Testing strategy for the assessment of skin and eye irritation potential of chemicals, mainly in the scope of REACH.
The presentation is partially in Italian
Advances in in vitro testing for regulatory compliance in the chemical industryDr Carol Barker-Treasure
This presentation, originally shared at the Chemical Hazards Communication Society in 2018, discusses the regulatory status of in vitro safety assessments for REACH, CLP Regulation and Biocidal Products Regulation, gives an overview of current key methods for skin irritation, genotoxicity and acute toxicity, shows how finished mixtures or products can be tested, how to interpret results and barriers to progress towards an entirely animal-free testing strategy.
Advances in in vitro testing for regulatory compliance in the chemical industryDr Carol Barker-Treasure
This presentation, originally shared at the Chemical Hazards Communication Society in 2018, discusses the regulatory status of in vitro safety assessments for REACH, CLP Regulation and Biocidal Products Regulation, gives an overview of current key methods for skin irritation, genotoxicity and acute toxicity, shows how finished mixtures or products can be tested, how to interpret results and barriers to progress towards an entirely animal-free testing strategy.
Parenterals are the sterile preparation that is directly administered into the circulatory system avoiding the enteral route. And these preparation provide rapid onset of action that is why the administered preparation must be safe.
Stability problem arise from microbial contamination of these products so sterility and stability must be ensured for these preparations.
To ensure their sterility and stability, regulations regarding to quality control through pharmacopeial specifications has great importance.
NOVEL IPQCL AND FPQC TEST FOR OPTHALMIC PREPARATION AS PER IP, BP A...roshan telrandhe
Ophthalmic preparation are the sterile liquid or semisolid preparation meant to installation in to the eyes in the space between eye lids and eye ball .
These product must be sterile and are prepare under the same condition as that of parenteral preparation
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the quality control tests of parenteral as referred in the pharmacopoeia.
Thank you for reading. Hope it was of help to you.
UIPS,PU team
Endotoxin Testing is performed to ensure that injectable preparations and medical devices are free from pyrogens and safe for human use.
Pyrogens constitute a heterogeneous group of fever causing substances which comprise both microbial and non-microbial substances. The most potent and most widely known are the endotoxins or lipopolysaccharides (LPS), which are cell wall components of gram-negative bacteria. Gram-positive bacteria are also sources of pyrogens, in particular lipoteichoic acid (LTA), as are particles from yeasts and viruses. Non-microbial pyrogens often emanate from production environments. Small particles of packaging materials are a typical example.
Introduction to Quality Control Tests for Containers
Quality control test for glass container, Quality control test for plastic container
Presented by
P . Sudheer Kumar
Department of Pharmaceutical Analysis
Parenterals are the sterile preparation that is directly administered into the circulatory system avoiding the enteral route. And these preparation provide rapid onset of action that is why the administered preparation must be safe.
Stability problem arise from microbial contamination of these products so sterility and stability must be ensured for these preparations.
To ensure their sterility and stability, regulations regarding to quality control through pharmacopeial specifications has great importance.
NOVEL IPQCL AND FPQC TEST FOR OPTHALMIC PREPARATION AS PER IP, BP A...roshan telrandhe
Ophthalmic preparation are the sterile liquid or semisolid preparation meant to installation in to the eyes in the space between eye lids and eye ball .
These product must be sterile and are prepare under the same condition as that of parenteral preparation
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the quality control tests of parenteral as referred in the pharmacopoeia.
Thank you for reading. Hope it was of help to you.
UIPS,PU team
Endotoxin Testing is performed to ensure that injectable preparations and medical devices are free from pyrogens and safe for human use.
Pyrogens constitute a heterogeneous group of fever causing substances which comprise both microbial and non-microbial substances. The most potent and most widely known are the endotoxins or lipopolysaccharides (LPS), which are cell wall components of gram-negative bacteria. Gram-positive bacteria are also sources of pyrogens, in particular lipoteichoic acid (LTA), as are particles from yeasts and viruses. Non-microbial pyrogens often emanate from production environments. Small particles of packaging materials are a typical example.
Introduction to Quality Control Tests for Containers
Quality control test for glass container, Quality control test for plastic container
Presented by
P . Sudheer Kumar
Department of Pharmaceutical Analysis
The MTT assay and the MTS assay are colorimetric assays for measuring the activity of enzymes that reduce MTT or close dyes (XTT, MTS, WSTs) to formazan dyes, giving a purple color The main application allows to assess the viability (cell counting) and the proliferation of cells (cell culture assays)
It can also be used to determine cytotoxicity of potential medicinal agents and toxic materials, since those agents would stimulate or inhibit cell viability and growth
Dr Carol Treasure's presentation to Cosmetics Business Regulatory Summit 2019 about the results of a 2 year R&D programme into supporting mildness claims. Essential reading for beauty brands and formulators looking for new methods to detect subtle differences between ultra-mild ingredients and products.
