An overview of the gentleness and safety of surfactants

1. Safety of surfactants

The biological changes caused by surfactants and their metabolites in the body, that is, the toxic side effects that may be caused to the body include acute toxicity, subacute toxicity, chronic toxicity, impact on fertility and reproduction, embryonic toxicity, teratogenicity, mutagenicity, carcinogenicity, sensitization, hemolytic and so on. The contact of surfactants with different parts of the human body in different ways will put different requirements on the above toxic side effects.

Surfactants are more and more widely used in human contact systems such as drugs, food, cosmetics and personal hygiene products. With the improvement of human living standards, people pay more and more attention to the toxic side effects of surfactants in various human contact formulations. According to different uses, the focus of attention on surfactants mainly focuses on the irritation of mucosa, sensitization to skin, toxicity, heritability, carcinogenicity, teratogenicity, hemolytic, digestive absorption, biodegradability and so on. For example, for cosmetics, the principle of selecting ingredients in the past was mainly to dress up beautiful, and the choice of surfactants was only to consider how to achieve the best first effect or main effect, such as cleaning, foaming, emulsification, dispersion, etc. The second is to play its secondary or auxiliary effect, and little or no consideration is given to the effect of surfactants on the natural state of skin, hair, etc. At present, the selection principle of surfactants gradually tends to meet the prerequisite of protecting the normal and healthy state of skin and hair and producing as little toxic and side effects on the human body as possible, before considering how to play the best main and auxiliary effects of surfactants. This development has led to surfactants raw material suppliers, formulators and manufacturers are faced with the challenge of how to re-understand and evaluate the safety and mildness of surfactants to provide consumers with the safest, mildest and most effective products. Therefore, it is necessary to re-evaluate the safety and gentleness of the original surfactants and new surfactants.

Cationic surfactants are often used as disinfection agents, which have strong killing effect on various bacteria, molds and fungi, but they also have toxic side effects. They degrade the central nervous system and respiratory system, and fill the stomach with blood. Anionic surfactant toxicity is low, in the usual application concentration range, will not cause acute toxic harm to the human body, but after oral administration will cause gastrointestinal discomfort, diarrhea phenomenon. Non-ionic surfactants belong to the low-toxicity or non-toxic class and are non-toxic when taken orally. The lowest toxicity is PEG class, the second is sugar ester, AEO, Span, Tween class, alkyl phenol polyethers toxicity is higher.

For aquatic animals, the toxicity of non-ionic surfactants is generally higher than that of anionic surfactants.

Subacute and chronic toxicity tests generally take a long time and are difficult to compare due to differences in the use of experimental animals and other experimental conditions. However, it is generally believed that the subacute and chronic toxicity test results of non-ionic surfactants are non-toxic, long-term use will not cause pathological reactions, but some varieties will increase the body's absorption of fats, vitamins or other substances, or cause reversible functional changes in some organs when taken orally in large doses, so non-ionic surfactants can be used as high-safety substances. Non-ionic surfactants are often used as emulsifiers in food, and sometimes need to use the foaming, defoaming, wetting, dispersion, anti-crystallization, anti-aging, anti-rejuvenation, water retention, sterilization, antioxidant and other functions of surfactants. The use of surfactants as food emulsifiers is strictly limited, generally only a few varieties can be approved for use, and some are also limited by the daily intake (ADI, mg/kg) index, that is, the maximum dose of an additive that the human body can continuously ingest without causing an invasive effect on the human body per unit weight.

1.2 Hemolytic

Non-ionic surfactants are commonly used as solubilizers, emulsifiers or suspensions in pharmaceutical or nutritional injections. Attention must be paid to the hemolysis of surfactants in the case of a large injection volume, especially in the case of intravenous injection. Anionic surfactants have the largest hemolytic properties and are generally not used in injections. The hemolysis of cationic type was the second, and the hemolysis of non-ionic type was the least. Among non-ionic surfactants, PEG esters of hydrogenated ricinoleate have the lowest hemolytic effect, which is the most suitable for intravenous injection. However, if the degree of PEG polymerization is increased, the hemolytic effect will exceed the Tween class. The sequence of nonionic hemolysis is Tween < PEG fatty acid ester < PRG alkyl phenol < AEO.

2. The gentleness of surfactants

The gentleness of surfactants on human skin, eyes and hair, especially on skin and eyes, is a difficult concept to define, and so far there is still no uniform standard. The irritability or sensitization of surfactants to mucous membranes is mainly caused by three factors:

(1) Dissolvability refers to the degree of dissolvability of surfactants to the skin's own moisturizing components (such as moisturizing factor NMF), intercellular lipids and free amino acids and fats in the stratum corneum. Excessive dissolution of these ingredients will destroy the skin's oil and surface layer, reduce the skin's water retention ability, and cause cells to fall off into zest, resulting in skin tightness, tingling or dryness. What's more, in addition to the peeling effect of the surfactant on the cell, it also has a dissolution effect on the cell, such as SDS is a very effective dissolution agent of the biofilm.

