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PubMed1990

Oxygen tension, oxygen metabolism, and microcirculation in vasogenic brain edema.

In cold brain injury edema, cerebral pO2, oxygen metabolism, and local CBF were investigated. In randomized groups of 10 rats each, pO2 was measured by polarography using a balanced multiwire surface electrode on the parietal cortex after trepanation. lCMRO2 was approximated by oxygen disappearance rate after sudden complete cerebral circulatory arrest (cervical cuff inflation). Using integrated platinum electrodes, the local CBF was measured by H2 clearance. All data were evaluated on-line by computer. In normal animals we found a regular, normally distributed pO2 histogram in barbiturate and in ketamine anesthesia. Oxygen consumption and local CBF, however, are significantly higher in ketamine narcosis. The local CBF is thereby coupled with metabolic requirements: The more oxygen consumed, the higher the local pO2. In animals 24 hr after cold brain injury, this metabolic coupling is disturbed: In the perifocal edema the pO2 histogram is flat and broad with different mean and median, but with a shifting toward higher oxygen values. Oxygen consumption is reduced; the local CBF, however, is significantly increased with large variations. Also over the contralateral, noninjured hemisphere a decrease in CMRO2 and an increase in pO2 are observed (diachisis). These disturbances with a maximum at 24 hr after injury show a recovery after 72 hr. After infusion of the calcium entry blocker nimodipine a normalization in pO2 distribution was found, combined with an increase in CMRO2. We assume a primary disturbance of oxidative glucose metabolism with uncoupling of metabolic flow control; local CBF and O2 availability are not primarily impaired. Ca2+ may be a main factor in this pathophysiology.

Animals↗

PubMed2004

Glycohemoglobin (A1C) distribution in school children: results from a school-based screening program.

OBJECTIVE: To establish the normal distribution for glycohemoglobin (A1C) in sixth and seventh grade children and to assess the practicality of a school-based fingerstick screening program. RESEARCH DESIGN AND METHODS: Fingerstick capillary whole blood was collected from 400 children aged 11 to 13 years and the percent A1C was determined on-site. RESULTS: Among the boys, the A1C was significantly higher among the minorities (4.88+/-0.37%, mean+/-S.D.) than among the non-hispanic whites (4.73+/-0.41%, P<0.01), but was similar in the two groups of girls (4.74+/-0.41 and 4.75+/-0.34, respectively, P=0.88). None of the students had abnormal glucose tolerance by the standards published for adults. CONCLUSIONS: A1C in boys was higher among minorities than among the non-hispanic whites, even at this young age of 11-13 years. This may be an early sign of predisposition to type 2 diabetes among the groups known to be at higher risk for type 2 diabetes. However, this difference was not seen among girls. Reasons for the discrepancy between boys and girls is unexplained. A school-based fingerstick screening program proved to be practical. As the risk of obesity-related diseases, such as type 2 diabetes mellitus, increases among youth, the classroom may become an important location for screening.

Adolescent↗

PubMed2005

An abnormal distribution of C-kit positive cells in the normoganglionic segment can predict a poor clinical outcome in patients with Hirschsprung's disease.

