Amended Final Report On the Safety Assessment of Pyrocatechol

1997 ◽  
Vol 16 (1_suppl) ◽  
pp. 11-58 ◽  
Author(s):  
F. Alan Andersen
Keyword(s):  
Bone Marrow ◽  
Safety Assessment ◽  
Female Rats ◽  
Tumor Promoter ◽  
Oral Exposure ◽  
Final Report ◽  
Hair Dyes ◽  
Absorption Data ◽  
Male And Female Rats

Pyrocatechol is a phenol used primarily in hair dyes but has one reported use in skin care preparations. When this ingredient was first reviewed it was concluded that Pyrocatechol was safe for use in formulations designed for discontinuous, brief use followed by rinsing from the skin and hair at concentrations of up to 1.0%. This amendment to that report was prepared in order to incorporate the results from several studies, including those reporting immunologic, carcinogenic, and cocarcinogenic effects of Pyrocatechol. In vitro, Pyrocatechol has been shown to affect several immunologic and other properties of murine bone marrow cells, both alone and when combined with hydroquinone. Pyrocatechol, when produced as an hepatic metabolite of benzene, has been reported to concentrate in the bone marrow and to adversely affect hematopoietic precursor cells. These effects are somewhat species specific. In vivo, dermal exposure of mice to Pyrocatechol affects the number and distribution of Langerhans cells at the site of exposure but is not associated with a change in contact sensitivity. Oral exposure of pregnant rats to Pyrocatechol did result in an increase in teratogenic effects. The results of a micromass teratogen test in vitro were also positive. Pyrocatechol was tested in a number of bacterial and mammalian mutagenesis systems. Both negative and positive results were observed. Carcinogenicity studies were conducted in rats and mice. Pyrocatechol was provided in the feed. While adenomatous hyperplasia was noted in both species, adenocarcinomas were seen in male and female rats only. In cocarcinogenesis studies there is a similar pattern of hyperplasia and adenomas of the glandular stomach in the groups exposed to Pyrocatechol alone. When administered with several other carcinogens, Pyrocatechol had a cocarcinogenic effects. Pyrocatechol was not a tumor promoter in dermal studies. Based on these data and the significant potential for skin absorption of Pyrocatechol in leave-on preparations, it was concluded that Pyrocatechol is unsafe for use in leave-on cosmetic formulations. Pyrocatechol used in a rinse-off application such as hair dyes may not present a similar concern if Pyrocatechol is completely and rapidly oxidized. Because no data were available, it was concluded that there are insufficient data to support the safety of this ingredient. The data needed to complete the safety assessment include the extent and rate of oxidation when used in hair dyeing. If not rapidly and completely oxidized, then further chemical characterization of cosmetic grade Pyrocatechol is needed, along with cutaneous absorption data in aqueous and alcohol vehicles and ultraviolet absorption data (if positive, photosensitization studies may be needed).

Final Report on the Safety Assessment of Disperse Blue 1

1995 ◽  
Vol 14 (6) ◽  
pp. 433-451 ◽  
Keyword(s):  
Urinary Bladder ◽  
Skin Irritation ◽  
Bladder Neoplasms ◽  
Urinary Bladder Neoplasms ◽  
Female Rats ◽  
Final Report ◽  
Hair Dyes ◽  
Bladder Calculi ◽  
Male And Female Rats

The anthraquinone color Disperse Blue 1 is used in many nonoxidative hair dyes, colors and rinses. In vitro dermal penetration studies using skin from miniature pigs indicate this ingredient is poorly absorbed. All rats given Disperse Blue 1 orally at concentrations up to 3 g/kg survived. Reduced body weights and blue tissue samples were observed in short-term, subchronic, and chronic animal studies. No skin irritation was observed with concentrations up to 10%, but Disperse Blue 1 was a moderate sensitizer in guinea pigs. Disperse Blue 1 was mutagenic in several test systems. In feeding studies, the ingredient produced a significant increase in urinary bladder neoplasms in male and female rats. Equivocal results were reported in studies with male mice and negative results were reported for female mice. A dermal carcinogenesis study in mice was negative. Further evaluation of the carcinogenesis data suggests that the urinary bladder neoplasms appear to be associated with bladder calculi rather than arising from a genotoxic mechanism. Such bladder calculi do not appear to form in humans. Based upon these data and the facts that dermal exposure produced no evidence of carcinogenesis, that the ingredient is poorly absorbed, and that exposure to hair dyes is brief, it was concluded that Disperse Blue 1 is safe for use in hair dyes at concentrations up to 1%.

