Artificial streams in the assessment of environmental hazard of chemicals.

Artificial streams are dynamic mesocosms, simulating aquatic systems and rivers. They are useful to study ecotoxicity of chemicals and their effects on flora and fauna colonizing the streams or introduced into the channels. These artificial rivers can also be used to study the influence of ecological and hydrodynamic parameters, such as the kind of substrate of river and flow rate. Responses of the bivalve Unio tumidus to substrate type (silt, sand, and pebbles) and water flow rate (high and low) were investigated after 15 and 35 days in the channels, in order to optimize the experimental conditions for ecotoxicity study with methyl methacrylate (MMA). The toxicological effects of different concentrations of MMA on bivalves and on communities of invertebrates and diatoms were determined after several weeks of exposure at a high flow rate. Biomarkers responses measured in the digestive gland and the gills of U. tumidus were the activities of detoxification systems as early indicators of toxicity and lipid peroxidation as a marker of cytotoxicity. Effects of MMA resulted in a decrease in antioxidant activities. Disturbances in bivalves appeared at lower concentrations than in communities. This indicates sensitivity of the biomarkers studied, which are predictive indicators of ecotoxicity.

"Cyclamen Red" colors based on a macrocyclic anthocyanin in carnation flowers.

The "cyclamen" red (or pink) colors in carnation flowers-cultivars Red Rox and eight others-are based on the presence of a new macrocyclic anthocyanin, pelargonidin 3,5-di-O-beta-glucoside(6' ', 6' "-malyl diester) identified by spectroscopic methods. The instability of the bridging malyl group with sugars in acidic medium readily causes the formation of the opened ring form, 3-O-(6' '-O-malylglucoside)-5-O-glucoside. The issue of cyclamen colors based in carnations on this original acylated pelargonidin derivative simulating those based on simpler cyanidin glycosides in Rosa cultivars is discussed using CIELAB colorimetric coordinates.

Comparative study of methods chosen by the Association Française de Normalisation (AFNOR) for evaluating sensitizing potential in the albino guinea-pig.

An evaluation was made of the different protocols recommended by the Association Française de Normalisation (AFNOR) for assessing the sensitizing potential of chemicals in the guinea-pig. The methods studied were those of Magnusson & Kligman (J. invest. Derm. 1969, 52, 268), Maguire (J. Soc. cosmet. Chem. 1973, 24, 151), Maurer et al. (Agents & Actions 1975, 5, 174), Klecak et al. (J. Soc. cosmet. Chem. 1977, 28, 53), Dossou & Sicard (1984, to be published) and a hitherto unpublished method of Guillot, Gonnet, Clément & Brulos. Results obtained by each method were compared in tests on the allergenic reference substances dihydrocoumarin, p-phenylenediamine, formalin, penicillin G and benzocaine (ethoform) and on propylene glycol (negative control). The results showed that the number of animals sensitized often varies with the choice of experimental protocol, that inclusion of tests on a control substance is essential, and that while quantitative differences were found, the methods were qualitatively similar in their capacity to identify allergens in the guinea-pig.

Anti-irritant potential of cosmetic raw materials and formulations.

Synopsis The investigation studied the anti-irritant potential of several substances commonly employed in cosmetic formulations as basic components of the emulsion or as active ingredients, and evaluated the effect of the emulsifier. Five different emulsions were made irritating by addition of croton oil, in sufficient quantity to provoke a clearly adverse reaction in the rabbit, i.e. primary cutaneous irritation index (PII) close to 2. The PII was determined according to the official French methods by applying to symmetrical areas of the back, the irritant base as control and the same base containing the test substance. Fifty-five ingredients were evaluated: gelling agents, plant extracts, molecules defined as healing, anti-inflammatory substances or anaesthesic compounds, etc. The test substances were added to the emulsion at concentrations close to the ones generally found in cosmetics. The qualitative and the quantitative composition of the oil phase was similar for each emulsion. Several gelling agents, thickeners and polymers which notably reduce skin contact with an irritant, gave good results. Some of the usual healing, anti-inflammatory, local anaesthesic compounds gave the expected results. Some ingredients, though well known, were ineffective. The type of emulsifier, by modifying cutaneous penetration and bio-availability of the active ingredients, may play an important role.

Evaluation of the cutaneous-irritation potential of 56 compounds.

The primary cutaneous irritation of 56 chemicals was tested in the rabbit using three different procedures. The three protocols selected for the tests were the method published by the French authorities for the testing of cosmetics and toiletries (Journal Officiel 21 April 1973, p. 3862; ibid 5 June 1973, p. 3953) and the methods proposed for the testing of chemicals by the Association Française de Normalisation (AFNOR) and, in 1979, by the Organisation for Economic Co-operation and Development. The results of the three sets of tests were compared and the effects of differences in procedure and numbers of animals were studied, together with the possible relation between irritancy and the pH of the test material. It was concluded that the AFNOR protocol best met the requirements for such tests and that gloves should be worn for the handling of all substances classified as moderately or severely irritant on that scale.

Evaluation of the ocular-irritation potential of 56 compounds.

