Toxic Effects Of Chemicals Research Articles

Direct toxicity assessment of toxic chemicals with electrochemical method

Electrochemical measurement of respiratory chain activity is a rapid and reliable screening for the toxicity on microorganisms. Here, we investigated in-vitro effects of toxin on Escherichia coli ( E. coli) that was taken as a model microorganism incubated with ferricyanide. The current signal of ferrocyanide effectively amplified by ultramicroelectrode array (UMEA), which was proven to be directly related to the toxicity. Accordingly, a direct toxicity assessment (DTA) based on chronoamperometry was proposed to detect the effect of toxic chemicals on microorganisms. The electrochemical responses to 3,5-dichlorophenol (DCP) under the incubation times revealed that the toxicity reached a stable level at 60 min, and its 50% inhibiting concentration (IC 50) was estimated to be 8.0 mg L −1. At 60 min incubation, the IC 50 values for KCN and As 2O 3 in water samples were 4.9 mg L −1 and 18.3 mg L −1, respectively. But the heavy metal ions, such as Cu 2+, Pb 2+ and Ni 2+, showed no obvious toxicity on E. coli. With the exception of Hg 2+, it showed 40.0 mg L −1 IC 50 value when E. coli was exposed to its solution for 60 min. The lower sensitivity of DTA for the heavy metal ions could be attributed to the toxicological endpoint and the experimental conditions used. All results suggest that the DTA is a sensitive, rapid and inexpensive alternative to on-site water and wastewater toxic analysis.

インビボマイクロダイアリシスとオペラント行動を用いて有害化学物質曝露後の神経伝達物質と学習行動を同時に評価するための動物モデルの確立

Most of the volatile organic compounds used in industrial and household products are reported to be toxic. While the effects of toxic chemicals on pulmonary and other systemic functions have been studied substantially, little is known about their effects on higher brain functions, particularly on the events in learning performance. From the particular perspective of environmental health, it is necessary to examine the toxic effects of environmental chemicals on higher brain functions. The aim of the present study is to establish a mouse model for simultaneous assessment of the effect of toluene (150 mg/kg, i.p.) on extracellular glutamate level in the hippocampus, using in vivo microdialysis and learning performance with a procedure of schedule-controlled operant behavior (SCOB). Different patterns of hippocampal glutamate level were observed in control and toluene-treated mice during learning performance. During learning performance in an operant chamber, control mice showed a saturated and persistent increased glutamate level with good learning performance, while toluene-treated mice showed a decreased glutamate level with poor learning performance. This is the first time to establish a new method to assess the effect of environmental chemical exposure on the brain neurotransmitter level during learning performance in an animal model.

Evolution of tolerance to PCBs and susceptibility to a bacterial pathogen ( Vibrio harveyi) in Atlantic killifish ( Fundulus heteroclitus) from New Bedford (MA, USA) harbor

A population of the non-migratory estuarine fish Fundulus heteroclitus (Atlantic killifish) resident to New Bedford (NB), Massachusetts, USA, an urban harbor highly contaminated with polychlorinated biphenyls (PCBs), demonstrates recently evolved tolerance to some aspects of PCB toxicity. PCB toxicology, ecological theory, and some precedence supported expectations of increased susceptibility to pathogens in NB killifish. However, laboratory bacterial challenges of the marine pathogen Vibrio harveyi to wild fish throughout the reproductive season and to their mature laboratory-raised progeny demonstrated comparable survival by NB and reference killifish, and improved survival by NB males. These results are inconsistent with hypothesized trade-offs of adaptation, and suggest that evolved tolerance in NB killifish may include mechanisms that minimize the immunosuppressive effects of PCBs. Compensatory strategies of populations persisting in highly contaminated environments provide a unique perspective for understanding the long-term ecological effects of toxic chemicals.

Human adult stem cells as the target cells for the initiation of carcinogenesis and for the generation of "cancer stem cells".

