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ALGIN YAPAR et al. Universal Journal of Pharmaceutical Research
ISSN: 2456-8058 35 CODEN (USA): UJPRA3
Available online on 15.11.2019 at http://ujpr.org
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Volume 4, Issue 5, 2019
REVIEW ARTICLE
AN OVERVIEW ON CURRENT REGULATION AND EVALUATION OF
BIOCIDAL PRODUCTS
Aslı ŞAHİNER1, Evren ALGIN YAPAR2*
1Department of Biology, Faculty of Science, Ege University, 35100 Bornova, Izmir, Turkey.
2Department of Analysis and Control Laboratories, Turkish Medicines and Medical Devices Agency, 06100 Sıhhiye, Ankara,
Turkey.
ABSTRACT
A biocidal product is a substance or mixture prepared to limit, destroy, neutralize or control the effects of a harmful
microorganism, plants and animals. The active substance in a biocidal product can be a natural oil or extract, a chemical substance
or a microorganism, virus or fungus. Biocides consist of four main groups: disinfectants, preservatives (wood, paint, etc.), pest
control and other type of biocidal products. A biocidal substance can also be added to a product to make the product itself into a
biocidal product. These products range from disinfectants, hand sanitizers, preservatives, insect repellents, to rodenticides and
insecticides and are used to protect humans, animals, materials and articles by controlling the intended target organism by a
chemical or biological action. To make sure the use of biocidal products do not have unacceptable risks for people, animals and the
environment, they are regulated to control their marketing, sale and use. In the current study biocidal products have been
overviewed in the scope of current European Union regulations, product types and conformity tests.
Keywords: Biocidal products, conformity tests for biocidal products, disinfectants.
Article Info: Received 18 September 2019; Revised 9 October; Accepted 7 November, Available online 15 November 2019
Cite this article-
ŞAHİNER A, ALGIN YAPAR E. An overview on current regulation and evaluation of biocidal products.
Universal Journal of Pharmaceutical Research 2019; 4(5): 35-39.
DOI: https://doi.org/10.22270/ujpr.v4i5.315
Address for Correspondence:
Assos. Prof. Evren ALGIN YAPAR, Department of Analysis and Control Laboratories, Turkish Medicines and Medical Devices
Agency, 06100 Sıhhiye, Ankara, Turkey. Tel: +90 312 565 53 70, E-mail: evrenalgin@yahoo.com
INTRODUCTION
According to the Biocidal Products Regulation [BPR,
Reg. (EU) 528/2012] of European Commission (EC), a
biocidal product is defined as a product or substance
intended to eliminate, control or prevent the effects of
harmful organisms for human and animal health and to
control organisms harmful to natural or manufactured
materials1. The use of chemical biocides is a
fundamental protection in the prevention and control of
microbial growth in medical, veterinary, domestic and
industrial environments2. Biocides are used a great
extent in the healthcare environment for the
disinfection of equipments, surfaces, water, and for
antisepsis of skin and wound. Besides biocides are used
for the preservation of pharmaceuticals and
sterilization of medical devices3. In the 20th century,
the development of cationic biocides such as
quaternary ammonium compounds, biguanides,
aldehydes, peroxigens and phenolics had been an
enormous increase in the number of active compounds
used for disinfection, sterilization and preservation4.
Biocides are the main armoury in the disinfection
programme of food industry to control pathogenic and
spoilage micro‐organisms5. Biocidal products also
constitute the antimicrobial component of
nanomaterials used in food packaging in recent years6.
Preservatives are an important part of biocides and
used to protect industrial products, cosmetics, metal
and wood materials, textile products from microbial
spoilage. Isothiazolinone biocides are broadly used in
various industrial applications for the control of
microbial growth.
Between the biocides, 5-chloro-2-methyl-4isothiazolin-
3-one (CMIT), 2-methyl-4-isothiazolin-3-one (MIT), 1,
2-Benzisothiazolin-3-one (BIT),4, 5-dichloro-2-noctyl-
4-isothiazolin-3-one (DCOIT) are the most commonly
used as preservative active substance7. Effective and
proper use of insecticide and rodenticide group
biocides is also important for the protection of human
and environmental health. Permethrin, tetramethrin,
cypermethrin are commonly used insecticide active
substance for product type8.
Misuse of biocidal products brings about some
problems such as resistance development and toxicity.
The spreading usage of products containing low
concentrations of commonly used biocides have raised
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ISSN: 2456-8058 36 CODEN (USA): UJPRA3
some concerns about the possible development of
microbial resistance. Laboratory studies have
demonstrated that bacteria can become resistant to a
biocide, and that resistant bacteria can develop cross-
resistance to other biocides and antibiotics9. High
concentrations of biocides generally have toxic effects
not only for humans but also for the environment.
