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Notes: Experimental demonstration of lasing in a broad area twin-contact semiconductor laser which operates as a phase-conjugation (PC) mirror in an external cavity configuration is reported. This allows "self-aligned" and self-pumped spatially nondegenerate four-wave mixing to be achieved without the need for external optical signals. The external cavity laser system is very insensitive to tilt misalignments of the external mirror in the PC regime and exhibits very good mechanical stability. The resonant frequency of the external cavity lies in the GHz range which corresponds to a subnanosecond time response of phase conjugation processes in the semiconductor laser. © 1997 American Institute of Physics.

Notes: Objective  To determine the risk of perinatal death among twins born at term in relation to mode of delivery.Design  Retrospective cohort study.Setting  Scotland 1985–2001.Population  All twin births at or after 36 weeks of gestation, excluding antepartum stillbirths and perinatal deaths due to congenital abnormality (n= 8073).Methods  The outcome of first and second twins was compared using McNemar's test and the outcome of twin pairs in relation to mode of delivery was compared using exact logistic regression.Main outcome measures  Intrapartum stillbirth or neonatal death of either twin.Results  Overall, there were six deaths of first twins and 30 deaths of second twins (OR for second twin 5.00, 95% CI 2.00–14.70). The odds ratio for death of the second twin due to intrapartum anoxia was 21 (95% CI 3.4–868.5). The associations were similar for twins delivered following induction of labour and for sex discordant twins. However, there was no association between birth order and the risk of death among 1472 deliveries by planned caesarean section. There was death of either twin among 2 of 1472 (0.14%) deliveries by planned caesarean section and 34 of 6601 (0.52%) deliveries by other means (P= 0.05, odds ratio for planned caesarean section 0.26 [95% CI 0.03–1.03]). The association was similar when adjusted for potential confounders. Assuming causality, we estimate that 264 caesarean deliveries (95% CI 158–808) would be required to prevent each death.Conclusion  Planned caesarean section may reduce the risk of perinatal death of twins at term by approximately 75% compared with attempting vaginal birth. This is principally due to reducing the risk of death of the second twin due to intrapartum anoxia.

Notes: 7 patients allergic to cocamidopropyl betaine (CAPB) were detected by positive patch test reactions to Tegobetaine L7TM. These patients were then asked to participate in further testing to its potential impurities, cocamidopropylamine and 3-dimethylaminopropylamine (DMAPA). 4 of the 7 patients were tested to purified CAPB and cocamidopropylamine, with 2 reacting to the purified betaine on allergy patch testing and 3 reacting to cocamidopropylamine 0.1%. At another date, 6 of the 7 were successfully recalled for testing to DMAPA in the presence of sodium lauryl sulfate (SLS) or pure CAPB; 1/6 reacted to DMAPA in water, but only at very high concentrations, at least 3 orders of magnitude higher than that to which skin exposure would occur from use of products containing CAPB. Both SLS and CAPB increased the number of reactions recorded to high levels of DMAPA. However, positive reactions to much lower concentrations of DMAPA (〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:01051873:COD450203:ges" location="ges.gif"/〉100 ppm) were found in only 1/6 subjects and then only in the presence of the irritant SLS. 0/6 reacted to pure CAPB alone. Taken together, these results suggest that DMAPA is unlikely to be an important contact allergen in CAPB of appropriate quality. They also confirm that CAPB of suitable purity, where levels of both cocamidopropylamine and DMAPA are minimized, is unlikely to trigger reactions in those ostensibly allergic to the material.

Notes: The murine local lymph node assay (LLNA) assesses skin sensitization potential as a function of proliferative responses induced in lymph nodes draining the site of topical exposure to test chemical. It has been shown that interpolation of LLNA dose-response data to define the concentration of test chemical required to induce a 3-fold stimulation of proliferation (EC3) offers the prospect of a quantitative index of the relative potency of a contact allergen. Initial studies have demonstrated that there exists a strong (inverse) correlation between EC3 values and contact allergenic potency in humans. Thus, materials with a low EC3 value were more potent contact allergens in humans. However, it is necessary to examine a wide range of allergens to demonstrate that such correlations are generally true. Thus, in the present study, 10 aldehydes of varying degrees of allergenicity in man were evaluated in the LLNA and their EC3 values derived. Formaldehyde was regarded as the strongest allergen in man and also had the lowest EC3 value, 0.35% (equivalent to 0.93% formalin). In contrast, the extremely weak allergen vanillin and the non-sensitizer ethyl vanillin both had EC3 values of 〉50%. For the remaining 7 aldehydes, there was a close similarity between what is judged to be their rank order of allergenicity in humans and EC3 values derived from analysis of LLNA data. These results support further the utility of EC3 determinations in the LLNA as a measure of the relative potency of a contact allergen.

Notes: The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) as a case study.

