Classification of hydrolytic enzyme preparations of microbiological synthesis according to the degree of danger

1st class – substances are extremely dangerous, strong allergens, have a strong irritating effect;

2nd class – highly hazardous substances, allergens of medium strength, have an irritating effect;

3rd class – moderately hazardous substances, weak allergens, have a weak irritating effect;

4th class – substances are low-hazard, weak allergens, have a weak irritating effect.

The determination of the threshold of acute inhalation action (Limac) is carried out in order to determine the hazard class of the drug by a single inhalation exposure to white rats with a four-hour exposure. Thresholds of acute general toxic and irritating action are set according to integral specific indicators.

Numerous studies of the effect of enzyme preparations on the skin have shown that their single exposure at a concentration of 25-50% does not have an irritating effect. Multiple applications on the skin cause slight irritation at a concentration of enzyme preparations of 2.5%, which increases with increasing concentration of preparations.

Since the mucous membrane of the eye is the most sensitive to the action of enzyme preparations, studies of the local action of enzyme preparations are carried out when they are introduced into the conjunctival sac of the eye. Rabbits are used as objects of study. An enzyme preparation is introduced into one eye of the animal in the form of either a powder (up to 50 mg) or a few drops of solutions of enzyme preparations of various concentrations. The other eye of the experimental rabbit serves as a control, into which the solvent is added.

The effect of the solution on the mucous membrane of the eye at a concentration of less than 0.1% characterizes the studied preparation as having a strong irritating effect not only on the mucous membrane of the eye, but also on the skin.

Numerous data of toxicological studies of enzyme preparations (alkaline protease, pectinase, cellulase, amylase) have shown that the leading factors in the development of intoxication of the body are their allergenic properties.

The threshold of allergenic action is set by inhalation seeding of albino guinea pigs for a month.

The detection of the state of sensitization of animals is determined by two methods: intradermal testing with an irritating dose and the method of histamine provocation. Animals of the experimental and control groups are injected intraperitoneally with 0.03 mg/kg of histamine, together with a resolving dose of the allergen. The result of a provocative test is evaluated 5-15 minutes after the introduction of the histamine-allergen complex.

Based on the results obtained, the hazard class of the enzyme preparation is established.

When substantiating the MPC of enzyme preparations belonging to the 1st or 2nd hazard classes, in the air of the working area for one or more indicators (LD50, Limac, Limai), in addition to those indicated in the research scheme, chronic inhalation seeding (4 months) of animals is additionally carried out to determine the threshold of chronic action (Lim ch).

If the drug belongs to the 3rd or 4th hazard classes, then their study is limited to the scheme described above. The study of the degree of toxicity of enzyme preparations (GZH pectinase, P10 X alkaline protease, amylase, etc.) showed its dependence on the activity of the preparation, the method of cultivation of the producer and the method of purification of the enzyme. Most enzyme preparations do not have a cumulative effect when they enter the body, their sensitizing properties are detected only when administered intradermally and intraperitoneally.

The MPC values for enzyme preparations in the air of the working area were established: for protease – 0.5 mg/m 3 , hazard class II “A”; for trichodermin – 0.1 mg / m 3 , I hazard class; for bacterial amylase – 1 mg / m 3 , II hazard class “A”.

In the study of antibiotics used to protect agricultural plants and stimulate the growth of animals, different degrees of toxicity were revealed. So, levoristatin, blasticidin are classified as highly toxic, bacitracin and vitaminycin are classified as low-toxic. A number of antibiotics have super-cumulative properties – for example, hygromycin B, levoristatin, etc. It was found that antibiotics such as polymycin, grisin, etc., can sensitize the body when taken aerogenically.

Of the antibiotics obtained by microbial synthesis, bacitracin (trade name – batsilichin), used as a feed additive, has found wide application in agriculture. A low degree of pathogenicity and low toxicity of the producer of this antibiotic Bacillus licheniformis and the preparation obtained on its basis were established. According to the degree of toxicity, batsilichin is classified as low-hazard, not capable of causing acute or chronic effects.

When studying tylosin (feed antibiotic) and nitragin (bacterial fertilizer), their general toxic effect was found.

In other drugs (dendrobacillin, etc.), sanitary and hygienic studies revealed an allergic effect.

The approved MPC values for products of microbiological synthesis are given in Table 1

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