Page 161 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

128 SECTION | I General

VetBooks.ir TABLE 7.10 Exceptional Off-Label (Extra-Label) Use of Authorized Medications (“Cascade” System)

No authorized veterinary medicinal product (VMP) in a member state for a specific condition (1) A VMP authorized in the member state
concerned for use for another animal species, or for another condition in the same species; or
Medicinal product Medicinal product or imported VMP
(2) A medicinal product for human use (2) If there is no such product authorized, either: (a) a medicinal product for human
authorized in the member state concerned use authorized in the member state concerned, or (b) a VMP authorized in another
member state for use in the same species or in another food-producing species for
the condition in question or for another condition may be used
(3) If, however, there is no such product, a VMP prepared extemporaneously by a person authorized to do so following a veterinary
prescription may be used

the Dangerous Substances Directive (EEC, 1967) and its manufacturers and importers need to demonstrate that
subsequent amendments, as well as the Council they have appropriately done so by means of a registra-
Regulation (EEC) No. 793/93 of March 23, 1993 on the tion dossier, which must be submitted to the ECHA. The
evaluation and control of the risks of existing substances ECHA is the driving force in implementing the EU’s
(EEC, 1993). On the other hand, REACH is the groundbreaking chemical legislation for the protection of
Regulation on Registration, Evaluation, Authorization and human health and the environment. The ECHA work
Restriction of Chemicals (EC, 2006). It entered into force helps ensure that chemicals are used safely and that the
on June 1, 2007. It streamlines and improves the former most hazardous ones are substituted by safer alternatives.
legislative framework on chemicals of the EU. The main ECHA may then check that the registration dossier com-
aims of REACH are to ensure a high level of protection plies with the regulation and must evaluate testing propo-
of human health and the environment from the risks that sals to ensure that the assessment of the chemical
can be posed by chemicals, the promotion of alternative substances will not result in unnecessary testing, espe-
test methods, the free circulation of substances on the cially on animals, but also that adequate information is
internal market, and enhancing competitiveness and inno- provided. Where appropriate, authorities may also select
vation. REACH makes industry responsible for assessing substances for a broader substance evaluation to further
and managing the risks posed by chemicals and for pro- investigate substances of concern. Six substances of very
viding appropriate safety information to their users. high concern will be banned within the next 3 5 years
Under the REACH Regulation, companies are responsible unless an authorization has been granted to individual
for providing information on the hazards, risks and safe companies for their use. These substances are carcino-
use of chemical substances that they manufacture or genic, toxic for reproduction, persist in the environment,
import. REACH information requirements to be consid- and accumulate in living organisms. The following
ered in the assessment embraces: (1) collecting existing substances are concerned: musk xylene, 4’,4’-methylene-
data on the substance or on similar substances including dianiline (MDA), hexabromocyclododecane (HBCDD),
information on use, exposure and risk management, and di-(2-ethylhexil) phthalate (DEHP), benzyl butyl phthalate
(2) data on analogous substances in a weight of evidence (BBP) and dibutyl phthalate (DBP).
approach, if “read-across” or membership of a “chemical REACH also foresees an authorization system aiming to
category” is possible as well as considering QSAR analy- ensure that substances of very high concern are properly
ses or estimation. Data generated from in vitro test meth- controlled and progressively replaced by suitable alternative
ods (validated and prevalidated) (Anado ´n et al., 2013) can substances or technologies where these are economically
be used either as a standalone to fill in a data gap or as and technically viable. Where this is not possible, the use
part of a weight of evidence approach under REACH pro- of substances may only be authorized where there is an
vided that the information for the hazard endpoint is suffi- overall benefit for society in using the substance. In addi-
cient for the purpose of classification and labeling and/or tion, EU authorities may impose restrictions on the manu-
RA. In parallel, the EU can take additional measures on facture, use, or placing on the market of substances causing
highly dangerous substances where there is a need for an unacceptable risk to human health or the environment.
complementing action at the EU level. All manufacturers The EU member states authorities are responsible for enfor-
and importers of chemicals must identify and manage cing REACH through inspections as well as penalties in
risks linked to the substances they manufacture and case of noncompliance. From June 1, 2009, Annex XVII of
market. For substances manufactured or imported in quan- the REACH Regulation replaced Directive 76/769/EEC
tities of 1 ton or more per year per company, (EEC, 1976) on the approximation of the laws, regulations