bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in hepatic biochemistry of mice intoxicated with MIC, carbaryl and thiram
Authors: Gupta Meenakshi , Amma M. K. P.
Published: October 2006

The effect of different doses of methyl isocyanate (MIC), carbaryl and thiram on liver microsomal mixed‐function oxygenases (MFO) was studied in adult Swiss Portan mice by intraperitoneal (i.p.) injection for different durations. The LD50 dose of all three toxicants after 0.75 h of administration could increase cytochrome P‐450 and cytochrome b5 contents (82–143%), and the 1/4LD50 of these compounds could elicit the same effect after 168 h (168–393%). The 1/4LD50 dose of thiram decreased the cytochrome P‐450 content below the control level (69.62%) in 0.75 h and the same dose of MIC could decrease the cytochrome P‐450 level by 40% compared to the control after 3 days of consecutive injection. The activities of drug‐metabolizing enzymes (aminopyrine demethylase—NADH and NADPH‐linked—and aniline hydroxylase) were found to increase with all three compounds in general. Marked changes in the activity of the marker enzyme glucose‐6‐phosphatase were also seen after i.p. injection if MIC, carbaryl and thiram. These findings suggested that these compounds were hepatotoxic, which could be due to their carbamylating nature.
Comparative study on the changes in AChE and ATPase activities in neonate and adult rat brains under thiobencarb stress
Authors: Pentyala Srinivas N. , Chetty C. S.
Published: October 2006

Thiobencarb (S‐(4‐chlorobenzyl)‐N,N‐diethyl thiol carbamate), a dithiocarbamate herbicide, was found to cause neuronal dysfunction in adult and neonate albino rats. In general, organocarbamates exert their action by inhibiting acetylcholinesterase (AChE) activity. Thiobencarb inhibited both acetylcholinesterase and adenosine triphosphatase (ATPase) activities in rat brain. Withdrawal of thiobencarb treatment resulted in the recovery of AChE activity to a normal level, whereas there was no recovery of Na+–K+‐ATPase activity in either neonate or adult rat brains. The results suggest that neuronal dysfunction caused by thiobencarb is mainly due to the inhibition of ATPase activity rather than to the inhibition of AChE activity.
The renal handling of calcium and phosphorus in environmental cadmium‐exposed subjects with renal dysfunction
Authors: Kido Teruhiko , Nogawa Koji , Hochi Yasushi , Hayano Masashi , Honda Ryumon , Tsuritani Ikiko , Ishizaki Masao
Published: October 2006

Clearance methods were used to clarify the renal handling of calcium (Ca) and phosphorus (P) in a population with renal dysfunction induced by exposure to environmental cadmium (Cd). Seventy‐six Cd‐exposed subjects (32 men and 44 women) and 36 non‐exposed subjects (18 men and 18 womén) took part in this study.

Fractional excretion of P was higher in the Cd‐exposed subjects than in the non‐exposed subjects, while that of Ca was equal to that of the non‐exposed subjects. The urinary excretion rates of Ca and P tended to be lower in the Cd‐exposed subjects than in the non‐exposed subjects. The urinary excretion rate of Ca was closely related to creatinine clearance, while that of P was related to creatinine clearance and the percentage tubular reabsorption of phosphorus. It is thought that in Cd‐induced renal dysfunction the urinary excretion of Ca depends on glomerular function, and no increased excretion of urinary Ca was observed by these clearance methods.

It is also clarified that the parallelism in the urinary excretion of Ca and Na persists in Cd‐exposed subjects with renal dysfunction.
Acute and subacute toxicity of 7.5% hypertonic saline–6% dextran‐70 (HSD) in dogs 2. biochemical and behavioral responses
Authors: Dubick Michael A. , Zaucha Gary M. , Korte Don W. , Wade Charles E.
Published: October 2006

7.5% Hypertonic saline–6% Dextran‐70 (HSD) is currently being evaluated in our laboratory as a resuscitation solution for the treatment of hypovolemia at a dose of 4 ml kg−1 body weight. A few reports of dextran toxicity, particularly of the kidney, have been cited in the literature, so the present study evaluated the acute and subacute toxicity of HSD administered i.v. to beagle dogs. In the acute toxicity studies animals were infused with a single dose of HSD, or its components of hypertonic saline (HS) or Dextran‐70 (D‐70), at the maximum tolerated dose (MTD: 20 ml kg−1). Controls received Ringers lactate (RL). In the HSD‐infused dogs, transient but significant increases in serum alanine (ala) aminotransferase (AT), aspartate (asp) AT and alkaline phosphatase (AP) were observed for the first 72 h. In most cases this increase was also observed in the HS group. In the subacute studies, dogs were infused daily with the MTD of the above test solutions. Serum ala AT activity was 2–3‐fold higher in the HSD than the RL group for the first 3 days. Again, a similar effect was observed in the HS group. Slight, transient increases in asp AT and AP activity were also observed in the HSD group. Higher lactate dehydrogenase (LDH) activity was only observed at Day 14 in dogs infused with the MTD of HSD or HS. In both studies, no adverse effects on blood urea nitrogen (BUN) or serum creatinine were observed and other transient changes in serum parameters were attributable to hemodilution induced by HSD. No gross or microscopic lesions were observed in any major organ. Considering that the proposed therapeutic dose of HSD is only 4 ml kg−1, it appears that its use should be associated with minimal or no adverse effects.
Effect of propane‐1,2‐diol ingestion on carbohydrate metabolism in female rat erythrocytes
Authors: Saini Mohini , Nagpaul J. P. , Amma M. K. P.
Published: October 2006

