GTL synthetic paraffin oil shows low liver and tissue retention compared to mineral oil.

Oral exposure to mineral oil may result in a narrow fraction of mineral oil saturated hydrocarbon (MOSH) being retained in tissues. Excess of MOSH hepatic retention may lead to the formation of lipogranuloma caused by predominantly multiring cycloalkanes (naphthenics) in a critical range of C25-C35. Although hepatic lipogranuloma is of low pathological concern, MOSH tissue deposition could be minimized by using an oil of similar quality but devoid of naphthenic structures to decrease hepatic retention. Synthetic Gas to liquid (GTL) oils offer an alternative to petroleum derived mineral oils, because they do not contain naphthenic structures. To demonstrate this point, SD rats were fed either GTL oil (99% iso-alkanes) or naphthenic mineral oil (84% cycloalkanes) at 200 mg/kg bw/day for 90 or 134 days with a recovery group. Liver, fat and mesenteric lymph nodes were analyzed for alkane sub-type levels using Online-HPLC-GC-FID and GCxGC-TOF-MS. Results indicate that at equal external dose, GTL hydrocarbons result in lower tissue levels and more rapid excretion than MOSH. GTL retained hepatic fractions were also qualitatively different than MOSH constituents. Because chemical composition differences, GTL oil show low absorption and tissue retention potential and thus an advantageous alternative to conventional mineral oil.

Impact of Different Mixing Methods on the Performance of Suspension-Based Transdermal Delivery Systems.

Suspension-based matrix transdermal delivery systems (TDSs) are specialized systems that maintain a continuous driving force for drug delivery over prolonged wear. The pressure-sensitive adhesive (PSA) is the most critical constituent of such systems. Our study aimed to determine the effect of different mixing methods on the performance of silicone PSA-based suspension TDSs. Lidocaine suspension TDSs were prepared using conventional slow rotary mixing, high-speed homogenization, bead-mill homogenization, vortex shaking, and by an unguator. Resultant TDSs were tested for tack, shear, and peel properties and correlated to coat weight, content uniformity, microstructure, and in vitro permeation across dermatomed human skin. Every mixing method tested caused a significant reduction in peel. However, bead-mill homogenization resulted in significant loss of all adhesive properties tested, while unguator-mixed TDSs retained most properties. Good linear correlation (R2 = 1.000) between the shear properties of the TDSs with the average cumulative amount of lidocaine permeated after 24 h was observed, with no significant difference between percutaneous delivery from slow rotary-mixed systems (1334 ± 59.21 µg/cm2) and unguator-mixed systems (1147 ± 108.3 µg/cm2). However, significantly lower delivery from bead-mill homogenized systems (821.1 ± 28.00 µg/cm2) was noted. While many factors affect TDS performance, careful consideration must also be given to the processing parameters during development as they have been shown to affect the resultant system's therapeutic efficacy. Extensive mixing with bead-mill homogenization demonstrated crystallization of drug, loss in adhesive properties, coat weight, and film thickness, with reduced transdermal delivery of lidocaine from the prepared system.

Evaluating the risk to humans from mineral oils in foods: Current state of the evidence.

Key issues around the evaluation of risks to humans from mineral oils in food and feedstuffs are discussed. MOHs (MOAH and MOSH) occur in food due to intentional use, contamination from environmental sources and during transport/processing, or through migration from food contact materials. Problems in setting and enforcing human health guidelines for MOH include uncertainty around MOH toxicity and the specialist expertise needed for analysis of complex food matrices. Currently, the method of choice for measuring mineral oils is LC-GC-FID, however some complex food matrices also require additional analytical techniques to differentiate between some naturally occurring hydrocarbons and those from other sources, including of petrogenic origin. This requires the skills of an experienced analyst. Significant toxicological gaps for MOHs prevent robust human health risk assessment and the derivation of guidance values. As food-grade mineral oils are virtually MOAH-free, the key issue explored here is the relevance to humans of liver (micro)granulomas observed in F344 rats following oral intake. Available data suggest that despite the ubiquitous nature of MOH in the human diet, the prevalence of liver lipogranulomas in the population is low. These are not associated with inflammation and based on current evidence are not considered of human health significance.