PURPOSE: The loss or decrease of interstitial cells of Cajal (ICCs) has been implicated in several disorders of human intestinal motility. We have encountered a few cases suffering from severe constipation or enterocolitis resulting in patient death after a definitive operation for HD, even though the normoganglionic intestine had been successfully pulled through. We investigated the distribution of ICCs using c-kit immunostaining in the normoganglionic segment and compared these findings with the clinical outcome after a definitive operation in each case. PATIENTS AND METHODS: The distributions of ICCs were investigated by using c-kit immunostaining in the normoganglionic segment in the resected bowel in 15 cases with HD. The distributions of protein gene product 9.5 (PGP 9.5) as a general neuronal marker and those of NADPH-diaphorase (NADPH-d) as a marker of nitric-oxide neurons were also examined. The numbers of ICCs and neurons were evaluated quantitatively. The histopathological results were compared with the clinical outcome after definitive operation in each case. RESULTS: C-kit immunoreactive cells showed a normal distribution in the normoganglionic segment in 13 cases, while they were markedly (less than 50% compared with the other cases) decreased in 2 cases. The distributions of PGP 9.5 and NADPH-d were almost the same in all cases. The bowel movements of 13 cases showing normal c-kit distribution were satisfactory. In contrast, the bowel movements were impaired in 2 cases with a decreased number of c-kit positive cells. One infant suffered from severe persistent constipation and thus had to undergo a resection of a dilated colon. The other infant died of sepsis due to postoperative enterocolitis and showed a markedly dilated colon. CONCLUSION: A decreased number of c-kit positive cells in the normoganglionic segment can thus allow us to predict a poor clinical outcome after definitive surgery, probably due to poor intestinal motility. Therefore examining the c-kit distribution in a resected bowel specimen in patients with HD should be mandatory in order to select the optimal postoperative treatment regimen for each case.

Child↗

PubMed2004

Ethnic differences in distribution of serum prostate-specific antigen: a study in a healthy Chinese male population.

OBJECTIVES: To evaluate the normal distribution of serum prostate-specific antigen (PSA) levels in healthy Chinese men, because, until recently, studies conducted to establish normal serum PSA values have not involved a Chinese population. METHODS: Between September 1999 and December 2001, 1096 healthy Chinese men aged 23 to 85 years, who had undergone a routine health examination, were recruited to this study. All underwent detailed clinical examinations, including serum PSA determination and digital rectal examination. All men with abnormal digital rectal examination findings and/or an abnormal serum PSA level (greater than 4.0 ng/mL) underwent transrectal ultrasound-guided sextant biopsy. RESULTS: The median serum PSA concentration was 0.50 ng/mL (95th percentile 1.20) for men 23 to 29 years old (n = 77); 0.55 ng/mL (95th percentile 1.21) for men 30 to 39 years old (n = 189); 0.54 ng/mL (95th percentile 1.23) for men 40 to 49 years old (n = 233); 0.82 ng/mL (95th percentile 2.35) for men 50 to 59 years old (n = 177); 0.93 ng/mL (95th percentile 3.20) for men 60 to 69 years old (n = 265); and 1.17 ng/mL (95th percentile 3.39) for men 70 years old or older (n = 155). The serum PSA concentration correlated with age (P <0.001), with an increase of approximately 1.1% annually. No change occurred in the median serum PSA value and 95th percentile in men younger than 50 years old; a gradual increase was observed in men older than 50 years. In those 50 years old or older, the median and 95th percentile serum PSA values for Chinese men were significantly lower than those for other races and even for other Asian men. CONCLUSIONS: These findings further confirm that the serum PSA level correlates with age. Moreover, the distribution and cutoff value of the serum PSA level differs along ethnic lines. In addition, our findings raise the question of whether lowering the PSA cutoff may enhance the detection of cancer in Chinese men who have the lowest prostate cancer rate.

Adult↗

PubMed1984

Mixture distributions in psychiatric research.

This paper describes the application of Gaussian mixture distributions to biological marker research in psychiatry. Mixtures of univariate and multivariate normal distributions can be used to determine if diagnostically similar psychiatric patients belong to biologically distinct subpopulations. The resulting biological subtypes may be important in understanding the etiology of psychiatric disorders. The general model and estimation procedure are described (EM algorithm; Dempster, Laird and Rubin 1977). The method is illustrated using two examples of biological data: (1) red cell membranes and monoamine oxidase activity data in normal individuals having no family history of psychiatric illness, the first-degree relatives of bipolar depressed patients and a heterogeneous patient population; and (2) smooth pursuit eye movements that classify relatives of schizophrenics, nonschizophrenics and normal controls into biologically distinct populations.

