RESUMEN
Styrene (S) is lung tumorigenic in mice but not in rats. S and its alkene-oxidized metabolite styrene oxide (SO) were not lung toxic in CYP2F2(-/-) [knockout] mice, indicating S-induced mouse lung tumors are mediated through mouse-specific CYP2F2-generated ring-oxidized metabolite(s) in lung bronchioles. The human relevance of the CYP2F MOA was assessed by insertion of a human CYP2F1, 2A13, 2B6 transgene into CYP2F2(-/-) mice; CYP2F1 expression and activity were confirmed in the transgenic (TG) mice. No evidence of cytotoxicity or increased cell proliferation (BrdU labeling) was seen in TG mice treated with either S or SO (200mg/kg/day ip for 5days). In contrast to S and SO, 4HS (105mg/kg/day ip for 5days) increased BrdU labeling 5-10-fold in WT mice, <3-fold increase in KO mice and 2-4-fold in TG mice. The limited response of 4HS in KO and TG mice may result from intrinsic toxicity or from further metabolism; regardless of the MOA, these findings indicate that the CYP2F-mediated tumorigenic MOA in WT mice is not operative for S, SO, or for 4HS putatively derived from metabolism of S by CYP2F1 in humans, and thus S-induced mouse lung tumors are unlikely to be relevant to human risk.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Compuestos Epoxi/toxicidad , Fenoles/toxicidad , Estireno/toxicidad , Animales , Hidrocarburo de Aril Hidroxilasas/genética , Proliferación Celular/efectos de los fármacos , Citocromo P-450 CYP2B6 , Sistema Enzimático del Citocromo P-450/genética , Familia 2 del Citocromo P450 , Femenino , Humanos , Neoplasias Pulmonares/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Oxidorreductasas N-Desmetilantes/genética , Especificidad de la EspecieRESUMEN
Styrene induces lung tumors in mice but not in rats. Although metabolism of styrene to 7,8-styrene oxide (SO) by CYP2E1 has been suggested as a mediator of styrene toxicity, lung toxicity is not attenuated in CYP2E1 knockout mice. However, styrene and/or SO metabolism by mouse lung Clara cell-localized CYP2F2 to ring-oxidized cytotoxic metabolite(s) has been postulated as a key metabolic gateway responsible for both lung toxicity and possible tumorigenicity. To test this hypothesis, the lung toxicity of styrene and SO was evaluated in C57BL/6 (WT) and CYP2F2â»/â» knockout mice treated with styrene (400 mg/kg/day, gavage, or 200 or 400 mg/kg/day, ip) or S- or R-SO (200 mg/kg/day, ip) for 5 days. Styrene treated WT mice displayed significant necrosis and exfoliation of Clara cells, and cumulative BrdU-labeling index of S-phase cells was markedly increased in terminal bronchioles of WT mice exposed to styrene or S- or RSO. In contrast, Clara and terminal bronchiole cell toxicity was not observed in CYP2F2â»/â» mice exposed to either styrene or SO. This study clearly demonstrates that the mouse lung toxicity of both styrene and SO is critically dependent on metabolism by CYP2F2. Importantly, the human isoform of CYP2F, CYP2F1, is expressed at much lower levels and likely does not catalyze significant styrene metabolism, supporting the hypothesis that styrene-induced mouse lung tumors may not quantitatively, or possibly qualitatively, predict lung tumor potential in humans.