Mineral oils and waxes in cosmetics: an overview mainly based on the current European regulations and the safety profile of these compounds.

Mineral oils and waxes are mixtures of predominantly saturated hydrocarbons consisting of straight-chain, branched and ring structures with carbon chain lengths greater than C14. They have been used for many decades in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. In contrast to vegetable oils, mineral oils are non-allergenic since they are highly stable and not susceptible to oxidation or rancidity. They have a long history of safe use which is confirmed by clinical and epidemiological data. In Europe, mineral oils are only permitted in cosmetics if compliant with purity specifications on polycyclic aromatic hydrocarbons and safety requirements laid down in the European pharmacopoeia and the EU cosmetics regulation EC/1223/2009. The high quality of these mineral oils is assured by robust quality assurance and a refining/purification process designed to exclude substances with carcinogenic potential and to minimize the presence of mineral oil aromatic hydrocarbons. Given their highly lipophilic properties, mineral oils do not penetrate human skin and, thus, are not systemically bioavailable in the body. Moreover, no significant changes in the skin and no effects on any internal organ system have been reported and attributed to the topical application of refined mineral oils. Regarding potential oral exposure from cosmetic lip care products, Cosmetics Europe, the European trade association for the cosmetics and personal care industry, has advised cosmetic manufacturers to only use mineral oil fractions for which recognized food acceptable daily intake (ADI) values apply. The estimated dose of mineral oils ingested via lip care products contributes to <10% of the ADI value and should therefore be considered of no toxicological concern.

Review of data on the dermal penetration of mineral oils and waxes used in cosmetic applications.

Mineral oils and waxes used in cosmetic products, also referred to as "personal care products" outside the European Union, are mixtures of predominantly saturated hydrocarbons consisting of straight-chain, branched and ring structures with carbon chain lengths greater than C16. They are used in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. Recently, concerns have been raised regarding potential adverse health effects of mineral oils and waxes from dermal application of cosmetics. In order to be able to assess the risk for the consumer the dermal penetration potential of these ingredients has to be evaluated. The scope and objective of this review are to identify and summarize publicly available literature on the dermal penetration of mineral oils and waxes as used in cosmetic products. For this purpose, a comprehensive literature search was conducted. A total of 13 in vivo (human, animal) and in vitro studies investigating the dermal penetration of mineral oils and waxes has been identified and analysed. The majority of the substances were dermally adsorbed to the stratum corneum and only a minor fraction reached deeper skin layers. Overall, there is no evidence from the various studies that mineral oils and waxes are percutaneously absorbed and become systemically available. Thus, given the absence of dermal uptake, mineral oils and waxes as used in cosmetic products do not present a risk to the health of the consumer.

Accumulation of mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats: Comparison with human data and consequences for risk assessment.

Female Fischer 344 rats were orally exposed to a mixture of mineral oil saturated hydrocarbons (MOSH) of broad molecular mass range at doses of 40, 400 and 4000mg/kg feed. Amounts and compositions of the MOSH were analyzed in liver, spleen, adipose tissue and the carcass after exposure during 30, 60, 90 and 120d as well as after 90d exposure followed by 30d depuration. At 40mg/kg in the feed, after 30d of exposure, 10.9% of the ingested MOSH were recovered from the animal body; after 90d plus 30d depuration it was 3.9%. In liver and spleen, the maximum retention in terms of molecular mass (simulated distillation) was at n-C29; in adipose tissue and carcass it was at n-C15/16. The differentiation between MOSH below and above n-C25 (Class I versus Class II and III oils), used for present regulation, is not supported by the present data on accumulation; structural characteristics seem more pertinent than molecular mass. Concentrations in the tissues increased far less than proportionally with the dose, rendering linear extrapolation to low doses questionable. No steady state was reached after 120d. In fact, comparing with the concentrations in human tissues at the estimated exposure, extrapolation from animal experiments seems to grossly underestimate human internal exposure. Comprehensive two-dimensional gas chromatography (GCxGC) was used to characterize the MOSH residues in the tissues with the aim of identifying the most strongly accumulated types. In the liver and spleen, the highly branched hydrocarbons dominated, whereas in the adipose tissue it was the n-alkanes and species with main n-alkyl moieties. Strong MOSH accumulation is not of concern per se, but the safety at the high concentrations in human tissues needs to be re-evaluated, possibly taking into account also end points other than granuloma formation.

