Alcohol consumption, blood alcohol level and the relevance of body weight in experimental design and analysis

In healthy male subjects, intake of alcohol is not closely related to body weight although there is a significant correlation between consumption and body weight in the younger age group. No association was observed between age and alcohol consumption. Age did show a significant association when expressed in terms of intake per weight. Eight hours after consumption blood alcohol did not vary significantly in people with different body weight; total body water is probably the key factor. This study raises doubts about experimental designs and calculations of blood alcohol whereby assumption is made that correcting alcohol dose for body weight would give precise information. Conclusions from such studies could in fact be misleading.     

The toxicity of behenyl alcohol. I. Genotoxicity and subchronic toxicity in rats and dogs

The genotoxic potential of behenyl alcohol, a saturated long-chain (C22:0) fatty alcohol, was examined in the Ames Salmonella typhimurium reverse mutation assay, the gene mutation, and chromosome aberrations assays in Chinese hamster V79 cells, and the micronucleus assay in NMRI mice. Behenyl alcohol did not increase the number of revertants per plate compared to controls in the S. typhimurium assay, with or without metabolic activation. No significant increases in the number of mutant colonies or in structural chromosome aberrations were observed in Chinese hamster V79 cells. In addition, behenyl alcohol did not increase the frequency of bone marrow polychromatic erythrocyte (PCE) micronuclei in mice in vivo. In two subchronic toxicity studies, CD rats and beagle dogs were administered behenyl alcohol by oral gavage for at least 26 weeks at doses of 0, 10, 100, or 1000 mg behenyl alcohol/kg body weight/day for rats and 0, 20, 200, or 2000 mg behenyl alcohol/kg body weight/day for dogs. Adverse effects were not observed following gross and histopathological evaluations of dosed rats. Compound-related effects in dogs were limited to observations of pale feces, indicative of unabsorbed behenyl alcohol, at doses of 2000 mg/kg body weight/day. There were no histopathological changes observed in dogs dosed with behenyl alcohol. The no-observed-adverse-effect-level (NOAEL) for behenyl alcohol was 1000 mg/kg body weight/day for rats, and 2000 mg/kg body weight/day for dogs, the highest doses used in these studies.     

Reproductive toxicity of DDT in adult male rats.

The reproductive toxicity of DDT was investigated in adult male rats exposed to 50 and 100 mg/kg body weight (b.wt) day(-1) for 10 successive days. Compared with control animals, administration of DDT led to a dose-dependent reduction of testicular weight and the number as well as the percentage of motile spermatozoa in the epididymis. Testicular histological observations revealed also a marked loss of gametes in the lumen of seminiferous tubules. In DDT-treated rats, the seminal vesicles weights dropped significantly, resulting from a decrease of testosterone production by testes, whereas serum LH and FSH increased after pesticide exposure. This increase of gonadotrophin levels may be related to an impairment of the negative feedback exerted by the steroid on the hypothalamic--pituitary axis. It is concluded that DDT induced adverse effects on male rat fertility by acting directly on the testes and altering the neuroendocrine function.     

Effects of prenatal exposure to alcohol on activity, anxiety, motor coordination, and memory in young adult Wistar rats

The objective of the present study was to examine the effects of prenatal exposure to ethanol on motor performance, emotionality, learning and memory in young-adult, male Wistar rats. Alcohol was delivered to the pregnant dams intragastrically, throughout gestation days (GD) 7-20, at the dose of 6 g/kg/day resulting in the peak blood alcohol concentration (BAC) of 350 mg/dl as assessed on GD 20. Isocaloric intubation and untreated control groups were included. Alcohol exposed rats were not impaired in the rotarod/accelerod tests. Their behavior in the open field and plus maze suggested increased neophobia. Hyperactivity was not observed. In the spatial-navigation task in the water maze, by the middle of the training, fetal alcohol rats showed a tendency towards a slower place acquisition compared to controls, but statistical analysis of the data did not yield between-group differences significant. Towards the end of the training, all rats reached a similar performance level. No detectable between-group differences were noted either in memory retention after a delay, in reversal learning, or in working memory task. Our findings demonstrate that the adverse behavioral effects of a binge-like alcohol administration during half of the first and throughout the second trimester equivalent are difficult to be disclosed in young-adult male Wistar rats. The possible reasons of the lack of significant behavioral deficits in the fetal-alcohol rats observed in the present study are discussed.     

