Screening of repeated dose toxicity data in safety evaluation reports of cosmetic ingredients issued by the Scientific Committee on Consumer Safety between 2009 and 2019

Abstract A focal point in the safety evaluation of cosmetic ingredients includes oral repeated dose toxicity testing, which is intended to address the most complex human endpoints. Seven years after the full implementation of the animal testing ban for cosmetic ingredients in the EU, there are still no alternative methods available capable of fully replacing oral repeated dose toxicity testing. Until this issue is resolved, the development of new cosmetic ingredients remains seriously hampered. The present paper describes a thorough screening of the oral repeated dose toxicity data included in safety evaluation reports of cosmetic ingredients addressed in the Annexes of the Cosmetics Regulation (EC) No 1223/2009, issued by the Scientific Committee on Consumer Safety between 2009 and 2019. The liver and the haematological system were identified as the potentially most frequently affected organs upon oral administration of cosmetic ingredients to animals. Evaluation of altered biochemical, morphological, and histopathological parameters related to hepatotoxicity indicated that the most recurrent events are liver weight changes, elevated liver enzymes, and alterations in serum cholesterol and bilirubin levels. Combined listing of affected parameters associated with steatosis and cholestasis indicated the possible occurrence of cholestasis, provoked by a limited number of cosmetic ingredients. The most frequently affected parameters related to the haematological system were indicative of anaemia. An in-depth analysis allowed characterisation of both regenerative and non-regenerative anaemia, pointing to direct and indirect haematotoxicity, respectively. The results presented in this study call for prioritisation of research targeted towards the development of new approach methodologies fit for animal-free repeated dose toxicity evaluation of cosmetic ingredients.

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Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients

Archives of Toxicology ◽

10.1007/s00204-011-0769-z ◽

2011 ◽

Vol 86 (3) ◽

pp. 405-412 ◽

Cited By ~ 20

Author(s):

Mathieu Vinken ◽

Marleen Pauwels ◽

Gamze Ates ◽

Manon Vivier ◽

Tamara Vanhaecke ◽

...

Keyword(s):

Repeated Dose ◽

Toxicity Data ◽

Cosmetic Ingredients ◽

Repeated Dose Toxicity

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Alternative Methods to Animal Testing for the Safety Evaluation of Cosmetic Ingredients: An Overview

Cosmetics ◽

10.3390/cosmetics4030030 ◽

2017 ◽

Vol 4 (3) ◽

pp. 30 ◽

Cited By ~ 1

Author(s):

◽

Keyword(s):

Safety Evaluation ◽

Alternative Methods ◽

Animal Testing ◽

Cosmetic Ingredients

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Preclinical Safety Evaluation of Intravenously Administered SAL200 Containing the Recombinant Phage Endolysin SAL-1 as a Pharmaceutical Ingredient

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02232-13 ◽

2014 ◽

Vol 58 (4) ◽

pp. 2084-2088 ◽

Cited By ~ 39

Author(s):

Soo Youn Jun ◽

Gi Mo Jung ◽

Seong Jun Yoon ◽

Yun-Jaie Choi ◽

Woo Suk Koh ◽

...

Keyword(s):

Clinical Trial ◽

Phase I ◽

Evaluation Studies ◽

Clinical Signs ◽

Safety Evaluation ◽

Phase I Clinical Trial ◽

Repeated Dose ◽

Daily Injection ◽

Toxicity Studies ◽

Repeated Dose Toxicity

ABSTRACTPhage endolysins have received increasing attention as potent antibacterial agents. However, although safety evaluation is a prerequisite for the drug development process, a good laboratory practice (GLP)-compliant safety evaluation has not been reported for phage endolysins. A safety evaluation of intravenously administered SAL200 (containing phage endolysin SAL-1) was conducted according to GLP standards. No animals died in any of the safety evaluation studies. In general toxicity studies, intravenously administered SAL200 showed no sign of toxicity in rodent single- and repeated-dose toxicity studies. In the dog repeated-dose toxicity test, there were no abnormal findings, with the exception of transient abnormal clinical signs that were observed in some dogs when daily injection of SAL200 was continued for more than 1 week. In safety pharmacology studies, there were also no signs of toxicity in the central nervous and respiratory system function tests. In the cardiovascular function test, there were no abnormal findings in all tested dogs after the first and second administrations, but transient abnormalities were observed after the third and fourth administrations (2 or 3 weeks after the initial administration). All abnormal findings observed in these safety evaluation studies were slight to mild, were apparent only transiently after injection, and resolved quickly. The safety evaluation results for SAL200 support the implementation of an exploratory phase I clinical trial and underscore the potential of SAL200 as a new drug. We have designed an appropriate phase I clinical trial based on the results of this study.

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Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties

Frontiers in Medicine ◽

10.3389/fmed.2016.00045 ◽

2016 ◽

Vol 3 ◽

Cited By ~ 11

Author(s):

Jan Willem van der Laan ◽

Wenny H. W. Buitenhuis ◽

Laura Wagenaar ◽

Ans E. M. F. Soffers ◽

Eugene P. van Someren ◽

...

Keyword(s):

Repeated Dose ◽

Pharmacological Properties ◽

Toxicity Data ◽

Carcinogenic Potential ◽

Repeated Dose Toxicity

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The safety evaluation of phycocyanin-enriched Galdieria sulphuraria extract using 90-day toxicity study in rats and in vitro genotoxicity studies

Toxicology Research and Application ◽

10.1177/2397847320929991 ◽

2020 ◽

Vol 4 ◽

pp. 239784732092999

Author(s):

Axel Athané ◽

Julien Demol ◽

Sandra Brosset-Vincent ◽

Corinne Aguenou ◽

Stéphanie Krisa ◽

...

Keyword(s):

Adverse Effect ◽

Safety Evaluation ◽

Micronucleus Assay ◽

Industrial Applications ◽

Toxicity Study ◽

Repeated Dose ◽

Galdieria Sulphuraria ◽

Food Ingredient ◽

Repeated Dose Toxicity

The microalgae Galdieria sulphuraria, which belong to the class of cyanidiophyceae, are thermostable at temperatures up to 55°C and have successfully been cultivated under controlled fermentation conditions to produce a protein-rich biomass from which a natural blue proteinaceous pigment, C-phycocyanin can be isolated. The C-phycocyanin has potential use as a colour additive and as a dietary supplement. This C-phycocyanin is resistant to acidic pH down to 2.75, in contrast to the one from Spirulina, which is already used as a colouring agent in agri-food applications. To further promote its use for industrial applications, we report, here, the results of a safety evaluation on a G. sulphuraria extract enriched to 33% C-phycocyanin. This was conducted in a 90-day repeated dose toxicity study in rats at doses from 250 to 4000 mg/kg body weight/day, in bacterial reversal mutation test at doses from 312.5 to 5000 µg/plate and in micronucleus assay at doses from 500 to 2000 µg/mL. Overall, our results indicated that the C-phycocyanin extract from G. sulphuraria did not exert any noteworthy adverse effect of toxicological significance in any of the system used for its safety evaluation, even if some minor changes were observed. According to the 90-day repeated dose toxicity study, no observed adverse effect level of 4000 mg/kg/day could be estimated. In conclusion, this study supports the safety of soluble fraction enriched with C-phycocyanin from G. sulphuraria for its use as food ingredient or supplement.

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