Retention and excretion of ³H in rats following the intratracheal intubation of tritiated pump oil.

Saturated hydrocarbon mineral oils in vacuum pumps used in ³H handling facilities often contain significant amounts of ³H (as much as several hundred GBq L⁻¹), and during maintenance the air around an open pump may contain MBq L of volatile and aerosol species. It follows that H-contaminated pump oils pose a workplace hazard-especially if inhaled deposits are retained in the lung. A long-term study (1-y duration) was undertaken to establish the retention time of ³H-pump oil in the lungs of rats. Excretion data was collected to establish the mechanism of oil clearance from the lung. Finally, liver data was collected both to indicate the levels of H in the rat body and to indicate either the presence or absence of the transfer of unmetabolized pump oil within cells from the lungs to liver. Within 1 d following intubation into the trachea, ∼16.5% of the emulsified pump oil had been rapidly mechanically cleared to feces, and 1.1%, present as HTO, or exchangeable H, was excreted in urine. 69.4% of the instilled dose remained in the lungs as the initial alveolar burden. Subsequently, H cleared from the lungs with a retention half-time of of 223 d. The lung burden was mostly cleared to feces-indicating that the pump oil droplets remaining in the lungs were behaving like insoluble particles, but the kinetics of clearance of particles and oil droplets may be different. Overall, it is concluded that inhaled H-pump oil should most likely be regarded as an insoluble particulate (ICRP Inhalation Type S) for the purposes of radiological protection dosimetry, but the possibility of Type M behavior cannot be excluded.

Light white oils exhibit low tissue accumulation potential and minimal toxicity in F344 rats.

Female F344 rats were fed diets containing 0.02%, 0.2%, or 2.0% white mineral oil for 90 days. There were no gross or microscopic differences in target organs at the 0.02% level. In the higher-dose groups, relative liver and mesenteric lymph node (MLN) weights were increased, and MLN inflammation was observed. At the 2% level, there was very limited evidence of microgranuloma formation in the liver but at a lower incidence and at lesser severity than has been reported in studies of C22-C25 oils. Analysis of liver extracts from treated rats revealed that C15-C20 constituents were underrepresented by comparison to their corresponding concentrations in the test oil. These results provide evidence that although hydrocarbons with carbon numbers < C20 are absorbed, they are not preferentially retained and do not contribute to inflammatory processes in liver.

Comparative toxicokinetics of low-viscosity mineral oil in Fischer 344 rats, Sprague-Dawley rats, and humans--implications for an Acceptable Daily Intake (ADI).

Oral repeated-dose studies with low-viscosity mineral oils showed distinct species and strain differences, which are hypothesized to be due to differences in bioavailability, with Fischer 344 rats being more susceptible than Sprague-Dawley rats or dogs. Sensitive analytical methodology was developed for accurate measurement of low levels of mineral hydrocarbons and applied in single-dose toxicokinetics studies in rats and humans. Fischer 344 rats showed a 4-fold higher AUC(0-∞) and consistently higher blood and liver concentrations were found than Sprague-Dawley rats. Hepatic mineral hydrocarbon concentration tracked the blood concentration in both strains, indicating that blood concentrations can serve as functional surrogate measure for hepatic concentrations. In human volunteers receiving 1mg/kg body weight of low-viscosity white oil, all blood concentrations of mineral hydrocarbons were below the detection limit. Comparison with threshold blood concentrations associated with NOAELs in both rat strains, indicate that the margin-of-exposure is at least 37-fold. Using an internal dose metric rather than applied dose reduces the uncertainty around the temporary ADI considerably since it intrinsically accounts for intra- and inter-species differences. The current data support replacement of the temporary ADI of 0.01 mg/kg/day by a (permanent) ADI of at least 1.0mg/kg/day for low- and medium-viscosity mineral oils.

Evidence for cosmetics as a source of mineral oil contamination in women.

