China
Africa
Explore chapters and articles related to this topic
Consumer Safety Considerations of Cosmetic Preservation*
Published in Philip A. Geis, Cosmetic Microbiology, 2020
Corie A. Ellison, Alhaji U. N’jai, Donald L. Bjerke
Because these studies aim to determine NOAEL, at least three doses are typically selected: (1) a dose high enough to induce toxic effects in the animals, (2) a medium dose, and (3) a low dose that does not cause any adverse effects. Observations made during and immediately following testing include mortality, body weight, food consumption rate, blood and serum chemistries, hematology, clinical observations, gross pathology observations, organ weights, and histology. These tests yield information about toxicity with respect to target organs, types of effects, and reversibility of effects (if the study includes a recovery group) and help define dose–response relationships.
The "Health News"
Published in David Lightsey, The Myths about Nutrition Science, 2019
But there is more. Permethrin has an established NOAEL of 25mg/kg/day, according to the National Pesticide Information Center.25 The NOAEL is the exposure level at which no negative health effects can be attributed to the pesticide in question. The EPA uses the NOAEL to calculate the daily safe levels of exposure to any given pesticide. So just how much spinach could an individual safely consume equivalent to the NOAEL dose of permethrin on spinach? According to Dr. Krieger’s calculations, this would allow the safe consumption of 3,205 cups of spinach per day for women, 4,487 for men, 3,344 cups for teens 12–19 years old, and 2,564 cups for children 2–5 years old without being harmed by the pesticide.26 Has any of the annual media reports who publish the “Dirty Dozen” list informed you of this?
Clinical Pharmacology Safety Studies
Published in Scott Patterson, Byron Jones, Bioequivalence and Statistics in Clinical Pharmacology, 2017
Preclinical pharmacology and toxicology data are used to choose the FTiH starting doses. The preclinical pharmacology and toxicology studies should identify a no-effect dose and a no-adverse-effect exposure level in multiple preclinical species. Allometric scaling ([371, 1027], Chapter 8 [95]) is then applied to estimate a safe starting dose. In essence, allometric scaling uses the NOAEL and accounts for differences in weight and physiology between species to yield a range of doses expected to be safe in humans. The NOAEL in the most sensitive species (i.e., the lowest NOAEL) is defined as the upper limit of human exposure (AUC and Cmax, as previously).
Applicability of organ-on-chip systems in toxicology and pharmacology
Published in Critical Reviews in Toxicology, 2021
Marlon R. Schneider, Michael Oelgeschlaeger, Tanja Burgdorf, Peter van Meer, Peter Theunissen, Anne S. Kienhuis, Aldert H. Piersma, Rob J. Vandebriel
The extrapolation of findings in animal studies to the human situation has by default been done conservatively. In the domain of industrial chemicals, animal studies provide the final information level for hazard and risk assessment. These may include acute, sub-chronic and chronic exposure testing, with specific additional testing protocols for e.g. carcinogenicity using lifetime exposures and for reproductive and developmental toxicity using mating, pregnancy and generation studies. These hazard assessment investigations might in some cases directly lead to a ban of the substance but in most cases an overall No Observed Adverse Effect Level (NOAEL) is derived, representing the highest exposure level at which no adverse health effect is observed. This NOAEL is then used to calculate a safe exposure level for humans, in which by default a hundred-fold uncertainty factor is applied, representing a factor of 10 for intraspecies differences and another factor of 10 for interspecies variation. However, dependent on the quality and extent of information available, other factors may be used case by case. Kinetic considerations may be considered in human safety assessment. Absorption, Distribution, Metabolism and Excretion (ADME) of a given substance may differ significantly among species, and may therefore affect the relevance of animal findings and require specific uncertainty factors for interspecies extrapolation. Increasingly, computational kinetic modeling is used to assess internal exposure, to underpin human safety assessments (Paini et al. 2017, 2019).
An update on the hazard of and exposure to diethyl hexyl phthalate (DEHP) alternatives used in medical devices
Published in Critical Reviews in Toxicology, 2020
Shalenie P. Den Braver-Sewradj, Aldert Piersma, Ellen V. S. Hessel
SCENIHR and Danish EPA have published the critical NOAELs for the DEHP alternatives (Tables 5 and 6), these are generally higher than for DEHP and associated with nonreprotoxic effects. The newly published literature studies do not give reason for reconsideration of NOAELs determined by SCENIHR, because for most compounds the studies available are from insufficient quality, no adverse effects are measured or the effect doses are higher than the current NOAEL (Table 6). With the exception of BTHC and COMGHA (based on oral studies) and the uncertain results of DINCH, all the other considered plasticizers can cause reproductive toxicity. This occurs at dosages several fold higher than DEHP and equal or higher than their respective critical endpoints. Additionally, ANSES concluded in a recent review that DINCH does not cause reproductive and developmental toxicity effects. However, based on various effects on the thyroid, DINCH may have ED activity (ANSES 2016a). Danish EPA noted that the available data on DINCH did not indicate a need for further testing. In the present review, no additional data on endocrine activity of the alternatives were found.
Metabonomics analysis of liver in rats administered with chronic low-dose acrylamide
Published in Xenobiotica, 2020
Yanli Liu, Ruijuan Wang, Kai Zheng, Youwei Xin, Siqi Jia, Xiujuan Zhao
Our previous metabonomics analysis of rat urine suggested that exposure to AA caused liver damage in rats (Shi et al., 2017), but the mechanism of AA-induced effects on the liver are still unclear. No observed adverse effect level (NOAEL) is defined as “the highest level of continual exposure to a chemical that causes no significant adverse effect on the morphology, biochemistry, functional capacity, growth, development or life span of individuals of the target species used in the study”, which is obtained using traditional toxicology methods (Du et al., 2013; van Ravenzwaay et al., 2014). It was reported by the JECFA at its 72th meeting that the NOAEL of AA for a non-carcinogenic end-point was 0.2 mg/kg bw per day. This end-point was based on the induction of morphological nerve changes in rats following administration of AA in drinking-water for 90 days (WHO, 2010). In view of the characteristic advantages of metabonomics, a liver metabonomics study was performed using ultraperformance liquid chromatography–mass spectrometry (UPLC-MS) combined with multivariate statistics, including principal components analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), to investigate whether chronic exposure to AA at NOAEL (WHO, 2010) can induce toxicity in rat liver at the body metabolism level. At the same time, we utilized UPLC-MS metabonomics platform to identify AA-induced metabolic signatures of liver in rats and explore the mechanism of the effects. Furthermore, liver histopathology examination and anti-oxidation indices were conducted to verify the results of metabonomics.