Bipolar Disorder↗

PubMed1989

Distributional shape of nutrition data.

Nutrition data from 111 undergraduate college students (51 males and 60 females, ranging in age from 17 to 24) were studied with respect to the shape of the underlying probability distributions. Three-day averages for total energy, percent protein, percent saturated fat, percent unsaturated fat, percent complex carbohydrates, percent refined carbohydrates, cholesterol, sodium, vitamin C, and iron (measured in milligrams) were computed, and their distributions were compared with the normal (Gaussian) distribution. The distribution of values of sodium for females and, to a lesser extent, cholesterol for females and of cholesterol and vitamin C for males, differed from the normal distribution. The remaining distributions appeared to be reasonably close to normal in shape. It is recommended that nutrition researchers verify the normal distribution assumptions prior to applying parametric techniques to their data and that they use nonparametric (distribution-free) techniques to analyze their data whenever those assumptions are not valid.

Adolescent↗

PubMed1987

Simulation of genetic control of reproduction in beef cows. I. Simulation model.

A stochastic computer simulation model was constructed to predict the reproductive performance of beef cows as a function of the postpartum interval from calving to first estrus and the single-service conception rate. Phenotypic values for single-service conception rate were obtained by truncation of an assumed underlying normal phenotypic distribution at a point corresponding to a cumulative frequency of conception of .70. The underlying phenotypic distribution was derived as the sum of independent, normally-distributed additive genetic, permanent environmental and temporary environmental effects. The phenotypic frequency distribution for postpartum interval has been shown to be skewed toward large intervals. This distribution was simulated by combining normal distributions of additive genetic and permanent environmental effects with a strongly skewed Pearson III gamma distribution of temporary environmental effects. The simulated management system involved a 63-d breeding season, thereby allowing females up to three opportunities to conceive. The reproductive outputs that were simulated from postpartum interval and single-service conception rate included date of first service, first-service conception rate, number of services received, annual conception rate, calving date and postpartum interval. A normally-distributed 205-d weaning weight was also simulated and converted to an actual weaning weight by adjustment for calving date. General simulation results in terms of frequencies, means and standard deviations were compared with values found in the literature and found to provide a reasonable model of bovine reproductive performance.

Animals↗

PubMed1998

Estimation of confidence intervals for area under the curve from destructively obtained pharmacokinetic data.

The area under the curve (AUC) of the concentration-time curve for a drug or metabolite, and the variation associated with the AUC, are primary results of most pharmacokinetic (PK) studies. In nonclinical PK studies, it is often the case that experimental units contribute data for only a single time point. In such cases, it is straightforward to apply noncompartmental methods to determine an estimate of the AUC. In this report, we investigate noncompartmental estimation of the AUC using the long-trapezoidal rule during the elimination phase of the concentration-time profile, and we account for the underlying distribution of data at each sampling time. For data that follow a normal distribution, the log-trapezoidal rule is applied to arithmetic means at each time point of the elimination phase of the concentration-time profile. For data that follow a lognormal distribution, as is common with PK data, the log-trapezoidal rule is applied to geometric means at each time point during elimination. Since the log-trapezoidal rule incorporates nonlinear combinations of mean concentrations at each sampling time, obtaining an estimate of the corresponding variation about the AUC is not straightforward. Estimation of this variance is further complicated by the occurrence of lognormal data. First-order approximations to the variance of AUC estimates are derived under the assumptions of normality, and lognormality, of concentrations at each sampling time. AUC estimates and variance approximations are utilized to form confidence intervals. Accuracies of confidence intervals are tested using simulation studies.

Algorithms↗

PubMed2005

Discussion of the paper "Cost effective policies for alternative distributions of stochastic water pollution" by Gren, Destouni and Tempone.