OECD Webinar | OECD Alternatives to in vivo eye irritation testing - Chantra ...OECD Environment
On 27 September 2019, Anne Gourmelon of the Environment Directorate presented an overview of the various alternative test methods developed as OECD Test Guidelines and relevant guidance material to address eye irritation and serious eye damage for hazard classification of chemicals.
Safer cosmetics through in vitro science - XCellR8 presentation to Cosmetics ...Susie Lee-Kilgariff
How to develop safer cosmetics through in vitro science. This presentation was given to the Cosmetics Business Regulatory Summit 2018 by Dr Carol Treasure of XCellR8. It includes case studies of in vitro safety tests for skin sensitisation, advice on testing finished products and progress on a new model to predict mildness to skin.
Safer cosmetics through in vitro science. XCellR8 presentation to Cosmetics B...Dr Carol Barker-Treasure
In vitro methods for key aspects of cosmetic safety, including skin and eye irritation and skin sensitisation, are now in widespread use for regulatory safety testing around the world. In many cases, they are now established as the default rather than the alternative approach, so it’s timely to ask, “where next?”
In vitro technologies offer so much more than basic regulatory compliance, and when used wisely, can provide the competitive edge, from ensuring that formulations are fully optimised before proceeding to human in vivo studies, to providing detailed mechanistic data for claim support purposes. Importantly, they are a powerful tool to support the current move towards exposure-led safety assessments, enhancing the long-term safety of products and limiting the risk of post-market adverse events.
This presentation, first shared at the Cosmetics Business Regulatory Summit 2018, examines case studies from some early-adopters who are taking the application of in vitro data to the next level and considers the feasibility of applying exciting new techniques to the cosmetics of the future.
This presentation explains the different in vitro skin corrosion test methods available and how organisations might use them within their safety testing strategy. It discusses the strengths, weaknesses and limitations of Human Reconstructed Epidermis method (OECD TG 431), In Vitro Membrane Barrier (OECD TG 435) and Transcutaneous Electrical Resistance (OECD TG 430).
Cleaning validation a risk integrated approachSambhujyoti Das
A risk integrated Cleaning validation based on Acceptable Daily Exposure. The presentation is prepared on recent EMEA requirement of health based cleaning validation and contamination control for shared facilities. The practical cases are demonstrated in this presentation to better understanding on the subject.
Any suggestion is highly expected.
Visual Inspection of Parentetal Drug Products in Pharmaceutical Quality testingKarishmaRK
This presentation aims to elaborate the regulatory & compendial requirements of Visual inspection in Pharmaceutical parenteral manufacturing and the methodology of carrying out the testing.
MicroPRO, A Rapid Microbiology Method Based on Flow Cytometryguest32bcc5
The MicroPRO is a rapid microbiology method based on flow cytometry to detect presence/absence of bacteria, yeast and molds in pharmaceutical and cosmetic products in 24 hours. It can also detect these micro-organisms quantitatively in 5 minutes in water and swabs.
Read-across (RAx) is probably the most used strategy to waive new demanding in vivo tests for toxicological assessment of chemicals. It is based on the possibility to translate available information from well-characterized chemicals (source) to the substance for which there is a toxicological data gap (target). In spite of the widespread use, regulatory acceptance is still limited,
New Approach Methods (NAM) may be used to confirm chemical and toxicological similarities and to contribute to the reduction of the uncertainty.
Some slides are in Italian
Summary and description of the principle of investigative toxicology, that is the use of in vitro methods and microphysiological systems for a better prediction of the effect of a drug into the huamn organism
QIVIVE extrapolation requires a precise correlation between exposure and the effective chemical concentration at the site where the MIE occurs.
This work demonstrates that intracellular distribution is not ruled only by physical-chemical parameters, rather it is mainly regulated by specific biological-mediated mechanisms. Substances with
apparent chemical similarity may show different distribution profile, as shown by the intra-nuclear distribution of polyphenols. While our results derive from a limited number of substances applied to
one cell line, it is plausible that using different substances and/or different cell lines would also have shown that intracellular distribution is not directly related to physical-chemical parameters.