Short-term toxicity of allyl alcohol in rats

Groups of 15 male and 15 female rats were give 0 (control), 50, 100, 200 or 800 ppm allyl alcohol in the drinking water for 15 weeks. There were no effects attributable to allyl alcohol in the results of the haematological examinations or analyses of serum. There was a dose-related reduction in the fluid intake at all treatment levels in both sexes, while growth and food consumption were reduced in both sexes given 800 ppm and in males give 200 ppm. Males given 100 ppm or above and females given 200 or 800 ppm produced less urine than the controls in a period without water or following a water load. The only changes in organ weight that could be attributed to treatment were increased values for the relative weights of liver, spleen and kidney. All 3 organs were affected in both sexes given 800 ppm and the kidneys were also affected in both sexes given 200 ppm and in females given 100 ppm. No effects attributable to allyl alcohol treatment were seen at autopsy or in the histopathological examination. The no-untoward-effect level established in this study was 50 ppm of the drinking water, a level equivalent to an intake in rats of between 4.8 and 6.2 mg allyl alcohol/kg/day.     

Adolescent alcohol use development and young adult outcomes

This study used latent growth modeling to examine the effects of level of alcohol use and development of alcohol use during adolescence, on young adult outcomes for males and females. Adolescents (N=480; mean=13.03 years, S.D.=1.44; 264 female) were assessed annually over a 4-year period and then 5–6 years later in young adulthood (mean=22.49 years, S.D.=1.50). Chronicity of alcohol use in adolescence was related to higher alcohol use, alcohol-related problems, aggressive behavior, theft, and suicide ideation in young adulthood among both males and females. Development of alcohol use during adolescence was related to alcohol-related problems in young adulthood for males and females, and to higher levels of alcohol use and aggressive behavior for males only. The results indicate that development of alcohol use as well as level of alcohol use in adolescence is important for future adjustment outcomes, and that these relationships vary as a function of gender.     

Subchronic toxicity study in rats and genotoxicity tests with polyvinyl alcohol.

The potential systemic and neurotoxicity of polyvinyl alcohol (PVA) was assessed when fed in the diet to male and female Sprague-Dawley rats for 90 days at doses of 2000, 3500 and 5000 mg/kg/day. Control rats received untreated standard laboratory diet. Assessments included clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalyses, motor activity and functional observational battery evaluations and gross and microscopic pathology. The only test-article-related finding observed during the study was unformed stool with brown/black anogenital staining in rats fed 3500 and 5000 mg/kg/day. This finding was attributed to the high levels of test article being consumed and subsequently excreted in the stool. It was not accompanied by macroscopic or microscopic changes in these rats. No test-article-related changes were seen in mortality, ophthalmology, body weight and food consumption data, hematology, clinical chemistry, urinalysis data, functional observational assessments, motor activity, organ weight data and macroscopic and microscopic examinations. Doses of 2000, 3500 and 5000 mg/kg/day of PVA administered as a dietary admixture to male and female Sprague-Dawley rats for up to 90 days did not result in any adverse, toxicological effects. The no-observed-adverse-effect level (NOAEL) was determined to be 5000 mg/kg/day. PVA showed no evidence of mutagenic activity in the Ames test, mouse lymphoma assay and the mouse micronucleus test. (A critical evaluation of the available information on PVA will appear in a review to be published in Food and Chemical Toxicology 2003, 41, 319-326)     

Prenatal effects of alcohol on adult learning in rats.