Notes: Changes to the European standard series which have taken place since the last officially recommended alterations in 1988, are explained. New to the series is the sesquiterpene lactone mix. The PPD black rubber mix and the quinoline mix have been replaced by single components: one of the p-hydroxybenzoates has been left out of the paraben mix. Ethylenediamine dihydrochloride has been dropped from the series.

Notes: Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P 〈 0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P 〈 0.001). Deodorants containing isoeugenol in the concentration range of 0.0063–0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.

Notes: The currently used 8% fragrance mix (FM I) does not identify all patients with a positive history of adverse reactions to fragrances. A new FM II with 6 frequently used chemicals was evaluated in 1701 consecutive patients patch tested in 6 dermatological centres in Europe. FM II was tested in 3 concentrations – 28% FM II contained 5% hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral®), 2% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10%α-hexyl-cinnamic aldehyde; in 14% FM II, the single constituents' concentration was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Positive reactions to FM I occurred in 6.5% of the patients. Positive reactions to FM II were dose-dependent and increased from 1.3% (2.8% FM II), through 2.9% (14% FM II) to 4.1% (28% FM II). Reactions classified as doubtful or irritant varied considerably between the 6 centres, with a mean value of 7.2% for FM I and means ranging from 1.8% to 10.6% for FM II. 8.7% of the tested patients had a certain fragrance history. Of these, 25.2% were positive to FM I; reactivity to FM II was again dose-dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history – certain and none – values for sensitivity and specificity were calculated: sensitivity: FM I, 25.2%; 2.8% FM II, 8.1%; 14% FM II, 13.5%; 28% FM II, 17.6%; specificity: FM I, 96.5%; 2.8% FM II, 99.5%; 14% FM II, 98.8%; 28% FM II, 98.1%. 31/70 patients (44.3%) positive to 28% FM II were negative to FM I, with 14% FM II this proportion being 16/50 (32%). In the group of patients with a certain history, a total of 7 patients were found reacting to FM II only. Conversely, in the group of patients without any fragrance history, there were significantly more positive reactions to FM I than to any concentration of FM II. In conclusion, the new FM II detects additional patients sensitive to fragrances missed by FM I; the number of false-positive reactions is lower with FM II than with FM I. Considering sensitivity, specificity and the frequency of doubtful reactions, the medium concentration, 14% FM II, seems to be the most appropriate diagnostic screening tool.

Notes: Conducting a sound skin sensitization risk assessment prior to the introduction of new ingredients and products into the market place is essential. The process by which low-molecular-weight chemicals induce and elicit skin sensitization is dependent on many factors, including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell-mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. Specifically, by estimating the exposure to the allergen and its allergenic potency, it is feasible to assess quantitatively the sensitization risk of an ingredient in a particular product type. This paper focuses on applying exposure-based risk assessment tools to understanding fragrance allergy for 2 hypothetical products containing the fragrance allergen cinnamic aldehyde. The risk assessment process predicts that an eau de toilette leave-on product containing 1000 ppm or more cinnamic aldehyde would pose an unacceptable risk of induction of skin sensitization, while a shampoo, containing the same level of cinnamic aldehyde, would pose an acceptable risk of induction of skin sensitization, based on limited exposure to the ingredient from a rinse-off product application.

Notes: That a cosmetic product must not cause damage to human health is enshrined in European legislation. Within the EU, the Scientific Committee for Cosmetic and Non-food Products (SCC NFP) of the Directorate General for Consumer Safety & Health Protection provides independent risk assessments of certain cosmetic ingredients. The evaluations depend largely on the completeness of dossiers submitted by industry. Requirements for submissions are published by the SCC NFP ) and cutaneous toxicology, including contact allergy, is only a part of the overall assessment.Opinions adopted by the SCC NFP are published in full (), presented to the Directorate General responsible for the legislation (Enterprise), who are risk managers, and discussed with Member States before the recommendations are included in the annexes of the Cosmetics Directive, if appropriate.The Cosmetics Directive () contains positive lists of certain ingredient types (including preservatives, UV filters) and only those substances listed may be used. Annex 3 lists substances that may be used under certain conditions (concentration, exposure sites, warnings, age).Increasingly, revision of assessments of risks related to contact allergy have been brought about by epidemiological and robust clinical data (elicitation studies) submitted by dermatologists. As illustrated with the examples of methyldibromo glutaronitrile and Lyral®, rapid responses to protect the consumer are possible when the Commission is provided with appropriate information. Similar examples illustrate failures to predict risks for the induction of contact allergy before the consumer was excessively exposed.In contrast to the above, some permanent hair dye chemicals (for which there is, as yet, no positive list) are important and potent allergens and are permitted only because of the absence of acceptable alternatives and social need. Warnings and recommendations for testing before use have not been validated despite the long history of complaints. The ‘damage’ experienced by the consumer with an adverse reaction to a hair dye must be balanced against their possible carcinogenic potential.The consumer expects products to be safe. Why do risk assessments fail?