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Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Release of prostaglandin E2 (PGE2) in cultured peritoneal macrophages of NMRI mice by skin irritant tumor initiators and promoters was investigated. Initiators of the polycyclic aromatic hydrocarbon type, e.g., DMBA, caused slight irritation on the mouse ear but even relatively high doses did not stimulate PGE2-release to any measurable extent within 4 h after administration in vitro. Apparently there is no correlation between irritation and initiating activity in mouse skin and PGE2-release in macrophages. On the other hand, promoters of the diterpene ester type, e.g., TPA, were strong irritants on the mouse ear. Even low doses of these compounds stimulated PGE2-release from macrophages dramatically within 1 h after administration in vitro. Moreover, a good correlation was established between irritant and promoting activity in mouse skin and PGE2-release in macrophages of a series of tigliane, ingenane and daphnane type diterpene derivatives. These results suggest that also in mouse skin PGE2-release may occur following exposure of the target cells to promoters of the diterpene ester type resembling one of the most early molecular events of promotion. This event could initiate both skin irritation and cell proliferation.
Cancer Lett 1978 Jun
PMID:Inflammatory, tumor initiating and promoting activities of polycyclic aromatic hydrocarbons and diterpene esters in mouse skin as compared with their prostaglandin releasing potency in vitro. 9 35

A method is described for measuring rapid, specific, and saturable binding of the skin irritant and tumour-promoting secretagogue thapsigargin (sesquiterpene lactone) to the microsomal fraction from mouse brain. Employing the tritium-labelled compound its apparent dissociation constant, Kd, and the maximal amount of binding Bmax are shown to be 9.8 nM and 1.9 pmol/mg protein respectively. Such a Kd for thapsigargin is similar to (a) its IC50 value for inhibiting Ca2+ uptake in the microsomal fraction from rat brain and (b) its EC50 values for inducing a rise in the cytoplasmic Ca2+ concentration of human platelets and histamine release from rat peritoneal mast cells. A positive correlation is found between the binding affinities of thapsigargin, thapsitranstagin, and trilobolide, their potencies as secretagogues and their lipophilicities. This correlation does not extend to the skin-irritant activities of the compounds thus emphasizing that their mechanism of action is unlike that of 12-O-tetradecanoylphorbol 13-acetate.
J Cancer Res Clin Oncol 1992
PMID:Toxicodynamics of tumour promoters of mouse skin. III. Specific binding of the tumour promoter thapsigargin as measured by the cold-acetone filter assay. 153 61

Dodecylbenzene in various concentrations, dissolved in acetone to a final volume of 50 microliters, was applied twice a week for 78 weeks to the back skin of hairless mice, with or without pretreatment with 51.2 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA). A negative control group was painted with acetone only and a positive control group was given a single application of 51.2 micrograms DMBA. A few tumours developed but there was no significant skin tumorigenicity--that is, occurrence of benign or malignant tumours--by acetone alone, or by 16% dodecylbenzene. More tumours developed in the group treated with 80% dodecylbenzene than in the group treated with acetone alone or with 16% dodecylbenzene, but there was no significant difference between treatments with 16% and 80% dodecylbenzene. There was only a suggestive increase in tumorigenesis in the group given 51.2 micrograms DMBA and thereafter painted with 40% dodecylbenzene twice a week compared with the group given 51.2 micrograms DMBA once. As regards histologically malignant tumours--that is, carcinogenicity--the group treated twice a week with 16% dodecylbenzene alone developed two skin malignancies, whereas only one carcinoma was observed in the group treated with 80% dodecylbenzene; both results are non-significant. There was only a suggestive increase in the occurrence of skin malignancies in the group treated with DMBA followed by 40% dodecylbenzene compared with that treated with DMBA alone. As regards other tumours, treatment with 80% dodecylbenzene led to six lymphomas in 56 animals, whereas the acetone control group had two lymphomas in 56 animals, a difference which is only suggestive. DMBA alone and DMBA followed by dodecylbenzene gave five and four lymphomas, respectively. There was no significant difference between controls and dodecylbenzene painted animals for lung adenomas or other tumours. A pronounced epidermal hyperplasia, an increase in melanin pigment ("blue spots"), pigment leakage, and skin ulcerations were seen, mainly after 80% dodecylbenzene and after DMBA followed by 40% dodecylbenzene. There was no obvious increase in amyloidosis after continual treatment with 80% dodecylbenzen. The results indicate that 80% dodecylbenzene alone is weakly tumorigenic but not carcinogenic in the skin of hairless mice, and it tends slightly to enhance DMBA initiated tumorigenesis and carcinogenesis. Dodecylbenzene may be a weak inducer of malignant lymphomas. It is a fairly strong skin irritant and may increase amyloidosis.
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PMID:Studies of the carcinogenesis and tumorigenesis of skin applications of dodecylbenzene on hairless mice. 235 57

