changes seem to be linked to sperm maturation. The interactions between maturing spermatozoa and their microenvironment must be understood before interference in sperm maturation through intervention of the formation of the microenvironment is possible. Several compounds have been shown to interfere in spermatozoal maturation in the epididymis although their use as male contraceptives requires further investigation.

Animals↗