Asunto(s)
Carcinógenos/toxicidad , Sistema Enzimático del Citocromo P-450/metabolismo , Compuestos Epoxi/toxicidad , Neoplasias Pulmonares/inducido químicamente , Estireno/toxicidad , Animales , Sistema Enzimático del Citocromo P-450/deficiencia , Sistema Enzimático del Citocromo P-450/genética , Femenino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
Tertiary-Butyl alcohol (TBA), tertiary-butyl acetate (TBAc) and methyl tertiary-butyl ether (MTBE) are chemicals to which the general public may be exposed either directly or as a result of their metabolism. There is little evidence that they are genotoxic; however, an earlier publication reported that significant results were obtained in Salmonella typhimurium TA102 mutagenicity tests with both TBA and MTBE. We now present results of testing these chemicals and TBAc against S. typhimurium strains in two laboratories. The emphasis was placed on testing with S. typhimurium TA102 and the use of both dimethyl sulphoxide and water as vehicles. Dose levels up to 5000 microg/plate were used and incubations were conducted in both the presence and absence of liver S9 prepared from male rats treated with either Arochlor 1254 or phenobarbital-beta-naphthoflavone. The experiments were replicated, but in none of them was a significant mutagenic response observed, thus the current evidence indicates the TBA, TBAc and MTBE are not mutagenic in bacteria.
Asunto(s)
Acetatos/toxicidad , Carcinógenos/toxicidad , Éteres Metílicos/toxicidad , Pruebas de Mutagenicidad/métodos , Salmonella typhimurium/efectos de los fármacos , Alcohol terc-Butílico/toxicidad , Acetatos/metabolismo , Animales , Carcinógenos/metabolismo , Dimetilsulfóxido/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Éteres Metílicos/metabolismo , Ratas , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Solventes/metabolismo , Solventes/toxicidad , Alcohol terc-Butílico/metabolismoRESUMEN
Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice.
Asunto(s)
Neoplasias Pulmonares/inducido químicamente , Pulmón/patología , Estireno/toxicidad , Administración por Inhalación , Animales , Relación Dosis-Respuesta a Droga , Femenino , Hiperplasia , Pulmón/efectos de los fármacos , Masculino , Ratones , Cavidad Nasal/patología , Nervio Olfatorio/patología , Estireno/administración & dosificaciónRESUMEN
Gasoline (CAS 86290-81-5) is one of the world's largest volume commercial products. Although numerous toxicology studies have been conducted, the potential for reproductive toxicity has not been directly assessed. Accordingly, a two-generation reproductive toxicity study in rats was conducted to provide base data for hazard assessment and risk characterization. The test material, vapor recovery unit gasoline (68514-15-8), is the volatile fraction of formulated gasoline and the material with which humans are most likely to come in contact. The study was of standard design. Exposures were by inhalation at target concentrations of 5000, 10 000, and 20 000 mg/m(3). The highest exposure concentration was approximately 50% of the lower explosive limit and several orders of magnitude above anticipated exposure during refueling. There were no treatment-related clinical or systemic effects in the parental animals, and no microscopic changes other than hyaline droplet nephropathy in the kidneys of the male rats. None of the reproductive parameters were affected, and there were no deleterious effects on offspring survival and growth. The potential for endocrine modulation was also assessed by analysis of sperm count and quality as well as time to onset of developmental landmarks. No toxicologically important differences were found. Therefore, the NOAEL for reproductive toxicity in this study was > or =20 000 mg/m(3). The only systemic effects, in the kidneys of the male rats, were consistent with an alpha-2 u-globulin-mediated process. This is a male rat-specific effect and not relevant to human health risk assessment.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Gasolina/toxicidad , Efectos Tardíos de la Exposición Prenatal , Administración por Inhalación , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Cámaras de Exposición Atmosférica , Peso Corporal/efectos de los fármacos , Estro/efectos de los fármacos , Femenino , Gónadas/efectos de los fármacos , Gónadas/patología , Crecimiento/efectos de los fármacos , Humanos , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/patología , Espermatozoides/efectos de los fármacos , Espermatozoides/patologíaRESUMEN
