Genetic Testing in Familial Hypercholesterolemia: Is It for Everyone?

PURPOSE OF REVIEW: Lipid measurements and genetic testing are the main diagnostic tools for FH screening that are available in many countries. A lipid profile is widely accessible, and genetic testing, although available worldwide, in some countries is only performed in a research context. Still FH is diagnosed late, showing lack of early screening programs worldwide. RECENT FINDINGS: Pediatric screening of FH was recently recognized by the European Commission Public Health Best Practice Portal as one on the best practices in non-communicable disease prevention. The early diagnosis of FH and the lowering of LDL-C values over lifespan can reduce the risk of coronary artery disease and offer health and socioeconomic gains. Current knowledge about FH shows that early detection through appropriate screening needs to become a priority in healthcare systems worldwide. Governmental programs for FH identification should be implemented to unify the diagnosis and increase patient identification.

Sexual dimorphism in Kinosternon scorpioides (Linnaeus, 1766) from the Brazilian Amazon.

The sexual dimorphism of the Kinosternon scorpioides was evaluated using two different techniques (linear and geometric morphometry) from images and linear measurements of the carapace and plastron of adults (male and female). Linear morphometry indicated that the height and width of carapace and plastron are statistically different between sexes, with females being wider and taller. In the evaluation of geometric morphometry, ANOVA demonstrated variation in the size of the plastron and the shape of the carapace and plastron, expressing a tendency in shape for each sex. Sexual dimorphism, therefore, is verified for this species, notably by the plastron. This study indicates an additional tool for the phenotypic knowledge of animals, contributing to the study of threatened populations.

Epidemiologic study of odontogenic and non-odontogenic cysts in children and adolescents of a Brazilian population.

BACKGROUND: the objective of this study was to describe the frequency of cystic lesions in a Brazilian population of patients histopathologically diagnosed in the first and second decade of life. MATERIAL AND METHODS: Retrospective descriptive cross-sectional study was performed. Biopsy records were obtained from the archives of a Brazilian referral center between 1980 and 2016. RESULTS: A total of 2.114 biopsy records of pediatric patients were analyzed with oral and maxillofacial lesions. Data such as gender, age, anatomical location, and histopathological diagnosis were collected and categorized. Among all oral and maxillofacial lesions (n=2.114), were diagnosed 294 cases of odontogenic cysts (13.9%) and 16 cases of non-odontogenic cysts (0.8%). The most frequent lesions in each group were, respectively: radicular cyst (n=145) and epidermoid cyst (n=4). These lesions were most common in female (n=158), with a mean age of 14 years. For intraosseous lesions, the mandible (n=148) was the most affected anatomic site; moreover, the floor of the mouth (n=6) was most affected by cysts in soft tissues. CONCLUSIONS: Odontogenic cysts were relatively common in population studied, but non-odontogenic cysts were rare in these patients.

Genotype x environment interaction on experimental hybrids of chili pepper.

In Brazil, cultivation of hybrid plants comprise near 40% of the area grown with vegetables. For Capsicum, hybrids of bell and chili peppers have already exceeded 50% and over 25% of all are commercialized seeds. This study aimed to evaluate new pepper hybrids in two environments, Cáceres, MT, and Campos dos Goytacazes, RJ, Brazil. Nine experimental hybrids of C. baccatum var. pendulum were tested and trials were performed in a randomized block design, with three replications and eight plants per plot. In each environment, plants were assessed for canopy diameter, plant height, number of fruit per plant, mean fruit mass per plant, fruit length and diameter, pulp thickness, and content of soluble solids. Seven of the eight traits have differed significantly due to environment variation. Furthermore, genotype and environment interaction was highly significant for number of fruit per plant, mean fruit mass per plant, fruit length, and fruit diameter. Choosing a hybrid to be grown in one of the studied locations must be in accordance with the sought characteristics since there is a complex interaction for some studied traits.

Molecular and agronomic analysis of intraspecific variability in Capsicum baccatum var. pendulum accessions.

