scholarly journals Scientific discrepancies in European regulatory proposals on endocrine disruptors—REACH regulation quo vadis?

2021 ◽  
Author(s):  
Andreas Natsch
Keyword(s):  
Low Dose ◽  
Endocrine Disrupting Chemicals ◽  
Test Methods ◽  
Consumer Products ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Animal Testing ◽  
European Regulatory ◽  
Quo Vadis

AbstractThe EU chemical strategy for sustainability places a high focus on endocrine-disrupting chemicals (ED), the importance of their identification with increased testing and a ban in consumer products by a generic approach. It is assumed that for ED no threshold and hence no safe dose exists, leading to this generic approach. This view appears to be linked to the claim that for ED ‘low-dose non-monotonic dose response’ (low-dose NMDR) effects are observed. Without this hypothesis, there are no scientific reasons why classical risk assessment cannot be applied to the ED mode-of-action. Thus, whether for ED low-dose NMDR effects are considered a reproducible scientific fact by European authorities is Gretchen’s question in this politicized field. Recent documents by the SCCS, EFSA and ECHA reviewed herein illustrate the diverging views within European scientific bodies on this issue. Furthermore, ED researchers never replicated findings on low-dose NMDR in blinded inter-laboratory experiments and the CLARITY-BPA core studies could not find evidence for reproducible NMDR for BPA. ECHA proposes a battery of in vitro tests to test all chemicals for ED properties. However, these tests were never validated for relevance and their high positivity rate could lead to increased follow-up animal testing. Based on (i) lack of reproducibility data for low-dose NMDR, (ii) diverging views within European authorities on NMDR and (iii) lack of fully validated in vitro test methods it might be premature to fast-track the wide-ranging changes in the regulatory landscape proposed by the authorities ultimately leading to drastically increased animal testing.

Ocular Safety: A Silent (In Vitro) Success Story

2002 ◽  
Vol 30 (2_suppl) ◽  
pp. 69-74 ◽  
Author(s):  
Rodger D. Curren ◽  
John W. Harbell
Keyword(s):  
Raw Materials ◽  
Test Methods ◽  
In Vitro Tests ◽  
High Dose ◽  
Animal Testing ◽  
Animal Test ◽  
Ocular Irritation ◽  
Irritation Test ◽  
Dose Levels

Ocular irritation testing has been one of the animal test methods most criticised by animal welfare advocates. Additional criticism has arisen from within the scientific community, based on the variability of the animal test results and the questionable relevance of the extremely high dose levels employed. As a result, the Draize eye irritation test has been one of the main targets for in vitro replacement. Despite extensive efforts, however, there is still no in vitro method that is fully validated as a regulatory replacement. In spite of this, many individual companies are using diverse in vitro ocular irritation tests to gain important safety and efficacy information about their products and raw materials, eliminating the need for animal testing in the process. This is done in a safe fashion by applying intelligent testing paradigms. ECVAM has played a major role in this success, through its many programmes that have emphasised the importance of understanding the true toxicological need, and then using in vitro tests to provide that information. Thus, even in the absence of a successfully validated regulatory assay, the desired result of reducing animal testing is being met.

In Vitro Toxicology and the Test Guidelines

1996 ◽  
Vol 24 (3) ◽  
pp. 435-438
Author(s):  
Kimmo Louekari
Keyword(s):  
Cost Effective ◽  
Test Methods ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
Effective Manner ◽  
Genotoxic Carcinogens ◽  
Vitro Test

Ethical, economical and scientific considerations should encourage the development of alternative and in vitro test methods. Before their adoption, in vitro methods need to be validated and scientifically justified. Demand for rigorous validation schemes for in vitro tests must be emphasised, even more than in the case of in vivo tests. The OECD has adopted in vitro guidelines for testing genotoxicity; several endpoints and mechanisms can be studied in a cost-effective manner in vitro. Similar advantages could be afforded if acute irritation and corrosion, as well as the non-genotoxic carcinogenic effects of chemicals, could be studied in vitro. Evaluation of the validation status of various methods used to study non-genotoxic carcinogens was begun by the Nordic Working Group on In Vitro Methods for Non-genotoxic Mechanisms in 1996. In some established OECD test guidelines (for example, the dermal irritation/corrosion test), there is already room for the application of in vitro methods which have not been formally validated. In January 1996, the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods set the basis for internationally acceptable principles to be followed in the validation of in vitro test methods.