2 Final Report on the Safety Assessment of p-Aminophenol, m-Aminophenol, and o-Aminophenol

1988 ◽  
Vol 7 (3) ◽  
pp. 279-333 ◽  
Keyword(s):  
Topical Application ◽  
Guinea Pigs ◽  
Safety Assessment ◽  
Mutagenic Activity ◽  
Skin Irritation ◽  
Final Report ◽  
Hair Dyes ◽  
Hair Dye ◽  
Mutagenicity Tests

p-Aminophenol (PAP), m-Aminophenol (MAP), and o-Aminophenol (OAP) are used in permanent (oxidative) hair dyes at concentrations from 0.1 to 5%. In vivo and in vitro skin absorption studies indicated that 11% of the dermally applied 14C-PAP was detected in the excreta, viscera, and skin of the test animals. The oral LD50s of PAP, MAP, and OAP in rats ranged from 600 to 1300 mg/kg. Topical application of PAP at concentrations up to 8.00 g/kg to the skin of New Zealand white (NZW) rabbits produced no skin irritation and no mortality. PAP, MAP, and OAP were irritating to eyes of NZW rabbits at a concentration of 2.5%. MAP at 3% was nonsensitizing in guinea pigs; PAP at 2% sensitized 9 of 10 guinea pigs. Neither PAP nor MAP produced photosensitization in guinea pigs. No treatment-related toxicity was found in three separate four-generation chronic dermal toxicity and reproduction studies of hair dye formulations containing the three Aminophenols. Additional studies on the pure ingredients were also nonteratogenic; embryotoxicity was reported. A range of results was obtained from studies assessing the mutagenic activity of the Aminophenols. PAP tested positive in six of eight mutagenicity tests. MAP and OAP gave positive results in two of eight and five of seven mutagenicity tests, respectively. Oxidative hair dye formulations containing PAP, MAP, and OAP did not produce gross or microscopic alterations or have carcinogenic effects after chronic topical application to mice. Feeding of OAP-HCl and PAP to rats at a dose of 8 mmol/kg produced neither hepatic cirrhosis nor neoplastic lesions. A 3% solution of MAP in an aqueous vehicle was neither a significant irritant nor sensitizer in two clinical studies. A variety of epidemiological studies have not indicated that occupational exposure to, and personal use of, hair dyes containing the Aminophenols presented a carcinogenic risk. A discussion of the significance of the mutagenic data in the safety assessment and the potential for human effects is presented. On the basis of the available animal and clinical data presented in this report it is concluded that p-, m-, and o-Aminophenols are safe as cosmetic ingredients in the present practices of use and concentrations.

Final Report on the Safety Assessment of HC Yellow No. 51

2007 ◽  
Vol 26 (2_suppl) ◽  
pp. 113-124
Keyword(s):  
Patch Test ◽  
Safety Assessment ◽  
Coal Tar ◽  
Skin Irritation ◽  
Laboratory Animals ◽  
Test Material ◽  
Oral Exposure ◽  
Final Report ◽  
Hair Dyes ◽  
Hair Dye

HC Yellow No. 5 is a direct hair dye. Hair dyes containing HC Yellow No. 5, as “coal tar” hair dye products, are exempt from the principal adulteration provision and from the color additive provision of the Federal Food, Drug, and Cosmetic Act of 1938 when the label bears a caution statement and “patch test” instructions for determining whether the product causes skin irritation. Preliminary testing on or by individuals should be done using an open patch test that is evaluated at 48 h after application of the test material. Users, therefore, would be able to determine their individual reactions to hair dye products containing HC Yellow No. 5. Absorption of HC Yellow No. 5 is minimal through skin ( < 0.2%). The oral LD50 for rats is 555.56 mg/kg. No significant toxic effects were observed after chronic oral exposure of HD Yellow No. 5 to dogs. Mild dermal irritation, but no dermal sensitization or ocular irritation was observed in laboratory animals. Results of fertility and reproductive performance, teratology, and developmental studies were negative. HC Yellow No. 5 was found to be nonmutagenic and noncytotoxic in standard laboratory assays. A current review of the hair dye epidemiology literature identified that use of direct hair dyes, although not the focus in all investigations, appears to have little evidence of an association with cancer or other adverse events. Based on the available safety test data on HC Yellow No. 5, the Panel determined that this ingredient likely would not have carcinogenic potential as used in hair dyes. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that HC Yellow No. 5 is safe as a hair dye ingredient in the practices of use and concentration as described in this safety assessment.

