Effects of adult exposure to bisphenol A on genes involved in the physiopathology of rat prefrontal cortex

Several neurological and behavioral dysfunctions have been reported in animals exposed to bisphenol A (BPA). However, little is known about the impact of adult exposure to BPA on brain physiopathology. Here, we focused on prefrontal cortex (PFC) of rats, because it is an important area for cognitive control, complex behaviors and is altered in many psychopathologies. Gamma-aminobutyric acid (GABA) and serotonin (5-HT) systems are essential for PFC function. Therefore, we examined the effects of adult exposure to BPA on 5α-Reductase (5α-R) and cytochrome P450 aromatase (P450arom), enzymes that synthesize GABAA receptor modulators, and tryptophan hydroxylase (Tph), the rate-limiting enzyme in 5-HT biosynthesis. To gain better understanding of BPA’s action in the adult PFC, 84 genes involved in neurotoxicity were also analysed. Adult male and female rats were subcutaneously injected for 4 days with 50 µg/kg/day, the current reference safe dose for BPA. mRNA and protein levels of 5α-R, P450arom and Tph were quantified by real-time RT-PCR and Western blot. Genes linked to neurotoxicity were analyzed by PCR-Array technology. Adult exposure to BPA increased both P450arom and Tph2 expression in PFC of male and female, but decreased 5α-R1 expression in female. Moreover, we identified 17 genes related to PFC functions such as synaptic plasticity and memory, as potential targets of BPA. Our results provided new insights on the molecular mechanisms underlying BPA action in the physiopathology of PFC, but also raise the question about the safety of short-term exposure to it in the adulthood.This research was supported by grants from Ministerio de Ciencia e Innovación (BFU2008-05340) and by the Junta de Andalucía (CTS202-Endocronología y Metabolismo)

A randomised controlled trial of intravenous dexmedetomidine added to dexamethasone for arthroscopic rotator cuff repair and duration of interscalene block.

Prolongation of peripheral nerve blockade by intravenous dexamethasone may be extended by intravenous dexmedetomidine. We randomly allocated 122 participants who had intravenous dexamethasone 0.15 mg.kg <sup>-1</sup> before interscalene brachial plexus block for day-case arthroscopic rotator cuff repair to intravenous saline (62 participants) or intravenous dexmedetomidine 1 μg.kg <sup>-1</sup> (60 participants). The primary outcome was time from block to first oral morphine intake during the first 48 postoperative hours. Fifty-nine participants reported taking oral morphine, 25/62 after placebo and 34/60 after dexmedetomidine, p = 0.10. The time to morphine intake was shorter after dexmedetomidine, hazard ratio (95%CI) 1.68 (1.00-2.82), p = 0.049. Median (IQR [range]) morphine doses were 0 (0-12.5 [0-50]) mg after control vs. 10 (0-30 [0-50]) after dexmedetomidine, a difference (95%CI) of 7 (0-10) mg, p = 0.056. There was no effect of dexmedetomidine on pain at rest or on movement. Intra-operative hypotension was recorded for 27/62 and 50/60 participants after placebo vs. dexmedetomidine, respectively, p < 0.001. Other outcomes were similar, including durations of sensory and motor block. In conclusion, dexmedetomidine shortened the time to oral morphine consumption after interscalene block combined with dexamethasone and caused intra-operative hypotension

SCCS Opinion on Silver Zinc Zeolite (CAS No. 130328-20- 0, EC No. 603-404-0) - SCCS/1650/23 - Preliminary Opinion

International audienceSCCS Opinion on Silver Zinc Zeolite (CAS No. 130328-20- 0, EC No. 603-404-0) - SCCS/1650/23 - Preliminary OpinionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C.L. Galli, E. Panteri , V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, N. Cabaton, A. Koutsodimou, W. Uter, N. von GoetzThe SCCS adopted this document at its plenary meeting on 21-22 March 202 (36 Pages)Mise en ligne : 4 Avril 2023https://health.ec.europa.eu/publications/silver-zinc-zeolite-cas-no-130328-20-0-ec-no-603-404-0_enhttps://health.ec.europa.eu/system/files/2023-04/sccs_o_270.pdfDetailsPublication date : 4 April 2023Author : Scientific Committee on Consumer Safety (SCCS)DescriptionSCCS members: U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads (Chairperson and Rapporteur), M. Dusinska, J. Ezendam, E. Gaffet, C.L. Galli, E. Panteri (Rapporteur), V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. WijnhovenSCCS external experts: N. Cabaton, A. Koutsodimou, W. Uter, N. von GoetzContact: [email protected] request from: European CommissionSCCS Number: SCCS/1650/23Adopted on: 21-22 March 2023Conclusion of the opinion: (1) In light of the data provided and taking under consideration the classification as Toxic for reproduction Cat. 2, does the SCCS consider Silver Zinc Zeolite safe when used as a preservative in cosmetic products according to the specifications and concentration limits provided in the dossier submission?The SCCS considers that Silver Zinc Zeolite (CAS No. 130328-20-0) incorporating a maximum silver content of 2.5% is safe in spray deodorant and powder foundation when used at the proposed concentration of 1%.(2) Alternatively, what is, according to the SCCS, the maximum concentration considered safe for use of Silver Zinc Zeolite as a preservative in cosmetic products? /(3) Does the SCCS have any further scientific concerns with regard to the use of Silver Zinc Zeolite in cosmetic products? /Keywords:SCCS, scientific opinion, silver zinc zeolite, Regulation 1223/2009, CAS No. 130328-20- 0, EC No. 603-404-0Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on silver zinc zeolite (CAS No. 130328-20- 0, EC No. 603-404-0), preliminary version of 21 March 2023, SCCS/1650/23