In an initial study, the rate of blood alcohol disappearance was not significantly different in pregnant compared to nonpregnant rats, but blood alcohol levels were significantly different depending on dose. In a second study, pregnant rats received daily administrations (p.o.) of ethanol (30% w/v) in single doses throughout gestation. Pair-fed vehicle-treated, and nondrug-treated rats fed ad lib served as controls. All pups were removed from their biological mothers at birth and were raised by nondrug-treated surrogate mothers. At five months of age, both male and female offspring prenatally exposed to ethanol weighed less than controls and female offspring performed significantly worse than the offspring of vehicle-injected pair-fed control mothers, on a two-way shock-avoidance task. There were no significant group differences, however, for either sex in water-escape maze learning.     

The toxicity of behenyl alcohol. II. Reproduction studies in rats and rabbits

Behenyl alcohol is a saturated 22-carbon, long-chain aliphatic alcohol, which has potential for use in foods as an oil-structuring and -solidifying agent in fats. Previously completed studies with behenyl alcohol indicated an absence of mutagenic or genotoxic potential. In addition, subchronic toxicity studies in rats and dogs reported no adverse effects following gross and histopathological examinations. Compound-related effects were limited to the observation of pale feces in dogs treated with high doses of behenyl alcohol, and were attributable to unabsorbed behenyl alcohol. The reproductive effects of behenyl alcohol were investigated in a fertility and reproduction study, and an embryonic development study in rats and rabbits, respectively. No evidence of maternal or fetal toxicity was observed in either study. Behenyl alcohol demonstrated no effects on the fertility or reproduction of rats dosed up to 1000 mg/kg body weight. Similarly, behenyl alcohol had no reproductive effects on rabbits treated with doses up to 2000 mg/kg body weight. The observation of pale feces was the only compound-related effect reported, limited to rabbits treated with 2000 mg behenyl alcohol/kg body weight. Based on these findings, there is no evidence to suggest that behenyl alcohol is teratogenic or embryotoxic.     

Sibling influence on alcohol use in a young adult, high-risk sample

OBJECTIVE: Previous research has found that siblings resemble each other in terms of alcohol use but has not examined sibling influence in young adult or high-risk siblings. The current study tested whether siblings prospectively influenced each other's alcohol use and how gender matching, age differences, and family conflict might moderate such effects. METHOD: Data from sibling pairs (n=169 pairs) in an ongoing longitudinal study of children of alcoholics and matched controls were collected at two time points 5 years apart. RESULTS: Older sibling alcohol use predicted younger sibling alcohol use, even after controlling for membership in a shared peer group and for parental alcoholism. However, moderator variables qualified this effect, such that older sibling influence was significant only among sibling pairs who were of the same gender, closer in age, and from higher conflict families. Younger sibling influence was significant only for sibling pairs close in age, suggesting the presence of reciprocal peer-like effects in this subgroup. CONCLUSIONS: The current study provides evidence for sibling influence on alcohol use into adulthood, but the extent of this influence depends on sibling similarity in age and gender and on levels of family conflict. Implications for family-based theory and intervention efforts are discussed.     

Comparative toxicity of some selected pesticides in neonatal and adult rats.

Toxicity of two groups of pesticides was studied in adult and newborn rats. The chlorinated group of pesticides, heptachlor, chlordane, and DDT are less toxic in the newborn when compared to the adult, but phenobarbital pretreatment potentiates their toxicity in the newborn. The organophosphorus insecticide, parathion, is more toxic in the newborn when compared to adult, but phenobarbital pretreatment antagonized the toxicity of this cholinesterase inhibitor. Chlorinated pesticides are generally less toxic in the newborn, while the pesticides of the cholinesterase inhibitor group are more toxic.     

Self-estimates of blood alcohol concentration in drinking-driving context

A total of 72 social drinkers between the ages of 20 and 57 years participated in an ad lib social drinking session. At various intervals throughout the session participants provided estimates of their blood alcohol concentration (BAC) along with breath samples for objective determination of their BAC. Participants were classified into three groups, based on the pattern of their BAC estimation errors-Underestimators, Overestimators, or Mixed Pattern estimators. Underestimators consumed more alcohol and attained higher BACs during the drinking session than the other two groups. Underestimators also rated their level of intoxication significantly lower than other groups and were most likely to judge themselves fit to drive when their actual BAC was in excess of the statutory limit.