This study was undertaken to assess the effect of propane‐1,2‐diol(PD) ingestion on carbohydrate metabolism in female rat erythrocytes. For this purpose, two different groups of adult albino female rats were treated orally with PD at two different dose levels of 73 and 294 mg 100 g−1 body wt. The blood samples drawn from the retro‐orbital sinus prior to the treatment served as the controls, whereas the treated samples were collected at peak periods (1/2 and 2 h) 2 and 7 days after the treatment. A' single dose of PD was found to elevate levels of blood glucose, lactate, pyruvate and the lactate/pyruvate ratio at the peak periods (P < 0.001) and after 2 days (P < 0.001) in both the groups. A significant (P < 0.05) increase in the contents of erythrocyte 2,3‐diphosphoglycerate (2,3‐DPG) was observed only at the peak periods. All these parameters returned to their base level after 7 days of treatment. The activities of hexokinase (HK), 2,3‐diphosphoglycerate phosphatase (2,3‐DPG Pase), lactate dehydrogenase (LDH), glucose‐6‐phosphate dehydrogenase (G‐6‐PD), 6‐phosphogluconate dehydrogenase (6‐PGD) and aldehyde reductase II (AR II) declined markedly, whereas those of pyruvate kinase (PK) and aldose reductase increased as a result of PD ingestion. The changes in the activities of 2,3‐DPG Pase and LDH were persistant up to 8 days post‐treatment. The [14C]glucose flux through glycolysis and the hexose monophosphate shunt pathway in erythrocytes was found to be lowered (P < 0.001) in response to PD treatment. The present work revealed that a single oral dose of PD was capable of producing significant alterations in carbohydrate metabolism in female rat erythrocytes.
Effect of acute pretreatment of lead on picrotoxin‐induced convulsions in rats
Authors: Krishnamoorthy M. S. , Parthiban N. , Muthu P. , Paul V. , Balagopal G. , Kumaravel T. S.
Published: October 2006

The effect of acute exposure to lead acetate (LA)/lead nitrate (LN) on onset and severity of convulsions induced by a low dose of picrotoxin was examined in rats. Both LA and LN reduced the time of onset and exacerbated the severity of convulsions, with a resultant high lethality. On comparison, it was noted that in the LA‐pretreated group, convulsion scores and incidence of tonus and mortality were much higher; the appearance of tonus was more delayed than in the LN‐pretreated group. In lead‐pretreated animals, the potentiation of picrotoxin‐induced convulsions was accompanied by higher lead levels in blood (p<0.001). However, the whole‐brain lead levels were not significantly different in these animals compared to the controls. The difference in the degree of potentiation by the two forms of lead could possibly be attributed either to the role of a combination of anions and cations or to the variable cerebral uptake and regional distribution of lead or due partly to the extent of competitive interaction involving d‐aminolaevulinic acid—whose level is known to be elevated consequent to lead‐induced disruption of haem biosynthesis–at GABA receptors.
Soman‐induced morphological changes: An overview in the non‐human primate
Authors: Baze Wallace B.
Published: October 2006

A review of the literature was conducted to provide an overview of organophosphorus (OP)‐induced morphological changes in the non‐human primate. Most studies have evaluated effects of the OP nerve agent soman (pinacolyl methylphosphonofluoridate), an irreversible inhibitor of acetylcholinesterase. Soman‐induced acute and chronic morphological changes have been examined. The effects of nerve agent therapy (i.e. pyridostigmine, praloxidime chloride and atropine), with and without an anticonvulsant (i.e. diazepam, midazolam), on soman‐induced lesions have also been studied. Acute changes in the central nervous system of rhesus and cynomolgus monkeys exposed to soman alone or soman and therapy, without an anticonvulsant, were characterized by neuronal degeneration and necrosis and neuropil edema. The lesions were usually present in the frontal cortex, entorhinal cortex, amygdaloid complex, caudate nucleus, thalamus and hippocampus. Morphologically, these lesions resemble lesions produced by hypoxic‐ischemic injury or by seizures and are similar to soman‐induced changes in other laboratory animals. Nerve agent therapy supplemented with an anticonvulsant reduced or prevented soman‐induced acute neural lesions. Acute changes in non‐neural tissues were limited to the heart (e.g. hemorrhage, myofiber necrosis, myocarditis) and skeletal muscle (e.g. myofiber necrosis). Heart lesions in the non‐human primate are similar to OP‐induced heart lesions in man. The pathogenesis of the acute lesions in both the central nervous system and heart is discussed. Consistent soman‐induced chronic morphological changes have not been produced in the rhesus monkey or baboon.
Maximum dosage level in testing low‐toxicity chemicals for carcinogenicity in rodents
Authors: Apostolou Alexander , Helton Edward D.
Published: October 2006

Owing to the lack of sufficient theoretical and empirical information, the initial guidelines regarding animal carcinogenicity testing of chemicals adopted the most conservative approach possible. One of the recommendations was that non‐toxic chemicals be tested at a level as high as 5% of the diet. Since then, a wealth of information has been accumulated, which indicates that such highly exaggerated dosage levels are not only unnecessary but produce scientifically misleading and regulatorily detrimental results that impede the development and evaluation of useful chemicals, including human drugs. This paper presents the rationale supporting the necessity of revision of the outdated maximum level of dietary exposure from 5% to 1% or 1000 mg kg−1 day−1 when the test chemical is administered in drinking water or by gavage.
Relationship between physicochemical properties of prussian blue and its efficacy as antidote against thallium poisoning
Authors: Kravzov J. , Rios C. , Altagracia M. , Monroy‐Noyola A. , López F.
Published: October 2006