(2) Penetrability refers to the ability of surfactants to penetrate through the skin, and this effect is thought to be one of the causes of various skin inflammation. The infiltration of surfactants changes the original structural state of the skin and the compatibility between adjacent molecules, resulting in contact dermatitis, dermatitis, skin irritation and even allergic reactions, causing erythema and edema on the skin. Cations were the most active surfactants, anions were the second, and nonionic and zwitterionic surfactants were the least.

(3) Reactivity refers to the adsorption of surfactant on protein, resulting in protein denaturation and changing skin pH conditions. The experimental results show that the reactivity of PEG is lower than that of LAS and other anions.

2.1 Methods for evaluating gentleness

There are many methods to evaluate the gentleness of surfactants, but there is no uniform standard at present. At present, the commonly used methods for gentleness evaluation are mainly divided into two categories: in vivo test and in vitro test. For safety reasons and to meet the needs of animal protection movement, in vitro test method is strongly advocated at present, but most of the legislation still takes the results of live test as the test standard.

2.1.1 Live experiment

(1) Draize rabbit skin test Draize rabbit skin test mainly uses rabbit skin, and sometimes also uses rat or Dutch pig skin test, with various concentrations of samples on the skin after the observation of erythema and edema degree comprehensive score (see Table 4). The Draize rabbit skin test can be used as an independent test or as a preliminary test for human skin tests. Some rabbit skin test results are listed in Table 5. In vivo tests are mainly carried out on human skin, rabbit skin and rabbit eye mucosa. The two more commonly used methods are Driaize rabbit skin test and Draize rabbit eye test. Sometimes the Duhring chamber test or Cupshaking test is also used, that is, the spot test is carried out on the flexion side of the human forearm to observe the erythema and edema caused by the intermittent test of surfactants on the human body. There are also hand immersion methods, that is, the hands are immersed in a certain concentration of surfactant solution to simulate the washing action or washing dishes, and after a certain period of time to test the skin surface before and after soaking sebulosis rate or protein dissolution.

2.1.2 In vitro experiment

In vitro tests simulate organisms with cells or proteins in vitro, and observe the effect of surfactants on proteins or cells in vitro, so as to infer the degree of effect on living tissues. The two most commonly used in vitro tests are the red blood corpuscle test (RBC test) and the Zein test.

(1) RBC test generally believes that if an irritant reacts with a living protein, the reaction will first occur in the cell membrane. RBC test (red blood cell test) uses isolated red blood cells as a cell substitute for experiments to observe the effects of various surfactants on red blood cells. In this test, the hemolysis effect of surfactants on red blood cells was recorded as L value, the denaturation effect of hemoglobin was recorded as D value, and the stimulation effect on cells was evaluated by L/D characterization index. The following table lists RBC test results for some common surfactants.

(2) Zein test Zein is a specific corn protein that itself is almost completely insoluble in water. If zein has a large interaction with surfactants, the water solubility of zein will increase after the interaction. In Zein test, zein was used to simulate living proteins. The change of zein solubility was determined by the increase of nitrogen content in aqueous solution before and after the interaction with surfactants. This change in solubility reflected the strength of the interaction between surfactants and zein, thus indirectly characterizing the effect of surfactants on living proteins.

2.2 Influence of surfactant structure on gentleness

Due to the lack of a comprehensive legal method to evaluate the irritability of surfactants, it is difficult to determine the order of gentleness of various specific varieties, and can only point out the general law of the effect of surfactant structure on gentleness.

(1) Molecular size

Some of the zeintest results for surfactants are listed in order of irritation from highest to lowest:

1. Sodium dodecyl benzene sulfonate

2. Sodium lauryl sulfate

3, C12C18 alcohol sulfate sodium salt

4, secondary alkyl sulfonates

5, lauryl sulfate monoethanolamine salt

6, lauryl sulfate ammonium salt

7, lauryl sulfate triethanolamine salt

8. Sodium lauryl ether sulfate

9. Lauryl alcohol ether

(2) ammonium sulfate

10, lauryl ether (2) sulfate triethanolamine salt

11, dodecyl/tetradecyl alcohol ether (3) sodium sulfate salt

12. Lauryl ether sulfosuccinic acid monosodium disodium salt

13, special laurel/oleol ether sulfate sodium/magnesium mixture

14, lauryl alcohol ether sulfate magnesium salt

15, amide ether sulfate

16, lauryl polypeptide potassium salt

Small molecule surfactant is easy to cause transdermal penetration and irritates the skin. However, macromolecular surfactants are not easy to penetrate through the skin, and due to the influence of the secondary and tertiary structure of macromolecules, polar groups and hydrophobic branch chains are not easy to have direct and strong effects on the skin or hair, so they are relatively mild. At present, surfactants and emulsifiers used in cosmetics and personal hygiene products have a tendency to develop in the direction of macromolecules and polymers, or to modify natural polymers, such as starch, peptides, hydrolyzed cellulose, gum, or synthetic polymers, such as polyamide or polyacrylic acid as emulsifiers and thickeners for cosmetic emulsions. High efficiency, low stimulation and mild effects were obtained.