BACKGROUND: There is strong evidence that mineral oil hydrocarbons are the greatest contaminant of the human body, amounting to approximately 1 g per person. Possible routes of contamination include air inhalation, food intake, and dermal absorption. The present study aims to identify the most relevant sources of mineral oil contamination. METHODS: One hundred forty-two women undergoing elective cesarean section were enrolled. A specimen of subcutaneous fat was removed prior to wound closure. On days 4 and 20 postpartum, milk samples were collected from the women. Fat and milk samples were analyzed for mineral oil saturated hydrocarbons (MOSH). All women completed a questionnaire on personal data, nutrition habits, and use of cosmetics. MOSH concentrations in fat tissue were compared with data from the questionnaire and with MOSH concentrations in corresponding milk samples. RESULTS: The predominant predictor for MOSH contamination of fat tissue was age (p<0.001). Furthermore, body mass index (p=0.001), country of main residence (p=0.03), number of previous childbirths (p=0.029), use of sun creams in the present pregnancy (p=0.002), and use of hand creams and lipsticks in daily life (p=0.011 and p=0.007, respectively) were significant independent determinants. No association was found with nutritional habits. A strong correlation was seen between MOSH concentration in fat tissue (median 52.5 mg/kg) and in the corresponding milk fat sample from day 4 (median 30 mg/kg) (p<0.001) and day 20 (median 10 mg/kg) (p=0.028). CONCLUSIONS: The increase in MOSH concentration in human fat tissue with age suggests an accumulation over time. Cosmetics might be a relevant source of the contamination.

An investigation into the influence of counterion on the RS-propranolol and S-propranolol skin permeability.

The effects of two contra-ions, namely benzoate (Bz) and oleate (Ol), on the in vitro human skin permeability of propranolol racemate (RS-PR) or S-enantiomer (S-PR) were studied. Saline solution (SS) or mineral oil (MO) were selected as vehicles. The MO increased the permeability coefficient (K(p)) of PR-Bz (pK(p) approximately 4) of about four times with respect to SS (pK(p) approximately 8) probably due to the ion pair formation. The steady-state flux of S-enantiomers resulted about twofold higher than that of racemates according to their lower melting temperatures with the exception of (S)-PR-Ol and (RS)-PR-Ol vehicled in SS which not resulted statistically different. This anomalous result could be explained considering the behavior of (RS)-PR-Ol or (S)-PR-Ol in aqueous solutions: these salts formed ion pairs which associated to form aggregates up to a concentration of 20 microg/mL as verified by light scattering. Therefore, their effective concentrations in SS resulted similar and justified the overlapped skin permeation profiles. All three considered variables, namely counterion, vehicle, and chirality, resulted mutually interfering on and deeply influenced the passive diffusion process of PR.

Dermatotoxicity of cutting fluid mixtures:in vitro and in vivo studies.

Cutting fluids are widely used in the metal-machining industry to lubricate and reduce heat generation when metals are cut by a metal-cutting tool. These cutting fluids have caused occupational irritant contact dermatitis (OICD), and many of the additives used in these cutting fluid mixtures are thought to be responsible for OICD in workers. The purpose of this study was to assess single or various combinations of these additives in initiating the OICD response following an acute 8-hour exposure in porcine skin in vivo and in vitro using the isolated perfused porcine skin flap (IPPSF) and human epidermal keratinocytes (HEK). Pigs (n = 4) were exposed to 5% mineral oil (MO) or 5% polyethylene glycol (PEG) aqueous mixtures containing various combinations of 2% triazine (TRI), 5% triethanolamine (TEA), 5% linear alkylbenzene sulfonate (LAS), or 5% sulfurized ricinoleic acid (SRA). Erythema and edema were evaluated and skin biopsies for histopathology were obtained at 4 and 8 hours. IPPSFs (n = 4) were exposed to control MO or PEG mixtures and complete MO or PEG mixtures, and perfusate samples were collected hourly to determine interleukin- (IL-) 8 release. The only significant (p < 0.05) mixture effects observed in IPPSFs were with SRA + MO that caused an increase in IL-8 release after 1 or 2 hours' exposure. In vivo exposure to TRI alone appeared to increase erythema, edema, and dermal inflammation compared to the other additives, while SRA alone was least likely to initiate a dermal inflammatory response. In 2-component mixture exposures, the presence of TRI appeared to increase the dermal inflammatory response at 4 and 8 hours especially with the PEG mixtures. In the 3- and 4-component mixtures, MO mixtures are more likely to incite an inflammatory response than PEG mixtures. TRI exhibited the highest toxicity toward HEK, which correlates well to the in vivo irritation and morphology results. In summary, these preliminary studies suggest that the biocide, TRI, is the more potent of the 4 performance additives in causing dermal irritation, and this may vary depending on whether the worker is exposed to a synthetic (PEG)- or MO-based fluid. These findings will however require further clinical studies to validate these acute dermal effects as well as human cumulative irritation following exposure to similar cutting fluid formulations in the workplace.