For investigations of biochemical and molecular mechanism(s) involved in carcinogenesis the three stage initiation/promotion/progression approach in mouse skin provides one of the most developed experimental models. As initiators (and as progressors), solitary carcinogenic polycyclic aromatic hydrocarbons (PAH), such as 7,12-dimethylbenz [a]anthracene (DMBA), are used. As promoters in the last about 15 years, cocarcinogenic skin irritant polyfunctional diterpene esters of plant origin have become most powerful tools. Their low activity "cryptic forms" are activated metabolically by hydrolases yielding highly active skin irritants and cocarcinogens of the "ultimate promoter" type such as the phorbol-12,13-diester TPA and congeners of the ingenane- and daphnane type. In their target cells the ultimate promoters are bound to specific binding sites both through their ester moieties as well as through their diterpene moieties as revealed by structure/activity relationships. In such investigations most recently, also fine structural comparison of threedimensional computergraphs of prototype promoters were included. In correlation with their irritant and promoting activities, diterpene ester promoters exhibit agonist type specific (non-covalent) binding to the particulate fraction of epidermis and other organs or cells. The specifically bound portion of certain electron spin and photoaffinity labeled phorbol ester analogs indicates their distinct molecular orientation in membranes and, in their microenvironment, presence of phospholipids essential for activity of the Ca++ dependent proteinkinase C (PKC). Specific bindings to and activation of PKC was shown for TPA and congeners particularly also in mouse epidermis as one of the target organs of initiation/promotion by DMBA/TPA. Diterpene ester promoters are postulated to interact with the second messenger system operated by inositolphospholipid/diacylglycerol which is linked to (i) receptors of certain (endocrine) hormones or growth factors and (ii) to certain oncogene derived (autocrine) molecular signals. In this way, diterpene ester promoters, mostly taylor-made by partial syntheses, have lead to new dimensions the investigations of specific mechanistic problems of processes of carcinogenesis. Interlinkage of parts of these processes with receptor research opens up new and fascinating aspects of mechanisms of carcinogenesis at the cell and/or molecular level. They will provide important leads in gaining a more differentiated system of assessment of environmental risk factors of cancer for cancer prevention and in developing more purposeful and selective antineoplastic drugs for clinical use.
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PMID:Cell membrane associated protein kinase C as receptor of diterpene ester co-carcinogens of the tumor promoter type and the phenotypic expression of tumors. 300 5

Dinophysistoxin-1, 35-methylokadaic acid, is a causative agent of diarrhetic shellfish poisoning. The biological activities and tumor-promoting activity of dinophysistoxin-1 were studied together with those of okadaic acid and 7-O-palmitoyl okadaic acid. Dinophysistoxin-1 is a skin irritant and induces ornithine decarboxylase in mouse skin with the same potency as okadaic acid. 7-O-Palmitoyl okadaic acid induced a lower activity than the other compounds. Dinophysistoxin-1 inhibited the specific [3H]okadaic acid binding to a particulate fraction of mouse epidermis. The binding affinities of dinophysistoxin-1 and okadaic acid to a particulate fraction were almost the same. Dinophysistoxin-1 showed a tumor-promoting activity as strong as that of okadaic acid in a two-stage carcinogenesis experiment on mouse skin. The percentages of tumor-bearing mice in the groups treated with 100 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) followed by 5 micrograms of dinophysistoxin-1, twice a week, and with DMBA followed by 5 micrograms of okadaic acid twice a week were 86.7% and 80.0% in week 30, respectively. The average number of tumors per mouse was 4.6 in the former group and 3.9 in the latter. Dinophysistoxin-1 and okadaic acid act on cells through different pathways from the 12-O-tetradecanoylphorbol-13-acetate-type tumor promoters.
Jpn J Cancer Res 1988 Oct
PMID:Diarrhetic shellfish toxin, dinophysistoxin-1, is a potent tumor promoter on mouse skin. 314 97