Capsicum baccatum is one of the most important chili peppers in South America, since this region is considered to be the center of origin and diversity of this species. In Brazil, C. baccatum has been widely explored by family farmers and there are different local names for each fruit phenotype, such as cambuci and dedo-de-moça (lady's finger). Although very popular among farmers and consumers, C. baccatum has been less extensively studied than other Capsicum species. This study describes the phenotypic and genotypic variability in C. baccatum var. pendulum accessions. Twenty-nine accessions from the Universidade Estadual do Norte Fluminense Darcy Ribeiro gene bank, and one commercial genotype ('BRS-Mari') were evaluated for 53 morphoagronomic descriptors (31 qualitative and 22 quantitative traits). In addition, accessions were genotyped using 30 microsatellite primers. Three accessions from the C. annuum complex were included in the molecular characterization. Nine of 31 qualitative descriptors were monomorphic, while all quantitative descriptors were highly significant different between accessions (P < 0.01). Using the unweighted pair group method using arithmetic averages, four groups were obtained based on multicategoric variables and five groups were obtained based on quantitative variables. In the genotyping analysis, 12 polymorphic simple sequence repeat primers amplified in C. baccatum with dissimilarity between accessions ranging from 0.13 to 0.91, permitting the formation of two distinct groups for Bayesian analysis. These results indicate wide variability among the accessions comparing phenotypic and genotypic data and revealed distinct patterns of dissimilarity between matrices, indicating that both steps are valuable for the characterization of C. baccatum var. pendulum accessions.

Occurrence and use of an estuarine habitat by giant manta ray Manta birostris.

Based on the knowledge of local artisanal fishermen and on direct observations, this study presents evidence that the giant manta ray Manta birostris uses the Paranaguá estuarine complex in south Brazil, south-western Atlantic Ocean, in a predictable seasonal pattern. Behavioural observations suggest that the estuary can act as a nursery ground for M. birostris during the summer.

Uso de biomarcador histopatológico em brânquias de Centropomus undecimalis (Bloch, 1972) na avaliação da qualidade da água do Parque Ecológico Laguna da Jansen, São Luís - MA / Using histopathological biomarker in gills of Centropomus undecimalis (Bloch, 1972) in assessing the water quality at Ecological Park Laguna da Jansen, São Luís -MA

Com o objetivo de analisar a intensidade das alterações histológicas em brânquias de Centropomus undecimalis para avaliar a qualidade da água do Parque Ecológico Laguna da Jansen, em São Luís, Estado do Maranhão, coletaram-se exemplares de peixes no período chuvoso de 2012 e amostras de água nos períodos seco de 2011 e chuvoso de 2012 para análises físico-química e bacteriológica. Os resultados mostraram que a maioria dos parâmetros físico-químicos e bacteriológicos estava de acordo com os valores estabelecidos pela Resolução do CONAMA nº 357 de 2005. As alterações histológicas observadas foram: elevação do epitélio lamelar; proliferação excessiva de células dos epitélios filamentar e lamelar causando fusão total ou parcial das lamelas; alteração da estrutura das lamelas; hiperplasia das células mucosas; ruptura do epitélio lamelar; espessamento descontrolado do tecido proliferativo filamentar e lamelar e aneurismas de vários tamanhos. Também foi observada a presença de parasito em alguns exemplares. O Índice de Alteração Histológica (IAH) por indivíduo variou de 2 a 114. O valor médio do IAH obtido foi de 40,3, demonstrando que as brânquias dos indivíduos amostrados da espécie C. undecimalis apresentaram alterações de moderadas para severas no tecido. As alterações histológicas encontradas indicam que esses indivíduos desenvolveram mecanismos de defesa contra a ação de estressores presentes na água da laguna e a um provável desequilíbrio parasito-hospedeiro-ambiente associado à baixa qualidade do ambiente...

Aiming to analyze the intensity of the histological changes in the gills of Centropomus undecimalis to assess the water quality at Ecological Park of the Laguna da Jansen, in São Luís, State of Maranhão, specimens of fish were collected during the rainy season of 2012 and water samples during the dry season in 2011 and rainy season in 2012 for physical-chemical and bacteriological analyses. The results showed that most of the physical-chemical and bacteriological parameters analyzed agreed with the values established by CONAMA Resolution nº 357 of 2005. The histological changes were elevation of the lamellar epithelium, excessive cell proliferation of the filamentum and lamellar epithelium causing total or partial melting of the lamellar; changing the structure of the lamellar, hyperplasia of mucous cells, disruption of the lamellar epithelium, uncontrolled proliferative tissue filamentum thickening and lamellar and aneurysms in various sizes. We noted the presence of parasites in some samples. The Index Histological Amendment (IAH) per individual ranged from 2 to 114. The mean IAH obtained was 40.3, demonstrating that the gills of the individuals of the C. undecimalis species showed moderate to severe changes in the tissue. The histological findings indicate that these individuals have developed defense mechanisms against the action of stressors present in the water of the Laguna da Jansen and a probable parasite-host-environment imbalance associated with the environment's low quality...