Chemical uptake should be specifically measured and simple extrapolations based on physical-chemical properties may provide misleading decision
EU REACH regulation changed the way to do chemical risk assessment. All chemicals marketed or manufactured in the EU must have its own dossier. Non standard methods including alternatives to animal testing are accepted.
Half Italian, half English
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
3. Slide 2 of 60
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Skin corrosion/irritation
in vivo in vitro
4. Slide 2 of 60
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5. I risultati negativi di un test in vitro
non sono accettati
dagli enti regolatori e
vanno obbligatoriamente sempre
confermati in vivo
6. 1.4. In vitro methods
…….
If the results obtained from the use of such in vitro methods do not indicate a
certain dangerous property, the relevant test shall nevertheless be carried out at
the appropriate tonnage level to confirm the negative result, unless testing is not
required in accordance with Annexes VII to X or the other rules in this Annex.
Such confirmation may be waived, if the following conditions are met:
(1) results are derived from an in vitro method whose scientific validity has been
established by a validation study, according to internationally agreed validation
principles;
(2) results are adequate for the purpose of classification and labelling and/or risk
assessment; and
(3) adequate and reliable documentation of the applied method is provided.
9. OECD 404:
Description of the evaluation
and testing strategy
• Step 1: Evaluation of existing human and animal data
• Step 2: Analysis of structure activity relationships
(SAR)
• Step 3: Physicochemical properties and
chemical reactivity
• Step 4: Dermal toxicity
• Step 5 and 6: Results from in vitro or ex vivo tests
• Step 6 and 7: In vivo test in rabbits
Slide 4 of 60
10. 1. Human data:
a. Occupational exposure
b. (consumer exposure)
2. Old animal data:
a. Impurities
b. GLP
Valutazione dei dati esistenti
11. Raccolta
di tutte le informazioni disponibili
• Step 3: Physicochemical properties and chemical
reactivity
• Step 4: Dermal toxicity (and other data)
14. Slide 5 of 60
Skin irritation Eye irritation
Not irritant Not irritant
Category 2 – H315
Causes skin irritation
Category 2 – H319
Causes serious eye irritation
Category 1 – H314
Causes severe skin burns
and eye damage
Category 1 – H318
Causes serious eye damage
Category 1A / 1B / 1C (Packing group I, II, III)1
Skin irritation Eye irritation
Not irritant Not irritant
Not irritant Category 2 - H319
Causes serious eye irritation
Category 2 – H315
Causes skin irritation
Category 2 - H319
Causes serious eye irritation
Category 2 – H315
Causes skin irritation
Category 1- H318
Causes serious eye damage
Category 1 – H314
Causes severe skin burns and eye damage
15. • I dati esistenti, le proprietà chimico-fisiche (sperimentali o stimate)
e lo studio SAR permettono una previsione preliminare della
possibilita per una sostanza di essere irritante o corrosiva per la
pelle e per gli occhi.
Slide 5 of 60
CORROSIVO? IRRITANTE?
TOP DOWN APPROACH
(irritation category)
BOTTOM UP APPROACH
Top Down e Bottom up
19. Thioanisole and similar substances:
Anisole
EUH066 (repeated exposure may cause skin dryness or cracking) Observed in an in vivo skin irritation study.
20. Thioanisole: mild irritant?
As described in the ECHA database
Guideline B46: In Vitro Skin Irritation:
Reconstructed Human Epidermis Model Test
GLP Study
Test substance: 10 µL undiluted
Duration of treatment:
15 minutes followed by washing and incubation for 42 hours at 37°C
Test animal: human
Species and strain, number of animals: not relevant
control animals: Other, negative control tissues treated with PBS;
positive control tissues treated with 5% SDS
Results: The relative mean tissue viability obtained after 15 minutes treatment
compared to the negative controls was 11% (< 50%)
H315: Causes skin irritation
21. Thioanisole: eye irritant?
As described in the ECHA database
OECD Guideline 437:
Bovine Corneal Opacity and Permeability (BCOP)
GLP Study
Test substance: 750 µL undiluted
Duration of treatment: 10 minutes
Test animal: Bovine
Species and strain, number of animals: not relevant
Results: IVS range from 2.9 and 4.8, average 3.9
H318: Causes eye irritation
I risultati del BCOP sono molto vicini alla non classificazione. Questo, in
teoria, dovrebbe indurre nuovi test di valutazione.
Tuttavia, questa sostanza è già classificata irritante per la pelle.