The Application of in Vitro Models to Research on Demineralization and Remineralization of the Teeth

1995 ◽  
Vol 9 (3) ◽  
pp. 175-193 ◽  
Author(s):  
D.J. White
Keyword(s):  
Analytical Techniques ◽  
Test Methods ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
In Vitro Testing ◽  
In Vitro Test ◽  
Dental Tissues ◽  
Testing Protocols

Progress in in vivo and in situ experimentation has led many researchers to speculate as to the relevance and importance of in vitro testing protocols in caries research. A Medline/Biosis search for the present review revealed well over 300 citations (since 1989) documenting in vitro tests associated with caries research on mineralization and fluoride reactivity. The present survey documents these recent applications of in vitro test methods in both mechanistic and 'profile'* caries research. In mechanistic studies, in vitro protocols over the past five years have made possible detailed studies of dynamics occurring in mineral loss and gain from dental tissues and the reaction dynamics associated with fluoride anticaries activity. Similarly, in profile applications, in vitro protocols make possible the inexpensive and rapid-yet sensitive-assessment of F anticaries efficacy within fluoride-active systems, and these tests represent a key component of product activity confirmation. The ability to carry out single variable experiments under highly controlled conditions remains a key advantage in in vitro experimentation, and will likely drive even further utilization, as advances continue in physical-chemical and analytical techniques for substrate analysis in these protocols. Despite their advantages, in vitro testing protocols have significant limitations, most particularly related to their inability to simulate the complex biological processes involved in caries.

The Use of Biomarkers as Alternatives to Current Animal Tests on Food Chemicals

1998 ◽  
Vol 26 (4) ◽  
pp. 421-480
Author(s):  
Krys Bottrill
Keyword(s):  
Animal Studies ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
In Vitro Test ◽  
Animal Testing ◽  
Dietary Biomarkers ◽  
Recent Developments ◽  
Mechanistic Basis ◽  
The Three Rs

Recent developments in biomarkers relating to the interrelationship of diet, disease and health were surveyed. Most emphasis was placed on biomarkers of deleterious effects, since these are of greatest relevance to the subject of this review. The area of greatest activity was found to be that relating to biomarkers of mutagenic, genotoxic and carcinogenic effects. This is also one of the major areas of concern in considerations of the beneficial and deleterious effects of dietary components, and also the area in which regulatory testing requires studies of the longest duration. A degree of progress has also been made in the identification and development of biomarkers relating to certain classes of target organ toxicity. Biomarkers for other types of toxicity, such as immunotoxicity, neurotoxicity, reproductive toxicity and developmental toxicity, are less developed, and further investigation in these areas is required before a comprehensive biomarker strategy can be established. A criticism that recurs constantly in the biomarker literature is the lack of standardisation in the methods used, and the lack of reference standards for the purposes of validation and quality control. It is encouraging to note the growing acknowledgement of the need for validation of biomarkers and biomarker assays. Some validation studies have already been initiated. This review puts forward proposals for criteria to be used in biomarker validation. More discussion on this subject is required. It is concluded that the use of biomarkers can, in some cases, facilitate the implementation of the Three Rs with respect to the testing of food chemicals and studies on the effects of diet on health. The greatest potential is seen to be in the refinement of animal testing, in which biomarkers could serve as early and sensitive endpoints, in order to reduce the duration of the studies and also reduce the number of animals required. Biomarkers could also contribute to establishing a mechanistic basis for in vitro test systems and to facilitating their validation and acceptance. Finally, the increased information that could result from the incorporation of biomarker determinations into population studies could reduce the need for supplementary animal studies. This review makes a number of recommendations concerning the prioritisation of future activities on dietary biomarkers in relation to the Three Rs. It is emphasised, however, that further discussions will be required among toxicologists, epidemiologists and others researching the relationship between diet and health.

Animal Models and Alternatives in the Quality Control of Vaccines: Are In Vitro Methods or In Vivo Methods the Scientific Equivalent of the Emperor's New Clothes?

1995 ◽  
Vol 23 (1) ◽  
pp. 61-73
Author(s):  
Coenraad Hendriksen ◽  
Johan van der Gun
Keyword(s):  
Quality Control ◽  
Test Methods ◽  
In Vitro Test ◽  
Large Numbers ◽  
Alternative Approach ◽  
Inactivated Vaccines ◽  
Vitro Test

In the quality control of vaccine batches, the potency testing of inactivated vaccines is one of the areas requiring very large numbers of animals, which usually suffer significant distress as a result of the experimental procedures employed. This article deals with the potency testing of diphtheria and tetanus toxoids, two vaccines which are used extensively throughout the world. The relevance of the potency test prescribed by the European Pharmacopoeia monographs is questioned. The validity of the potency test as a model for the human response, the ability of the test to be standardised, and the relevance of the test in relation to the quality of the product are discussed. It is concluded that the potency test has only limited predictive value for the antitoxin responses to be expected in recipients of these toxoids. An alternative approach for estimating the potency of toxoid batches is discussed, in which a distinction is made between estimation of the immunogenic potency of the first few batches obtained from a seed lot and monitoring the consistency of the quality of subsequent batches. The use of animals is limited to the first few batches. Monitoring the consistency of the quality of subsequent batches is based on in vitro test methods. Factors which hamper the introduction and acceptance of the alternative approach are considered. Finally, proposals are made for replacement, reduction and/or refinement (the Three Rs) in the use of animals in the routine potency testing of toxoids.

scholarly journals Recombinant in vitro test T-SPOT.TB as a screening method for early diagnosis of tuberculosis infection