Phenotypic and genotypic variation among Capsicum annuum recombinant inbred lines resistant to bacterial spot.

A breeding program carried out under Brazilian growing conditions to obtain Capsicum annuum cultivars with disease resistance to bacterial spot (BS) produced 8 promising recombinant inbred lines (RILs). The present study aimed to characterize these RILs using phenotypic descriptors and molecular markers (inter-simple sequence repeat) and to confirm their resistance to BS. Twenty-two phenotypic descriptors and 15 inter-simple sequence repeat primers were used to characterize the RILs. The parent, UENF 1381, which is resistant to BS, and 'Casca Dura Ikeda', a traditional cultivar, were used as standards. Variability among genotypes was observed considering either binary or multicategorical characteristics, such as fruit length, fruit diameter, and fruit longitudinal and transversal section. Such variability in fruit traits can be exploited to develop new genotypes with BS resistance for various types of market consumption. RILs numbered 1, 3, and 6 were the most homogenous, whereas those coded 2, 5, 8, and 11 had the same level of heterogeneity as that observed in 'Casca Dura Ikeda'. Molecular analysis clustered the genotypes into 5 groups, with RILs 1, 2, 3, and 5 allocated in isolated groups. RILs 1, 2, 6, and 8 confirmed resistance to BS. Considering homogeneity level and BS resistance, RILs 1 and 6 were suitable for use as pre-cultivars in final tests to register and release two new C. annuum cultivars.

Genetic divergence among African cowpea lines based on morphoagronomic traits.

The aim of this study was to estimate the genetic divergence between African cowpea lines from the Cowpea Germplasm Bank of Embrapa Meio-Norte, Brazil. The morphoagronomic diversity of 57 cowpea lines was assessed using multivariate analysis. The germplasm was evaluated in August 2009 using a randomized block design with three replications based on the following traits: number of pods per peduncle, pod length (PL), number of grains per pod (NGP), grain length (GRL), grain width, 100-grain weight (W100G), and yield. The heritability values of the traits PL, NGP, GRL, and W100G were all higher than 70%, indicating the possibility of genetic progress with selection. The crosses between the lines IT82D-889 and IT89KD-245, IT85F-1380 and IT89KD-245, and IT89KD-245 and IT98K-1092-1 could result in promising genetic combinations. The characteristics that contributed most to genetic divergence were W100G (49.7%), PL (16.7%), GRL (12.0%), and NGP (9.7%).

Occupational and individual risk factors for dysphonia in teachers.

BACKGROUND: In recent decades several groups of researchers have been interested in describing and understanding vocal morbidity in teachers in order to explain the large number of teachers diagnosed with dysphonia and account for the absenteeism attributed to vocal disability. AIMS: To determine the proportion of teachers who reported a diagnosis of dysphonia and measure associations between individual and contextual factors and the event of interest. METHODS: Teachers were recruited from the city of Belo Horizonte and invited to complete a web-based institutional intranet questionnaire. RESULTS: In total, 649 teachers responded; 32% (CI 28.5-35.5) reported that they had received a physician diagnosis of dysphonia. This prevalence was significantly higher among female teachers (prevalence ratio (PR) 2.33; CI 1.41-3.85), and groups who reported limited technical resources and equipment (PR 1.56; CI 1.14-2.15), a diagnosis of gastritis (PR 1.59; CI 1.28-1.98), not being summoned for an annual physician examination (PR 0.47; CI 0.32-0.68), or absenteeism (PR 1.39; CI 1.06-1.81). CONCLUSIONS: The high prevalence of dysphonia in teachers was not associated with any individual variables, except for sex and comorbidity (diagnosis of gastritis). Limited technical resources and equipment were associated with dysphonia and suggests policy change is important in preventing dysphonia.

Ichthyofauna diversity of Taperoá II reservoir, semi-arid region of Paraíba, Brazil.

