Cochineal red is an organic compound widely used in food, cosmetics, pharmaceuticals, textiles, and other fields due to its excellent safety profile. Poisoning caused by eating foods containing cochineal red is rare, and repeated atrial arrhythmia due to cochineal red poisoning is even rarer.

An 88-year-old Asian female patient was admitted to hospital due to a disturbance of consciousness. Twelve hours prior to presentation, the patient consumed 12 eggs containing cochineal red over a period of 2 h. At presentation, the patient was in a coma and had a score of 6 on the Glasgow Coma Scale (E2 + VT + M4). The patient's skin and mucous membranes were pink. Electrocardiography (ECG) revealed rapid atrial fibrillation without any signs of ischemia. We prescribed cedilan and fluid replacement for arrhythmia correction. Shortly after admission, the atrial fibrillation corrected to a normal sinus rhythm. On the day 2 of admission, the patient had a sudden atrial flutter accompanied by hemodynamic instability and rapidly declining arterial oxygen saturation between 85% and 90%. The sinus rhythm returned to normal after two electrical cardioversions. Six days after admission, the skin color of the patient returned to normal, and the ECG results were normal. The patient was transferred out of the intensive care unit and eventually discharged after 12 d in hospital. At the 2-mo follow-up visit, the patient was in good health with no recurrence of arrhythmia.

Although cochineal red is a safe, natural food additive, excessive consumption or occupational exposure can induce cardiac arrhythmias.

A significant part of adult-onset asthma is caused by occupational exposure to both high- and low-molecular-mass agents. Insects are occasionally described to cause occupational allergy in professions including anglers and fishers, laboratory workers, employees of aquaculture companies, farmers, bakers, sericulture workers and pet shop workers. Occupational insect allergies are often respiratory, causing asthma or rhinoconjunctivitis, but can be cutaneous as well. The European Union recently approved three insect species for human consumption, enabling an industry to develop where more employees could be exposed to insect products. This review overviews knowledge on occupational insect allergy risks and the tools used to diagnose employees. Despite the limited availability of commercial occupational insect allergy diagnostics, 60.9% of 164 included reports used skin prick tests and 63.4% of reports used specific IgE tests. In 21.9% of reports, a more elaborate diagnosis of occupational asthma was made by specific inhalation challenges or peak expiratory flow measurements at the workplace. In some work environments, 57% of employees were sensitized, and no less than 60% of employees reported work-related symptoms. Further development and optimization of specific diagnostics, together with strong primary prevention, may be vital to the health conditions of workers in the developing insect industry.

Carminic acid is an aromatic polyketide found in scale insects (i.e., Dactylopius coccus) and is a widely used natural red colorant. It has long been produced by the cumbersome farming of insects followed by multistep purification processes. Thus, there has been much interest in producing carminic acid by the fermentation of engineered bacteria. Here we report the complete biosynthesis of carminic acid from glucose in engineered Escherichia coli. We first optimized the type II polyketide synthase machinery from Photorhabdus luminescens, enabling a high-level production of flavokermesic acid upon coexpression of the cyclases ZhuI and ZhuJ from Streptomyces sp. R1128. To discover the enzymes responsible for the remaining two reactions (hydroxylation and C-glucosylation), biochemical reaction analyses were performed by testing enzyme candidates reported to perform similar reactions. The two identified enzymes, aklavinone 12-hydroxylase (DnrF) from Streptomyces peucetius and C-glucosyltransferase (GtCGT) from Gentiana triflora, could successfully perform hydroxylation and C-glucosylation of flavokermesic acid, respectively. Then, homology modeling and docking simulations were performed to enhance the activities of these two enzymes, leading to the generation of beneficial mutants with 2-5-fold enhanced conversion efficiencies. In addition, the GtCGT mutant was found to be a generally applicable C-glucosyltransferase in E. coli, as was showcased by the successful production of aloesin found in Aloe vera. Simple metabolic engineering followed by fed-batch fermentation resulted in 0.63 ± 0.02 mg/L of carminic acid production from glucose. The strategies described here will be useful for the design and construction of biosynthetic pathways involving unknown enzymes and consequently the production of diverse industrially important natural products.

: Carmine is a widely used "natural" food additive that has been reported to provoke both an immediate hypersensitivity and a delayed systemic response with cutaneous expression. Systemic contact dermatitis describes the hypersensitivity reaction following systemic re-exposure of the inciting allergen in previously sensitized individuals. In individuals with recalcitrant dermatitis and a positive carmine intolerance history and/or patch test, it is important to consider a trial topical and dietary elimination of carmine-associated products and foods.

Food colors are added to different types of commodities to increase their visual attractiveness or to compensate for natural color variations. The use of these additives is strictly regulated in the European Union, the United States, and many other countries worldwide. There is a growing concern about the safety of some commonly used legal food colorants and there is a trend to replace the synthetic forms with natural products. Additionally, a number of dyes with known or suspected genotoxic or carcinogenic properties have been shown to be added illegally to foods. Robust monitoring programs based on reliable detection methods are required to assure the food is free from harmful colors. The aim of this review is to present an up to date status of the various concerns arising from use of color additives in food. The most important food safety concerns in the field of food colors are lack of uniform regulation concerning legal food colors worldwide, possible link of artificial colors to hyperactive behavior, replacement of synthetic colors with natural ones, and the presence of harmful illegal dyes-both known but also new, emerging ones in food. The legal status of food color additives in the EU, United States, and worldwide is summarized. The reported negative health effects of both legal and illegal colors are presented. The European Rapid Alert System for Food and Feed notifications and US import alerts concerning food colors are analyzed and trends in fraudulent use of color additives identified. The detection methods for synthetic colors are also reviewed.