(2) Hydrophobic chain length It is generally believed that the longer the hydrophobic chain, the smaller the degree of branching, and the milder the surfactant is to the human body, which has been proved by many facts. However, exceptions have also been found, such as P&G when developing AGS (alkyl glycerol ether sulfonates), it was found that it was not a derivative of long-chain alkyl, but a derivative of eight-carbon alkyl that had the lowest irritation and good foaming.

(3) PEG-type nonionic surfactants introduced into the molecule are lower than negative and cationic surfactants in terms of irritation to skin mucosa or eye mucosa. Increasing the length of PEG in the molecule further reduces the irritation, and even the introduction of PEG chains into ionic surfactants to form so-called hybrid surfactants also increases the genteness of the molecule, as is well illustrated by the introduction of PEG bonds to form AES in SDS. The introduction of glycerol or other polyols into the molecule will also receive the same results as the introduction of PEG chains.

(4) The similarity between the structure of the surfactant and the skin itself is more complex, and the surfactant with a certain similarity or proximity to the skin structure is mild to the skin. Therefore, some mild surfactants newly developed in cosmetics and personal hygiene products have a relatively complex structure, which is no longer a simple combination of long chain alkyl and hydrophilic groups, but a polymolecular condensation type. For example, Witco introduced SBCS (Disodium PEG-5 Laurylcitrate Sulfosuccinate), which combines the structure of citrate and sulfosuccinate into one, which is said to have low skin irritation and good application performance. In addition, the introduction of amide bonds or the introduction of hydrolyzed protein, amino acid structure, etc., increases the similarity of surfactant molecules to skin tissues, and also helps to increase the genteness of surfactants, such as modified soap AM (N-acylmethyltaurine sodium), acylpropyl betaine, oleyl polypeptides, etc. If the alcohol ether sulfonyl succinate sodium salt is changed to the alcohol amide sulfonyl succinate sodium salt, the irritation to the skin and eye mucosa is less than the former, and both are lower than the AES. Acute toxicity test showed that LD50 increased from 12000mg/kg to 20000mg/kg. The potassium salt or ammonium salt of acylβ-alanine is very water-soluble and has a soft structure of carboxylate. When used as a shampoo ingredient, the calcium and magnesium modified soap formed with calcium and magnesium ions in water can form a layer crystal with good lubricity around the hair, so that the hair can be gently conditioned and protected, and will not produce stiffness and astringency caused by general soap.

(5) The polarity of the ionic group The smaller the polarity of the ionic group, the milder it is to the skin and hair. AES formed by the introduction of PEG group into SDS structure has greatly reduced the degreasing power of skin and hair. If the sulfonate group is further changed into a carboxylate group to form ECH (alkyl ether acetate), a milder class of surfactant emulsifiers is formed. Changing the type of counter ion of the ionizing group, that is, changing the degree of ionization of the ionic group in aqueous solution, also helps to change the gentleness of the surfactant molecule. If the sodium ion in AES is changed to ammonium ion, it helps to reduce the degree of ionization of the molecule, so the mild character of AES ammonium salt is increased, and it can be used as the main surfactant of shampoo and bath wave. If the sodium ions in AES are changed to bivalent ions such as magnesium, the smoothness and softness of hair after washing can be greatly increased. A small amount of fatty acid calcium and magnesium soap mixed with a large amount of sodium soap can give the skin a smooth, clean and refreshing feeling after the bath, which is not possessed by the strong hydrophilic group sulfonate and sulfate.

2.3 Compatibility and gentleness

The development of new surfactant varieties with special structure, the pursuit of gentleness is a time-consuming, costly and never-ending thing, using the combination of surfactants, or the original surfactant varieties to improve the process, chemical structure is another way to improve the gentleness of products.

(1) Purification of surfactants Many of the pure products of surfactants are tested to be low irritant, high mild varieties, but industrial products due to raw materials, processes, side reactions and many other reasons, will bring some impurities into the product, such as unreacted raw materials, by-products, toxic colored substances, etc., limiting these surfactants as high quality, mild