To determine the fish species present in Taperoá II Reservoir, and their relevance to the local economy, this research aimed to evaluate the composition, abundance, degree of dominance and constancy of species, along with diversity, richness, evenness and similarity indices in a tropical semi-arid fish assemblage, during one year. Six 24 hour-long samplings were carried out between October 2005 and October 2006 using cast, seine and gillnets. The 889 collected individuals belonged to 11 species from 9 families. Temporal variation was observed in the capture frequency of different species, and a significant negative correlation between precipitation and number of individuals was also observed. Among the recorded families, Characidae showed a higher frequency of occurrence (38.4%), mostly due to Astyanax bimaculatus (Linnaeus, 1758) and A. fasciatus (Cuvier, 1819). Eight species were categorised as constant, two as accessory and one as accidental. Diversity index values were intermediate with low fluctuation throughout the study period, and no correlation with precipitation or water volume. However, the greatest diversity value was recorded in March 2006, when the peak of the precipitation was recorded. Evenness values showed a similar trend to the diversity index.

Molecular diagnosis of familial hypercholesterolemia: an important tool for cardiovascular risk stratification.

UNLABELLED: Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. Molecular identification of these patients can reduce the burden of mortality from cardiovascular disorders simply by the correct identification of the disease early in life, followed by counseling and appropriate lifestyle modifications, and therapeutic measures when required. Recent studies show that, in Portugal, this disease is severely under-diagnosed. After more than 10 years of research through the Portuguese FH Study, it is now possible to translate the original research results into clinical application. AIMS: The main aims of the present work were to determine whether clinical characterization is sufficient to identify these individuals at high risk of developing CHD and to evaluate the clinical applicability of molecular diagnosis for FH. METHODS: All patients described in this study were recruited for the Portuguese FH Study. The diagnostic criteria used to select the index patients were adapted from the Simon Broome Heart Research Trust. To analyze the usefulness of the molecular diagnosis, graphs of total and LDL cholesterol values by age were constructed for 622 possible FH patients. The lipid profile of patients genetically identified as having FH, before and under medication, were analyzed to assess whether these patients were receiving appropriate treatment. The data are shown separately for children and adults and for female and male propositi (index cases and hypercholesterolemic relatives), both with and without a detectable mutation in the LDLR gene. RESULTS: The Portuguese FH Study has already genetically identified 404 individuals (171 index patients and 233 relatives) among more than one thousand individuals sent for study. A total of 78 different mutations in the LDLR gene were found in 171 index patients, 2 different mutations were found in the apoB gene of 4 patients and 2 patients had a unique PCSK9 mutation. Statistical analysis revealed that there are significant differences between total cholesterol (p < 0.001) and apoB (p = 0.026) values in the group of children (male and female) with and without a mutation in LDLR. For female children LDL values were also significantly different (p < 0.001) between subgroups but for male children this difference did not reach statistical significance. In adult women there is a statistically significant difference for total cholesterol (p = 0.049), LDL cholesterol (p = 0.031) and apoB (p = 0.003) values in the subgroups with and without a LDLR mutation. In adult males there is a statistical difference for total cholesterol (p = 0.002). LDL cholesterol (p = 0.003) and apoB (p = 0.0023) in subgroups with and without an LDLR mutation. Nevertheless there was considerable dispersion of values and individually it is not possible to distinguish between patients with and without a mutation in the LDLR gene, based only on lipid profile. CONCLUSIONS: By analysis of the clinical data of 696 possible FH patients, the present report shows evidence that clinical characterization is not sufficient to distinguish between patients with genetic or environmental dyslipidemia, and so molecular diagnosis is useful in clinical practice, allowing correct identification of FH patients and their relatives, and the early implementation of therapeutic measures to reduce the elevated cardiovascular risk of these patients. In general, molecular diagnosis of FH is feasible and could be obtained in 1-2 months if the technology is available. In Portugal the test will be offered to the population by our Institute at a cost of about 500 euros, like many other genetic tests or exams such as nuclear magnetic resonance.

Update of the Portuguese Familial Hypercholesterolaemia Study.