Human skin permeation of branched-chain 3-0-alkyl ester and carbonate prodrugs of naltrexone.

PURPOSE: Physicochemical characterization and in vitro human skin diffusion studies of branched-chain ester and carbonate prodrugs of naltrexone (NTX) were compared and contrasted with straight-chain ester and carbonate NTX prodrugs. METHODS: Human skin permeation rates, thermal parameters, solubilities in mineral oil and buffer, and stabilities in buffer and plasma were determined. Partition coefficients between stratum corneum and vehicle were determined for straight- and branched-chain esters with the same number of carbon atoms. RESULTS: Branched prodrugs had lower melting points, lower buffer solubilities, and higher mineral oil solubilities than NTX. The transdermal flux values from all of these branched prodrugs were significantly lower than flux values from the straight-chain ester and the methyl carbonate prodrugs. Straight-chain prodrugs had higher partition coefficient values and higher calculated thermodynamic activities than their branched-chain counterparts. The prodrug hydrolysis to NTX in buffer and plasma was slower for prodrugs with increased branching. CONCLUSIONS: Branched-chain prodrugs with bulky moieties had smaller stratum corneum-vehicle partition coefficients and lower thermodynamic activities that resulted in smaller transdermal flux values than straight-chain prodrugs.

GARField magnetic resonance profiling of the ingress of model skin-care product ingredients into human skin in vitro.

A preliminary study of the ingress of mineral oil, decanol, and glycerine into samples of human abdominal skin tissue in vitro made using magnetic resonance profiling with a GARField magnet is reported. Two layers, each circa 50 microm thick and attributed to stratum corneum and viable epidermis, are spatially resolved. Clear differences are observed in the magnetic resonance response of these layers arising from the application of the model skin-care product ingredients. In the case of decanol and glycerine, it is suggested that the profiles show evidence for the effects of moisturization, as distinct from hydration. In the case of glycerine, the effective ingress diffusion coefficient is calculated to be 1.3 +/- 0.5 x 10(-9) cm2s(-1).

Avaliação experimental de técnica utilizada por enfermeiros no tratamento de equimoses / Experimental assesment on the technique utilizes by nurses on the treatment against ecchymosis

Este trabalho consiste em estudo experimental de processos técnicos utilizados como apoio à regressão de equimoses. Buscou-se a resposta em laboratório através da indução de equimose traumática em 72 ratos, testados em grupos de oito, sendo cada grupo tratado respectivamente por aplicação tópica de: 1§ solução fisiológica; 2§ bolsa de gelo; 3§ bolsa de água quente; 4§ agar-agar; 5§ éter etílico; 6§ óleo mineral; 7§ fenoftaleína, 8§ associação-A entre o éter+Agar+óleo+fenoftaleína e 9§ associção-B, aplicação de gelo nas primeiras 24 h após a lesão e depois bolsa de água quente. Os dados obtidos foram tratados e comparados entre si e com o grupo controle usando-se análise de variância (ANOVA) paramétrica de Student-Newman-Keuls. Os resultados revelaram que o uso da associação-A mostrou atividade terapêutica extremamente significativa quando comparada com o grupo controle e associação-B, podendo-se concluir que o uso tópico da associação-A é eficaz para o tratamento das equimoses traumáticas induzidas em ratos

Application of the transformed Potts-Guy equation to in vivo human skin data.

