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Медицинская Иммунология 2002, Т. 4, N° 3, стр 407-416 © 2002, СПб РО РААКИ
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CRITERIA FOR ALLERGENIC BUILDING MATERIALS
Diel F.*, Schubert H., Fischer M., Schbtz T., Weber K.-M., Gagelmann K.-M., Axt-Gadermann M., Khanferyan R.**, Diel E.
Institute of Environment and Health (IUG) and University of Applied Sciences FH Fulda Institute for Allergy and Asthma, Sedin 4, Krasnodar, Russia
Abstract. Allergenic building materials are increasingly problematic. This is true not only in occupational health, but can also be the reason for the increasing prevalence of indoor allergies. Particularly individuals with family heredity of increased sensitising potential are in need of special protection and practical criteria for the assessment of allergens in building materials. This article attempts to present a point scale scoring the allergenic potential of e.g. wooden chipboard containing formaldehyde, fixed virgin wool fitted carpet and/or loamy plaster containing nickel. Four easily understandable scores that are practical for patients as well as building experts are suggested: No or low - relevant - increased - and highly increased allergenic potential. “Direct allergens” have to be differentiated from the “indirect allergens”. Direct allergens are defined as (pseudo-) allergenic compounds, which are emitted from building materials into the indoor air. “Indirect allergens” are defined as spores from moulds, excrements from house dust mites and animal epithelia. These allergens are induced by building defects like increased humidity and anthropogenic facilities. Structure-response-analyt-ical knowledge and occupational hazard management serves as basic data for the assessment of indoor air allergenic potential. (MedJmmunol., 2002, vol.4, N 3, pp 407-416)
Key-words: Allergens, building material, indoor air, environmental health, hazard assessment
Introduction
Allergens in building materials have been a main topic in occupational health a long time. Especially the resorption of occupational allergens via skin, - as it is known e.g. with chromates in the case of bricklayers which led to minimizing the Cr-concentrations in cement, but also to increased efforts in personal occupational care like wearing protective work clothing. Currently the main focus of interest lies on the air-born indoor allergens which are chronically emitted and inhaled. It must be distinguished between Occupational Medicine/Industrial Safety = relatively high exposure, often short term, for certain clients: healthy adult workers working for 8 hours - and Environmental Medicine/Environmental Protection = relatively low pollution,
Адрес для переписки:
Prof. Dr. Friedhelm Diel, Head of Biochemistry,
Dept, of Nutrition, University of Applied Sciences FH Fulda D - 36039 Fulda - Germany.
E-mail: friedhelm.diel@he.fh-fulda.de Tel/Fax ++49-661-9640353/399
but frequently long-term 24 hours a day chronically incorporated indoor allergens, difficult to quantify: all sub-groups of the population and risk-groups. This is especially true for 25 - 30 % atopies in the German population. Last but not least, due to the complicated processes, which the German MAK-List outlines: “Currently it is not possible to set the threshold values for the induction of an allergy (sensitization) or the initiation of an allergic reaction in sensitized subjects.” (DFG 2000) The MAK-list distinguishes between “H” (Hautreaktion = skin reaction) and “S” (Sensitizing) and particularly “Sa” (respiratory sensitizing) and “Sh” (skin sensitizing), “Sha” (both) and “SP” (photosensitizing). The “Senatskommission” at the “DFG” assesses the sensitizing responses, even in cases where the pathomechanisms are largely unknown and/or in cases of pseudo-allergic responses. Pseudo-allergic responses are not based on antigen-an-tibody recognition. This is observed in small molecules like sulfite, benzene acid, acetyl salycyl acid as well as triazine and their derivatives. Interestingly the “DFG-Senatskom-mission” accepts structure-response-analyses as well as human and animal tests in the allergy assessment. A distinction is made between the sensitizing potential and the
sensitizing frequency of a substance. The sensitizing potential in the work place is much more important than in the “private environment”. Cases reported demonstrate that building materials like concrete are dangerous during processing. However, after the house is finished, the special hazard risk - e.g. chromate sensitizing - is diminished. Apart from the possibility of an allergic reaction, not only the penetration of (allergic) pollutants (through skin and mucosa) but also the form of the building materials (in this case water soluble compounds like ChromiumVI) are of importance. In the long run, the aging and abrasion in private houses can lead to chronical intake of subconcentrated hazards. Consequently the frequency of sensitization may be higher in private houses than is generally assumed. A relatively high number of unknown cases also has to be considered because epidemiological investigations are difficult in this complicated field...Obviously the area of hobbies has to be inspected. What type of risks have to be considered when houses are built privately? How well is personal working safety controlled? On the other hand, little is known currently about chronical mechanisms of sensitization when allergens in building materials come in contact with human skin immune factors and immune competent body cells. The problem becomes even more complex when allergens are absorbed at airbom carriers like house dust and penetrated through the mucose of the inhalative or the sensory organs. One of the most predominant cases not directly associated with the construction field which demonstrates the overlap between occupational and environmental protection is as follows: Occupational baker's asthma or baker’s ekzema show that after familiar heredity, many young bakers stop their training after noticing that they have been sensitized against the well-known allergens in the bakery work places. Every morning when they come into the bakery they suffer from attacks of hay fever, asthma and skin irritation... Not only the risk of contamination in the work place (e.g. flour dust in the bakery work place) but furthermore the predisposition (atopy) are main causes for changing professions. The number of unregistered cases is high.
