Allergens grouping names on packaging: Are the substances similar enough to ensure safety? The worst case scenarios question this.

OBJECTIVE: European Commission Regulation (EU) n°2023/1545 introduced the concept of grouping names in the cosmetics sector in July 2023. These groups bring together allergenic substances with the same level of skin sensitization. Their purpose is to lighten the list of ingredients on cosmetic packaging, by grouping together substances deemed to be similar under the same name. As this classification is based on a single toxic effect - skin sensitization - the present study aims to analyse the relevance of these groupings with regard to other toxic effects of substances in the same group. METHODS: This study was carried out by consulting an available database, various reports from 5 committees, 2 books and 5 articles in order to complete the toxicological profile of each substance. Then, in order to highlight any discrepancies within the classification, the worst cases were identified. For this purpose, the data for each substance in a group were compared, and in the event of greater criticality for a toxic effect, this was qualified as a worst case. In addition, similar toxic effects between several substances within the same group were also recorded. The aim of this additional research was to validate the definition of the grouping name and the similarities between substances in the same group. RESULTS: From the 17 grouping names, 5 presented worst cases. Two groups had 2 worst cases and the others only one. In total, from the 7 worst cases detected, 3 were due to the toxic effect "skin irritation". In most cases, the substances in the groupings shared the presence or absence of risk. Only the degree of risk criticality varied. CONCLUSION: Classification by grouping names appears justified regarding the similarities between substances, particularly in terms of skin sensitization. However, the presence of worst cases qualifies it and highlights the importance of being vigilant when assessing the risk of cosmetic products including these grouping names in their list of ingredients.

OBJECTIF: Le règlement (UE) n°2023/1545 de la Commission européenne a introduit la notion de « grouping names ¼ dans le domaine des cosmétiques en juillet 2023. Ces groupes rassemblent des substances allergènes ayant le même niveau de sensibilisation cutanée. Ils ont pour objectif d'alléger la liste des ingrédients figurant sur les emballages des produits cosmétiques, en regroupant sous un même nom des substances jugées similaires. Cette classification étant fondée sur un seul effet toxique ­ la sensibilisation cutanée ­ la présente étude vise à analyser la pertinence de ces regroupements au regard des autres effets toxiques des substances d'un même groupe. MÉTHODES: Cette étude a été réalisée en consultant une base de données disponible, différents rapports de 5 comités, 2 livres et 5 articles afin de compléter le profil toxicologique de chaque substance. Ensuite, afin de mettre en évidence les divergences au sein de la classification, les cas de criticité plus importante ont été identifiés. Pour ce faire, les données de chaque substance d'un groupe ont été comparées, et en cas de criticité supérieure d'un effet toxique, celui­ci a été qualifié de « worst case ¼. En outre, les effets toxiques similaires entre plusieurs substances d'un même groupe ont également été enregistrés. L'objectif de cette recherche complémentaire était de valider la définition du « grouping name ¼ et les similitudes entre les substances d'un même groupe. RÉSULTATS: Sur les 17 « grouping names ¼, 5 présentaient des « worst cases ¼. Deux groupes présentaient deux « worst cases ¼ et les autres un seul. Au total, sur les 7 « worst cases ¼ détectés, 3 étaient dus à l'effet toxique "irritation cutanée". Dans la plupart des cas, les substances des groupes partagent la présence ou l'absence de risque. Seul le degré de criticité du risque variait. CONCLUSION: La classification par « grouping names ¼ semble justifiée au regard des similitudes entre les substances, notamment en termes de sensibilisation cutanée. Cependant, la présence de « worst cases ¼ la nuance et souligne l'importance d'être vigilant lors de l'évaluation du risque des produits cosmétiques incluant ces « grouping names ¼ dans leur liste d'ingrédients.

Optimization of the method of the content-containing interaction evaluation for cosmetic products by gas chromatography-mass spectrometry.