In the present work we established a relationship between some physicochemical properties of two different batches of Prussian blue (PB) and their in vivo efficacy as an antidote against thallium poisoning. They physicochemical properties studied were crystallite size and thallium‐adsorbing capacity. One of the batches was synthesized and the other was obtained from commercial sources. The synthesized PB batch with the smallest crystallite size had both the highest adsorption capacity and antidotal efficacy. Synthesized PB protected 100% of the animals against one LD50 thallium dose, whereas the commercial PB batch protected only 80%. Thallium content in blood and tissues (liver, kidney, brain) was also analysed after antidotal PB treatment in rats previously intoxicated with a sublethal dose of Tl+, Animals treated with synthesized PB showed significantly less thallium in blood and tissue contents than those values of commercial PB‐treated rats, indicating better antidotal properties of the synthesized PB. According to the present study we suggest an in vivo evaluation of the compound before distribution of the product to toxicological units, if X‐ray diffractometric analysis is not available, in order to identify and determine the crystallite size of the compound as it plays an important role in the efficacy of PB.
Developmental toxicity of OTTO fuel II in the rat and rabbit
Authors: Cooper James R. , Lee Lanfong H. , Macys David A.
Published: October 2006

OTTO Fuel II (OFII) is a propellent used by the United States Navy in its Mk 46 and Mk 48 torpedoes. Owing to the possibility of human exposure during fueling and defueling operations, studies were initiated to determine if OFII was a developmental toxin. Phase I of the investigation involved dosing four groups of time‐mated Fischer‐344 rats with OFII. The fuel was administered dermally at the rate of 0, 400, 2000 and 4000 mg kg−1 day−1. A significant reduction in body weight was seen at necropsy in dams receiving 2000 and 4000 mg kg−1 day−1 of OFII. Fetuses from these dams also weighed significantly less than control fetuses.

Phase II of the investigation involved dosing of artificially inseminated rabbits with OFII. The fuel was administered to the skin of the animal's back at the rate of 0, 100, 316 and 1000 mg kg−1 day−1. Maternal toxicity was evidenced by a significant reduction in body weight of the dams in the 1000 mg kg−1 day−1 dose group on days 20 and 25 of gestation. There were no significant differences observed in maternal weight or fetal weight at necropsy. Morphological examination of both rat and rabbit fetuses failed to reveal significant evidence of fetal malformations.
Mechanism of testicular atrophy induced by Di‐n‐butyl phthalate in rats. part 4. changes in the activity of succinate dehydrogenase and the levels of transferrin and ferritin in the sertoli and germ cells
Authors: Fukuoka Masamichi , Kobayashi Tetsu , Zhou Yu , Hayakawa Takao
Published: October 2006

A single oral dose of di‐n‐butyl phthalate (DBP) to male rats caused a sloughing of the germ cells at 6 h both with a decrease in the activity of succinate dehydrogenase (SDH) in the Sertoli cells and in the Sertoli‐germ connection and with an increase in the activity of lactate dehydrogenase (LDH) in the germ cells. Increases in transferrin (Tf) concentrations were observed in the Sertoli cells, Sertoli‐germ connection, epididymis‐ductus deferens and liver of rats. Decreases in Tf and ferritin (Ft) levels were observed in the seminal vesicle and seminiferous lumen, respectively. An increase in favin adenine dinucleotide (FAD) level was found in the interstitial cells.
Lipid peroxidation and disintegration of the cell membrane structure in cultures of rat lung fibroblasts treated with asbestos
Authors: Iguchi Hiroshi , Kojo Shosuke , Ikeda Masayuki
Published: October 2006

Rat lung fibroblasts were cultured for 24 and 48 h with UICC standard reference asbestos samples of amosite, crocidolite or Canadian chrysotile at various concentrations, and thiobarbituric acid‐reactive substances (TBARS) in the media and the cells were measured. Tests by the trypan blue dye‐exclusion method showed that cell viability was 80 ± 5% (mean ± SD) and 71 ± 6% when cultured for 48 h in the presence of 500 μg ml−1 of amosite and crocidolite, respectively, but was not affected by chrysotile. In cultures for 24 and 48 h, both chrysotile and crocidolite at > 250 μg ml−1 significantly increased TBARS in the medium, whereas amosite did so at > 500 μg ml−1.

TBARS in the cells was not increased significantly by chrysotile at any concentration in the cultures for 24 and 48 h, but crocidolite at > 250 μg ml−1 significantly increased TBARS in the cells when cultured for 24 or 48 h. Although amosite at all concentrations tested did not increase significantly TBARS in the cells of the 24‐h culture, it did increase TBARS significantly in the cells when cultured for 48 h at a concentration of 500 μg ml−1 amosite.

The increases of TBARS in media of the cultures with asbestos were accompanied by increases of lactate dehydrogenase (LDH) activity in the media, indicating the leakage of the enzyme from the cell into the media. The activity of LDH and the amount of TBARS showed a good correlation with each other, with a significant correlation coefficient value of 0.655.