The role of skin irritation and other factors on the tumorigenic activity of petroleum middle distillates (PMDs) in mice was examined in a comprehensive research program. The program culminated in a 2-year dermal carcinogenicity study which compared the effects of equal weekly doses of irritating and nonirritating PMDs. Modified Ames mutagenicity studies and three- to seven-ring polycyclic aromatic compound (PAC) analyses indicated that the mutagenic activity of PMDs was correlated to PAC content. In subchronic and subacute studies, PMDs produced marked skin irritation which was ameliorated if the test samples were diluted in mineral oil. The reduction in irritation level was not a result of reduced dermal absorption. Straight-run kerosine (SRK), straight-run gas oil (SRGO), and catalytically cracked light cycle oil (LCO) were evaluated in the dermal carcinogenicity study. Test materials were applied either undiluted (2x/week) or as 28.5% (7x/week) or 50% (4x/week) concentrations in mineral oil for a total weekly dose of 100 microliters PMD per animal. All three materials produced moderate to marked skin irritation and increased tumor frequency when applied undiluted. When diluted, the irritant effects of SRK and SRGO, which contain low levels of PACs, were ameliorated, and there were no significant increases in tumors relative to controls. LCO, containing 8.7% three- to seven-ring PACs, increased tumor frequency when diluted, even when skin irritation was limited. These data indicate that the tumorigenic activity of straight-run MDs is likely a consequence of a nongenotoxic process, associated with frequent cell damage and repair. PMDs which contain low levels of three- to seven-ring PACs are unlikely to cause tumors in the absence of prolonged skin irritation. In addition, genotoxic mechanisms may also contribute to tumor formation for other PMDs containing higher levels of PACs, e.g., products blended with cracked stocks.
Asunto(s)
Carcinógenos/toxicidad , Petróleo/toxicidad , Neoplasias Cutáneas/inducido químicamente , Animales , Pruebas de Carcinogenicidad , Carcinógenos/química , Carcinógenos/farmacocinética , Fenómenos Químicos , Química Física , Irritantes/toxicidad , Masculino , Ratones , Ratones Endogámicos C3H , Pruebas de Mutagenicidad , Petróleo/análisis , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Absorción Cutánea , Neoplasias Cutáneas/patología , Análisis de SupervivenciaRESUMEN
Groups of 70 male and 70 female Charles River CD (Sprague-Dawley-derived) rats were exposed whole body to styrene vapor at 0, 50, 200, 500, or 1000 ppm 6 h/day 5 days/week for 104 weeks. The rats were observed daily, body weights and food and water consumption were measured periodically, and a battery of hematologic and clinical pathology examinations was conducted at weeks 13, 26, 52, 78, and 104. Nine or 10 rats per sex per group were necropsied after 52 weeks of exposure and the remaining survivors were necropsied after 104 weeks. Control and high-exposure rats received a complete histopathologic examination, while target organs, gross lesions, and all masses were examined in the lower exposure groups. Styrene had no effect on survival in males, but females exposed to 500 or 1000 ppm had a dose-related increase in survival. Levels of styrene in the blood at the end of a 6-h exposure during week 95 were proportional to exposure concentration. Levels of styrene oxide in the blood of rats exposed to 200 ppm or greater styrene were proportional to styrene exposure concentration. There were no changes of toxicologic significance in hematology, clinical chemistry, urinalysis, or organ weights. Males exposed to 500 or 1000 ppm gained less weight than the controls during the first year and maintained the difference during the second year. Females exposed to 200, 500, or 1000 ppm gained less weight during the first year; those exposed to 500 or 1000 ppm continued to gain less during months 13-18. Styrene-related non-neoplastic histopathologic changes were confined to the olfactory epithelium of the nasal mucosa. There was no evidence that styrene exposure caused treatment-related increases of any tumor type in males or females or in the number of tumor-bearing rats in the exposed groups compared to controls. In females, there were treatment-related decreases in pituitary adenomas and mammary adenocarcinomas. Based on an overall evaluation of eight oncogenicity studies, there is clear evidence that styrene does not induce cancer in rats.
