Cashmeran as a potential endocrine disrupting chemical: What does the weight-of-the-evidence indicate?

Cashmeran is a fragrance ingredient. Risk assessments are available but have not focused on its endocrine disruptor potential. The objective was to evaluate Cashmeran as a potential endocrine-disrupting chemical (EDC). The assessment was based on data from US EPA's CompTox Chemicals Dashboard, the Danish (Q)SAR Database, in vitro assays, and in vivo studies. ToxCast assays related to estrogen, androgen, thyroid, and steroidogenesis modalities were Inactive at non-cytotoxic concentrations. In vitro assays demonstrated no estrogenic activity in a human cervical epithelioid carcinoma HeLa cell line and indicated only weak agonist estrogenic activity in Chinese Hamster Ovary (CHO)-K1 cells. In the same test, no agonist or antagonist activity was detected for human androgen receptor (hAR) and thyroid hormone receptor ß (hTHRß) binding. The Danish QSAR database didn't indicate any ED potential. There were no adverse endocrine related effects in either a 90-day repeated gavage dosing study or a reproductive and developmental screening study. Regarding ED potential for environment, the data from two limited environmental ED related studies on Cashmeran did not raise any concern. Data from in vitro and in vivo studies were considered for environmental ED concern. Based on the weight-of-the-evidence, Cashmeran is not expected to cause endocrine effects.

Short-term biological variation of differential count in healthy subjects in a South Asian population.

Estimates of Within-Subject and between subject biological variation for the white blood cell differential count (DC) have not been reported in South Asia. Therefore, we attempted to measure the short-term biological variation estimates for DC. The study was conducted on 28 healthy volunteers (15 males and 13 females). Blood from the volunteers was collected in the morning in K3-EDTA vials and analyzed in triplicate on the Sysmex XN-1000 analyzer, for six consecutive days. The Within subject, between subject and analytical coefficient of variation of the DC was calculated from the results by nested repeated measures ANOVA after outlier exclusion. The Reference change values (RCV) were also calculated. The within-subject variation for eosinophil Count and between subject variation for basophils in our study from South Asia was greater than the published European and American studies. Males and females showed similar biological variation for DC. The within-subject variation of other parameters (Neutrophils, Lymphocytes, Monocytes and Basophils) were similar or showed only mild differences to the published studies. The markedly different within-subject variation for Eosinophil counts suggest that the RCV for DC in South Asians need to be different from the published data in order to have clinical relevance. The Within-subject variation values of the other parameters seem transportable from the published European and American studies, but the small differences found mean that further regional estimates need to be reported for robust evidence of the same.

Short term biological variation of common hematological parameters in healthy subjects in a South Asian population.

There is no rigorous publication on the biological variation of common hematological parameters in South Asians to date. Also, there are few publications worldwide dealing with a variation of Reticulocyte parameters. Therefore, an attempt was made to estimate the short term within-subject and between-subject biological variation of common hematological and reticulocyte parameters. Twenty-eight healthy individuals (fifteen males and thirteen females) were selected after clinical and laboratory examination. Blood was collected in K3-EDTA vials in the morning for six consecutive days and analysed in triplicate on the Sysmex XN-1000 analyzer. Outliers were excluded and the within-subject, between-subject and analytical coefficient of variation calculated after statistical analysis by nested repeated measures ANOVA. The Reference change values (RCV), and estimates for desirable imprecision, bias, total error and index of individuality calculated. The within-subject biological variation for the studied subset belonging to South Asia closely followed published European and American studies and were similar for males and females. The between-subject variation showed differences from the published studies for white blood cells, platelets, red blood cells, hemoglobin, platelet indices and reticulocyte hemoglobin as well as between males and females for hemoglobin, red blood cell count and hematocrit. All the indices of individuality were low. This study supports the contention that the conclusions from within-subject biological variation for common hematological parameters are important and transportable to a South Asian population for short-term serial measurements. For quality specifications dependent on between-subject variation, the lower estimates from European and American studies should be used.