Thus, the amount of TBARS produced during the culture seemed to change, depending on both the asbestos concentration and the inherent properties. The findings suggest that when certain types of asbestos are cultured with rat lung fibroblasts the cell membranes are peroxidized to cause disintegration of the membrane structure, followed by leakage of cellular LDH into the medium.
Phosphatase activities in pesticide‐treated growing and developing cells of Dictyostelium discoideum
Authors: Gayatri R. , Chatterjee S.
Published: October 2006

The effects of benzene hexachloride (BHC), an organochlorine pesticide, on cell growth and phosphatase activities were studied in the growing and developing stages of cells of the cellular slime mould Dictyostelium discoideum exposed to BHC (containing α‐, β‐, δ‐ and γ‐isomers) at concentrations of ≥ 60 μg ml−1. A significant increase in acid and alkaline phosphatase activities was recorded in both growing and differentiating Dictyostelium cells treated with different doses (≥ 60 μg/ml) of BHC. The cytotoxicity of BHC has been correlated with the stimulation of acid and alkaline phosphatase activities of this organism.
Gas chromatographic determination of vaporphase biomarkers formed from rats dosed with CCl4
Authors: Dennis K. J. , Ichinose T. , Miller M. , Shibamoto T.
Published: October 2006

Sprague‐Dawley rats dosed with CCl4 (3 ml kg−1) were placed in a glass chamber through which air was passed continuously at a rate of 60 ml min−1. Volatile aldehydes and ketones in expired air from rats were derivatized to thiazolidines by passing the effluent gas stream through an aqueous cysteamine solution. The thiazolidine derivatives were then extracted and analyzed by gas chromatography with a nitrogen‐phosphorus detector and gas chromatography/mass spectrometry. The compounds identified were formaldehyde, acetaidehyde, acetone and formyl chloride. There were no appreciable differences in levels of formaldehyde and acetaldehyde between CCl4‐dosed rats and control rats, whereas the levels of acetone in CCl4‐dosed rats showed an increase compared to those in control rats. Results suggest that acetone is the major volatile carbonyl compound produced following acute doses of CCl4. Results of thiobarbituric acid assay on the livers from a control rat and a CCl4‐dosed rat did not show any appreciable differences.
Decreasing 203Hg retention by intraperitoneal treatment with monoalkyl esters of meso‐2,3‐dimercaptosuccinic acid in rats
Authors: Kostial K. , Blanuša M. , Šimonović I. , Jones M. M. , Singh P. K.
Published: October 2006

The effect of nine monoalkyl esters of meso‐2,3‐dimercaptosuccinic acid (DMSA) on 203Hg retention after a single i.p. dose was evaluated in 6–7 week‐old female albino rats. The monoesters were the monomethyl (MMDMS), monoethyl (MEDMS), mono‐n‐propyl (Mn‐PDMS), monoisopropyl (Mi‐PDMS), mono‐n‐butyl (Mn‐BDMS), monoisobutyl (Mi‐BDMS), mono‐n‐amyl (Mn‐ADMS), monoisoamyl (Mi‐ADMS) and mono‐n‐hexyl (Mn‐HDMS). Dimercaptosuccinic acid or one of the monoesters were administered at a dose of 0.25 mmol kg−1 body wt. twice, i.e. 30 min and 24 h after 203Hg administration. The whole body (WB) radioactivity was determined on the 2nd, 4th and 6th days. The radioactivity in the carcass (C) whole body without the gastrointestinal tract), liver (L), both kidneys (K) and brain (B) was determined 6 days after 203Hg administration. All treated animals had a significantly lower body burden of mercury than the controls. The reduction of 203Hg retention in WB and other body compartments was higher in animals treated with monoesters than in rats treated with DMSA. The relative effectiveness of the monoesters was dependent on the nature of the alkyl groups, the efficiency being higher in higher analogues. Maximum activity was attained with the C5 (Mn‐ADMS, Mi‐ADMS) and C6 (Mn‐HDMS) esters. These chelators reduced WB, C, L, K and B mercury retention by 90, 89, 76, 93 and 80%, respectively. Iso derivatives were more efficient than the normal isomers (Mi‐PDMS > Mn‐PDMS; Mi‐BDMS > Mn‐BDMS; Mi‐ADMS > Mn‐ADMS). The effect of all monoesters was higher in reducing kidney than liver mercury retention.
Studies on the delayed neuropathic and anticholinesterase potential of quinalphos (diethyl 2‐quinoxalyl phosphorothionate) in hens
Authors: Jokanović Milan
Published: October 2006

Incidence of numerous human poisonings by quinalphos (Ekalux®, Bayrusil®) in agricultural areas near Belgrade initiated this study on the ability of the compound to inhibit hen brain neuropathy target esterase, acetylcholinesterase and plasma butyrylcholinesterase in vivo. Hens were treated with a single oral dose ranging from 25 to 600 mg kg−1 quinalphos (LD50 = 72 mg kg−1) or 500 mg kg−1 triorthocresyl phosphate (positive control), sacrificed 24–96 h later for enzyme assays and monitored for 25 days for evaluation of walking impairments. High inhibition (> 80%) of both cholinesterases was obtained with 25 and 50 mg kg−1 quinalphos. Doses of 200 and 600 mg kg−1 of the agent inhibited up to 23 and 28% of hen brain neuropathy target esterase activity, respectively. Clinical signs of neuropathy were not seen. Quinalphos was slowly absorbed from the gastrointestinal tract, as indicated by the severity of the cholinergic symptoms and the inhibiton of neuropathy target esterase, which reached its maximum 72 and 96 h after poisoning. The results suggest that quinalphos, at doses tested, has no ability to cause delayed neuropathy in hens without showing signs of severe cholinergic intoxication.
The toxicity of seed extracts and their fractions from Lupinus angustifolius L. and Lupinus albus L.
Authors: Stobiecki M. , Blaszczyk B. , Kowalczyk‐Bronisz S. H. , Gulewicz K.
Published: October 2006

Seed extracts obtained from Lupinus albus and Lupinus angustifolius by treatment with 48% ethanol contained ca. 10% alkaloids (on a dry weight basis) and were non‐toxic. Their acute toxicity (LD50) in the mouse is > 4000 mgkg−1 body wt.

After fractionation, the extract from L. angustifolius seeds afforded several fractions with differing toxicities (LD50 750–4000 mg kg−1 body wt.).