Asunto(s)
Carcinógenos/toxicidad , Neoplasias Mamarias Animales/inducido químicamente , Neoplasias Hipofisarias/inducido químicamente , Estireno/toxicidad , Administración por Inhalación , Animales , Recuento de Células Sanguíneas , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Tamaño de los Órganos , Ratas , Ratas Sprague-Dawley , Organismos Libres de Patógenos Específicos , Tasa de Supervivencia , Factores de Tiempo , Orina/químicaRESUMEN
The ecotoxicity of styrene was evaluated in acute toxicity studies of fathead minnows (Pimephales promelas), daphnids (Daphnia magna), amphipods (Hyalella azteca), and freshwater green algae (Selenastrum capricornutum), and a subacute toxicity study of earthworms (Eisenia fostida). Stable exposure levels were maintained in the studies with fathead minnows, daphnids, and amphipods using sealed, flowthrough, serial dilution systems and test vessels. The algae were evaluated in a sealed, static system. The earthworms were exposed in artificial soil which was renewed after 7 days. Styrene concentrations in water and soil were analyzed by gas chromatography with flame ionization detection following extraction into hexane. Test results are based on measured concentrations. Styrene was moderately toxic to fathead minnows, daphnids, and amphipods: fathead minnow: LC50 (96 hr), 10 mg/liter, and NOEC, 4.0 mg/liter; daphnids: EC50 (48 hr), 4.7 mg/liter, and NOEC, 1.9 mg/liter; amphipods: LC50 (96 hr), 9.5 mg/liter, and NOEC, 4.1 mg/liter. Styrene was highly toxic to green algae: EC50 (96 hr), 0.72 mg/liter, and NOEC, 0.063 mg/liter; these effects were found to be algistatic rather than algicidal. Styrene was slightly toxic to earthworms: LC50 (14 days), 120 mg/kg, and NOEC, 44 mg/kg. There was no indication of a concern for chronic toxicity based on these studies. Styrene's potential impact on aquatic and soil environments is significantly mitigated by its volatility and biodegradability.
Asunto(s)
Cyprinidae , Ecosistema , Contaminantes del Suelo/toxicidad , Estirenos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Chlorophyta/efectos de los fármacos , Crustáceos/efectos de los fármacos , Daphnia/efectos de los fármacos , Dosificación Letal Mediana , Oligoquetos/efectos de los fármacos , Estireno , Estirenos/análisisRESUMEN
Groups of 10 male and 10 female Charles River (CRL) CD (Sprague-Dawley-derived) rats were exposed to styrene vapor at 0, 200, 500, 1000, or 1500 ppm 6 hr per day 5 days per week for 13 weeks. Styrene had no effect on survival, hematology, or clinical chemistry. Males at 1500 ppm weighed 10% less after 13 weeks and males and females at 1000 and 1500 ppm consumed more water than controls. Histopathologic changes were confined to the olfactory epithelium of the nasal mucosa. Groups of 20 male and 20 female CRL CD-1 and B6C3F1 mice were exposed to styrene vapor at 0, 15, 60, 250, or 500 ppm 6 hr per day 5 days per week for 2 weeks. Mortality was observed in both CD-1 and B6C3F1 mice exposed to 250 or 500 ppm; more female mice, but not males, died from exposure to 250 ppm than from 500 ppm. Groups of 10 male and 10 female CRL CD-1 mice were exposed to styrene vapors at 0, 50, 100, 150, or 200 ppm 6 hr per day 5 days per week for 13 weeks. Two females exposed to 200 ppm died during the first week. Liver toxicity was evident in the decedents and in some female survivors at 200 ppm. Changes were observed in the lungs of mice exposed to 100, 150, or 200 ppm and in the nasal passages of all treatment groups, those exposed to 50 ppm being less affected. Satellite groups of 15 male rats and 30 male mice were exposed as described above for 2, 5, or 13 weeks for measurement of cell proliferation (BrdU labeling). No increase in cell proliferation was found in liver of rats or mice or in cells of the bronchiolar or alveolar region of the lung of rats. No increase in labeling index of type II pneumocytes was seen in mouse lungs, while at 150 and 200 ppm, an increased labeling index of Clara cells was seen after 2 weeks and in occasional mice after 5 weeks. Large variations in the labeling index among animals emphasize the need for large group sizes. For nasal tract effects, a NOAEL was not found in CD-1 mice, but in CD rats, the NOAEL was 200 ppm. For other effects, the NOAEL was 500 ppm in rats and 50 ppm in mice.