22. Thioanisole: corrosive?
As described in the ECHA database
Guideline B40: In Vitro Skin corrosion:
In vitro Skin Corrosion: Human Skin Model Test
GLP Study
Test substance: 50 µL undiluted
Duration of treatment: 3 minutes and 1 hour
Test animal: human
Species and strain: not relevant
number of animals: 4 tissues
Results: 3 minutes: viability 50%
1 hour: viability 59%
Not Corrosive, Classification H315 confirmed
23. Conclusions
Considerare le richieste regolatorie
Non esiste una strategia universale: anche la valutazione più semplice va adattata
alla sostanza (miscela) specifica e ad un determinato uso, nonchè ambito di
applicazione.
La valutazione di una sostanza va fatta in modo globale, e non endpoint per
endpoint
Le conclusioni sono una valutazione di tutti I dati disponibili, e non solo una mera
somma delle conclusioni dei singoli studi.
Un occhio anche ai costi e alla semplificazione dell'approccio
Ancora troppo basata sul giudizio degli esperti
Editor's Notes
The eChemPortal is an effort of the Organisation for Economic Co-operation and Development (OECD) in collaboration with the European Commission, the European Chemicals Agency, the United States, Canada, Japan, the International Council of Chemical Associations, the Business and Industry Advisory Committee, the World Health Organization's International Program on Chemical Safety, the United Nations Environment Programme on Chemicals and environmental non-governmental organisations.
Results obtained from suitable in vitro methods may indicate the presence of a certain dangerous property or may be important in relation to a mechanistic understanding, which may be important for the assessment. In this context, ‘suitable’ means sufficiently well developed according to internationally agreed test development criteria (e. g. the European Centre for the Validation of Alternative Methods (ECVAM)) criteria for the entry of a test into the prevalidation process). Depending on the potential risk, immediate confirmation requiring testing beyond the information
foreseen in Annexes VII or VIII or proposed confirmation requiring testing beyond the information foreseen in Annexes IX or X for the respective tonnage level may be necessary.
This report was vpublished by ECHA.
My complain is for missing dedicated pages in IUCLID
Even if I claim to apply OECD 404, I must follow those steps as explicitely requested by the guideline
Human tests (50-60s)
Study reports
Report from Occupational Doctor
(interview of workers) even if that is not useful for regulatory purposes, it is very important as it provides the idea of the real property of the substance
For the moment, it never happened to receive in vitro existing results. Let's see in the near future
Read across, but not only
there is usually no strict NOAEL or NOAEC identified in studies
on irritation, corrosion, or sensitisation. Therefore, in many, or even most cases, the lack of
NOAEL(C), dose-response or indication of potency will require that a more qualitative approach is
followed
No ex vivo
If there are "results" I've found them already
No TESTS, but test, because we want to perform only one
IVS: in vitro irritancy scores
Wikipedia is also useful
Under the test conditions of this study, Anisole was slightly irritating to the rabbit skin. The mean score over 24, 48 and 72 hours for individual animals was 1.7, 1.7 and 2.3 for erythema and 1.3, 1.3 and 1.3 for oedema. These cutaneous reactions were fully reversible within 7 days. Based on these results, no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).
In a primary dermal irritation study performed according to the OECD guideline No. 404 and in compliance with the GLP, three male
New Zealand rabbits were dermally exposed to 0.5 mL of undiluted Anisole for 4 hours under a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24 and 72 hours after removal of the dressing and then daily until day 15. The mean values of the scores for erythema and oedema were calculated for each animal.
Moderate reversible cutaneous reactions were observed after removal of the dressing applied during 4 hours. They consisted of erythema (scores of 1 to 3) and oedema (scores of 2). The mean score over 24, 48 and 72 hours for individual animals was 1.7, 1.7 and 2.3 for erythema and 1.3, 1.3 and 1.3 for oedema. By day 7, no erythema nor oedema were observed.
Between days 5 and 15, a dryness of the skin was observed at the treatment site of the three animals. No ulceration or necrosis was noted.
Under the test conditions of this study, Anisole is considered as slightly irritating to skin. However, according to the classification criteria laid down in Regulation (EC) 1272/2008 (CLP) and in Council Directive 67/548/EEC (and subsequent adaptations), the test item should not be classified as irritating to the skin.
This skin irritation study is classified as acceptable. It satisfies the guideline requirement for a skin irritation in the rabbit.
There is no clue for a possible severe irritation
There is no clue for a possible severe irritation
To conclude: mild result of the BCOP test supports the hypothesis that thioanisole is not corrosive
Skin irritant test makes further investigation on eye irritation useless
We are talking about an intermediate: it's neither a topical cream nor an eye drops
