The Russian system of chemicals management - Bef-de.org

The following parameters of acute effects are tested: average lethal dose DL 50
and average
time of lethality TL 50
in case of oral exposure. If there are data available about the substance’s
ability to penetrate skin, also acute skin exposure tests are performed. It is also
recommended to find out the dose causing effects in case of single exposures (Lim ac
).
These parameters together with physico-chemical parameters, biological constants, (Q)
SAR relationships and combined mathematical models are used to estimate the relevant
parameters for chronic toxicity tests. Also the calculated chronic toxicity parameters
from Stage 1 are used. The calculation of trigger doses for skin resorption effects are
performed, if considered necessary. Based on the calculated lowest observed chronic
effect concentration LC chr
and the established LC org.
and LC san
the substance is assigned
to one of the four hazard classes.
Investigations can be finished at this stage in case:
>> The substance belongs to a well-investigated structural row of substances having
a similar mode of action and estimation methods for chronic toxicity parameters
are based on representative data from several substances of the row already having
norms established.
> > According to the calculated lowest observed chronic effect concentration LC and chr
established LC оrg.
and LC san
the substance belongs to hazard class 4.
>> There is reliable information available that the substance causes no long-term effects.
>> The substance is easily hydrolysed within 24 hours and the degradation products
already have norms established.
Thus the MPC for hazard class 4 substances and temporary norms (ODU) for class
3-4 substances can be assigned at this stage. In all other cases species, sex and age
specific differences in sensitivity to a substance in acute toxicity tests are established
and Stage 3 is performed.
Stage 3: Sub-acute toxicity investigations involve testing on:
>> General toxicity: studying specific and integrated parameters, while applying every
day exposure for the substance to be tested, including releavant metabolites or
degradation products. Furthermore, dermal tests are performed for substances
showing similar or higher toxicity by skin resorption than via oral exposure as examined
already in previous stages.
>> Main long-term effects:
>> Impairment of reproduction: investigated at the end of sub-acute testing according
to functional parameters;
>> Embryotoxic effect: tested in case the effect is to be effected according to
literature data or properties of structural analogues;
>> Mutagenic effect: tested on laboratory animals, e.g. with micronucleus test;
>> Cumulative properties;
>> Substance take-up into organs and tissues, excretion of the substance and/
or its metabolites;
24 | The Russian System of Chemicals Management