The main aim of the Portuguese Familial Hypercholesterolaemia Study is to identify the genetic cause of hypercholesterolaemia in individuals with a clinical diagnosis of Familial Hypercholesterolaemia (FH). A total of 1340 blood samples were collected from 482 index patients and 858 relatives with the collaboration of clinicians from several hospitals all over the country. The genetic diagnosis of FH in this study is based on the analyses of three genes: LDLR, APOB and PCSK9. In the last 10 years, the Portuguese FH Study identified a genetic defect in a total of 171 index patients, corresponding to an overall of 48% of the total received cases with clinical diagnosis of FH. Although the Simon Broome FH register criteria have been adapted to our study, 59 patients that did not fulfil all criteria were included in the study and a mutation causing disease was identified in 8 of these patients. In the LDLR gene were found 80 different mutations in 165 unrelated index patients: 159 heterozygous, 3 compounds heterozygous and 3 true homozygous. The APOB p.Arg3527Gln and the PCSK9 p.Asp374His mutation were not found in any of our patients since our last report, but a novel mutation in the APOB gene, predicted to cause a single amino acid substitution p.Tyr3560Cys, was found in one patient. The cascade screening in relatives of these 171 index patients allowed the identification and genetic characterization of a total of 404 FH patients in Portugal.

Salinity and freshwater discharge determine rotifer distribution at the Mossoró River Estuary (Semiarid Region of Brazil).

The present study aimed at evaluating differences in rotifer distribution in three estuarine zones in an inverse estuary located in the Semiarid Region of Brazil. Zones were chosen based on their proximity to the ocean and river border as a means of reflecting a horizontal salinity gradient. High freshwater discharge during the rainy season was the major determinant of rotifer composition. On the other hand, due to higher salinity values during the dry season, very low values of species richness and abundance were observed in all zones. Therefore, the study highlights the constraints of salinity and the positive influence of seasonality and river proximity on rotifer species in a semiarid estuarine environment.

Salinity and freshwater discharge determine rotifer distribution at the Mossoró River Estuary (Semiarid Region of Brazil) / Salinidade e descarga de água doce determinam a distribuição de rotíferos no estuário do Rio Mossoró (região semiárida do Brasil)

The present study aimed at evaluating differences in rotifer distribution in three estuarine zones in an inverse estuary located in the Semiarid Region of Brazil. Zones were chosen based on their proximity to the ocean and river border as a means of reflecting a horizontal salinity gradient. High freshwater discharge during the rainy season was the major determinant of rotifer composition. On the other hand, due to higher salinity values during the dry season, very low values of species richness and abundance were observed in all zones. Therefore, the study highlights the constraints of salinity and the positive influence of seasonality and river proximity on rotifer species in a semiarid estuarine environment.

O presente estudo objetivou avaliar diferenças na distribuição de rotíferos em três zonas estuarinas em um estuário inverso localizado na região semiárida do Brasil. As zonas foram escolhidas com base em suas proximidades com o oceano e a margem do rio de forma a representar um gradiente de salinidade horizontal. A forte entrada de água doce durante o período chuvoso foi o maior determinante da composição de rotíferos. Do outro lado, devido aos maiores valores de salinidade durante o período seco, valores muito baixos de riqueza de espécies e abundância foram observados em todas as zonas. Dessa forma, o estudo demonstra as restrições da salinidade e a influência positiva da sazonalidade e da proximidade com o rio sobre as espécies de rotíferos em um ambiente estuarino do semiárido.

Immunoexpression of MMPs-1, -2, and -9 in ameloblastoma and odontogenic adenomatoid tumor.

OBJECTIVE: The aim of this study was to evaluate and compare the expression of metalloproteinases-1, -2, and -9 in solid ameloblastoma and adenomatoid odontogenic tumor. METHODS: A total of 20 cases of solid ameloblastoma and 10 cases of adenomatoid odontogenic tumors were selected and immunohistochemically assessed. Metalloproteinases-1, -2, and -9 immunoexpression and their distribution pattern were noted and semiquantitatively scored. The scores obtained were statistically analyzed. RESULTS: Matrix metalloproteinase (MMP)-1 showed a predominant expression in both tumors and was found in stroma and parenchyma. For MMP-2, there was a varied expression, with 80% and 60% of immunoreactive tumor cells in ameloblastoma and adenomatoid odontogenic tumor respectively. Regarding stromal cells, 65% of ameloblastomas and 80% of adenomatoid odontogenic tumors showed positivity. There was immunoexpression of the MMP-9 in parenchymal and stromal cells in all cases of both tumors analyzed. A statistically significant difference in the expression of MMP-1 in relation to the expression of MMP-2 and -9 in ameloblastomas (P < 0.001) was observed. CONCLUSION: The results suggest that these metalloproteinases are related to growth and progression of tumors analyzed, and particularly in ameloblastoma, its highest aggressiveness may be, in part, a result of the active participation of the stromal cells and their products, such as the MMPs studied.

