QSAR in Mexico.

The definitive guide.

The QSAR models are used in Mexico mainly for two purposes:

1. For registration purposes of technical pesticides by equivalence way.

2. To investigate the toxicity of impurities in the pharmaceutical field.

On the first point, the regulation allows to justify the toxicity of an impurity in
order to know if this is relevant or not. For this, it is necessary to report to the
authority, the value of oral median lethal dose in rat. This LD50 value can be
taken from recognized bibliographic sources or it can be predicted through a
QSAR study.
There are several providers of this service in Mexico and this can generate
confusion in the registering companies or the regulatory consultants.

Therefore, the most frequent questions are listed below:

1. What is the authority responsible for evaluating and authorizing

submissions for pesticides in Mexico?
R. In Mexico, the health authority in charge of evaluating submissions of
pesticides, medicines, food supplements, and other substances, is the
Federal Commission for the Protection against Sanitary Risk (COFEPRIS).

2. What endpoints are requested by COFEPRIS?

R. The only endpoint that is allowed is average lethal dose in rat. (LD50). Other
endpoints such as carcinogenicity, mutagenicity, teratogenicity, are not useful
or necessary.

3. What software are allowed to develop QSAR models?

R. The Mexican authority has no restrictions on specific software. QSAR
models can be developed on any platform, as long as they comply with the 5
principles of the OECD.

MolenTox
Brazil. México . Costa Rica . Chile
 4. Do laboratories need any type of accreditation or certification to perform
QSAR models?
R. So far, there is no certification or accreditation to develop QSAR models
and this is not required by COFEPRIS. Some laboratories have taken fast
courses in Barcelona, Spain on QSAR Toolbox, and promote their diploma as
a certification. However, up to now there is no official certification issued by
OECD.
5. Why are there laboratories or universities that sell QSAR models made
only with TEST or QSAR Toolbox?

R. Some universities or makeshift labs have taken quick courses to use QSAR
Toolbox or TEST and sell reports made with the technique click, click, click
clik and report, and often do not know what they are really doing. Be careful
because these two tools have important limitations.

6. What are the limitations of EPA TEST?

You can check it for yourself. If you run a prediction in EPA for these two
substances, both will have the same toxicity (1972.86 mg/kg)

This occurs because the software is unable to detect some important aspects
of the molecule such as its isomerism or minimal structural differences since
the software can only calculate topological descriptors, in addition to not taking
into account minimum energy states.

MolenTox
Brazil. México . Costa Rica . Chile
In some constitutional isomers, optical isomers, or large molecules, software
TEST is unable to correctly calculate the requested endpoint.

7. How can I determine if a laboratory is reliable?

a) If the laboratory can develop a model without using TEST or Toolbox.

b) If their reports comply with the 5 principles of the OECD.
c) If their reports can be used to register anywhere in the world.
d) If the laboratory has qualified personnel in chemoinformatics, QSAR,
QSPR, theoretical chemistry, and computational toxicology.
e) If the laboratory provides a written assurance that the report will be
accepted by COFEPRIS.

8. Why are there so many crappy QSAR providers?

R. Because there is no regulation or quality inspection to computational
chemistry laboratories. Today you yourself could download QSAR toolbox,
learn a tutorial and start selling QSAR models without anyone auditing or
questioning you. It is clear that we need in Mexico an organization that
regulates laboratories and universities and prevent them from continuing to
profit from free tools such as EPA TEST or Qsar Toolbox.

MolenTox
Brazil. México . Costa Rica . Chile