Final Report on the Safety Assessment of Pyrogallol

1991 ◽  
Vol 10 (1) ◽  
pp. 67-85 ◽  
Keyword(s):  
Aqueous Solution ◽  
Safety Assessment ◽  
Reproductive Toxicity ◽  
Female Rats ◽  
Final Report ◽  
Hair Dyes ◽  
Teratogenic Effects ◽  
Hair Dye ◽  
Carcinogenicity Study ◽  
Almost All

Pyrogallol, a benzenetriol, is used in oxidative hair dyes at concentrations ranging from ≤0.1 to 5.0%. The oral LD50's in rats ranged from 800 to 1270 mg/kg. Pyrogallol was not an ocular irritant when tested at a concentration of 1%. It was slightly irritating and induced sensitization reaction in the skin of guinea pigs. Sensitization reactions were noted in 3 of 25 patients patch tested with Pyrogallol. Significant teratogenic effects were not observed in the offspring of female rats dosed with Pyrogallol. No treatment-related effects were observed in a multigeneration reproductive toxicity study in which rats received dermal applications of a hair dye containing 0.4% Pyrogallol. Pyrogallol was mutagenic in almost all systems tested. However, in two carcinogenicity studies, the number of neoplasms in mice dermally treated with 50% Pyrogallol in acetone was not significantly different from that of controls. Similar results were reported in a carcinogenicity study in which a hair dye containing 0.49% Pyrogallol and H2O2 in aqueous solution was applied to the skins of mice. On the basis of the available animal and clinical data presented in this report, it is concluded that Pyrogallol is safe as a cosmetic ingredient in the present practices of use and concentration.

scholarly journals Investigation of Stem Cell Applications on In Vitro Fertilization in Rats

2021 ◽  
Vol 72 (3) ◽  
pp. 3067
Author(s):  
A GUMURDU ◽  
S OZTURK ◽  
I AYDEMIR ◽  
MI TUGLU
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
In Vitro Fertilization ◽  
Mesenchymal Stem Cell ◽  
Conditioned Media ◽  
Female Rats ◽  
Favourable Effect ◽  
Vitro Fertilization ◽  
Male And Female Rats

We aimed to search the effects of bone marrow-derived mesenchymal stem cell-conditioned media on in vitro fertilization by investigation of lifetime of germ cells cleavage, degeneration rates and embryo quality. For this purpose, firstly MSCs were isolated from femurs and tibias of the rat, and cells were cultured until the fourth passage. Sperm and oocytes were collected from male and female rats. Oocytes were added in Human Tubal Fluid Media (HTFM), Single Step Media (SSM), Alpha-MEM Media (AMM) and Bone Marrow-Derived Mesenchymal Stem Cell-Conditioned Media (CM). Thousand sperm were added into the media which including oocytes. Embryos were allowed to produce by IVF. The development of the embryos was followed until the 11th day, and the arrest, degeneration rates and alive embryos were established. The embryos reached 2, 4, 8, 16 cells stages and morula stage in the CM. While AMM had a negative effect on fertilization and embryo development, the most favourable effect was shown to be caused by CM in comparison with the other medias. These results have shown that the beneficial effects of CM in IVF would be a significant increase in the rate of fertility and development of embryos.

scholarly journals 10 Final Report on the Safety Assessment of Cholesterol

1986 ◽  
Vol 5 (5) ◽  
pp. 491-516 ◽  
Keyword(s):  
Clinical Studies ◽  
Safety Assessment ◽  
Final Report ◽  
Experimental Animals ◽  
Normal Metabolism ◽  
Hair Care ◽  
Uvb Exposure ◽  
High Doses ◽  
Skin Irritants

Cholesterol is used as an emulsifier in cosmetic skin and hair care products and eye and face makeup formulations at concentrations up to 5%. The normal metabolism and excretion of Cholesterol is well documented in man and experimental animals. Cholesterol is not a significant dermal or ocular irritant. Cholesterol does not appear to have any genotoxic activity in bacterial or mammalian cell in vitro mutagenic and transformation assays. High doses of Cholesterol were teratogenic in rats. Cholesterol has not been established as a promoter, cocarcinogen, or total carcinogen. Clinical studies to evaluate the safety of topically applied Cholesterol were restricted to products formulated with the ingredient. Most products were moisturizers containing 1.4% Cholesterol. The highest concentration of Cholesterol tested (6%) was evaluated in a modified prophetic test (110 subjects) and an RIPT (45 subjects); both assays had UVA and UVB exposure incorporated into the protocols. The Cholesterol-containing products were minimal to mild primary and cumulative skin irritants but not sensitizers or photosensitizers.