To provide guidelines for handling the very labile phorbol ester, RPA,2 its stability under various laboratory conditions was studied. RPA will remain undecomposed for 8 weeks if stock solutions are made in ethanol, ethyl acetate, or DMSO and stored in absolute darkness at -20 degrees C. When exposed to light RPA readily isomerizes to 13'-cis-RPA. Structure/activity investigations of irritant polyfunctional diterpene esters of phorbol, ingenol, and resiniferonol with saturated and unsaturated aliphatic or with aromatic acids indicate that their irritant activity is a necessary, yet insufficient prerequisite for initiation- (or tumor-) promoting activity (e.g., Refs. 3 and 4). For further testing of this hypothesis, the retinoic acid analogue of the mouse skin irritant and initiation-promoter TPA, i.e., RPA, was designed (7). In initiation/promotion experiments of skin of NMRI mice, it proved to be an irritant almost as active as TPA, but only marginally active as a promoter. In combination with TPA, it turned out to be a "second stage" promoter (PII-promoter) (1, 6) in our strain of mice (2, 7). RPA is a much more labile compound than TPA (5), especially in the solid form. If stored in solution, special precautions have to be taken to ascertain that the concentration or dose intended is represented by undecomposed RPA.
Cancer Res 1985 May
PMID:Stability of the "second stage" promoter 12-O-retinoylphorbol-13-acetate. 398 82

A strong skin irritant, lyngbyatoxin A, isolated from the marine blue-green alga Lyngbya majuscula is structurally related to teleocidin. Since lyngbyatoxin A satisfied our short-term screening tests for possible tumor promoters, viz. irritation of mouse ear, induction of ornithine decarboxylase (ODC) in mouse skin, and adhesion of human promyelocytic leukemia cells (HL-60), a two-stage carcinogenesis experiment was carried out. Tumor incidences in the groups treated with 7,12-dimethylbenz(a)anthracene (DMBA) plus lyngbyatoxin A and with DMBA plus 12-O-tetradecanoylphorbol-13-acetate (TPA) were 86.7% and 93.3% in week 30, respectively. The average number of tumors per mouse was 3.7 in the former group and 10.5 in the latter group. This paper reports for the first time the potent tumor-promoting activity of lyngbyatoxin A and also the histological examination of tumors.
J Cancer Res Clin Oncol 1984
PMID:A two-stage mouse skin carcinogenesis study of lyngbyatoxin A. 643 Sep 9

A crude ethylacetate extract was isolated from Euphorbia bougheii by a combination of solvent-solvent and chromatographic methods. The extract exhibited significant skin irritant activity on the mouse ear as well as a tumour promoting activity on the mouse back skin. This indicates that the use of this plant as a medicine must be discouraged since the latex extract causes cancer.
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PMID:Skin irritant and tumour promoting extract from the latex of Euphorbia bougheii. 830 85

Lactating goats were fed on aerial parts of the herb Euphorbia peplus L. admixed with their usual green fodder. During the experimental feeding period they showed symptoms of general poisoning. In necropsy the main toxic effects were seen in the heart, lung and liver. Histopathological examinations revealed that the primary toxic effects originated from degenerative changes in parenchymal and endothelial cells. Adverse symptoms in the liver and kidney were also reflected in an alteration of the levels of certain serum enzymes and of blood urea nitrogen. The milk of the goats fed on E. peplus, consumed by their young kids, caused poisoning and even death, with signs similar to those observed in the adult dams. These observations support the hypothesis that the poisoning observed in both milk-raised kids and mother goats is caused by diterpene ester type toxins present in the aerial parts of the herb contaminating the dams fodder. Generally, such skin irritant and hyperplasiogenic toxins are known to be highly active tumour promoters of skin and other organ, e.g. in mice. Lactating goats--as an important source of milk around the world--in a setting similar to that described, may provide a valid experimental etiological model for investigation of food polluted by tumour-promoting diterpene ester toxins.
J Cancer Res Clin Oncol 1998
PMID:Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). II. Pathophysiological investigations in lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk-raised kids. 961 44