Therefore, a legal guideline for environmental risk
evaluation for biocidal products is being prepared10.
The toxicity of some biocides associated with
dermatitis, occupational asthma and irritation has been
reported11,12,13.
The use of commercially available biocidal products is
regulated according to the EU Biocidal Products
Regulation. In this study biocidal products have been
overviewed in the scope of current EU regulations,
product types and conformity tests.
RULES FOR BIOCIDAL PRODUCTS
The aim of the Biocidal Products Regulation (Reg.
(EU) 528/2012) is to determine the rules for the
production and the use of biocidal products, as well as
to provide a protection from health and environmental
risks. The main rule is that biocidal products must be
authorized before they are placed on the market. This
regulation applies to biocidal products containing or
forming one or more active substances.
A biocidal product is a substance or mixture designed
to limit, destroy, neutralize or control the effects of a
harmful organism. All biocidal products contain one or
more active substances. The active ingredients give the
product the desired biocidal properties. Active
substances used in biocidal products must be
authorised within the EU before they can be put on the
market. Before the approval of an active substance, its
effect on the environment and human health is
assessed. To ensure legal certainty, Active substances
from the Union list approved for use in biocidal
products has been established. In order to market an
active substance that has not been previously
authorized or under examination, It must be applied for
authorization to The European Chemical Agency
(ECHA)14.
The following conditions must be met in order to
license a biocidal product:
The active substances must be approved for the
type of product concerned and the conditions
specified for these active substances must be met.
It must be sufficiently effective.
The biocidal product must not produce
unacceptable resistance or cross-resistance on target
organisms. There should be no unacceptable effects
such as unnecessary pain and suffering for
vertebrates.
The biocidal product or its residues must not have
an unacceptable effect on food and feed, directly or
indirectly.
The biocidal product or its residues must not have an
unacceptable effect on the environment, groundwater,
surface water, drinking water, soil and air.
It should not have undesirable effects on non-target
organisms.
It should not have undesirable effects on the
ecosystem and biodiversity.
The chemical identity, quantities and technical
equivalence of the active and inactive substances in
the biocidal product should be determined.
Toxicological and ecotoxicological information
should be provided where appropriate.
PRODUCT TYPES
In order to make a suitable assessment of exposure and
risk to health and the environment as a result of a
biocidal product’s use, the EU has determined the
different product types of biocidal products. According
to the Biocidal Products Regulation (EU) 528/2012,
biocides are classified in four main categories and
twenty-two specific product types1.
Disinfectants
PT 1- Human hygiene: Products are used for human
hygiene. The primary purpose of these products is to
disinfect human skin and scalp.
PT 2- Disinfectants and algaecides: The aim of these
products is to disinfect surfaces and equipment that are
not contact with food or feeding stuff. Areas of use
include air conditioning systems, aquariums,
swimming pools, and private, public and industrial
areas. It is also used for disinfection of air, water other
than human or animal consumption, waste water,
hospital waste and soil. They are incorporated into
textiles, textures, paints and other articles to produce
treated products.
PT 3- Veterinary hygiene: Antiseptics and
disinfectants that are used for veterinary hygiene. Used
for disinfecting animal shelters and transport
equipment and surfaces.
PT 4- Food and feed area: It is used disinfecting
equipment, surfaces or piping related to the production,
transportation, storage of food or feed.
PT 5- Drinking water: Products in this group are
used for disinfection of drinking water for human and
animal consumption.
Preservatives
PT 6- In-can preservatives: It is used for the
protection of cosmetic products, medical products or
medical devices and manufactured products with
microbial deterioration and control to ensure shelf life.
PT 7- Film preservatives: These products are
used for the protection of films and coatings by
controlling microbial deterioration or algae growth for
the purpose of protecting the objects such as paint,
plastic, wall adhesives, paper.
PT 8- Wood preservatives: These products are used
for the protection of wood and wood products by
controlling organisms that damage wood, including
insects.
PT 9- Fibre, leather, rubber and polymerised
materials preservatives: These preservatives are used
for the preservation of polymers and fibres, such as
textile, rubber, leather or paper by the control of
microbiological degradation.
PT 10- Construction material preservatives: The
purpose of these products are to preserve masonry,
construction materials and composite materials except
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for wood by the control of bacterial, fungal and algal
attack.
PT 11- Preservatives for liquid-cooling and
processing systems: Products in this group are used to
protect liquids used in cooling water and other water
systems from microorganisms.
PT 12- Slimicides: This group is used to control or
prevent the formation of slime in equipment and
materials used in industrial areas.