Asunto(s)
Estirenos/toxicidad , Administración por Inhalación , Animales , Conducta Animal/efectos de los fármacos , Ingestión de Líquidos/efectos de los fármacos , Epitelio/patología , Femenino , Hígado/patología , Masculino , Ratones , Ratones Endogámicos , Mucosa Olfatoria/patología , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie , Estireno , Estirenos/administración & dosificación , Factores de TiempoRESUMEN
A series of range-finding studies was conducted in a limited number of male F344 rats on the relation between cell proliferation and styrene oxide (SO) given as gavage doses in corn oil ranging from 550 to 1500 mg SO/kg. In each study, rats were injected with [3H]thymidine (0.50 mCi/g, ip) at intervals from 1 to 48 hr after dosing with SO. One hour later, stomachs were removed and fixed in formalin. Autoradiograms were prepared and labeling index (LI) was determined as the percentage of epithelial cells with 3H-labeled nuclei. Mean LI increased with a peak at approximately 15 hr after one or nine doses of SO. The increases were multifocal and not restricted to the area near the limiting ridge. The magnitude of the response in LI at 24 hr after dosing tended to decrease with progressive multiple doses (3/week). Dose-related morphologic lesions from SO (particularly submucosal) were multifocal and variable across the forestomach; they appeared unrelated to LI in a given area. In a final study, groups of 10 rats were given a single dose of 0, 20, 50, 125, 250, 500, or 800 mg/kg and LI was determined 15 hr later. Mean LI was dose-related with increases up to 250 mg/kg. A maximum response had apparently been reached and higher doses did not cause any further increase in LI. The degree of involvement of cell proliferation in the tumorigenicity of SO remains uncertain; additional studies are suggested to help in the understanding of such a possible relation.
Asunto(s)
Compuestos Epoxi/toxicidad , Estómago/efectos de los fármacos , Estómago/patología , Administración Oral , Animales , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Compuestos Epoxi/administración & dosificación , Masculino , Índice Mitótico/efectos de los fármacos , Ratas , Ratas Endogámicas F344RESUMEN
Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).
Asunto(s)
Carbazoles , Petróleo/toxicidad , Compuestos Policíclicos , Absorción Cutánea , Administración Cutánea , Anemia Aplásica/inducido químicamente , Animales , Disponibilidad Biológica , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas EndogámicasRESUMEN
A model for skin irritation was developed for simultaneous evaluation of the influence on irritation of abrasion, occlusion, and duration of treatment and for fulfillment of requirements for labeling considerations under DOT, CPSC-FHSA, OSHA, and EEC. This model greatly reduces the number of animals required to address submissions under multiple agencies compared to performing each test separately. In this model, which we have called a Composite Skin Irritation test, a test material is placed on three pairs of intact and abraded sites on each rabbit; one pair of sites is occluded for 4 hours, one for 24 hours, and the other left unoccluded for 24 hours. Results are presented from 88 composite tests with 80 petroleum-related materials. For the materials tested, abrasion of the skin had no effect on the irritation response. Occlusion of the test site generally did not result in dramatic increases in response, except for petroleum refinery streams with a boiling range below 500 degrees F. Exposure for 4 hours rather than 24 hours generally resulted in less irritation; however, for individual compounds, the irritation from the 4-hour exposure could not be predicted from the response to the 24-hour exposure. Of the 80 materials tested, 12 would be labeled as skin irritants under CPSC guidelines, three under OSHA, and 20 under EEC. Of the 20 that would be labeled under EEC criteria, only seven would be labeled under CPSC criteria. At least for petroleum-related materials, results from skin irritation studies performed under one set of conditions cannot be used to predict the degree of irritation that would be produced under a different set of exposure conditions.