None of the fractions tested in vitro were toxic. The results obtained showed that, in spite of the alkaloids, other low‐molecular‐weight constituents present significantly modified the toxicity of the lupin extracts.
In Vitro Cytotoxicities of 1,4‐Naphthoquinone and Hydroxylated 1,4‐Naphthoquinones to Replicating Cells
Authors: Babich H. , Stern A.
Published: October 2006

Using the human hepatoma cell line, HepG2, and the BALB/c mouse fibroblast cell line, 3T3, as the bioindicators in the neutral red cytotoxicity assay, the effect of hydroxyl substitution on the toxicity of 1,4‐naphthoquinone was studied. The sequence of potency for the quinones was 5,8‐dihydroxy‐1,4‐naphthoquinone > 5‐hydroxy‐1,4‐naphthoquinone > 1,4‐naphthoquinone > 2‐hydroxy‐1,4‐naphthoquinone. Pretreatment of the cells with dicoumarol, an inhibitor of DT‐diaphorase, enhanced the cytotoxicity of 1,4‐naphthoquinone but not of the hydroxylated naphthoquinones. Pretreatment of the BALB/c cells with buthionine sulfoximine, an inhibitor of glutathione synthesis, enhanced the sensitivity of the cells to all the hydroxylated naphthoquinones but not to 1,4‐naphthoquinone. A similar pretreatment of the HepG2 cells with buthionine sulfoximine enhanced the toxicity of the 2‐hydroxy‐ and 5,8‐dihydroxy‐1,4‐naphthoquinones but not of 5‐hydroxy‐1,4‐naphthoquinone or of 1,4‐naphthoquinone.

Some differences were noted in the responses to the hydroxylated 1,4‐naphthoquinones between buthionine sulfoximine‐treated replicating cells and buthionine sulfoximine‐treated isolated rat hepatocytes, a non‐replicating cell in culture. The use of a replicating cell system in studying the mechanisms of the cytotoxicity of quinones may be an important adjunct to studies using the isolated rat hepatocytes, which is the standard model system.
Dominant lethal study of sulfur mustard in male and female rats
Authors: Sasser L. B. , Cushing J. A. , Dacre J. C.
Published: October 2006

Sulfur mustard (HD) (bis(2‐chloroethyl)sulfide) is a strong alkylating agent with known mutagenic and suspected carcinogenic properties, but occupational health standards have not been established. The purpose of this study was to determine the dominant lethal effect in male and female rats dosed orally with HD, for which currently available data are ambiguous.

Sprague‐Dawley rats of each sex, 6–7 weeks old, were orally administered 0, 0.08, 0.20 or 0.50 mg kg−1 HD 5 days a week for 10 weeks, after which dominant lethal studies were conducted during the post‐exposure period. The studies were conducted in two phases: a female dominant lethal phase in which treated or untreated males were mated with treated females and their fetuses were evaluated 14 days after copulation; and a male dominant lethal phase in which treated males cohabited with untreated females for 5 days and fetuses were evaluated 14 days after the mid‐point of the week of cohabitation, for each of 10 weeks. In addition, motility, population size and morphology were measured in sperm obtained from the cauda epididymis.

Parental growth rates were reduced in both sexes treated with the high level of HD. Female dominant lethal effects were not observed, although significant male dominant lethal effects were observed in HD‐exposed male rats mated to untreated females at 2 and 3 weeks' post‐exposure. These effects, which included increases of early fetal resorptions and preimplantation losses and decrease in total live embryo implants, were most consistently observed at a dose of 0.50 mg kg−1. A significant P(P<0.05) increase in the percentage of abnormal sperm was detected in males exposed to 0.50 mg kg−1 HD. The timing of dominant lethal effects is consistent with an effect during the post‐meiotic stages of spermatogenesis, possibly involving the generally sensitive spermatids.
Kidney function in male and female rats chronically exposed to potassium dichromate
Authors: Vyskočil A. , Viau C. , Čížková M. , Truchon G.
Published: October 2006

Male and female Wistar rats were given 25 mg I−1 chromium (as potassium dichromate) in drinking water for 6 months. Lactate dehydrogenase, lysozyme, total proteins, N‐acetyl‐β‐D‐glucosaminidase, albumin and β2‐microglobulin (β2‐m) were measured in 24‐h urine after 3 and 6 months of exposure. Body and kidney weight and chromium excretion were also examined.

Except for the chromium excretion, no statistically significant changes were observed in the exposed male rats. In female rats there were significant increases in the urinary excretion of albumin after 3 and 6 months of exposure and the urinary excretion of β2‐m after 3 months of exposure.
Risk assessment and management of chemical contaminants in fishery products consumed in the USA
Authors: Ahmed Farid E. , Hattis Dale , Wolke Richard E. , Steinman David
Published: October 2006

In the USA a small proportion of fishery products are contaminated with appreciable amounts of potentially hazardous contaminants. However, risks to consumers are not generally high. Inorganic contaminants with the greatest potential for toxicity are antimony, arsenic, cadmium, lead, mercury, selenium and sulfites. Among organic compounds, polychlorinated biphenyls, dioxins, several chlorinated hydrocarbon insecticides, certain processing‐related and aquaculture‐related contaminants pose potential risks for consumers.

Log‐normal distributions appear to provide good descriptions of the pattern of variation of contaminant concentrations among different geographic areas, and some contaminants (mostly organic) appear to be much more variable than others. This variability offers a solution for reduction of exposure through restricting the harvest of aquatic organisms from specific sites, and by excluding certain species.