Genetic diagnosis of familial hypercholesterolaemia: the importance of functional analysis of potential splice-site mutations.

Familial hypercholesterolemia (FH) results from defective low-density lipoprotein receptor (LDLR) activity, mainly due to LDLR gene defects. Of the many different LDLR mutations found in patients with FH, about 6% of single base substitutions are located near or within introns, and are predicted to result in exon skipping, retention of an intron, or activation of cryptic sites during mRNA splicing. This paper reports on the Portuguese FH Study, which found 10 such mutations, 6 of them novel. For the mutations that have not been described before or those whose effect on function have not been analysed, their effect on splicing was investigated, using reverse transcriptase PCR analysis of LDLR mRNA from freshly isolated blood mononuclear cells. Two of these variants (c.313+6 T-->C, c.2389G-->T (p.V776L)) caused exon skipping, and one caused retention of an intron (c.1359-5C-->G), whereas two others (c.2140+5 G-->A and c.1061-8T-->C) had no apparent effect. Any effect of c.1185G-->C (p.V374V) on splicing could not be determined because it was on an allele with a promoter mutation (-42C-->G) that was probably not transcribed. Variants in four patients lost to follow-up could not be tested experimentally, but they almost certainly affect splicing because they disrupt the invariant AG or GT in acceptor (c.818-2A-->G) or donor (c.1060+1G-->A, c.1845+1delG and c.2547+1G-->A) spice sites. These findings emphasise that care must be taken before reporting the presence or absence of a splice-site mutation in the LDLR gene for diagnostic purposes. The study also shows that relatively simple, quick and inexpensive RNA assays can evaluate putative splicing mutations that are not always predictable by available software, thereby reducing genetic misdiagnosis of patients with FH.

Familial hypercholesterolaemia in Portugal.

Familial hypercholesterolaemia (FH) is characterised clinically by an increased level of circulating LDL cholesterol that leads to lipid accumulation in tendons and arteries, premature atherosclerosis and increased risk of coronary heart disease (CHD). Although Portugal should have about 20,000 cases, this disease is severely under-diagnosed in our country, this being the first presentation of Portuguese data on FH. A total of 602 blood samples were collected from 184 index patients and 418 relatives from several centres throughout Portugal. Fifty-three different mutations were found in 83 index patients, 79 heterozygous and 4 with two defective LDLR alleles. Additionally, 4 putative alterations were found in 8 patients but were not considered mutations causing disease, mainly because they did not co-segregate with hypercholesterolaemia in the families. Three unrelated patients were found to be heterozygous for the APOB(3500) mutation and two unrelated patients were found to be heterozygous for a novel mutation in PCSK9, predicted to cause a single amino acid substitution, D374H. Cascade screening increased the number of FH patients identified genetically to 204. The newly identified FH patients are now receiving counselling and treatment based on the genetic diagnosis. The early identification of FH patients can increase their life expectancy and quality of life by preventing the development of premature CHD if patients receive appropriate pharmacological treatment.

Evaluation of skin sensitization response of dialkyl (C6-C13) phthalate esters.

Isolated case reports suggest that dermal contact with some phthalate esters may result in skin sensitization. This issue was investigated in guinea pig sensitization tests, but the results were inconclusive. Consequently, 7 dialkyl phthalate esters, (diisohexyl, diisoheptyl, di(2-ethylhexyl), diisononyl, diisodecyl, diundecyl and ditridecyl phthalates), ranging in carbon number from C6 to C13, were tested in a 104-person panel human repeated insult patch test (HRIPT) using the modified Draize procedure. Test concentrations of 100% were selected for the induction and challenge phases of the HRIPT based upon a 24-h occluded irritation test on 15 panelists. Under the conditions of this HRIPT, no evidence of dermal irritation or sensitization for any of the 7 phthalate esters was observed in the 104-person panel. These HRIPT data provide evidence for the lack of experimental skin sensitization potential for the phthalate esters tested.