PT 13- Working or cutting fluid preservatives:
These products aim to control microbial deterioration
in fluids used for metal, glass or other materials.
PEST CONTROL
PT 14- Rodenticides: These products aim to control
of rodents, except for attraction or repulsion.
PT 15- Avicides: Purpose of use is to control birds,
except for attraction or repulsion.
PT 16- Molluscicides, vermicides and products to
control other invertebrates: Used for the control of
invertebrates such as molluscs, worms and other, by
means other than attraction or repulsion.
PT 17- Piscicides: These products purpose is to
control of fish.
PT 18- Insecticides, acaricides and products to
control other arthropods: These products are used for
the control of arthropods such as insects, crustaceans
and spiders.
PT 19- Repellents and attractants: These are used
to control harmful organisms by attracting or repelling,
are used for directly on the skin or indirectly in
environments of human or animal.
PT 20- Control of other vertebrates: These products
are used for controlling vertebrates other than those
included by the other product types.
OTHER BIOCIDAL PRODUCTS
PT 21- Antifouling products: These products aim to
control the growth of fouling microorganisms, plant or
animal species on vessels, aquaculture equipment or
other construction used in water.
PT 22- Embalming and taxidermist fluids: These
products are used for the disinfection and preservation
of human or animal corpses and parts.
CONFORMITY TESTS OF BIOCIDAL
PRODUCTS
Physical and Chemical Properties of the Active
Substance
When evaluating the physicochemical properties of the
active substances in the biocidal product, the
appropriate method should be selected and
experimental results given priority, provided that it
operates within the validity range. Data on
physicochemical properties should be reliable15.
Physical parameters
Appearance: The physical parameters of the product
should be measured and reported at 20 °C ambient
temprature, and 101.3 kPa atmospheric pressure. The
physical state of the product may be solid, liquid, or
gaseous. The colour and odour must be reported at
parameters mentioned above, Odour associated with
the active substance described in laboratories or
production plants, must be reported. This can be e.g.
odourless, characteristic of aromatic compounds,
ammonia-like, biting, faint, pungent, slight, sweetish or
other. Substances that are hazardous by inhalation
should not be investigated for their odour properties15.
Melting and freezing points: The melting point must
be measured up to 360 °C. Generally, it should be
determined if the freezing point of liquid substances is
above –20°C. EC method A.1 (Melting / Freezing
Temperature) should be used as the test method. The
use of Differential Scanning Calorimetry (DSC) or
Differential Thermo Analysis (DTA) is
recommended16.
Acidity and alkalinity: For water-containing active
substances, the pH of the active substance itself must
be tested according to the CIPAC method MT 75.317. If
solid and nonaqueous liquid active substances are to be
used in biocidal products, the pH of an aqueous
dilution of 1% of the active substance should be
determined. Acidity (pH <4) or alkalinity (pH >10) of
the products should be determined according to the
CIPAC method MT 19118.
Boiling point: The boiling point must be measured up
to 360 °C according to EC method A.2 (Boiling
temperature)19. The boiling point should be measured
at of 101.3 kPa (Standart atmospheric pressure) unless
decomposition occurs.
Density: Density for liquids and solids is tested
according to OECD Test Guideline 109 (Density of
Liquids and Solids)20. The relative density of gases can
be calculated from their molecular weight and the Ideal
Gas Law. Polymer density should be determined by
buoyancy methods.
Additional physical tests may be performed depending
on the product type.
Chemical Properties:
Approved analytical methods should be used for the
determination of active substances and, where
necessary, residues. Methods should be able to fully
characterize analytes and quantitatively identify them.
Therefore, the methods should be validated by
laboratories. The method validation parameters should
include recovery, repeatability, selectivity/specificity,
limit of detection and limit of quantification. Methods
should avoid hazardous substances and where possible,
use commonly available techniques/equipment. The
active substance analysis is carried out using
titrimetric, spectroscopic or chromatographic methods
according to the chemical properties of the substance.
HPLC, GC, GC-MS, AAS, ICP systems are the most
commonly used analytical methods. In the analyzes, it
is evaluated whether the content of the active substance
is in accordance with the manufacturer's declaration. It
is accepted that the content of the active substance will
vary with each batch and as a result of sampling and
analytical errors. These changes must be within a
certain limit. The tolerance limits applied to the active
substances are given in the table below15.
Storage stability tests:
Tests to prove that the biocidal product is stable during
storage and shelf life.
Accelerated storage test:
Stability tests are performed with CIPAC method MT
46.3 accelerated stability results are used to indicate
that the biocidal product will remain stable over a two-
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year shelf life. However, the biocidal product must also
be tested under ambient temperature conditions.
