scholarly journals Risk Assessment Paradigm for Glutamate

2018 ◽  
Vol 73 (Suppl. 5) ◽  
pp. 53-64 ◽  
Author(s):  
Ashley Roberts ◽  
Barry Lynch ◽  
Ivonne M.C.M. Rietjens
Keyword(s):  
Safety Assessment ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Daily Intake ◽  
Toxicity Study ◽  
Acceptable Daily Intake ◽  
Uncertainty Factor ◽  
Point Of Departure ◽  
Breast Fed ◽  
Toxicokinetic Data

Background: Re-evaluation of the use of glutamic acid and glutamate salts (referred to as glutamate hereafter) by the European Food Safety Authority (EFSA) proposed a group acceptable daily intake (ADI) of 30 mg/kg body weight (bw)/day. Summary: This ADI is below the normal dietary intake, while even intake of free glutamate by breast-fed babies can be above this ADI. In addition, the pre-natal developmental toxicity study selected by EFSA, has never been used by regulatory authorities worldwide for the safety assessment of glutamate despite it being available for nearly 40 years. Also, the EFSA ignored that toxicokinetic data provide support for eliminating the use of an uncertainty factor for interspecies differences in kinetics. Key Messages: A 3-generation reproductive toxicity study in mice that includes extensive brain histopathology, provides a better point of departure showing no effects up to the highest dose tested of 6,000 mg/kg bw/day. Furthermore, kinetic data support use of a compound-specific uncertainty factor of 25 instead of 100. Thus, an ADI of at least 240 mg/kg bw/day would be indicated. In fact, there is no compelling evidence to indicate that the previous ADI of “not specified” warrants any change.

scholarly journals Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats

2021 ◽  
pp. 109158182098607
Author(s):  
Narendra S. Deshmukh ◽  
Shailesh Gumaste ◽  
Silma Subah ◽  
Nathasha Omal Bogoda
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Toxicity Study ◽  
High Dose ◽  
Pregnant Rats ◽  
Human Dose ◽  
Adverse Effect Level ◽  
Female Wistar Rats ◽  
Effect Level

Palmitoylethanolamide (PEA) is an endogenous ethanolamine playing a protective and homeodynamic role in animals and plants. Prenatal developmental toxicity of PEA was tested following oral administration to pregnant female Wistar rats, from days 0 to 19 of gestation, at dosage of 250, 500, or 1,000 mg/kg body weight, according to Organisation for Economic Co-operation and Development Test Guideline No. 414. On gestation day 20, cesarean sections were performed on the dams, followed by examination of their ovaries and uterine contents. The fetuses were further examined for external, visceral, and skeletal abnormalities. Palmitoylethanolamide did not cause any alterations at any of the given dosages in the measured maternal parameters of systemic toxicity (body weight, food consumption, survival, thyroid functions, organ weight, histopathology), reproductive toxicity (preimplantation and postimplantation losses, uterus weight, number of live/dead implants and early/late resorptions, litter size and weights, number of fetuses, their sex ratio), and fetal external, visceral, or skeletal observations. Any alterations that were recorded were “normal variations” or “minor anomalies,” which were unrelated to treatment with PEA. Under the condition of this prenatal study, the no-observed-adverse-effect level of PEA for maternal toxicity, embryotoxicity, fetotoxicity, and teratogenicity in rats was found to be >1,000 mg/kg body weight/d. It indicates that PEA is well tolerated by and is safe to pregnant rats even at a high dose of 1,000 mg/kg body weight/d, equivalent to a human dose of greater than 9.7 g/d. This prenatal developmental toxicity study contributes greatly in building a robust safety profile for PEA.

Final Report on the Safety Assessment of Cetethyl Morpholinium Ethosulfate

2001 ◽  
Vol 20 (3_suppl) ◽  
pp. 99-102 ◽  
Keyword(s):  
Safety Assessment ◽  
Developmental Toxicity ◽  
Quaternary Salt ◽  
Skin Penetration ◽  
Toxicity Study ◽  
Final Report ◽  
Inhalation Toxicity ◽  
Absorption Data ◽  
Dermal Irritation ◽  
Safety Test

Cetethyl Morpholinium Ethosulfate is a quaternary salt used as an antistatic agent and as a surfactant in several hair care products. The concentration at which this ingredient is used is unknown, although data reported in 1984 indicated a maximum concentration of 1%. In an inhalation toxicity study, the approximate lethal concentration of Cetethyl Morpholinium Ethosulfate was 0.403 mg/mm3. This ingredient was shown to be a severe ocular irritant in an animal study. No other safety test data on this ingredient were available. These data were clearly insufficient to support the safety of Cetethyl Morpholinium Ethosulfate in cosmetics. Data available on Morpholine were summarized, but these data themselves were insufficient to support safety. The data needed in order to complete the safety assessment of Cetethyl Morpholinium Ethosulfate include: methods of manufacture and impurities, especially nitrosamines; current concentration of use; skin penetration; if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity and a reproductive and developmental toxicity study are needed; two genotoxicity studies, at least one in a mammalian system, if positive, then a 2-year dermal carcinogenisis study using National Toxicology Program (NTP) methods may be needed; ultraviolet (UV) absorption data, if significantly absorbed, then photosensitization data are needed; dermal irritation and sensitization; and ocular toxicity, if available.