SCCS Opinion on Silver Zinc Zeolite (CAS No. 130328-20- 0, EC No. 603-404-0) - SCCS/1650/23 - Final Opinion

International audienceSCCS Opinion on Silver Zinc Zeolite (CAS No. 130328-20- 0, EC No. 603-404-0) - SCCS/1650/23 - Final OpinionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C.L. Galli, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, N. Cabaton, A. Koutsodimou, W. Uter, N. von GoetzThe SCCS adopted this document by written procedure on 21 December 2023 (37 pages)Mise en ligne : 22 Décembre 2023https://health.ec.europa.eu/publications/silver-zinc-zeolite-cas-no-130328-20-0-ec-no-603-404-0_enhttps://health.ec.europa.eu/document/download/a0d039be-384c-4b39-b069-9358dbfe5c7b_en?filename=sccs_o_270_final.pdfDetailsPublication date : 22 December 2023Author : Scientific Committee on Consumer Safety (SCCS)DescriptionSCCS members: U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads (Chairperson and Rapporteur), M. Dusinska, J. Ezendam, E. Gaffet, C.L. Galli, E. Panteri (Rapporteur), V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. WijnhovenSCCS external experts: E. Benfenati, N. Cabaton, E. Corsini, A. Koutsodimou, H. Louro, W. Uter, N. von GoetzContact: [email protected] request from: European CommissionSCCS Number: SCCS/1650/23Adopted on: 21 December 2023Conclusion of the opinion:(1) In light of the data provided and taking under consideration the classification as Toxic for reproduction Cat. 2, does the SCCS consider Silver Zinc Zeolite safe when used as a preservative in cosmetic products according to the specifications and concentration limits provided in the dossier submission?The SCCS considers that Silver Zinc Zeolite (CAS No. 130328-20-0) incorporating a maximum silver content of 2.5% is safe in spray deodorant and powder foundation when used at the proposed concentration of 1%.(2) Alternatively, what is, according to the SCCS, the maximum concentration considered safe for use of Silver Zinc Zeolite as a preservative in cosmetic products?/(3) Does the SCCS have any further scientific concerns with regard to the use of Silver Zinc Zeolite in cosmetic products?/Keywords:Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on silver zinc zeolite (CAS No. 130328-20- 0, EC No. 603-404-0), preliminary version of 21 March 2023, final version of 21 December 2023, SCCS/1650/23

SCCS OPINION on Sodium Bromothymol Blue (C186) (CAS No. 34722-90-2, EC No. 252-169-7) – SCCS/1645/22 - Preliminary Version

International audienceSCCS OPINION on Sodium Bromothymol Blue (C186) (CAS No. 34722-90-2, EC No. 252-169-7) – SCCS/1645/22 - Preliminary VersionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraad, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, N. Cabaton, A. Koutsodimou, W. Uter, N. von GoetzThe SCCS adopted this document at its plenary meeting on 24 – 25 October 2022 (47 pages)Mise en ligne le 28 Octobre 2022 https://health.ec.europa.eu/publications/sccs-sodium-bromothymol-blue-c186-cas-no-34722-90-2-ec-no-252-169-7_en DetailsPublication date : 28 October 2022Author : Scientific Committee on Consumer Safety (SCCS)DescriptionSCCS members: U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads (Chairperson), M. Dusinska, J. Ezendam (Rapporteur), E. Gaffet, C.L. Galli, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. WijnhovenSCCS external experts: N. Cabaton, A. Koutsodimou, W. Uter, N. von Goetz (Rapporteur)Contact:[email protected] request from: European CommissionSCCS Number: SCCS/1645/22Adopted on: 24-25 October 2022Conclusion of the opinion:In light of the data provided, does the SCCS consider Sodium Bromothymol Blue safe when used in non-oxidative hair colouring products up to a maximum on-head concentration of 0.5 %?Having considered the data provided, the SCCS is of the opinion that the safety of sodium bromothymol blue cannot be assessed because:- The Applicant used TTC approach to justify the safety of sodium bromothymol blue, whereas the SCCS estimated the SED to exceed the TTC threshold for Cramer class III substances (section 3.5).- the use of TTC on its own to justify the safety of the substances that are regulated under the EU Cosmetic Regulation is not sufficient to waive the information requirements on essential toxicological endpoints.2. Does the SCCS have any further scientific concerns with regard to the use of Sodium Bromothymol Blue in cosmetic products?- While the use of TTC is acceptable to justify the safety of impurities and cosmetic ingredients that are added to a final product at low concentrations, it is not acceptable for the substances that are regulated under the EU Cosmetic Regulation. For this, data from NAMs that are scientifically-accepted for the purpose, and/or other acceptable in vivo data on systemic toxicity, are required in an overall weight of evidence for safety.- The Applicant has provided data on two batches of sodium bromothymol blue. The SCCS has concerns about the impurities identified in one of the batches (Guanghua batch), as the levels of these impurities exceed the TTC threshold both individually and collectively. Therefore, the SCCS considers that the presence of these impurities is not safe, and a batch of sodium bromothymol blue matching the impurity profile of Guanghua batch cannot be recommended for use in marketed products.Keywords:SCCS, scientific opinion, sodium bromothymol blue, C186, hair dye, Regulation 1223/2009, CAS No. 34722-90-2, EC No. 252-169-7Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on sodium bromothymol blue (C186) (CAS No. 34722-90-2, EC No. 252-169-7), preliminary version of 24-25 October 2022, SCCS/1645/2