Abstract 17462: Relevance of Regulatory T Cells to Gender Dimorphism in Pulmonary Hypertension

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Rasa Tamosiuniene ◽  
Linh Nguyen ◽  
Ayala Luria ◽  
Joshua Sante ◽  
Toshie Saito ◽  
...  
Keyword(s):  
T Cell ◽  
Vascular Wall ◽  
Reciprocal Relationship ◽  
Female Rats ◽  
Gender Dimorphism ◽  
Control Male ◽  
Control Female ◽  
Male And Female Rats ◽  
Endogenous Estrogen

Idiopathic Pulmonary Arterial Hypertension (IPAH) is a disease with female predominance. A growing body of evidence shows reciprocal relationship between sex steroids and the immune system. The aim of the present study was to determine whether the absence of Tregs with the presence of endogenous estrogen mediate the development of PH in a gender-specific manner and if protective signaling pathways of Tregs prevent gender dimorphism of PH susceptibility in T cell deficient animal model of PH. Methods and Results: in two utilized models of PH inbred Wag T cell deficient athymic (AT) nude male and female rats were given s/c SU5416 in normoxia or treated with chronic hypoxia (CH) for 21d. In IR experiments, AT rats received purified CD4+CD25+hi/Tregs. We also tested the effect of murine/human Tregs or CD4+CD25- on primary rat lung, cardiac and human lung microvascular ECs (RLMECs, HLMECs, RCMECs) with set-up of cocultures. In both PH models treatment resulted in development of PH with significantly higher RVSP and particular significantly pronounced RVH in female than in male in both SU5416 and CH groups (Fulton index: 0.41±0.01vs.0.33±0.02 and 0.52±0.03vs.0.37±0.01, p< 0.05). However, circulating estrogen levels were found to be significantly elevated in female than in male in all animal groups. For both female and male AT animals IR of Tregs prevented PH with RV remodeling, as well as decreased perivascular fibrosis and increased estrogen receptor (ER)β expression in lung and RV vascular wall. In vitro studies on coculture of Tregs with RLMECs and RCMECs resulted in an upregulation of IL-10, HO-1, PDL1, ERα, ERβ, activation of pAKT pathway, and endothelial nitric oxide synthase (eNOS), which was abrogated with ER antagonist ICI182,780. In addition, compared with control male AT rats, control female animals had increased expression of HO1, HO2 enzymes in lung and RV vascular wall endothelial/Reca+ cells as well as increased capillary density in RV. Thus, differential HO expression between the genders might account for the PH susceptibility. Conclusions: Our data suggest that Tregs signaling is required as a major mechanism with possible mutual interaction of endogenous estrogen to prevent endothelial injury related gender dimorphism for the development of PH.

scholarly journals A Pilot Safety Assessment for Recombinant Epinephelus lanceolatus Piscidin Yeast Powder as a Drug Food Additive after Subacute and Subchronic Administration to SD Rats

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 586
Author(s):  
Bor-Chyuan Su ◽  
Chao-Chin Li ◽  
Chia-Wen Liu ◽  
Jyh-Yih Chen
Keyword(s):  
Safety Assessment ◽  
Food Additive ◽  
Female Rats ◽  
Feed Additive ◽  
Gallus Gallus Domesticus ◽  
Sd Rats ◽  
Male And Female Rats ◽  
Liver And Kidney ◽  
Yeast Powder

Recombinant Epinephelus lanceolatus piscidin (RELP) was previously shown to improve growth performance and immune response when used as a feed additive for Gallus gallus domesticus. However, the long-term toxicity of RELP has not be thoroughly investigated. In the present study, we evaluated the subacute and subchronic oral toxicities of RELP in SD rats by hematological, biochemical, and histopathological analyses. To determine subacute and subchronic toxicities, male and female rats were fed with RELP 1000 mg/kg bodyweight/day for 28 and 90 days, respectively. Bodyweight and food intake were unchanged by RELP treatment over the course of the studies. After exposure, samples of blood, heart, lung, liver, and kidney were collected and analyzed. Results demonstrated that RELP exposure did not cause any observable hematological, biochemical, or histological abnormalities in SD rats. Thus, RELP may be a safe feed additive for use in agriculture and aquaculture.

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.

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