This discussion addresses some aspects of a recent paper appearing in this journal which investigates cost effective coastal water management based on different assumptions of the probability distributions (normal and log-normal) of pollutant transport. We also suggest an alternative approach to overcome the technical problems of using the theoretical correct distribution for characterising environmental data (log-normal) within a probabilistic programming framework.

Data Interpretation, Statistical↗

PubMed1973

Measurement of the size distribution of zymogen granules from rat pancreas.

Zymogen granules are obtained in pure form and processed for electron microscopy. Thin sections are photographed and diameters measured with a Zeiss particle size analyzer. Since sectioning cuts any given particle in random way, these diameters are not the true diameters of the particles. The true size distribution is obtained by comparing the observed diameter distribution with a generated diameter distribution. The generated distribution is constructed from an assumed parent distribution (of true diameters) by the Monte-Carlo technique. "Goodness of fit" is judged by the value of "chi-squared" resulting from the comparison. Appropriate adjustments of the parameters of the true distribution are made on the basis of minimizing chi-square. A result of this process is that the zymogen granules follow a normal distribution: mean = 0.984 +/-0.005 mum, SD = 0.190 +/-0.005 mum. A second preparation of granules was made and diameters were measured directly with a scanning electron microscope. The distribution was again found to be normal, thus supporting the first result.

Animals↗

PubMed1995

Experimental study of ureteral free grafts. I. Surgical findings in transplanted and abandoned ureter.

OBJECTIVE: To develop two experimental models in rats to study the ureter under conditions of total devascularization and denervation. METHODS: The ureter was autotransplanted as an integrated autologous free graft (IAFG) or abandoned in the retroperitoneum as a non integrated autologous free graft (NIAFG). Both models were compared with a normal group and a surgical control group. Sixty-two rats were randomly distributed: Normal ureter (NU) group (n = 20); surgical control, only ureterolysis (SC) group (n = 15); abandoned ureter as NIAFG (AU) group (n = 13); reimplanted ureter as IAFG (RU) group (n = 14). RESULTS: SC group: in all cases a ureter with no alterations was observed although with slight periureteral fibrosis. AU group: some ureter specimens had a smaller caliber. Periureteral fibrosis was observed in all the cases. Vessel distribution was similar to that of the NU group. All the ureters conserved their lumen. 53.8% of the ureters showed spontaneous contractions and 100% contractions after mechanical stimulation. Cyst formation, necrosis, fistulas or stenosis of the lumen were not observed. RU group: microscopic findings of the ureter segment used as IAFG were compatible with those of a normal ureter. In all the cases a moderate degree of periureteral fibrosis was observed. In the majority of the cases a vascular framework of the fat immediately adjacent to the ureter was observed. In 13 of the 14 operated cases spontaneous contractions were observed. The ureteral segment used as IAFG showed no alterations in 10 cases and with alterations of various types in 4 cases. In 8 cases there was a greater or lesser degree of stenosis of the proximal suture. CONCLUSIONS: The surgical findings and the macroscopic aspects of the four groups show the viability of the ureter free graft, IAFG as well as the NIAFG, in spite of the macroscopic changes.

Animals↗

PubMedDate not supplied

The pharmacology of furosemide in the horse. V. Pharmacokinetics and blood levels of furosemide after intravenous administration.

Studies were undertaken to determine blood levels of furosemide in horses after 0.5- and 1.0-mg/kg doses administered iv. Analyses indicated that the pharmacokinetic parameters were dose independent and best described by a three-compartment open model. The alpha-, beta-, and gamma-phase half-lives of 5.6, 22.3, and 158.5 min, respectively, were observed after the 0.5-mg/kg dose. Similarly, the respective half-lives after the 1.0-mg/kg dose were 5.8, 24.1, and 177.2 min. After a 0.5-mg/kg dose of furosemide, population frequency distributions were evaluated at 1 hr and 4 hr post-drug administration. At 1 hr after dosing, the blood levels of furosemide in 30 horses were normally distributed. The mean plasma level was 97.9 ng/ml with a range of 41.9 ng/ml to 155.8 ng/ml and a SD of 25.0 ng/ml. Analyses of blood levels of furosemide in 47 horses at 4 hr after drug administration indicated that the population distribution was better fit by a normal curve after log transformation of the values. The mean plasma level at 4 hr post-dosing was 9.6 ng/ml with a range of 4.0 ng/ml to 19.4 ng/ml and a SD of 3.1 ng/ml. Based on this population distribution of the plasma levels, the probability of finding furosemide plasma concentrations above 24.6 ng/ml at 4 hr after anti-epistaxis dose was estimated at less than 1 in 1000.