In spite of the fact that it is difficult to define responses and threshold values for indoor pollutants, particularly in the field of environmental medicine, the attempt is undertaken to present a system for the allergenic potency of building materials and compounds.
This is based on the increased prevalence of allergies as mentioned at the beginning, as well as the redundently references to indoor allergens like molds, house dust mite, and cats and pats epithelia. However, more attention should be payed to the increasing (pseudo-) allergenic potency of indoor pollutants in building materials. Therefore direct allergens (compounds incorporated directly from the building materials) will be distinguished from indirect allergens (e.g. molds after humidity). After this, summaries of currently known relevant allergengroups will be outlined and a first attempt will be made to define threshold values for allergens in building materials. The tolerance values can not be proven allergotoxicologically, but they are recom-
mended by the Institut fur Umwelt und Gesundheit (Institute of Environment and Health - IUG) in Germany based on 20 years of indoor assessments. In the case of allergens like formaldehyde [9,10], nickel [32], pyrethrum [3], terpe-nes [33], and isocyanates [35], the expert literature is referred to. Based on specific studies on the effects of pyre-throids on the human immune system, “no observed effect levels” (NOEL) are indicated in relation to changes of the signal transduction in human lymphocytes [8,9-12]. Considering the limited research in this field further development of mechanistic models of building related allergen-material responses requires more time and the recommendations presented in this paper will have to be modified in the future. Similarly, the descriptions of the “...allergy assessments of building materials” outlined in the including chapters will have to be adapted to the rapidly developing analytical methods in the allergotoxicological determination techniques. Without any claim to finality and/or totality, the authors present a point scale which allows the definition of four classes of the building material allergenic potency allergenity:
1 No or little allergenic potency
2 Relevant allergenic potency
3 Increased allergenic potency
4 Highly increased allergenic potency
This score may be helpful for anyone who uses building materials. This includes construcion experts such as architects, engineers or producers, tradesmen or patrons, building supervisors or officials. In the spirit of interdisciplinary environmental medicine, it is the aim that physicians and chemists, as well as toxicologists and construction experts reach an agreement that would offer standards for the better mutual understanding of the people in the construction industry. In this extent it could initiate a new profession - the indoor expert. This profession must mainly grounded on the development of the construction market and consumer care.
I. Direct allergic potency
With relation to the German hazard decree (GefStoffV, Anhang I and TRGS 540) [30] and the announcements of the Hazard-Commission (AGS) the following criteria of building material are outlined in respect to their allergenity. In this context the range of the user's atopy (= risk for sensitization) is of particular importance. The clinical definitions of “Allergy” [29] are outlined by J. Ring in his book “Angewandte Allergologie” and serve as a basis to explain the so-called familiar predisposition. Total IgE serum concentration is the main correlate to allergies of respiratory lung airways. Normal values for adults are in the range < 100 IU. In the case of allergic skin diseases IgE-levels can be considered normal in a large range. But specific hyper-
reactivity can be observed against specific compounds (allergens). These can be me measured partly with blood tests. Skin tests are, however, easier, safer, and cheaper (epicu-tantest, pricktest etc.). Furthermore it can be stated, that a major percent of the population does not have elevated IgE-values, but is hyperreactive to single substances. These can also be measured serodiagnosticly. In representative studies of German health insurance companies the prevalence of any type of allergy is as much as 30 % with increasing tendency, affecting more children than adults. In a recent publications it is suggested that currently one of every two human beings suffers from an allergy against at least one substance [17].