It is recommended that: (i) existing State and Federal regulations and environmental monitoring be strengthened and enforced to minimize contamination of the aquatic environment; (ii) a program of shared responsibility be instituted, where Federal agencies develop a set of monitoring and inspection practices and state agencies assume responsibility for primary control, site closures and advisories issue; (iii) research and public education by government agencies and health professionals be expanded to determine actual risks and approaches to manage them; (iv) mandatory labeling be considered for specific contaminants; (v) a better system requiring international agreements be developed in order to minimize the differences among various national regulatory approaches.
Toxicity of diethanolamine. 1. Drinking water and topical application exposures in F344 rats
Authors: Melnick Ronald L. , Mahler Joel , Bucher John R. , Thompson Morrow , Hejtmancik Milton , Ryan Michael J. , Mezza Lawrence E.
Published: October 2006

Toxicology studies of diethanolamine were conducted in male and female F344 rats for 13 weeks' duration to characterize and compare effects of exposure in the drinking water with those caused by topical application. Doses of diethanolamine ranged from 160 to 5000 ppm in the drinking water study (equivalent to daily doses of 25–440 mg kg−1 in males and 15–240 mg kg−1 in females) and from 32 to 500 mg kg−1 in the topical application study. Dose‐dependent toxic effects due to exposure to diethanolamine included hematological changes (a poorly regenerative, microcytic anemia), as well as toxic responses in the kidney (increased weight, tubular necrosis, decreased renal function, and/or tubular mineralization), brain and spinal cord (demyelination), testis (degeneration of the seminiferous tubules) and skin (site of application: ulceration, inflammation, hyperkeratosis and acanthosis). A no‐observed‐adverse‐effect level was not achieved for hematological changes, nephropathy or hyperkeratosis of the skin. Differences in dose‐response between the drinking water and topical application exposures were attributed largely to the limited dermal absorption of this chemical.
Toxicity of diethanolamine. 2. Drinking water and topical application exposures in B6C3F1 mice
Authors: Melnick Ronald L. , Mahler Joel , Bucher John R. , Hejtmancik Milton , Singer Allen , Persing Ronald L.
Published: October 2006

Toxicology studies of diethanolamine were conducted in male and female B6C3F1 mice to characterize and compare effects of exposure in the drinking water with those caused by topical application and to compare responses in mice to those observed in rats. Each study consisted of five dose groups plus controls and the size of each group was 10 animals per sex. Doses of diethanolamine ranged from 630 to 10 000 ppm in the drinking water study (approximately equivalent to daily doses of 100–1700 mg kg−1 in males and 140–1100 mg kg−1 in females) and from 80 to 1250 mg kg−1 in the topical application study. Exposure to diethanolamine caused dose‐dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myocyte degeneration) and skin (site of application: ulceration, inflammation, hyperkeratosis, and acanthosis). Cytological alterations in the liver consisted of multiple hepatocyte changes, including enlarged cells that were frequently multinucleated, increased nuclear pleomorphism, increased eosinophilia and disruption of hepatic cords. A no‐observed‐adverse‐effect level (NOAEL) was not achieved for hepatocellular cytological alterations or for acanthosis in the skin.
Effect of tordon 2,4‐D 64/240 triethanolamine BR on the energy metabolism of rat liver mitochondria
Authors: Pereira Luiz Fernando , Campello Annibal P. , Silveira Orieta
Published: October 2006

Tordon herbicide, which is a mixture of 4‐amino‐3,5,6‐trichloropicolinic acid (picloram) and 2,4‐dichlorophenoxyacetic acid (2,4‐D), depresses the phosphorylation efficiency of the rat liver mitochondria, as inferred from the decrease of the respiratory control coefficient and the ADP/O ratios when NAD+‐dependent substrates were used; NADH oxidase and NADH cytochrome c reductase were also inhibited, without any effect on the other enzymatic complexes of the respiratory chain. Tordon (66.2 nmol picloram + 270 nmol 2,4‐D mg−1 protein) affected the amplitude of swelling induced by glutamate, succinate, (N,N,N′,N′‐tetramethyl‐p‐phenyldiamine + sodium ascorbate and ATP. These results characterize an interaction of Tordon with complex I of the respiratory chain and also a partial collapse of the proton motive force of the mitochondrial inner membrane without affecting its elasticity.
Cardioteratogenic dose of ethanol reduces both lactic dehydrogenase and succinic dehydrogenase activity in the bulbar ridges of the embryonic chick heart
Authors: Bruyere Harold J. , Stith Charles E. , Thorn Thomas A.
Published: October 2006

It has been established previously that the chick embryo is an appropriate model for studying the pathogenesis of ethanol‐induced ventricular septal defect and that the growth and fusion of the proximal bulbar ridges are critical to ventricular septation within the embryonic heart. To determine whether enzyme activity was altered significantly in bulbar ridges in response to a cardioteratogenic dose of ethanol, we injected 0.32 ml of 50% ethanol in chick Ringer's saline (CRS) into the air cells of 3‐day‐old chick embryos (72–84 h incubation, Hamburger‐Hamilton stages 18–19, Dekalb Delta strain). Embryos were harvested 48–60 h after treatment (stages 26–27). Hearts were removed, frozen and sectioned, and the tissues were processed for enzyme histochemical demonstrations of lactic and succinic dehydrogenase. Twelve ethanol‐treated embryos and 12 CRS‐treated controls were compared for lactic dehydrogenase (LDH) levels. Fourteen ethanol‐treated embryos and 14 controls were compared for succinic dehydrogenase (SDH) levels. Formazan deposits were quantified by means of computer‐assisted microdensitometry. Our results showed that ethanol decreased the mean LDH activity level by 36.3% (P = 0.05) and the mean SDH level by 40.8% (P < 0.02). Furthermore, ethanol significantly reduced LDH activity in 41.7% of the matched embryo pairs and significantly reduced SDH activity in 57.1% of the matched embryo pairs. Although some investigators have proposed that a disturbance in neural crest cell migration plays a major role in the pathogenesis of ethanol‐induced cardiac malformations, this study provides evidence that the bulbar ridges of the embryonic heart are also potential target tissues for ethanol.
Cardioteratogenic dose of ethanol in the chick embryo results in albumin ethanol concentrations comparable to human blood alcohol levels
Authors: Bruyere Harold J. , Choudhury Somesh , Nelson Eric , Stith Charles E.
Published: October 2006