Data developed by Wenkers and Lippold for the flux of 10 nonsteroidal anti-inflammatory drugs from light mineral oil (MO) through human skin in vivo has been analyzed using the transformed Potts-Guy equation. The analysis shows that the flux is dependent not only on the solubility in MO (S(MO)), but also on the solubility in acidic water (S(AQ)). This dependence of flux on S(AQ) shows that the previously reported dependence of flux on S(AQ) from in vitro experiments using hairless mouse skin is not an artifact of the in vitro experiments but is due to a characteristic of the skin barrier. Further inspection of the equations used by Wenkers and Lippold in their analyses of their data shows that the equations are variations of the transformed Potts-Guy equation.

Secondary ion mass spectrometric investigation of penetration of coconut and mineral oils into human hair fibers: relevance to hair damage.

An attempt has been made to show the difference in the penetrability of coconut oil and mineral oil in human hair. We have used secondary ion mass spectrometry (SIMS) in combination with a time-of-flight (TOF) mass spectrometer. Characteristic ions formed by the pure components when bombarded with gallium ions have been identified with their m/z values. The distribution of the ion, characteristic of the particular treatment, has been established in the cross sections of hair treated with coconut and mineral oils. The results show that coconut oil penetrates the hair shaft while mineral oil does not. The difference may be due to the polarity of the coconut oil compared to the nonpolar nature of the mineral oil. The affinity of the penetrant to the protein seems to be the cause for this difference in their behavior. This study also indicates that the swelling of hair is limited by the presence oil. Since the process of swelling and deswelling of hair is one of the causes of hair damage by hygral fatigue, coconut oil, which is a better penetrant than mineral oil, may provide better protection from damage by hygral fatigue.

Tests of potential functional barriers for laminated multilayer food packages. Part I: Low molecular weight permeants.

The advent of the functional barrier concept in food packaging has brought with it a requirement for fast tests of permeation through potential barrier materials. In such tests it would be convenient for both foodstuffs and materials below the functional barrier (sub-barrier materials) to be represented by standard simulants. By means of inverse gas chromatography, liquid paraffin spiked with appropriate permeants was considered as a potential simulant of sub-barrier materials based on polypropylene (PP) or similar polyolefins. Experiments were performed to characterize the kinetics of the permeation of low molecular weight model permeants (octene, toluene and isopropanol) from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick oriented PP) into the food stimulants olive oil and 3% (w/v) acetic acid. These permeation results were interpreted in terms of three permeation kinetic models regarding the solubility of a particular model permeant in the post-barrier medium (i.e. the food simulant). The results obtained justify the development and evaluation of liquid sub-barrier simulants that would allow flexible yet rigorous testing of new laminated multilayer packaging materials.

A toxicological review of topical exposure to white mineral oils.

White mineral oils have a long history of safe use by humans in orally ingested and topically applied products. A re-evaluation of the use of certain mineral hydrocarbons in the preparation of food items by regulators in the UK, however, has prompted additional safety studies and a critical assessment of the toxicological effects of white mineral oils. As white mineral oils are present in many topically applied drug and non-drug products, it is of interest to review the toxicological effects of mineral oil produced by this route of exposure. Specifically, the concern regarding the safety of white mineral oils has arisen, in part, from results of subchronic (e.g 90 day) feeding studies that reported the presence of granulomas in liver and histiocytosis in mesenteric lymph nodes of Fischer 344 rats after oral ingestion of select white mineral oils. In contrast to these subchronic oral studies, repeated topical exposure to white mineral oils has not been found to produce liver granulomas, histiocytosis in the mesenteric or other lymph nodes, or any local or systemic toxicity including tumour formation in Fischer 344 rates, C3H mice, New Zealand White rabbits or beagle dogs at similar or higher exposures (mg/kg/day). On the basis of these findings and reports on negligible epidermal penetration of topically applied white mineral oils, there is no evidence of any hazard identified for topical exposure to white mineral oils at any dose in multiple species. This conclusion is supported by the long and uneventful human use of white mineral oils in drug and non-drug topically applied products.