The fact that some allergens obtain additional cancero-genic potential makes it difficult to elucidate the special risk of danger. Indoor formaldehyde is a prominent example, where at least higher concentrations can lead to nasal cancer in animal tests. The relatively small formaldehyde molecule shows high chemical reactivity but is not an antigen of itself. Only after interaction with protein side chains, can the derivated structure be recognized as an immunogen by the human immune system. Heavy/colour-metals like nickel, chromium and palladium also obtain allergen potential. This depends on the oxidation level. Chromium penetrates the skin by an oxidation level VI. However, the dangerous and cancerogenic response of chromium is oxidation level III... The following Table I outlines the overlapping toxicology.
The prognoses for the allergen pollution in indoor-air or house-dust and material/product-abrasion is based on experiences during indoor assessments, which are published and discussed by the Institute for Environment and Health (IUG) [6-10,14,19].
The following priority should be mentioned: (Tab. I)
Regarding allergic reaction/response, the most important allergens are those which affect anaphylactic immediate reaction like shock, urticaria, hay fever or bronchial asthma, but also late reactivity in ekzema attacks etc. following the sensitization period. (Type I) [4] From a clinical perspective this type of allergic reactivity composes
about the range 70 % of all cases. Sensitivity is only possible, if the human immune system is able to recognize the allergenic molecule and after receptor interaction at the cell surface of immune competent cells a signal transduction can initiate the regulatory downstream influencing nuclear factors at the DNA-level. Two criteria are preconditional:
1 Size of the molecule (Mr > 500)
2 The specific allergenic site of the molecule (determinant)
Further immunogen factors influence the intensity of the reaction: Secundary chemical factors (e.g. azo-colours develop allergenic amines, metals develop allergenic organic metal complexes, aldehydes interact with body-proteins and develop antigens etc.); mitogenic factors (for instances, in the presence of lipopolysaccarides or plant alkaloids where e.g. house dust can further aggravate allergies); and carriers (antigens e.g. pollen are absorbed by dust, proteins or other aerosols which then reach the irritated mucose of the bronchial/lung). The most dangerous lipophilic hazards are definitely epoxides (e.g. rest-monomeres in plastics) and azo-colours, which can penetrate down to the nucleus and initiate a long-term effect on the DNA-level (e.g. cancero-gens). Caseins are exclusively sensitizing (aero-)allergens in natural colourants. Once painted and dried, it can be considered that they lose their ability to be incorporated into the human body. However, dependent on the surface properties corrosion and rub-off can develop a dangerous mixture which can be inhaled. This is true for natural textile surfaces (e.g. cotton carpets) or thatched roofs (thatch, sisal, bambus etc.).
Contact allergens (Type IV) [4] are habitually listed in occupational health and can be characterized as relatively small molecules. Ni in corrosioned alloys with the oxidation level II and formaldehyde in chipboards are included in this group. As mentioned earlier, both substances contain additional sensitizing potential, which can be explained by the high chemical reactivity during interaction with foreign or bodily proteins.
Table I. INDOOR ALLERGENITY - SCHEMATIC CLASSIFICATION AND EXAMPLES
1 Allergens with other additional toxic potential (particularly cancerogenity) e.g. Epoxide, Azo-colours [14]
2 Sensitizing and Contact-Allergens (Type I and Type IV) e.g. Formaldehyde [4]
3 Sensitizing Allergens (only Type I) [4] e.g. Caseine In Nature-colours, from animals and plants
4 Primarily Contact-Allergens (Type IV) [21] e.g. Ni in fittings, Amines [20]
5 Pseudoallergens e.g. diverse so-called Histamine-1iberators like alkaline peptides and ionophores [7]
Contact allergens can initiate a delayed response which typically manifests allergic symptoms two days after contact. The causal allergen can be detected via skin test (epi-cutan test).
Pseudo-allergens are substances which stimulate allergic symptomes like true allergens. They are defined as anaphylactoid as opposed to anaphylactic reactions. Most of these substances are not able to sensitize the organism and therefore cannot induce the typical long-term sensitizing effect. [7] Anaphylactoid responses bypass the immunological reaction chain provoting the mediator cells (mast cells, basophils) directly. Furthermore, there are hazards which can mimick the mast cell mediators like histamine. These and other mediators stimulate immediate symptoms in any individual levels of intensity. Pseudo-allergens include volatile acids, ketones, or amines; particularly basic peptides; but also formaldehyde - which belongs to all groups in Table I. Preconditionally the contaminants can be incorporated and penetrate the skin. There are also contaminants which stabilize the mediator cells, such as distinct alkalines and carbon monoxide. Table I summarizes the substances on a priority score. As it is mentioned earlier, formaldehyde has a relatively high value as (pseudo-)allergen as it belongs to all five groups.