In July 2013, the European Regulation (EC) No 1223/2009 came into effect in order to secure cosmetic products. The content-containing interaction between the packaging and the product must be considered for the safety assessment. Indeed, some compounds are able to migrate from the packaging to the product and may be harmful to the consumer health. This is why a first test was established by EXPERTOX laboratory in 2012 to deal with this new regulation. A new analytical method was developed and validated for the quantification of 23 substances able to migrate from the packaging to the product. It was applied on a plastic packaging with the five simulants of migration. To evaluate the content-containing interaction, a gas chromatography-mass spectrometry method was developed and validated. Liquid-liquid extraction was used to extract contaminants (thirteen phthalates and ten substances of very high concern) from migration simulants. Calibration curves showed good linearity regression from 2 to 50 µg mL-1 for nineteen molecules and from 5 to 45 µg mL-1 for the others. The limits of quantification were respectively 2 and 5 µg mL-1 . The accuracy, precision, repeatability of the analytical method and extraction yields were acceptable. No molecule was found in simulants of migration, so the potential contaminants present in the packaging did not migrate. A gas chromatography-mass spectrometry method and liquid-liquid extraction were validated for 23 molecules and can be used for the evaluation of the content-containing interaction of cosmetic products. Both quantification and extraction procedures are more robust and faster than previous method.

Comparison of the compact dry TC method with the standard method ISO 21149:2006 for determining aerobic colony counts in cosmetic emulsion.

OBJECTIVE: Compact Dry TC, a rapid method kit for determining aerobic colony counts, has been developed by Nissui Pharmaceutical Co. for food application. These plates are pre-sterilized and contain culture medium, a cold-soluble gelling agent and a colour redox indicator for rapid enumeration. In this study, the alternative method is compared with the standard method ISO 21149:2006 - Cosmetic - Microbiology - Enumeration and detection of aerobic mesophilic bacteria, for cosmetic emulsions application. METHODS: An oil-in-water (o/w) cosmetic emulsion was contaminated with a pool of bacterial strains (Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027). One millilitre of samples was spread on agar as described in ISO 21149. The colonies were enumerated after 3 days of incubation. At the same time, 1.2 mL samples were spread on Compact Dry TC kits. The kit was incubated at 35°C ± 1°C for 48 h, and the colonies were enumerated. Accuracy determination was carried out using six replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL-1 ). The repeatability study was carried out using 12 replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL-1 ). Variations relative to the analyst and to the batch of emulsion have been investigated. RESULTS: The linear correlation coefficients of Compact Dry TC Kit enumeration with standard method ISO 21149:2006 was 0.9999. In comparison study, no apparent differences were noted between the Compact Dry TC kit and the reference method ISO 21149, for the detection level of aerobic microorganisms. Relative accuracy, repeatability and intermediate precision studies were acceptable. In the repeatability study, the Shapiro-Wilk test has confirmed the normally distribution of the twelve assays. No significant variations in Compact Dry TC count results were observed with different analysts and different batches of emulsion. CONCLUSION: The results showed that the two compared methods 'Compact Dry TC' vs. 'conventional pour plate' performed equally well. Demonstration was achieved that the Compact Dry TC method may constitute a useful alternative tool for rapid enumeration of aerobic mesophilic bacteria in cosmetic emulsions.

Predictive microbiology for cosmetics based on physicals, chemicals and concentration parameters.

OBJECTIVE: Challenge test (CT) is essential to assure the efficiency of the preservative system in products. A previous study realized by our staff in 2012, carried out to evaluate the influence of three parameters (ethanol, pH and water) on the microbiological cosmetics products conservation. Following this work, a correlation between aw (based on the glycerine concentration) and the selected parameter has been demonstrated. In the present study, smaller limits of ethanol, pH and glycerine were applied to determinate CT necessity. METHODS: Sixteen stables O/W cosmetics creams with different concentration of ethanol (1-19%), glycerine (3-16%) and different pH (6-11) were formulated. To evaluate the efficiency of the different formulations, CTs were performed according to the International Standard ISO 11930:2012. To determine the influence of the parameters, a D-optimal plan generated by Design Expert(®) was applied. Design of Experiments software offers to plan, estimate and control the statistics and models for factorial and no-factorial designs. RESULTS: Challenge tests results show that 10 formula passed criteria A, two passed criteria B and four are not conform. Mostly, an ethanol concentration higher than 16% exempts products of CT. It has been shown that an ethanol concentration between 10.5% and 16%, and an glycerine concentration >10%; or if the ethanol concentration is between 5% and 10.5%, glycerine is >6% and pH is ≥10, the CT is not required. Ethanol has a significant impact on conservation and especially when it is correlated with glycerine and pH. Finally, a glycerine concentration higher than 16% exempts products of CT. CONCLUSION: Following the analysis of the different concentration, a correlation between glycerine and ethanol that directly influence microbiological protection of cosmetics products has been established. Indeed, by controlling ethanol, pH and glycerine, many products may be exempted from the CT.

