Лако-красочные материалы — производство

In some instances, it is not the material as applied to the skin that causes the allergic reaction, but a combination of the material and exposure to sunlight. In the late 1970s, the cause of an unusual number of cases of dermatitis in people using a sunscreen preparation was traced to the presence of 6-methylcoumarin, which was in the fragrance in the product (Kaidbey and Kligman, 1978). It has since been shown that a number of coumarin derivatives are capable of causing skin sensitization, but only when they are exposed to sunlight (see Table 10.2). As soon as it became apparent that 6- and 7-methylcoumarins and 7-methoxycoumarin were photosensitizers, their use was pro­hibited by IFRA.

However, some essential oils, such as fig leaf absolute and certain citrus peel oils, contain natural phototoxic ingredients, usually referred to as furocoumarins (Marzulli and Maibach, 1970; Fisher and Trama, 1979). For example, some grades of Bergamot oil (expressed or cold — pressed varieties) are known to contain 5-methoxypsoralen (bergap — tene, 20), which is a potent phototoxic agent (Zaynoun et al., 1977). The use of these grades of oil, which can contain up to 0.3% of bergaptene, is restricted by IFRA, although the industry now tends to use citrus oils from which the furocoumarins have been removed by distillation or extraction. Fig leaf absolute is banned from use, for even at levels of 0.001% it can still elicit a photoallergic reaction (Opdyke, 1982).

Neurotoxicity

It is obvious that if a fragrance ingredient can penetrate through the skin, it must have the potential to affect all the body systems, not just
the immune system. This was found to be true for two materials that both exhibited neurotoxic effects. The first material, 6-acetyl-7-ethyl- 1,1,4,4-tetramethyltetralin (AETT, 21), a synthetic musk, was found to cause damage to the nervous system of rats when it was applied dermally at a level of 9 mg/kg bodyweight per day, over a 26-week period (Spencer et al, 1979; Ford, 1994). Although RIFM established a No Observable Adverse Effect Level (NOAEL), the expert panel decided that there was insufficient evidence to recommend the contin­ued use of this material, and acting on this advice AETT was banned by IFRA. It is interesting that the related and very widely used musk material 7-acetyl-1,1,3,4,4,6-hexamethyltetralin (22) does not show any neurotoxic effects. When neurotoxic effects were reported for the second material, Musk Ambrette (23), RIFM undertook a research program to enable a comprehensive risk assessment to be made (Spencer et al., 1984).

RIFM first established a dose level that a consumer may be exposed to by normal usage of a wide range of fragranced consumer products that contained musk ambrette. This level, which was weighted to the maximum likely exposure, was calculated to be 0.3 mg/kg bodyweight per day. RIFM also determined that musk ambrette had a NOAEL of 10 mg/kg bodyweight, which gave a safety factor of only 33 (NOAEL/ daily exposure). However, skin penetration studies had shown that only 2% of an applied dose of musk ambrette was actually absorbed through the skin. Thus, the dermally applied daily exposure figure was

really 50 times lower than calculated, giving a 50-fold higher safety factor. This evidence would almost certainly allow the industry to continue using musk ambrette, but when it was also reported to have photoallergic effects it was banned from use by IFRA (Cronin, 1984). It is interesting to note that other nitrated musk ingredients, such as Musk Ketone (24) and Musk Xylene (25) do not show any evidence of neurotoxic or phototoxic effects (Lovell and Sanders, 1988; Ford and Арі, 1990).

Reproductive Effects

Any chemical, including a fragrance ingredient, that enters the blood­stream could affect the reproductive system and/or the growing foetus, leading to a range of problems including infertility and birth defects. Thankfully, there has only ever been one case of a fragrance ingredient being implicated as causing adverse effects in the offspring of pregnant rats (Mankes et al., 1983). The ingredient was phenylethanol (PEA, 11), which is the major component of rose oil and has been used in perfumery for several centuries. When RIFM examined the results of this study, in which PEA was fed in enormous quantities to pregnant rats by way of a stomach tube (gavage), it concluded that a more appropriate study on dermally applied PEA should be undertaken (Spencer et al., 1979). The results of these studies, which included skin penetration and metabolism studies, showed that the PEA that did penetrate the skin was quickly metabolized to phenylacetic acid (PAA, 26), a natural component of human blood. It was concluded that the very tiny increase in PAA level in the blood stream from the use of PEA posed no significant risk to the consumer, and combining the results of other studies, a safety factor of many thousands was calculated. The adverse effects seen in the original study highlight the difficulties of extrapolating academic animal studies to the actual conditions encoun­tered by the consumer.

О

ОН

Phenylacetic acid
(26)