The inference to stem cells has been found in ancient myths and the concept of stem cells has existed in the fields of plant biology, developmental biology and embryology for decades. In the field of cancer research, the stem cell theory was one of the earliest hypotheses on the origin of a cancer from a single cell. However, an opposing hypothesis had it that an adult differentiated somatic cell could "de-differentiate" to become a cancer cell. Only within the last decade, via the "cloning" of Dolly, the sheep, did the field of stem cell biology really trigger an exciting revolution in biological research. The isolation of human embryonic stem cells has created a true revolution in the life sciences that has led to the hope that these human stem cells could lead to (a) basic science understanding of gene regulation during differentiation and development; (b) stem cell therapy; (c) gene therapy via stem cells; (d) the use of stem cells for drug discovery; (e) screening for toxic effects of chemicals; and (f) understand the aging and diseases of aging processes.

Population‐level ecological effect assessment: estimating the effect of toxic chemicals on density‐dependent populations

AbstractWe examined the relationship between individual‐level and population‐level effects of toxic chemicals, employing the equilibrium population size as an index of population‐level effects. We first analyzed two‐stage matrix models considering four life‐history types and four density‐dependent models, and then we analyzed ecotoxicological and life‐history data of the fathead minnow (Pimephales promelas) and brook trout (Salvelinus fontinalis) as real examples. Our elasticity analysis showed that toxic impacts on density‐dependent populations depended largely on the differences in density‐dependence and in life histories of the organisms. In particular, the importance of adult survivability was considerably increased in iteroparous organisms with density‐dependent juvenile survivability or fertility. Our results also suggested that population‐level effects, as indicated by the percentage reduction in equilibrium population size, were often greater than the percentage reductions in vital rates of individuals. Our analysis indicates that assessing population‐level risk and developing a risk‐reduction strategy without considering density‐dependence can be risky.

Stage‐dependent differences in effects of carbaryl on population growth rate in Japanese medaka (Oryzias latipes)

Fish embryo toxicology is important because embryos are considered more susceptible than adult fish to the effects of toxic chemicals. Recently, fish embryo bioassay was proposed to replace the conventional fish acute toxicity chemical test of the Organization for Economic Cooperation and Development guidelines because it offers the advantages of fewer reagents, easy handling, and efficient data production. To accelerate the establishment of a chemical toxicity database for the protection of environmental and human health, we need to determine whether the conventional toxicity test can safely be replaced by such fish embryo toxicity tests. For instance, it is unclear how the presence of the chorion moderates the toxic effects of some chemicals. If such chemical toxicities do differ between embryos and, for example, the larval stage, then different toxic effects should appear in later life. We tested the later-life effects of the neurotoxic insecticide carbaryl at sublethal concentrations (0 [control] and 5 and 10 mg/L) in embryos and posthatch larvae of the freshwater fish medaka, Oryzias latipes. Although embryos exposed until hatching showed multiple developmental malformations and reductions in subsequent survival rates over three months, no significant reduction was observed in tolerance to starvation for 7 d and in intrinsic population growth rate (r). Exposure of larvae for 96 h resulted in dose-responsive vertebral fracture, significant reduction in tolerance to starvation for 7 d, and reduced three-month survival rate; r was reduced significantly and consistently. These results suggested that posthatch larvae were more susceptible than embryos to carbaryl exposure and that the toxic cascades may differ between larvae and embryos. The influences of carbaryl exposure on population growth rate differed significantly with developmental stage.

Transcriptome profiling in crustaceans as a tool for ecotoxicogenomics

Chemicals released into the environment have the potential to affect various species and it is important to evaluate such chemical effect on ecosystems, including aquatic organisms. Among aquatic organisms, Daphnia magna has been used extensively for acute toxicity or reproductive toxicity tests. Although these types of tests can provide information on hazardous concentrations of chemicals, they provide no information on their mode of action. Recent advances in toxicogenomics, the integration of genomics with toxicology, have the potential to afford a better understanding of the responses of aquatic organisms to pollutants. In a previous study, we developed an oligonucleotide-based DNA microarray with high reproducibility using a Daphnia expressed sequence tag (EST) database. In this study, we increased the number of genes on the array and used it for a careful ecotoxicogenomic assessment of Daphnia magna. The DNA microarray was used to evaluate gene expression profiles of neonate daphnids exposed to beta-naphthoflavone (bNF). Exposure to this chemical resulted in a characteristic gene expression pattern. As the number of the genes on an array was increased, the number of genes that were found to respond to the chemicals was also increased, which made the classification of the toxic chemicals easier and more accurate. This newly developed DNA microarray can be useful for a obtaining a better mechanistic understanding of chemical toxicity effects on a common freshwater organism.