For centuries, food additives have been used for flavouring, colouring and extension of the useful shelf life of food, as well as the promotion of food safety. During the last 20 years, the studies implicating the additives contained in foods and medicine as a causative factor of allergic reactions have been proliferated considerably. In this review, we aimed to overview all of the food additives which were approved to consume in EU and find out how common and serious allergic reactions come into existence following the consuming of food additives.

Food preservatives sodium benzoate and propionic acid and colorant curcumin are demonstrated to suppress in a dose-dependent manner Th1-type immune response in human peripheral blood mononuclear cells (PBMC) in vitro. Results show an anti-inflammatory property of compounds which however could shift the Th1-Th2-type immune balance towards Th2-type immunity.

Carmine is a natural red pigment obtained from dried gravid female cochineal insects (Dactylopius coccus or Coccus cacti). There have been several reports of allergies to carmine, but the major allergens responsible have not been identified.

To identify the major allergenic proteins in cochineal.

Immunoblots of purified cochineal extract were probed with sera from 3 patients with allergy. Partial amino acid sequences were determined for the proteins bound by IgE, and the corresponding cDNA, containing a complete coding region, was cloned by 5' and 3' rapid cDNA extension and PCR. The recombinant protein was expressed in yeast and subjected to immunoblotting.

We identified a full-length cDNA encoding a protein, which we named CC38K, with 335 amino acids and a molecular mass calculated as 38 kd. This amino acid sequence included all the partial amino acid sequences obtained from the purified proteins identified by IgE from patients with allergy. Recombinant CC38K protein was recognized by patients' sera, indicating that this is a major allergen present in carmine. The CC38K sequence showed homology to phospholipases.

We have, for the first time, identified the major allergen in cochineal extract. This protein may be a phospholipase or related enzyme, both of which are known to be allergens in other insects.

Workers in the food industry are exposed to multiple respiratory hazards that include irritants, allergens, and substances capable of causing destruction and scarring of the lungs. Cases of constrictive bronchiolitis obliterans, a severe potentially disabling lung disease, have been identified in workers exposed to flavorings. Workplace engineering controls, work practices, and respiratory protection can minimize potential exposures. Medical surveillance of workers exposed to known respiratory hazards will help to identify disease early, facilitate the prompt removal of workers from the causative exposure(s), and prevent further worsening and/or permanence of disease. When companies or employees suspect occupational respiratory disease, they can involve public health agencies to investigate any excess risk of lung disease, risk factors among processes and exposures, and effectiveness of interventions, if needed.

Hypersensitivity to carmine (E120) has been identified as a cause of food intolerance and occupational asthma. We present a case of occupational asthma following exposure to carmine in a manufacturer of sausages and review the literature.

A 42-year-old non-atopic male presented with a 5-year history of rhinoconjunctivitis and asthma on occupational exposure to food additive dusts. Symptoms increased after work. The patient had been exposed for more than 20 years.

Skin prick tests were performed with a battery of common inhalant allergens and spices. Cochineal, carmine lake and additive mixes used by the patient were extracted and subsequently used for skin prick test, bronchial provocation and in vitro measurements (specific IgE, Western blot and chromatographic fractionation).

Prick tests were positive to carmine and carmine-containing additives; carmine-specific IgE and bronchial challenge tests were also positive (PC20 = 0.0004 mg/ml and 1.6 kU/l). Western blot showed IgE binding to bands of about 30 kDa on cochineal extract and a diffuse pattern at 40-97 kDa on carmine. This result was confirmed by gel filtration chromatography and dot blot. Carmine completely inhibited IgE binding to cochineal extract.

Carmine is a potential sensitizer in an occupational setting: 18 cases of occupational asthma have been described to date. Carmine allergens are poorly defined; in general, proteins from cochineal not removed by the extraction process are considered as the main allergens in carmine. Our results are consistent with this, but show that these proteins may be subject to chemical modification.

Occupational asthma (OA) caused by carmine (E-120) has been reported.

We sought to evaluate the prevalence of sensitization and OA at a natural dye processing factory in which 2 workers had been given a diagnosis of carmine-induced OA 6 years previously.

The 24 current employees and one worker who had recently left work because of asthma completed a questionnaire and underwent skin testing (carmine, cochineal, carminic acid, curcuma, annato, and chlorophyll), carmine IgE dot-blot analysis, and methacholine inhalation testing. Workers exhibiting positive occupational skin test responses, work-related asthma, or bronchial hyperresponsiveness underwent specific inhalation challenge and serial peak expiratory flow rate recording.

Positive skin test responses to carmine (41.7%), cochineal (29.2%), and carminic acid (4.2%) were observed. Carmine IgE dot-blot results were positive in 4 subjects. No difference in atopy or smoking was observed between occupationally sensitized and nonsensitized subjects. Among the 5 employees reporting work-related asthma, 2 had positive skin test responses, and 4 had bronchial hyperresponsiveness. Five subjects underwent specific inhalation challenges: 2 workers had early asthma responses to carmine and cochineal challenges, and the remaining subjects did not have suggestive peak expiratory flow recordings. The subject who had left his job was given a diagnosis of carmine-induced OA.

The prevalence of sensitization and OA caused by carmine was 41.6% and 8.3%, respectively. When the 3 workers who had left their jobs were included, the cumulative incidence of sensitization and OA was 48.1% and 18.5%, resembling the healthy worker effect. Prevention programs to establish the permissible levels of airborne allergen should be implemented.