Animals↗

PubMedDate not supplied

Are low plasma levels of 25-(OH)vitamin D a major risk factor for hyperparathyroidism independent of calcitriol in renal transplant patients?

BACKGROUND: Recently, some studies have emphasized the role of plasma 25-(OH)vitamin D (25OHD) levels in mineral metabolism dysregulation in chronic kidney diseases (CKDs). However, to date little attention has been paid to 25OHD metabolism abnormalities after renal transplantation (Tx). This cross-sectional study aimed to focus on its role in mineral metabolism dysregulation in functioning Tx. METHODS: Twenty-eight out of 75 Caucasian Tx patients were selected following strict inclusion and exclusion criteria. Two blood samples were effected at the end of the winter for the measurements of plasma 25OHD and calcitriol levels. Serum creatinine (Cr), alkaline phosphatase (SAP), immunoreactive intact parathyroid hormone (PTH), electrolytes and 24-hr proteinuria were also determined. The Kolmogorov-Smirnov test was used to evaluate the data distribution: serum Cr, Cr clearance, dialysis duration and PTH levels were non-normally distributed and were log-transformed. Values of p<=0.01 were assumed as statistically significant. RESULTS: Median serum Cr and PTH levels were, respectively, 1.0 mg/dL and 90.0 pg/mL (range 27-420; normal range 10-65); most of our Tx patients (78.5%) had serum PTH levels above the upper limit of normal values. Mean plasma 25OHD concentration was 19.6 +/- 8.9 SD ng/mL (range: 6-36). None had levels <5 ng/mL (severe deficiency); 10 patients (35.7%) had mild deficiency (5-15 ng/mL); 14 patients (50%) had vitamin D insufficiency (16-30 ng/mL); and only four patients (14.3%) had target levels (>30 ng/mL). Mean plasma calcitriol levels were 69.7 +/- 19.0 pg/mL (range 47-105; normal range 35-85). They were not significantly correlated to plasma 25OHD levels. Proteinuria (292.6 +/- 147.0 mg/24 hr) inversely correlated to plasma 25OHD levels (r=-0.480; p<0.01). The bivariate correlation analysis between logPTH and the other parameters showed a significant correlation for SAP (r=0.494; p=0.008), plasma 25OHD levels (r=-0.442; p=0.01), proteinuria (r=0.452; p=0.01), log serum Cr (r=0.551; p=0.002) and log Cr clearance (r=-0.534; p=0.003). The other parameters did not correlate significantly with logPTH, notably plasma calcitriol and serum phosphate levels. Only the parameters significantly correlated to logPTH in the bivariate correlation analysis were included in the back stepwise multiple linear regression analysis as independent variables (model: p<0.0001; R2=0.54): among them, only plasma 25OHD levels (Beta=-0.486; p=0.001) and log serum Cr levels (Beta=0.589; p=0.0002) were the dependent variable logPTH predictors. CONCLUSIONS: This cross-sectional study demonstrated that plasma calcitriol levels in a highly selected group of Tx patients were normal and not significantly correlated to either plasma 25OHD or serum PTH levels. Most patients (85.7%) had plasma 25OHD levels below the target value of 30 ng/mL; the latter were inversely correlated with serum PTH levels. Therefore, our study strengthens the suggestion that low plasma 25OHD levels are a major risk factor for secondary hyperparathyroidism (sHPTH) in Tx patients and stresses the importance of monitoring these patients.