Interindividual variability of cytochrome P450 (CYP)-dependent alkoxyresorufin-dealkylase activities in human lung and relevance for the risk assessment of chemicals

Background : The lung represents an important target for the toxic effects of chemicals. Target tissue toxicity can be explained by local metabolic activation. As demonstrated by mRNA and Western Blot analysis, xenobiotic metabolizing CYPs are expressed in human lung. Their variation within the human population isnot known, although this is important for the risk assessment of chemicals. From interindividual variability , pathway-specific assessment factors (AFs) can be derived. This is of special importance in the lung, where metabolism is capacity-limited due to low abundance of CYPs. We determined the variability of CYP450-related ethoxyresorufin- O -deethylase- (EROD-), methoxyresorufin- O -demethylase- (MROD) and pentoxyresorufin- O -depentylase- (PROD) activities in a large panel of human lung samples. The activities are related to CYP1A1/1B1 (EROD), CYP1A2 (MROD) and CYP2B enzymes (PROD). Methods : Human lung tissue was obtained after informed consent. Microsomes were prepared and total protein content was determined. Enzyme activitieswere determined using fluorometric methods for dealkylation of alkoxyresorufins modified for human lung tissue. Assessment factorswere derived by the ratio of the 95% percentile (P95)/median. Results : EROD-, MROD-, and PROD activities were determined in 110 samples. The following P95/median ratios were obtained: 2.7 (EROD), 2.9 (MROD) and 3.2 (PROD). For an improved risk assessment, enzymes involved in chemical metabolism should beidentified. Determination of enzyme variation allows replacing the default AF of 3.16 for the kinetic part of intraspecies variability by apathway-specific AF. Our results demonstrate that the pathwayspecific AF for the enzyme activities investigated in the lung is almost equal to the default AF of 3.16.

Sequential toxicity identification evaluation (TIE) for characterizing toxicity of Venice Lagoon sediments: Comparison of two different approaches

A toxicity identification evaluation phase-I (TIE-1) procedure was carried out on five pore water samples extracted from sediments of the Venice Lagoon previously investigated to assess both chemical contamination and toxic effects on the biota. Two different sequential TIE procedures were tested. A first sequence (TIE-1) provided for adding Na 2S 2O 3, adding Na-EDTA, filtering, elution through a C18-SPE column and removing ammonia using the macroalgae Ulva rigida Agardh 1823, while a second procedure (TIE-2) was set up using U. rigida treatment for ammonia removal as first step, keeping unchanged the sequence of the other manipulations. Two different exposure time to the macroalgae were tested (3-h and 15-h). Sperm-cell toxicity test with the echinoid Paracentrotus lividus and embryotoxicity tests with the bivalves Mytilus galloprovincialis and Crassostrea gigas were performed on pore-water samples to assess the effect of the sequential treatments on the overall toxicity. The results confirmed that ammonia contribution to toxicity is strong in most of the samples and that metals, specially Cu, are of concern at least in three sites. The TIE-2 procedure provided more reliable results for the samples characterized by high ammonia contribution to the overall toxicity, whereas the results of TIE-1 and TIE-2 were equivalent for the samples where ammonia contribution was not prevailing. Chemical analyses and test results showed that a 3-h U. rigida exposure is suitable to remove ammonia toxicity minimizing potential metal up-take.