The ocular irritancy of 56 chemicals was tested in the rabbit eye, with and without rinsing, using a procedure that complied with the main requirements of three protocols, namely those proposed by the Association Française de Normalisation (AFNOR) in 1982 and by the Organisation for Economic Co-operation and Development in 1979 for the testing of chemicals and that published by the French authorities (Journal Officiel 21 April 1971, p. 3862; ibid 5 June 1973, p. 3953) for the testing of cosmetics and toiletries. The results obtained were used to establish the extent to which the assessment of a chemical's irritation potential was affected by the differences between the three protocols in respect of the observation times prescribed, the inclusion and timing of rinsing, the number of animals used and the interpretation procedure. Conclusions were also drawn about the influence of the physical state and pH of a material on its potential irritancy and about the level of irritancy that necessitates the use of eye protection.

Safety evaluation of gums and thickeners used in cosmetic formulations.

Synopsis Safety tests have been carried out on gums and thickeners, continuing a study involving commonly used cosmetic ingredients (1, 2, 3, 4). The ocular and cutaneous tolerance tests have been conducted on the rabbit following the official French methods (5, 6) but with some complements or modifications (1, 2, 3, 4, 7). The test substances (listed in Table 1) were products from various suppliers and of different types and grades. None of the fifty samples tested provoked pathological lesions of the ocular mucous membrane; nevertheless, corneal irritation was noted with silicates, silica and bentonite, probably due to mechanical effect, when applied at relatively high concentration. The highest score on the primary cutaneous irritancy test (moderately irritant) was that for the gelled volatile hydrocarbon solvents. The repeated application test was continued for 6 weeks: no significant pathological reaction was observed. Only a slight intolerance was noted with the gels of volatile hydrocarbons and isopropyl myristate, but the irritant reactions were significantly reduced compared to those previously observed with the pure oils (1, 2). Consequently, based on these data, it can be concluded that the use of gums and thickeners involved in this publication presents no hazard for the skin.

Safety evaluation of some humectants and moisturizers used in cosmetic formulations.

Synopsis Safety tests have been carried out on some humectants and moisturizers, continuing a study involving commonly used cosmetic ingredients (1-6). The test substances (listed in Table I) were products from various suppliers and of different types and grades. The ocular and cutaneous tolerance tests have been conducted on animals following the official French methods but with some complements or modifications (28-36). Each compound has been tested as supplied and diluted in water. Pathological lesions of the ocular mucous membrane were provoked by lactic acid at 20 and 10% concentrations. A slight corneal opacity was also noted with ethoxydiglycol and polyamino sugar condensate and a significant irritation with hexylene glycol (non-diluted). In dilutions of 10 or 20%, these substances were non-irritating. Only one product (lactic acid) has given a moderate primary cutaneous irritation (PII = 2.50), when applied undiluted. The indices obtained with the other raw materials correspond to a non-irritating application. With the exception of lactic acid (the study being terminated after 1 week), no significant adverse reaction was macroscopically and histologically observed after daily application (neat) for 6 weeks. Finally, the predictive sensitizing tests (guinea-pig) carried out with two samples of propylene glycol proved to be negative.

[Not Available].

Summary On 26 July 1976, the European Directive relating to cosmetics products added lanolin to the list of substances which cannot be used in these products beyond previously fixed restrictions and conditions (annexe III) with the obligation that labelling bears the wording 'contains lanolin'. The French legislation laid down the term 'Important' with the above condition, thus drawing attention to the presence of one of the most used substances in the cosmetic industry. Without making an account of the comments which have led to that decision, it is admitted that some dermatologists have noticed for 20 years allergic reactions on few persons, after using ointments containing lanolin or lanolin derivatives. Two facts have been noted after a thorough survey of the observed cases: these reactions occurred first with persons suffering from leg ulcers or chronic eczema, and were caused by the free fatty alcohols fraction. On the other hand, literature does not mention any case of allergic reaction on a healthy skin, whether it is human or animal. As we are aware of the importance of the problem and as we have carried out a routine examination of local tolerance. of the main raw materials, already used in cosmetics, for 3 years (1-4), we considered it was of primary importance to study the results obtained from various samples of anhydrous lanolin and its derivatives. The ocular and cutaneous tolerance tests have been made on the rabbit following.

Eye and skin irritation tests on the rabbit of several fatty acid esters.

Summary Continuing preceding work (1,2), a series of tests has been carried out on the toxicological evaluation of samples of different fatty esters obtained from several manufacturers. Eye irritation tests and skin irritation and sensitisation tests were carried on the rabbit following the official French methods with minor modifications. When tested pure, nearly all the isopropyl and butyl esters used gave some adverse reactions. Only one sample (out of two tested) of isopropyl stearate appeared to be well tolerated although the primary irritation index on skin was greater than one. The two esters with the greatest adverse skin reactions were isopropyl isostearate and one of two isopropyl linoleates. Ten per cent aqueous dispersion showed considerable diminution of the adverse reactions in the majority of the cases. Considering the results obtained in this paper together with those published previously (1) being twenty-seven samples covering fifteen different fatty esters, the worse reactions were obtained with the C(8), C(12), C(14) saturated together with the oleate and linoleate esters. Isopropyl palmitate, stearyl heptonate and arachidyl propionate were the best tolerated as pure materials. Other adverse reactions were obtained with the isopropyl, butyl and octyl stearates and isostearates (except for one of two isopropyl stearates) and from these results appears that the alcohol moiety plays little part in irritation when compared with the fatty acid chain. Examination of peroxy values indicates that these have a significant adverse effect for oleates and linoleates.