2020 ◽  
Vol 98 (4) ◽  
pp. 48-52
Author(s):  
E. P. Eremenko ◽  
E. A. Borodulina ◽  
I. A. Sergeeva ◽  
D. A. Kudlay ◽  
B. E. Borodulin
Keyword(s):  
Screening Method ◽  
Latent Tuberculosis ◽  
Tuberculosis Infection ◽  
Mantoux Test ◽  
Skin Tests ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Healthy Children ◽  
Vitro Test

In addition to standard skin tests (Mantoux test with 2 TU PPD-L and diaskintest) for the diagnosis of tuberculosis infection, in vitro tests are used. One of these tests is T-SPOT.TB being more widely used in recent years.The objective: to evaluate the effectiveness of T-SPOT.TB test for early detection of tuberculosis infection in children and adolescents in Samara Region.Subjects and methods. From 2016 to 2019, results of T-SPOT.TB tests performed in 596 children aged 2 to 17 years inclusive were analyzed; those children had no immunodiagnosis of tuberculosis infection using skin tests since their parents refused to have it.Results. It was found out that the major reason for refusing skin tests was the “fear” of visiting a TB dispensary if the result had been positive — 38.43% (n = 229). The latent tuberculosis infection according to the results of T-SPOT.TB among children with concomitant pathology made 2.6%, among healthy children – 0.7%.Conclusion. T-SPOT.TB test may be used as an alternative method for diagnosis of tuberculosis infection, should the parent refuse to have skin tests. In children with concomitant pathology, T-SPOT.TB test can serve as a leading method for immunodiagnosis of tuberculosis.The authors state that they have no conflict of interests.

scholarly journals UJI DAYAHAMBAT EUGENOL DARI DAUN CENGKEH HASIL FRAKSINASI TERHADAP PERTUMBUHAN JAMUR PATOGEN Fusarium oxysporum f.sp. Cubense Eugenol Inhibitory Test From Clove Leaf Fractionation Of Fungal Patogen Growth Fusarium oxysporum f.sp. cubense

AgriPeat ◽  
2019 ◽  
Vol 20 (02) ◽  
pp. 107-113
Author(s):  
Admin Journal
Keyword(s):  
Fusarium Oxysporum ◽  
Vacuum Distillation ◽  
Pathogenic Fungus ◽  
Lethal Concentration ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Microsoft Excel ◽  
Vitro Test

ABSTRACTThis study aims to determine the inhibition of eugenol derived from fractionation clove leaf essentialoils (CLEO) on the growth of pathogenic fungus Fusarium oxysporum f. sp. cubense (Foc) and LC50(Lethal Concentration 50). This research was in vitro, started with purification of clove leaf essentialoil, fractionation by vacuum distillation and bioassay. In vitro tests include exploration of minimuminhibition and preventability tests. Data were analyzed with Microsoft Excel 2010 program. Theresults of minimum inhibition showed at 218,75 ppm concentration of each level was able to inhibitthe growth of Foc fungi. The minimum inhibition exploration was carried out at 218,75 ppm, 109,38ppm, 54,69 ppm and 27,34 ppm. Exploration results showed that fractionated CLEO has been able toinhibit the growth of Foc fungi at 27,34 ppm in the amount of 15,60%. This concentration is used asthe lowest concentration in the inhibitory test. Furthermore, the inhibitory test was carried out startingat the highest concentration of 218,75 ppm, 109,38 ppm, 54,69 ppm and 27,34 ppm. Observationswere made for 7 days after inoculation (DAI). The results showed the best inhibition was at aconcentration of 218,75 ppm at 90,70% and LC50 at 11.17 µL.Keywords: CLEO, fractionation, Foc, in vitro test and LC50

Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 91-109 ◽  
Author(s):  
Robert Combes ◽  
Christina Grindon ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Decision Tree ◽  
Systemic Toxicity ◽  
Toxicity Tests ◽  
In Vitro Tests ◽  
The European Union ◽  
Animal Testing ◽  
Pbpk Modelling ◽  
Joint Research Project ◽  
The Eu

Liverpool John Moores University and FRAME conducted a joint research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews in vitro tests based on basal cytotoxicity and target organ toxicity, along with QSAR models and expert systems available for this endpoint. The use of PBPK modelling for the prediction of ADME properties is also discussed. These tests are then incorporated into a decision-tree style, integrated testing strategy, which also includes the use of refined in vivo acute toxicity tests, as a last resort. The implementation of the strategy is intended to minimise the use of animals in the testing of acute systemic toxicity and toxicokinetics, whilst satisfying the scientific and logistical demands of the EU REACH legislation.

Animal, human, and in vitro test methods for predicting skin irritation

2012 ◽  
pp. 268-273
Author(s):  
Yakir S. Levin ◽  
Cheryl L. Levin ◽  
Howard I. Maibach
Keyword(s):  
Skin Irritation ◽  
Test Methods ◽  
In Vitro Test ◽  
Vitro Test
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