The effects of waterborne uranium on the hatching success, development, and survival of early life stages of zebrafish (Danio rerio)

In this study, we investigated the effects of the radioactive metal uranium (U) on the embryonic development, hatching success, growth rate, and survival of juvenile zebrafish (Danio rerio). We studied the effects of depleted uranium (20–500 μg L −1 of DU), inducing mainly chemical toxicity due to its low specific activity, and the combined effects of chemical and radiological toxicity by using a higher specific activity uranium isotope (20 and 100 μg L −1 of 233U). Results showed that early life stages are significantly affected by uranium exposure through both chemical and combined (chemical and radiological) toxicity. Experiments showed significant effects of U on hatching success starting at the concentration of 250 μg L −1 of DU, causing a 42% delay in median hatching times relative to control. Furthermore, a reduction of growth (decrease in body length and weight) was observed followed by a high mortality of pro-larvae stage (up to 100% at DU concentrations of 250 μg L −1 upon a 15 day exposure). Bioaccumulation measurements highlighted that U was mainly localised in the chorion but penetrated in the embryo inside eggs at a higher concentration. The effects differed depending on the isotopic composition of the uranium: sublethal defects in the tail detachment process were more pronounced for 233U than DU exposure, while the presence of 233U specifically affected embryo development and led to higher mortality rates of the prolarvae. The results from this study showed that the early life stages of zebrafish seems to be more sensitive to uranium contamination than more mature stages, and underline the importance of including pro-larval stages into toxicity tests in order to improve the relevancy for environmental risk assessments.

An Hypothesis to Account for the Renewal of Outer Segments in Rod and Cone Photoreceptor Cells: Renewal as a Surrogate Antioxidant

It is undisputed that glutathione (GSH) is an important cellular antioxidant. Although it is commonly believed that GSH is present in all retinal cells, several publications show that GSH is not immunologically detectable in outer segments of rod and cone photoreceptor cells, but is present in inner retinal cells and the pigment epithelium. Using these intriguing and surprising findings as a starting point, an hypothesis is proposed that the renewal of outer segments serves as a surrogate antioxidant for GSH and that the exceptional vulnerability of photoreceptor cells to certain toxic chemicals is linked to the deficiency in GSH in outer segments as a reductant, a detoxicant, and as an enzymatic cofactor. It is suggested that this deficiency of GSH is not damaging to outer segments under normal conditions, because renewal serves to replace any damaged molecules before they increase to detrimental levels. However, when photoreceptors are stressed, the renewal of outer segments alone is not capable of overcoming the higher rates of oxidizing and detrimental chemical reactions, and the health of the entire photoreceptor cell is at risk. The hypothesis is supported by a consideration of the essential role of the NADPH-dependent retinol reductase, by the different localization within photoreceptor cells of two key metabolic enzymes that are sensitive to oxidation, glyceraldehyde-3-phosphate dehydrogenase and the sodium-potassium ATPase, and by a consideration of the effects of toxic chemicals that selectively damage photoreceptor cells.

A New Day for Global Environmental Health

A New Day for Global Environmental Health

Influence of metal concentrations, percent salinity, and length of exposure on the metabolic rate of fathead minnows ( Pimephales promelas)

Understanding the effects of chemical toxicants on energetic processes is an important aspect of ecotoxicology. However, the influence of toxicant concentration and time of exposure on metabolism in aquatic organisms is still poorly understood. The purpose of this investigation was to determine the influence of increasing levels of three stressors (Cu, Cd, percent salinity) and exposure time (24 h and 96 h) on the metabolic rate of fathead minnows ( Pimephales promelas). In all 24-h exposures, there existed a threshold concentration, above which metabolic rate decreased significantly compared to the control and lower concentrations. In contrast, the metabolic rate of fish exposed for 96 h increased significantly in all concentrations compared to fish from the control. We suggest fathead minnows exhibit a consistent pattern of metabolic response to stressors, regardless of the physiological mechanisms involved, and that this response differs as a function of time of exposure.