Adult↗

PubMedDate not supplied

[An example of size characterization of synthetic vitreous fibers].

BACKGROUND: The size characterization of synthetic vitreous fibres must be carried out to include or exclude them from classification as a carcinogen and to conduct in vivo and in vitro toxicity studies. The length weighted geometric mean diameter, together with its standard error, determines the toxicity of fibres according to Italian legislation relating to the provisions for classification, packaging and labelling of dangerous substances as formulated in the European Commission Directive 97/69/EC. Up to now there is no national or European guideline, which provides a technical procedure to obtain the size characterization parameters. OBJECTIVES: The aim of this paper was to measure the fibre size of some rock wool and ceramic fibre samples in order to estimate the length weighted geometric mean diameter and its standard error, and to calculate the related toxicity parameter. We also wanted to analyse whether the measured lengths and diameters were log-normally distributed or not. METHODS: We reduced the fibre length by the two most used techniques: cutting the rock wool fibres with a blade and pressing the ceramic fibre material in a die for infrared spectroscopy. Each sample was suspended in water by ultrasonic agitation and a small amount of it was filtered on a polycarbonate membrane. The diameter and length measurements of 300 fibres were carried out by a scanning electron microscope and the experimental data were analysed to calculate the main statistical parameters. The size distributions obtained for each sample were studied using the Kolmogorov-Smirnov test for normality and Q-Q plot. RESULTS: The fibre dispersion on the polycarbonate membrane area was suitable: there was a sufficient number of fibres to be measured without an excessive fibre overlapping. The main statistical parameters were calculated for two different cutting times (t = 20 min and t = 1 h) and two different applied forces (F = 1.2 t, corresponding to a pressure of 90 MPa, and F = 1.6 t, corresponding to a pressure of 120 MPa). For each substance the two sets of measurements were acquired by two different operators. This gave us an estimation of the variability of the calculated statistical parameters in the worse case (different applied forces or cutting times, and different operators). For the ceramic fibres only, one of the two operators carried out the measurements for both the applied forces to obtain more close information about the variability related to the method itself. The normality tests and the Q-Q plots showed that some of the data were far from having a lognormal distribution due to the tails of the distributions. CONCLUSIONS: Both fibre length reduction methods were effective, but the press method was found to be much easier and quicker. The data obtained showed that it is relatively easy to estimate the main statistical parameters related to the size characterization of synthetic vitreous fibres. Nevertheless, further studies must be carried out in order to better evaluate the method reproducibility and the variability of the parameters estimated by one and more operators, and to associate an error with the cancerogenicity parameter.

Glass↗

PubMed1975

Retinogeniculate projections in the rabbits of the albino allelomorphic series1.

Retinogeniculate pathways have been studied by fiber degeneration and autoradiographic methods in rabbits that are homozygous for alleles of the albino series of genes. It has been found that albino and Himalayan rabbits, which both lack all melanin pigment in the eye, have a similar abnormality of the retinogeniculate pathway. The number ofipsilateral optic fibers going to the lateral geniculate nucleus is reduced in these rabbits, the ipsilateral projection forms a discontinuous terminal zone instead of the normal continuous zone, and some of the ipsilateral axons terminate in an inappropriate part of the nucleus, so that regions receiving a crossed input in normal rabbits receive an uncrossed input in the abnormal rabbits. Chinchilla rabbits show a slightly reducedfur pigmentation but have a normal distribution of pigment in the retinal pigment epithelium and these rabbits have normal retinogeniculate pathways. In addition,the normalretinogeniculate pathway was studied. Autoradiographic methods show that the beta segment of the lateral geniculate nucleus receives a contralateral input. Hence, earlier views that this segment projects to the visual cortex but receives no retinal input, areuntenable. Further, in the autoradiographic material it was not possible to identify seperate ipsilateral laminae and it was concluded that in the normally pigmented rabbit the ipsilateral retinogeniculate projection forms one relatively continuous group.