Three‐day‐old chick embryos (Hamburger‐Hamilton stages 18–19) were exposed to a dose of ethyl alcohol (0.32 ml of 50% ethanol) that causes cardiac malformations in 96.6% of the animals. Ethanol was administered into the air sac after 72–80 h of incubation. Samples of albumin at the opposite pole of the egg were drawn 0–50 h after treatment and quantitated for ethanol concentration with capillary gas‐liquid chromatography. Ethanol concentrations in the albumin increased significantly (P < 0.05) at 2, 5 and 15 h after injection of ethanol, reached a maximum mean ethanol concentration at 20 h (217.3 ± 23.5 mg dl−1), decreased significantly at 30 h to 175.4 ± 27.5 mg dl−1, then increased again and stabilized at 40–50 h. Individual sample concentrations ranged from 0 mg dl−1 (at 0.5–2 h) to 286.5 mg dl−1 at 40 h. Ethanol concentrations in the albumin were comparable to human blood alcohol levels during intoxication ( > 150 mg dl−1). Our results suggest that a potent cardioteratogenic dose of ethanol in the chick embryo is reasonable in terms of potential human embryo exposure.
Isoflurane increases the anaerobic metabolites of halothane
Authors: Rahman Mustafizur , Fujii Kohyu , Sato Nobuyoshi , Yuge Osafumi
Published: October 2006

The effect of isoflurane on the anaerobic metabolism of halothane to chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE) was studied with microsomes of guinea pig liver by gas chromatography. The reaction mixture used to measure the end products of anaerobic metabolism consisted of a microsomal suspension, 3 mM NADPH, halothane and isoflurane (except in control groups) in 0.1 M potassium phosphate buffer solution (pH 7.4). The Km values for CDE formation were 601.61 ± 266.91, 254.22 ± 86.58, 257.92 ± 129.11, 268.55 ± 125.66 and 319.22 ± 86.76 μM (mean ± SD, n = 5) at 0 mM (0%), 0.12 mM (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM (2.59%) isoflurane, respectively. The Km values for CTE formation were 1204.74 ± 551.64, 553.75 ± 177.89, 521.14 ± 249.77, 560.67 ± 229.61 and 711.05 ± 317.13 μ (n = 5) at 0 mM (0%), 0.12 mM (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM (2.59%) isoflurane, respectively. In contrast, the Vmax values for CDE and CTE formation at these isoflurane concentrations were not significantly different than in the control groups. In this study the production of CDE and CTE was significantly (P < 0.05) increased by isoflurane, at concentrations up to 0.58 mM (1.30%).
Coronary vessel alterations following chronic carbon monoxide exposure in the adult rat
Authors: Penney David G. , Giraldo Alvaro A. , Van Egmond Eve M.
Published: October 2006

Adult male rats were exposed to 500 ppm CO continuously for 30 days, while litter‐mate controls remained in room air (AIR). Heart weight‐to‐body weight ratio and hematocrit were increased significantly. Right ventricle (RV) free wall thickness was increased significantly as was right to left heart diameter and average heart diameter. Cross‐sectional areas of the left ventricle (LV) free wall, interventricular septum (S) and RV midway between the apex and base were increased significantly. Morphometric analysis of the CO‐exposed and AIR hearts revealed no significant differences in the number of small (27–114 μm) or larger (>114 μm) blood vessels in any region; however, there was a trend towards an increased number of the smaller vessels, both arterioles and venules, in the CO‐exposed rats. The larger arteries in the S and RV were significantly larger in the CO‐exposed rats. There was a significant overall effect of CO on larger artery diameter across all heart regions, consistent with the appearance of heart radiographs taken. There were no differences in the diameter of the small vessels in any region of the heart between the CO‐exposed and AIR rats. The vessel cross‐sectional area of the larger vessels tended to be increased in all regions of the heart. The cross‐sectional area of the large arteries in the LV was increased significantly. Arterial wall thickness was decreased significantly in RV and there was a significant overall effect of CO in decreasing wall thickness and the ratio of wall thickness‐to‐vessel luminal diameter in these vessels. No vascular pathology was observed. The results of this study suggest changes in coronary vessel architecture during chronic CO‐induced cardiac hypertrophy and are consistent with earlier hemodynamic and morphometric studies of CO‐exposed hearts.
Validation of an improved nose‐only exposure system for rodents
Authors: Pauluhn J.
Published: October 2006

Several types and modifications of nose‐only inhalation chambers for exposing rodents are described. The improvement of this ‘flow‐past’ ‐like nose‐only exposure system is that it is modular, i.e. it can be used for acute studies with a maximum of 20 rodents (one segment) or for chronic inhalation studies with 100 (or more) rodents per chamber with five (or more) segments. Another goal was to design a nose‐only exposure system that provides maximal computer support and automatization, as well as robust aerosol collection conditions. The evaluation of the five‐segment chamber, charged with 98 rats, revealed that a flow rate of 0.75 I air min−1 or approximately 2.5 times the rat minute ventilation volume per exposure port is sufficient to provide homogeneous temporal and spatial exposure conditions. Also, the aerosol size distribution was constant throughout the chamber. Experimental data suggest that computer‐controlled sampling of the test atmosphere up to ca. 6 I air min−1 did not alter the flow dynamics of the exposure system. The nose‐only inhalation chamber developed is suitable for short‐term and long‐term inhalation toxicity studies using small laboratory rodents with minimal consumption of test compound.
Flow cytometric analysis of the direct toxic effects of paraquat on cultured MDCK cells
Authors: Yamagami Kazunobu , Matsubara Mineo , Kitazawa Yasuhide , Takeyama Naoshi , Tanaka Takaya , Kawamoto Keiji
Published: October 2006