Accelerated stability data are also indicative of the
stability of the biocidal product when exposed to a
higher temperature than optimum temperatures. If the
biocidal product should not be stored at high
temperatures, the label should contain a warning
statement. If the active substance is sensitive to high
temperature, the accelerated stability test can be carried
out at lower temperatures for longer periods21.
Long term storage test:
Long term stability test is carried out at 25°C for 2
years to determine whether the product will remain
stable in the commercial packaging during the shelf
life. During this time the condition of the product is
supported by chemical analysis data.
Low temperature stability test (liquids):
The relevant test method for low temperature stability
is the CIPAC method MT 39.3. The product is stored
for seven days at 0 °C, and its stability is examined.
Some types of formulations may need to be
investigated for stability to freeze/thaw22.
Efficacy Tests:
To determine the claimed efficacy of the biocidal
product or active substance, itsbiological/
microbiological activity needs to be evaluated using
appropriate methods. Efficacy is described as the
ability of a biocidal product to perform the claimed
activity when used according to the instructions
recommended on the product label. Studies should be
conducted using appropriate methods to demonstrate
that the product is sufficiently effective against
organisms under conditions of use (concentration,
duration, application method, etc.).
There are different types of studies to determine the
efficacy of the product23.
Screening tests:
Screening tests are generally not related to
practical/field conditions and are only performed with
the active substance. Therefore, such tests are used
during product development.
Laboratory studies: These are the studies performed
according to the standard criteria for determining the
efficiency in the laboratory.
Simulation tests in the laboratory:
Simulation tests are more appropriate to demonstrate
effectiveness. It simulates the field conditions where
the product will be used under laboratory conditions.
For example, for a product intended for disinfection of
hard surfaces, a suspension test and surface test with
the relevant EN standards is sufficient.
Field tests: Field tests are a good indicator to see how
the efficacy of the biocidal product is affected by field
conditions. The results of biocidal treated samples or
areas are compared with those of untreated control
samples or areas.
Efficacy tests should be carried out in according to
CEN, ISO, OECD, ASTM standard protocols. If
standard method are not available, validated in-house
methods can be used. For the disinfectant group, the
product must have at least “cidal” effect on the target
organisms of the relevant standard when tested
according to the phase 1 and phase 2 step 1 suspension
methods of the EN standards. An appropriate method
should be selected considering the area where the
disinfectant is used24-27. For preservatives group,
biocidal activity is mostly a static activity showed on
challenge tests on some target organisms, in the related
product matrix. When a curative effect is claimed, it is
sufficient to show that the microbial reduction in the
treated samples is significantly greater than that of the
untreated control samples. For pest control products,
only biological activity can be demonstrated for a
target organism (eg, control of mice or mosquito
control).
Testing for Skin Irritation:
Disinfectants used for human hygiene and insecticides
that contact with the skin should be tested for irritation.
In vitro and in vivo assays are used to study the skin
irritation potential of a biocidal product28.
The EC method B.46 and OECD Test Guideline 439,
known as Reconstructed Human Epidermis Model
Test, are the methods used for in vitro skin irritation29-
30. Animal testing should be used as a last resort to
determine the irritant potential of the products. In vivo
tests can be used if there are certain limitations to
conducting the in vitro test to study the irritation
potential of the biocidal product. EC method B.4 Acute
Toxicity: Dermal Irritation/Corrosion, OECD Test
Guideline 404: Acute Dermal Irritation/Corrosion test
methods may be used31-32.
CONCLUSION
As a conclusion, the use of chemical biocides is a
fundamental protection in the prevention and control of
microbial growth in medical, veterinary, domestic and
industrial environments. Biocides are used a great
extent in the healthcare environment for the
disinfection of equipments, surfaces, water, and for
antisepsis of skin and wound. Misuse of biocidal
products brings about some problems such as
resistance development and toxicity. The spreading
usage of products containing low concentrations of
commonly used biocides has raised some concerns
about the possible development of microbial resistance.
Laboratory studies have demonstrated that bacteria can
become resistant to a biocide, and that resistant bacteria
can develop cross-resistance to other biocides and
antibiotics. High concentrations of biocides generally
have toxic effects not only for humans but also for the
environment. In this context biocidal products need to
be enlarged in regulations and control in terms of
traceability due to their extensive and increase in use.
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Table 1: Tolerance limits of the active substance content.
Declared nominal content
of active [g/kg or g/L]
Tolerance limit
≤25
±15% (homogenous formulations)
±25% (non-homogenous preparations)
25 - 100
±10%
100 - 250
±6%
250 - 500
±5% o
> 500
±2.5%