In vitro investigations for the QSAR mechanism of lymphocytes apoptosis induced by substituted aromatic toxicants

The objective of this study was to assess the chemicals-induced apoptosis effects on fish lymphocytes and to use the QSAR model to interpret the relationships between apoptotic effects and chemical structures to identify the immune toxicology mechanism. By the use of a simple in vitro toxicological assay, the measured apoptotic parameter (EC50) is used in a QSAR to interpret the apoptotic effects of 25 substituted benzenes at low exposure levels. The apoptotic effects of all tested substituted aromatic chemicals with Carassius auratus lymphocytes were confirmed by DNA ladder and nucleus condensation. For both chlorobenzenes and PCBs, the EC50 values increase with increasing Cl number in the molecule, a result reflecting probably the increased p–π conjugation of the C–Cl bonds that lowers the molecular reactivity. Furthermore, the apoptotic EC50 data were best correlated with the dipole moment ( μ) and the energy of the lowest unoccupied molecular orbital (ELUMO) such that: log ( 1 / EC 50 ) = 0.325 + 0.222 μ − 0.163 ( ELUMO ) (with R 2 = 0.879). The dependence on the electronic ELUMO factor of the established correlation suggests that during the apoptotic process the ROS (reactive oxygen substance) produced by cells acts as a Lewis base in substituted nucleophilic reactions with toxic chemicals behaving as an electron acceptor. On the basis of the test results, the present toxicological assay offers a rapid tool for assessing the toxic effects of chemicals at low exposure levels.

Prediction of Toxicity of Phenols and Anilines to Algae by Quantitative Structure-activity Relationship

To measure the toxicity of phenol, aniline, and their derivatives to algae and to assess, model, and predict the toxicity using quantitative structure-activity relationship (QSAR) method. Oxygen production was used as the response endpoint for assessing the toxic effects of chemicals on algal photosynthesis. The energy of the lowest unoccupied molecular orbital (E(LUMO)) and the energy of the highest occupied molecular orbital (E(HOMO)) were obtained from the ChemOffice 2004 program using the quantum chemical method MOPAC, and the frontier orbital energy gap (deltaE) was obtained. The compounds exhibited a reasonably wide range of algal toxicity. The most toxic compound was alpha-naphthol, whereas the least toxic one was aniline. A two-descriptor model was derived from the algal toxicity and structural parameters: log1/EC50 = 0.268,logKow - 1.006deltaE + 11.769 (n = 20, r2 = 0.946). This model was stable and satisfactory for predicting toxicity. CONCLUSION Phenol, aniline, and their derivatives are polar narcotics. Their toxicity is greater than estimated by hydrophobicity only, and addition of the frontier orbital energy gap deltaE can significantly improve the prediction of logKow-dependent models.

Tricuspid Valve Disease

The normal tricuspid valve anatomy and function have several dissimilarities to the corresponding mitral valve in the left heart, in part, based on lower pressures in the right heart chambers. The functional abnormalities resulting from tricuspid valve disease are classified as primary and secondary. Primary valve disease is any associated intrinsic valve pathology. The list of responsible conditions includes congenital, rheumatic, infective endocarditis, carcinoid heart disease, toxic effects of chemicals, tumors, blunt trauma, and myxomatous degeneration. The secondary tricuspid valve disease does not involve intrinsic anatomic abnormalities of the valve apparatus, aside from tricuspid annular dilation secondary to right ventricular dilation and dysfunction. The most common cause of tricuspid valve disease is secondary to left heart disease, either myocardial, valvular, or mixed. Although bedside diagnosis of advanced tricuspid valve disease is feasible, echocardiography provides valuable clues to the presence and severity of tricuspid valve stenosis and/or regurgitation with considerable accuracy. The tricuspid regurgitation signal using Doppler techniques is utilized for estimation of right ventricular systolic pressure, which, in the absence of right ventricular outflow obstruction, corresponds to pulmonary arterial systolic pressure. This is clinically useful since nearly 80 to 90% of patients exhibit some degree of tricuspid regurgitation. The treatment of tricuspid valve disease is guided by underlying etiology and pathology. Tricuspid valve repair is increasingly advocated for patients with advanced tricuspid regurgitation, especially when combined with surgery on the left heart pathology. Primary tricuspid valve disease is often treated by surgical approach specific to the underlying pathology.