Safety assessment of dietary diacylglycerol oil: A two-generation reproductive toxicity study in rats

2008 ◽  
Vol 46 (9) ◽  
pp. 3059-3068 ◽  
Author(s):  
Osamu Morita ◽  
John F. Knapp ◽  
Yasushi Tamaki ◽  
Mark D. Nemec ◽  
Bennett J. Varsho ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Reproductive Toxicity ◽  
Toxicity Study ◽  
Diacylglycerol Oil

scholarly journals Corrigendum to “Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake”

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
James A. Edwards ◽  
Dirk Cremer
Keyword(s):  
Adverse Effects ◽  
Developmental Toxicity ◽  
Daily Intake ◽  
Safety Data ◽  
Safety Evaluation ◽  
Acceptable Daily Intake ◽  
Fetal Toxicity ◽  
Toxicological Data

Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which forms the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high-purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in cynomolgus monkeys at doses of 0.2 and 20 mg/kg  bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a two-generation study in rats, the NOAEL was 150 mg/kg  bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an acceptable daily intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission. Recent reevaluation of the data from the two-generation study indicated that the NOAEL should be redefined as the high dosage of 500 mg/kg bw/day, rather than the intermediate dosage of 150 mg/kg bw/day. The NOAEL of this study was formally amended to the high dosage. Also in 2018, JECFA raised the group ADI of lutein and zeaxanthin to “not specified,” due to the low toxicity of these substances.

Levels of Pesticide Residues in Egyptian Human Milk Samples and Infant Dietary Intake

1991 ◽  
Vol 74 (1) ◽  
pp. 89-91 ◽  
Author(s):  
Salwa M Dogheim ◽  
Mohamed EL-Shafeey ◽  
Abla M H Afifi ◽  
Fatma E Abdel-Aleem
Keyword(s):  
Human Milk ◽  
Dietary Intake ◽  
Pesticide Residues ◽  
Daily Intake ◽  
Heptachlor Epoxide ◽  
Dietary Intakes ◽  
Acceptable Daily Intake ◽  
Milk Samples ◽  
Hexachlorocyclohexane Isomers ◽  
Breast Fed

Abstract Contamination of human milk with residues of organochlorlne pesticides and polychlorlnated blphenyls was studied In a series of Investigations concerned with the monitoring of these chemicals In Egyptian food. The DDT complex was the most frequently found pesticide, followed by total hexachlorocyclohexane Isomers. Heptachlor and its epoxide, dleldrln, hexachlorobenzene, and oxychlordane were also found but less frequently. Estimated dietary Intakes (EDIs) of these contaminants by the breast-fed Infants were compared to acceptable dally Intakes (ADIs). EDIs of DDT complex, lindane (gamma-HCH), heptachlor + heptachlor epoxide, and oxychlordane were below ADIs. Dleldrln EDI exceeded the acceptable daily intake.

Amended Final Report On the Safety Assessment of Pentaerythrityl Rosinate

1998 ◽  
Vol 17 (4_suppl) ◽  
pp. 83-94
Author(s):  
F.A. Andersen
Keyword(s):  
Chemical Structure ◽  
Safety Assessment ◽  
Additional Data ◽  
Developmental Toxicity ◽  
Toxicity Study ◽  
Final Report ◽  
Cosmetic Products ◽  
Carcinogenicity Study ◽  
Ocular Irritation ◽  
Dermal Irritation

Pentaterythrityl Rosinate (previously called Pentaerythritol Rosinate) is the ester of rosin acids with the polyol pentaerythritol. It is used as a skin conditioning agent-emollient and viscosity increasing agent-nonaqueous in a few cosmetic formulations. In a previous safety assessment, it was concluded that the available data were insufficient to support the safety of this ingredient in cosmetic products. Additional data needed included: concentration of use, source and method of manufacture, chemistry (ultraviolet [UV] spectral analysis, pH, and impurities), ocular irritation, human dermal irritation and sensitization, and photosensitization (only if Pentaerythritol Rosinate absorbs UVA or UVB light). It was also noted that the carcinogenic potential of this ingredient was still of concern because of the low concentration tested in the available carcinogenicity study. Additional data were received. This ingredient is produced by the fractional distillation of crude tall oil to form rosin, which is then esterified with monopentaerythritol. It is typically used at concentrations of 0. 5-10%. It does not significantly absorb in the UVA or UVB portion of the spectrum. Formulations with 10% Pentaerythrityl Rosinate produced only minimal ocular irritation. Likewise tests of formulations with the ingredient at concentations of 7-9.2% resulted in minimal dermal irritation. The ingredient was nonsensitizing in animal maximization tests. Clinical tests of formulations with the ingredient at concentrations of 7-9.6% resulted in neither irritation nor sensitization. No data, however, were provided on possible impurities. Absent information on the actual chemical structure, the lack of information on impurities was considered significant. On further review, a single carcinogenicity study with negative results reported in the earlier safety assessment was considered inadequate. The absence of genotoxicity data was also considered significant. The lack of impurity and chemical structure information also raised a concern about the need for reproductive and developmental toxicity data. On the basis of this further review, it was concluded that the available data are still insufficient to support the safety of this ingredient in cosmetic products. Additional data needed include: (1) two genotoxicity assays, at least one in a mammalian system; if positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods is needed; (2) dermal absorption; if significantly absorbed, then both a 28-day dermal toxicity study and a reproductive and developmental toxicity study may be needed; and (3) chemical properties, including structure and impurities.

scholarly journals Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
James A. Edwards
Keyword(s):  
Adverse Effects ◽  
Developmental Toxicity ◽  
Daily Intake ◽  
Safety Data ◽  
Safety Evaluation ◽  
Acceptable Daily Intake ◽  
Fetal Toxicity ◽  
Toxicological Data

Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series ofin vitroandin vivotests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission.

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