We used flow cytometry to assess the cell cycle kinetics of cultured Maden Darby canine kidney cells after exposure to paraquat. Fluorescein diacetate fluorescence was used as a marker of cell viability, while bromodeoxyuridine incorporation was detected with a monoclonal antibody and propidium iodide staining to assess DNA synthesis. Flow cytometry was performed immediately, 48 h and 96 h after exposure to paraquat for 24 h. Lactate dehydrogenase release was also measured to determine the extent of cytolysis. Flow cytometry of paraquat‐treated cells showed a marked increase of the S phase population immediately after exposure, at a time when there was no increase of lactate dehydrogenase release. In contrast, the cell cycle profile returned towards normal at 48 and 96 h after paraquat exposure, but lactate dehydrogenase release increased. These findings indicate that paraquat arrested cells in the S phase and that inhibition of DNA synthesis by this agent appeared to influence cell viability because S phase block occurred before cytolysis. In addition, this method proved useful for assessing the effects of paraquat on DNA synthesis by cultured cells.
Cytogenetic studies on commercial hexane solvent
Authors: Daughtrey W. C. , Putman D. L. , Duffy J. , Soiefer A. I. , Kirwin C. J. , Curcio L. N. , Keenan T. H.
Published: October 2006

Commercial hexane is a solvent mixture of six‐carbon isomers, consisting principally of n‐hexane, 3‐methylpentane, methylcyclopentane and 2‐methylpentane. The potential of commercial hexane to produce chromosome aberrations was evaluated in both an in vitro assay using Chinese hamster ovary (CHO) cells and an in vivo cytogenetics assay using Sprague‐Dawley rats. The CHO cells were exposed to media containing commercial hexane at concentrations of 0.014–0.42 μl ml−1 in the presence and absence of an S‐9 activation mixture. Cellular toxicity was observed at the higher dose levels, but no increase in chromosome aberrations was observed in either the non‐activated or S‐9‐activated systems. For the in vivo cytogenetics assay, rats were exposed nose‐only for 6 h per day for 5 consecutive days to commercial hexane vapor at target concentrations of 900, 3000 and 9000 ppm. Bone marrow cells were collected at 6 and 24 h after the midpoint of the last exposure. Metaphase cells were examined microscopically for chromosome aberrations. No statistically significant increases in aberrant cells were observed in the commercial hexane‐exposed animals of any dose group at either of the bone marrow harvest times. In conclusion, commercial hexane did not produce chromosomal mutations under the conditions of these studies.
Snake poisoning in rural Zimbabwe—A prospective study
Authors: Nhachi Charles F. B. , Kasilo Ossy M. J.
Published: October 2006

Over a period of 2 years (January 1991 to December 1992) 274 cases of snake bite were admitted to hospital in the eight provinces of Zimbabwe. Of these patients, 54% were males and 88% belonged to the 6–40‐year age group. Five deaths (1.8% of the total cases) were reported. The majority of snake bites (63%) occurred at night (between 6.30 p.m. and midnight) and over 74% took place during the hot rainy season, i.e. between November and April. In over 58% of the cases the victim accidentally stepped on the snake, the snake being cobra in 37%, puff adder in 20% and the black and green mamba in 18% of the cases. Most of the bites occurred on the leg, below the knee.

Treatment of snake envenomation consisted mainly of the administration of antibiotics (151 cases), analgesics (144 cases), antivenom tropical snake polyvalent (ATT) (89 cases), antitoxoid tetanus (TT) (61 cases), antihistamines (47 cases) and traditional medicines (43 cases). This study indicates that snake envenomation in rural Zimbabwe is common but fatalities are relatively rare.
Initial interlaboratory validation study of FETAX: Phase I testing
Authors: Bantle John A. , Rayburn James R. , Burton Dennis T. , Turley Steven D. , Dawson Douglas A. , Dumont James N. , Finch Robert A. , Maurice Margaret A. , Fort Douglas J. , Linder Greg , Buchwalter David
Published: October 2006

An interlaboratory validation study was undertaken to evaluate the repeatability and reliability of the Frog Embryo Teratogenesis Assay‐Xenopus (FETAX), which is a whole embryo developmental toxcity screening assay. A three‐phase experimental program with seven participants was carried out. Phase I was a training and protocol evaluation phase where the identity of the three test materials was known. Hydroxyurea, isoniazid and 6‐aminonicotinamide were tested in Phase I. Because the chemicals has been tested previously in FETAX, the same concentrations needed to establish the 96‐h median lethal concentration (LC50) and the concentration inducing malformations in 50% of the surviving embryos (EC50) were used by all laboratories. The results of Phase I are presented in this report, and FETAX has proved to be as repeatable and reliable as many other bioassays. Some excess variation was observed in individual laboratories. Some of this variation may have been due to training difficulties. One change in protocol design necessitated by this study was the use of 6‐aminonicotinamide as a reference toxicant. While 6‐aminonicotinamide provided excellent concentration‐response data in most laboratories, the protocol was written too strictly based on historical FETAX data. Phases II and III are currently in progress.