Albinism↗

PubMed2006

Efficient estimation of log-normal means with application to pharmacokinetic data.

In this paper, the problem of interest is efficient estimation of log-normal means. Several existing estimators are reviewed first, including the sample mean, the maximum likelihood estimator, the uniformly minimum variance unbiased estimator and a conditional minimal mean squared error estimator. A new estimator is then proposed, and we show that it improves over the existing estimators in terms of squared error risk. The improvement is more significant with small sample sizes and large coefficient of variations, which is common in clinical pharmacokinetic (PK) studies. In addition, the new estimator is very easy to implement, and provides us with a simple alternative to summarize PK data, which are usually modelled by log-normal distributions. We also propose a parametric bootstrap confidence interval for log-normal means around the new estimator and illustrate its nice coverage property with a simulation study. Our estimator is compared with the existing ones via theoretical calculations and applications to real PK studies.

Area Under Curve↗

PubMed2003

Genetic susceptibility, predicting risk and preventing cancer.

A polygenic approach to disease prevention has become a realistic goal that has arisen from the sequencing of the human genome. Some believe it will be possible to identify individuals as susceptible by their genotype and to prevent disease by targeting interventions to those at risk. However, doubts have been expressed about the magnitude of these genetic effects, and hence the potential to apply them either to individuals or to populations. Published data suggest that the familial aggregation of breast cancer not due to the known high penetrance genes is polygenic, which implies that the distribution of risk in the population is continuous. This model is likely to apply to other common cancers. The utility of a continuous distribution for identifying a high-risk group of the population for targeted preventive intervention depends on the spread of that risk distribution. For breast cancer, the data are compatible with a log-normal distribution of genetic risk in the population which is sufficiently wide to provide useful discrimination of high- and low-risk groups. Assuming all the susceptibility genes could be identified, the half of the population at highest risk would account for 88% of all cases. In contrast, if currently identified risk factors for breast cancer were used to stratify the population, the half of the population at highest risk would account for only 62% of all cases. These results suggest that in the future the construction and use of genetic risk profiles may provide significant improvements in the efficacy of population-based programmes of intervention for cancers and other diseases.

Breast Neoplasms↗

PubMed1995

Toxicological potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to 100 other compounds: a relative potency analysis of in vitro and in vivo test data.

A common definition of relative potency is the dose of a reference compound required to cause a particular incidence of a specific toxic response divided by the dose of a test compound needed to cause an equal incidence of that same effect. In this simple manner, toxicological assessments for a chemical of concern can be made in terms of another compound about which much is known from a human health perspective. Relative potency factors were used to compare 2,3,7,8-tetrachlorodibenzo-p-dioxin CAS # 1746-01-6 (TCDD) with 100 other compounds both individually and collectively. All results were standardized to a common scale that spanned many orders of magnitude and was indexed to an arbitrary potency of unity for benzo(a)pyrene [B(a)P]. From comparisons between 2,771 pairs of bioassay results (i.e., matched experimental design conditions) for TCDD compared with the 100 other compounds, it was found that TCDD is about 600 times as toxic as B(a)P (interquartile range of 130 to 1,900). The distribution of relative potency values is fitted accurately with a log-normal distribution function having an untransformed mean of 550 and an untransformed slope (i.e., the inverse of the standard deviation of the distribution) of 140. These factors combined with (a) a reference lifetime carcinogenic risk level of 1/100,000 and (b) a universal, potency-dependent risk coefficient (estimated from the collection of epidemiologically-based carcinogens) yielded estimates that equally toxic concentrations for TCDD should be in the range of 13 pg/m3 and 7 pg/L in air and water, respectively.

Animals↗