Лако-красочные материалы — производство

It was realized by the fragrance industry some 30 years ago that this absence of regulations concerning the ingredients that could be used in fragrances, or on the safety of fragrances in consumer products, could expose the consumer to unacceptable risks which would lead to governmental intervention in the industry. To avoid such problems, the industry decided to establish a self-regulatory system involving the

two major international fragrance organizations: the Research Insti­tute for Fragrance Materials (RIFM) and the International Fragrance Association (IFRA).

RIFM was established in 1966 by the American Fragrance Manu­facturing Association as a non-profit-making, independent body, whose task was to evaluate the safety of fragrance ingredients. To date, RIFM has tested over 1300 fragrance materials, including all of the commonly used ingredients. Once the test results for each material examined have been reviewed and discussed by an independent inter­national panel from academia, which comprises toxicologists, pharma­cologists and dermatologists, the results are published as monographs in the journal Food and Chemical Toxicology. RIFM also collates all the information available for an ingredient from the scientific literature and from the aroma chemical manufacturers for inclusion in these monographs. Should there be any cause for concern about the use of an ingredient, this is immediately signalled to the industry by publication by RIFM of an advisory letter, which is then acted upon by IFRA.

The types of basic test carried out by RIFM include acute oral toxicity, acute dermal toxicity if the oral toxicity is significant, skin irritation and sensitization, and phototoxicity if the material adsorbs in the UV range. Where there is a need, much more detailed studies are undertaken which involve subchronic feeding studies, dermal absorp­tion and metabolic fate. Through IFRA, RIFM also collects from the industry consumer exposure data on fragrance ingredients. This ensures that the test data it uses are relevant to the market situation and also provides guidance on the nature of future research. Thus, RIFM undertakes a review of its safety data, or instigates further research if the results of these surveys indicate that a particular ingredient is occurring in a wider range of products and/or at higher concentration than when it was first examined.

IFRA was established in 1973 by a number of fragrance trade associations and represents over 100 fragrance manufacturers in 15 countries. With its headquarters in Geneva, IFRA represents the scientific and technical expertise of the industry and is responsible for issuing and up-dating the Code of Practice (IFRA 1973) upon which the whole self-regulation policy is based. IFRA is funded by these fragrance manufacturing companies, who all agree to abide by the code of practice whilst they remain members of the association. This code of practice has many functions, including setting standards for good manufacturing practice within the industry, for quality control, for labelling and advertising, as well as setting limits on, or prohibiting the use of, certain ingredients.

Although IFRA and RIFM are independent of each other they obviously work closely together and it is only after considerable discussion between RIFM and IFRA that restrictions or prohibitions are imposed. It is always the IFRA board, in conjunction with the technical advisory committee, that makes the final decision in such matters, as the IFRA board is ultimately responsible for the implemen­tation of any restrictions, by way of the code of practice.

The strict code of practice applied by IFRA not only protects the consumer, but also protects the health and well-being of those employed within the industry. This is highlighted by a study carried out in 1985 in which it was found that there was no increase in mortality from any type of cancer in a group of workers employed in the flavour and fragrance industry, where exposure to a wide range of aroma chemicals is far higher than the consumer would ever encounter (Guberan and Raymond, 1985).

As the fragrance industry does not use toxic, carcinogenic or corrosive substances, why are there use restrictions on some ingredi­ents? The most common cause for such a restriction is the ability of some materials to be skin sensitizers. Unlike skin irritation, which usually disappears soon after the irritant has been removed, skin sensitization involves the activation of the immune system and reac­tions can persist for much longer after the initial exposure and can become more severe on subsequent contact.

Skin sensitization was recognized as a major problem almost at the very outset of ingredient testing and a simple strategy was devised to deal with it. Ingredients were tested in a human, predictive sensitization patch test at a concentration ten times greater than the consumer was likely to be exposed to. If this test (which used exaggerated levels under occluded patches as a ‘worse case’ scenario) proved to be negative, then no further action was taken. However, in the early days, if there were signs of sensitization, RIFM would issue an advisory letter and the material would no longer be used in fragrances.

As this approach did not differentiate between weak and strong sensitizers, IFRA subsequently adopted a modified approach. The IFRA technical advisory committee studied the results of the human patch tests, and if necessary asked for further work to be undertaken, to see if a ‘no effect’ level could be determined for each material. If such a level could be determined, the committee set a guideline value that allowed only one-tenth of the no effect level to be used in a consumer product. Obviously, in some cases this level was below that at which the ingredient made any useful contribution to the fragrance and IFRA recommended a complete ban. However, it did allow many useful

ingredients, such as hydroxycitronellal (1), cinnamic alcohol (2) and isoeugenol (3) to be used without exposing the consumer to unneces­sary risk. An interesting example of this approach is trans-hex-2-enal (4), which has an intense green, fruity, vegetable-like odour. This material was found to be a sensitizer at a level of 0.2%, but not at 0.02%. IFRA thus set a use level of 0.002% (20p. p.m.) for a consumer product, at which level it can still have a strong influence on a fragrance, especially as its odour threshold has been measured at less than 0.1 p. p.m.

SAFETY ASSESSMENT

It was realized many years ago that the only difference between a medicine and a poison was the dose administered, as is demonstrated by the tragic consequences of overdosing on paracetamol. It is thus clear that it is not accurate to say a material is safe, as safety cannot be measured in absolute terms. The safety of any material cannot be measured directly, but can only be estimated as part of a risk assess­ment. This type of assessment examines the potential of any material to cause harm and the likelihood of that potential being reached during normal-use conditions. If the probability of causing harm under normal-use conditions is high, then the material is not used, or a different use-regime is developed to reduce greatly the chance of a hazardous situation occurring. It has been found that for the rat, the LD50 value for sugar is around 33 g/kg body weight (this drops to just 3.5 g/kg bodyweight for table salt). If this result is translated to a 50 kg

human, then the quantity of sugar needed to kill half of the recipients would be 1650 g. Thus, on adding sugar to tea or coffee (probably 4g per teaspoon) the acute risk to our health is very small. In this trivial example, the risk assessment shows that there is a safety factor between the applied and possibly harmful dose of over 400, and sugar would be considered safe.

For fragrance ingredients, before a risk assessment can be under­taken, the route of exposure has to be considered. Although LD50 values are available for some fragrance ingredients, it is obvious that fragrances are not intended for consumption. Inhalation is the most obvious pathway to examine, as fragrances are produced because of their odour. However, it is well known that the human nose is capable of detecting a vast range of materials at levels measured in parts per million and less. For example, if 0.2 ml of a fragrance is applied to the skin (a dab behind each ear), it is detectable to the human nose for several hours after application (to anyone close to the wearer). For a fine fragrance that contains 10% of the fragrance compound, this means that only 0.02 ml of active ingredients are applied to the skin. If we now say that the fragrance can only be detected within 1 m of the wearer, then 0.02 ml of fragrance diffuses into 8 m3 of air, equivalent to a concentration of 2.5p. p.m. (assuming 0.02 ml of fragrance weighs 2 x 104 fig). This assumes that all of the fragrance evaporates immedi­ately. As the fragrance is detectable for some hours after application, the actual concentration in the air must be lower than this, and the concentration of any individual ingredient even lower. If any of these ingredients were toxic by inhalation at these levels, then they would probably be used as chemical warfare agents rather than fragrances.

As inhalation and ingestion under normal-use conditions are of little consequence for the risk assessment, the role of the fragrance upon the skin must be examined as a route of exposure. In this case two effects need to be considered. The first is whether the material irritates when applied to the skin and the second is whether the material can penetrate through the skin and affect the immune system and organs of the body.