Determination of the influence of factors (ethanol, pH and a(w) ) on the preservation of cosmetics using experimental design.

OBJECTIVE: Ethanol, pH and water activity are three well-known parameters that can influence the preservation of cosmetic products. With the new constraints regarding the antimicrobial effectiveness and the restrictive use of preservatives, a D-optimal design was set up to evaluate the influence of these three parameters on the microbiological conservation. METHODS: To monitor the effectiveness of the different combination of these set parameters, a challenge test in compliance with the International standard ISO 11930: 2012 was implemented. The formulations established in our study could support wide variations of ethanol concentration, pH values and glycerin concentration without noticeable effects on the stability of the products. RESULTS: In the conditions of the study, determining the value of a single parameter, with the tested concentration, could not guarantee microbiological conservation. However, a high concentration of ethanol associated with an extreme pH could inhibit bacteria growth from the first day (D0). Besides, it appears that despite an aw above 0.6 (even 0.8) and without any preservatives incorporated in formulas, it was possible to guarantee the microbiological stability of the cosmetic product when maintaining the right combination of the selected parameters. CONCLUSION: Following the analysis of the different values obtained during the experimentation, there seems to be a correlation between the aw and the selected parameters aforementioned. An application of this relationship could be to define the aw of cosmetic products by using the formula, thus avoiding the evaluation of this parameter with a measuring device.

Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans.

BACKGROUND: Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine. METHODS: Plasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography-tandem mass spectrometry with limits of quantitation of 0.1 µg/L. RESULTS: Maximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3 ± 1.0, 44.5 ± 4.8, 85.2 ± 7.7, 124.6 ± 16.6, and 137.7 ± 18.8 µg/L, respectively. Maximum norbuprenorphine concentrations occurred 10-15 min (3.7 ± 0.7 µg/L) after 16 mg IV administration. CONCLUSIONS: Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2-16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg.

Smoking ban in a psychiatry department: are nonsmoking employees less exposed to environmental tobacco smoke?

Staff members of psychiatric facilities are at high risk of secondhand smoking. Smoking exposure was assessed in 41 nonsmoking employees of a psychiatry department before and after a ban. Subjective exposure measures decreased in 76% of the subjects. Salivary cotinine decreased in the subsample of seven subjects with high pre-ban levels (32+/-8 vs 40+/-17 ng/ml, p=.045).

A critical review of the causes of death among post-mortem toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths.

AIMS: To assess the trends in the number, mortality and the nature of forensic cases involving toxicological detection of buprenorphine or methadone among toxicological investigations performed in Paris from June 1997 to June 2002. DESIGN: Retrospective, 5 year study with review of premortem data, autopsy, police reports, hospital data, and post-mortem toxicological analyses. SETTING AND PARTICIPANTS: 34 forensic cases of buprenorphine and 35 forensic cases of methadone detection among 1600 toxicological investigations performed at the Laboratory of Toxicology in the Medical Examiner's Office in Paris. MEASUREMENTS AND RESULTS: Therapeutic, toxic or lethal drug concentrations were defined based upon the results of blood analyses and the published literature. Drug concentrations were cross-referenced with other available ante- and post-mortem data. Subsequently, we classified a 'clear responsibility', 'possible responsibility' or 'not causative' role for buprenorphine or methadone in the death process, or 'no explanation of death'. Buprenorphine and methadone can be regarded as being directly implicated in, respectively, four of 34 death cases (12%) and three of 35 death cases (9%), and their participation in the lethal process is strongly plausible in eight (buprenorphine) and 11 (methadone) additional deaths. CONCLUSIONS: Analysis of causes of death reveals the difficulties in determining the role of substitution drugs in the death process, as many other factors may be involved, including circumstances surrounding death, past history, differential selection of subjects into either substitution modality and concomitant intake of other drugs (especially benzodiazepines and neuroleptics). The potential for synergistic or additive actions by other isolated molecules-particularly opioids, benzodiazepines, other psychotropes and alcohol-must be also considered.