This report reviews the safety of Aluminum, Calcium, Lithium Magnesium, Lithium Magnesium Sodium, Magnesium Aluminum, Magnesium, Sodium Magnesium, and Zirconium Silicates, Magnesium Trisilicate, Attapulgite, Bentonite, Fuller's Earth, Hectorite, Kaolin, Montmorillonite, Pyrophyllite, and Zeolite as used in cosmetic formulations. The common aspect of all these claylike ingredients is that they contain silicon, oxygen, and one or more metals. Many silicates occur naturally and are mined; yet others are produced synthetically. Typical cosmetic uses of silicates include abrasive, opacifying agent, viscosity-increasing agent, anticaking agent, emulsion stabilizer, binder, and suspending agent. Clay silicates (silicates containing water in their structure) primarily function as adsorbents, opacifiers, and viscosity-increasing agents. Pyrophyllite is also used as a colorant. The International Agency for Research on Cancer has ruled Attapulgite fibers >5 microm as possibly carcinogenic to humans, but fibers <5 microm were not classified as to their carcinogenicity to humans. Likewise, Clinoptilolite, Phillipsite, Mordenite, Nonfibrous Japanese Zeolite, and synthetic Zeolites were not classified as to their carcinogenicity to humans. These ingredients are not significantly toxic in oral acute or short-term oral or parenteral toxicity studies in animals. Inhalation toxicity, however, is readily demonstrated in animals. Particle size, fibrogenicity, concentration, and mineral composition had the greatest effect on toxicity. Larger particle size and longer and wider fibers cause more adverse effects. Magnesium Aluminum Silicate was a weak primary skin irritant in rabbits and had no cumulative skin irritation in guinea pigs. No gross effects were reported in any of these studies. Sodium Magnesium Silicate had no primary skin irritation in rabbits and had no cumulative skin irritation in guinea pigs. Hectorite was nonirritating to the skin of rabbits in a Draize primary skin irritation study. Magnesium Aluminum Silicate and Sodium Magnesium Silicate caused minimal eye irritation in a Draize eye irritation test. Bentonite caused severe iritis after injection into the anterior chamber of the eyes of rabbits and when injected intralamellarly, widespread corneal infiltrates and retrocorneal membranes were recorded. In a primary eye irritation study in rabbits, Hectorite was moderately irritating without washing and practically nonirritating to the eye with a washout. Rats tolerated a single dose of Zeolite A without any adverse reaction in the eye. Calcium Silicate had no discernible effect on nidation or on maternal or fetal survival in rabbits. Magnesium Aluminum Silicate had neither a teratogenic nor adverse effects on the mouse fetus. Female rats receiving a 20% Kaolin diet exhibited maternal anemia but no significant reduction in birth weight of the pups was recorded. Type A Zeolite produced no adverse effects on the dam, embryo, or fetus in either rats or rabbits at any dose level. Clinoptilolite had no effect on female rat reproductive performance. These ingredients were not genotoxic in the Ames bacterial test system. In primary hepatocyte cultures, the addition of Attapulgite had no significant unscheduled DNA synthesis. Attapulgite did cause significant increases in unscheduled DNA synthesis in rat pleural mesothelial cells, but no significant increase in sister chromosome exchanges were seen. Zeolite particles (<10 microm) produced statistically significant increase in the percentage of aberrant metaphases in human peripheral blood lymphocytes and cells collected by peritoneal lavage from exposed mice. Topical application of Magnesium Aluminum Silicate to human skin daily for 1 week produced no adverse effects. Occupational exposure to mineral dusts has been studied extensively. Fibrosis and pneumoconiosis have been documented in workers involved in the mining and processing of Aluminum Silicate, Calcium Silicate, Zirconium Silicate, Fuller's Earth, Kaolin, Montmorillonite, Pyrophyllite, and Zeolite. The Cosmetic Ingredient Review (CIR. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that the extensive pulmonary damage in humans was the result of direct occupational inhalation of the dusts and noted that lesions seen in animals were affected by particle size, fiber length, and concentration. The Panel considers that most of the formulations are not respirable and of the preparations that are respirable, the concentration of the ingredient is very low. Even so, the Panel considered that any spray containing these solids should be formulated to minimize their inhalation. With this admonition to the cosmetics industry, the CIR Expert Panel concluded that these ingredients are safe as currently used in cosmetic formulations. The Panel did note that the cosmetic ingredient, Talc, is a hydrated magnesium silicate. Because it has a unique crystalline structure that differs from ingredients addressed in this safety assessment, Talc is not included in this report.
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PMID:Final report on the safety assessment of aluminum silicate, calcium silicate, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, sodium magnesium silicate, zirconium silicate, attapulgite, bentonite, Fuller's earth, hectorite, kaolin, lithium magnesium silicate, lithium magnesium sodium silicate, montmorillonite, pyrophyllite, and zeolite. 1285 Nov 64


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