Exploiting Gene‐Environment Interaction to Detect Adverse Health Effects of Environmental Chemicals on the Next Generation

There is increasing evidence from epidemiological studies that genetic susceptibilities may modify the teratogenic effects of toxic chemicals. However, in contrast to tobacco smoke, few epidemiological studies have addressed environmental chemicals, such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls in regard to genetic susceptibility. Recent studies, including the Hokkaido Study of Environments and Children's Health, have investigated the impacts of both environmental and genetic factors on children's development. Several xenobiotic-metabolizing genes have been reported to confer genetic susceptibility to low birth weight. These genes seem to be influenced functionally by maternal smoking during pregnancy, itself a significant risk factor. In our study, we found that birth weight was significantly lower among infants born to smoking women having the specific AHR, CYP1A1, GSTM1, CYP2E1 and NQO1 genotypes. When combinations of these genotypes were considered, birth weight was even lower. On the other hand, congenital anomalies such as hypospadias seemed to be caused by environmental factors in conjunction with genetic predisposition as suggested by linkage in several case-control studies reported to low birth weight. We have found an association between maternal CYP1A1 genotype or low birth weight and the risk of hypospadias irrespective of smoking. At the same time, birth weight was negatively correlated with maternal blood concentrations of polychlorinated dibenzofurans. Further studies should elucidate the impact of genetic factors on adverse effects of exposures to dioxin-related chemicals.

Potential adverse effects of phthalic acid esters on human health: A review of recent studies on reproduction

Various phthalic acid esters (PAEs) have been used for a wide range of products. PAEs and their metabolites produce reproductive and developmental toxicities in laboratory animals. These findings have raised concern about the possibility of PAEs as contributors to reproductive and developmental adverse effects in humans. This paper focuses on PAE exposure and health effects in human populations and summarizes recent studies. The exposure data in human populations indicate that the current methodology of estimation of PAE exposure is inconsistent. It is therefore important to obtain improved data on human PAE exposure and better understanding of the toxicokinetics of PAEs in each subpopulation. Studies on health effects of PAEs in humans have remained controversial due to limitations of the study designs. Some of findings in human populations are consistent with animal data suggesting that PAEs and their metabolites produce toxic effects in the reproductive system. However, it is not yet possible to conclude whether phthalate exposure is harmful for human reproduction. Studies in human populations reviewed in this paper are useful for showing the strength of the association. It is sometimes claimed that the use of animal data for estimating human risk does not provide strong scientific support. However, because it is difficult to find alternative methods to examine the direct toxic effects of chemicals, animal studies remain necessary for risk assessment of chemicals including PAEs.

Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects

BackgroundEnvironmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established.ObjectivesWe assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent).MethodsGrowth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17α-ethinyl-estradiol (EE2)], and to EE2 alone.ResultsIn addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE2 were modified when it was present in a complex mixture (i.e., spiked into effluent), suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes.ConclusionThese data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures.

Assessment of the Long-Term and Transgenerational Consequences of Perturbing Preimplantation Embryo Development in Mice1

Perturbations of the development of preimplantation embryos may have long-term consequences for the health of progeny. There are no standardized methods for assessing such risks. The OECD/OCDE 416 Guideline for Testing of Chemicals (Two-Generation Reproduction Toxicity Study) is a standardized assay for detecting potential toxic effects of chemicals. The present study assessed the utility of this guideline for identifying long-term consequences of perturbing preimplantation development. Extended culturing of mammalian zygotes commonly results in retarded preimplantation development. Mouse zygotes were cultured in vitro for 96 h until the blastocyst stage (cultured blastocysts) or blastocysts were collected from the Day-3.5 uterus (in vivo blastocysts). The resulting blastocysts were transferred to the uteri of pseudopregnant recipients (P generation). Progeny from both treatments were mated for a further two generations (F1 and F2 generations). There was no effect of treatment group on gross fertility across the generations tested. Progeny of the cultured blastocysts had lower body weights to the time of weaning compared to in vivo blastocysts in the P and F1 generations, but not in the F2 generation. At maturity, there was no effect of treatment group on body weight, although thyroid weight was higher in the in vivo blastocyst group in the P generation, while the brain, pituitary, and kidneys were larger in the progeny of the cultured blastocysts of the F1 generation. The OECD/OCDE 416 assessment may have a role as a standardized test for the assessment of the biological consequences of perturbing the growth environment of the preimplantation embryo. Embryo culture influenced the somatometric parameters of the resulting progeny, some of which were maintained across a generation.