SCCS OPINION on salicylic acid (CAS No. 69-72-7, EC No. 200-712-3) - SCCS/1646/22 - Preliminary Opinion

International audienceSCCS OPINION on salicylic acid (CAS No. 69-72-7, EC No. 200-712-3) - SCCS/1646/22 - Preliminary OpinionU. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, N. Cabaton, A. Koutsodimou, W. Uter, N. von GoetzThe SCCS adopted this document by writen procedure on 14 Décember 2022 (91 Pages)Mise en ligne 15 December 2022https://health.ec.europa.eu/publications/salicylic-acid-cas-no-69-72-7-ec-no-200-712-3_enhttps://health.ec.europa.eu/system/files/2022-12/sccs_o_268.pdfDetailsPublication date : 15 December 2022Author : Scientific Committee on Consumer Safety (SCCS)DescriptionSCCS members: U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads (Chairperson), M. Dusinska, J. Ezendam, E. Gaffet, C.L. Galli, E. Panteri (Rapporteur), V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. WijnhovenSCCS external experts: N. Cabaton, A. Koutsodimou (Rapporteur), W. Uter, N. von GoetzContact:[email protected] request from: European CommissionSCCS Number: SCCS/1646/22Adopted on: 14 December 2022Conclusion of the opinion:(1) In light of the data provided and taking under consideration the concerns related to potential endocrine disrupting properties of Salicylic acid,a) does the SCCS consider Salicylic acid safe when used as a preservative in cosmetic products up to a maximum concentration of 0.5%?Based on the safety assessment carried out in consideration of all available information, including the potential endocrine effects, the SCCS is of the opinion that:- the use of salicylic acid as a preservative up to a maximum concentration of 0.5% is safe in either oral or dermal products, but not safe in oral and dermal products together for adults, adolescents, and children (>3 years).- the provided information shows that salicylic acid is an eye irritant with the potential to cause serious damage to the eye. - this Opinion is not applicable to any sprayable product that may lead to exposure of end-user’s lungs by inhalation. Since the Cosmetic Regulation does not allow the use of salicylic acid in products for children under 3 years of age, this age category has not been considered in this Opinion.b) does the SCCS consider Salicylic acid safe when used in cosmetic for purposes other than inhibiting the development of micro-organisms at a concentration up to:i. 3.0% for the cosmetic rinse-off hair products, ii. 2.0% for other products except body lotion, eye shadow, mascara, eyeliner, lipstick, non-spray deodorant, andiii. 0.5% for body lotion, eye shadow, mascara, eyeliner, lipstick, oral products and non-spray deodorantThe SCCS assessment has shown that: - the use of salicylic acid as a restricted ingredient for purposes other than inhibiting the development of micro-organisms at the concentrations specified in Annex III/98 of the Cosmetic Regulation (EC) No. 1223/2009 is safe in either oral or dermal products, but not safe in oral and dermal products together for adults, adolescents and children (>3 years). - this Opinion is not applicable to any sprayable product that may lead to exposure of end-user’s lungs by inhalation. Since the Cosmetic Regulation does not allow the use of salicylic acid in products for children under 3 years of age, this age category has not been considered in this Opinion.(2) Alternatively, what is according to the SCCS the maximum concentration considered safe for use of Salicylic acid in cosmetic products? For safe use of salicylic acid in cosmetic products, the Applicant may consider either reducing the maximum use levels of salicylic acid in one or more product categories, and/or excluding the use for one or more product categories. (3) Does the SCCS have any further scientific concerns with regard to the use of Salicylic acid in cosmetic products? The conclusions of this Opinion refer only to Salicylic Acid as a cosmetic ingredient and not to other salicylates or salicylic acid salts.Keywords:SCCS, scientific opinion, salicylic acid, Regulation 1223/2009, CAS No. 69-72-7, EC No. 200-712-3)Opinion to be cited as:SCCS (Scientific Committee on Consumer Safety), Opinion on salicylic acid (CAS No. 69-72-7, EC No. 200-712-3), preliminary version of 14 December 2022, SCCS/1646/22