II. Indirect allergic potency
Classical indoor allergens are/include:
1 microorganisms (molds and bacteria)
2 house dust mite (-excrements)
3 animal epithelia, hair and secretions
4 other organic compounds (In the kitchen, indoor plants etc.)
The indirect allergenic building materials include all materials which allow or stimulate the growth/distribution of microorganisms or other above mentioned classical indoor allergens. The outlined characteristics in buildings and homes can induce these processes:
-cold bridges
- leaks
- surface
—> —» —» —>
- substrates
for microorganisms —>
- accumulation
of dust, animal epithelia —»
- others
condensed water water penetration allergen penetration large surface dirt absorption difficult to clean (textile carpets)
after abrasion
electrostatic
thermore, materials which provide nutrition for the smallest animals should also be avoided; particularly prefabricated wooden houses, which can sometimes invite rodents to gnaw at the wood and get inside the house.
III. Relevant allergen-groups
The presented catalogue does not distinguish between allergens that contact at the inhalation organs, skin, or other target organs. This differs from the GefStoffV in
Table II. RELEVANT ALLERGEN-GROUPS
People who are allergic should avoid use of building materials, which alone or after construction support the growth of germs and germ carriers (bacteria or molds). Fur-
Examples:
Aldehyde/
Dialdehyde - Formaldehyde - Glutardialdehyde
Anhydride -1,1 -Cyclohexanedicarbonsacidanhydride - Phthalateanhydride -1,2,4,5-Benzynetetracaitonaciddlanhydride - Tetraphthalateanhydrid
Metals/
Metalcomplexes - organic Hg-compounds - Colour-metals (Cr, Ni, Co complexes)
Amine/Ammonia-
compounds/Amide - p-Amlnodiphenylamine - Ammoniapersulfate - 2-Chloracetamine - N-(2-hydroxyethyl)-3-methyl-2-chinoxa-lin-carboxamid-1,4-dioxid - N-isopropyl-N'-phenyl-4-phenylendiamin
Terpenes - (epoxidated)
Thiazine/Thiazole - 2-Chlor-10-(3-dimethyl-aminopropyl)-phenothiazine - MCI/MI (3:1) - 2-Mercaptobenzothiazol - N-cyclohexylbenzothiacylsulfenamid - Benzisothiazolinon
Thiurame - Tetramethylthiuramdisulfid - Dipentamethylenthiuramdisulfid (see also Metal-complexes of Zn)
Nitrile/Cyane /Nitro-/Para-
compounds - o-Nitro-p-phenylendiamine - 1,2-Dibrom-2,4-dicyanobutan
Triazine - N,N',N"-tris(fl-hydroxyethyl)-hexahydro-1,3,5-triazlne
Mixtures - acrylates - wood (ref. TRGS 907) - Pyrethrum/Pyrethrolds - Natural latex - Terpentine oil - Polyurethane (Isocyanate) - Lanoline - Dithiocarbamates - Colourents (Azo- and antrachinon-)
Germany. Obviously, the localization of the point of incorporation can be difficult, for instance as airborn exposure - less via the gas phase than as aerosol particles -simultaneously takes place via skin/mucose more or less dependent on the inflammatory ekzemateous status. (Tab.
II)
It is recommended that the allergens outlined in Table II should be avoided or minimized in building materials. The current guidelines must be noted e.g. chromate poor cement. Bound metals in concrete or plaster cannot induce allergies even in atopies. This is similar in wood; however, in wooden dust, particularly from tropical timber, are allergens as well as cancerogens. In this case, the special risk can be found when atopic people build there own homes, use wood-material during renovation, and consumers are contaminated with wood dust. Those or other opportunities must be taken into account when assessments of the allergenity of building materials are carried out.
In the following Table III, some building material relevant index values are summarized. These values are not quantified by means of immunotoxicological background, but they can be used for atopic and chemical-sensitive consumers according to long-term experiments on indoor assessments by the IUG:
Formaldehyde. It must always be considered that there exist products containing formaldehyde and formaldehyd releasing preservatives, but also indirect formaldehyde emittants like ethoxylated surfactants must be taken in account.
Complaints caused by the use of formaldehyde-emitting materials in e.g. school buildings are clearly demonstrated. A significant dose related sensitization rate was seen in Guinea Pig Maximization test after induction with formaldehyde. Currently an OEL (occupational exposure limit) 0.3 ppm was recommended. The authors calculate one tenth of this level -
0.03 ppm (= 0.36 mg/kg) - as a safety range in environmental health. (Tab. Ill)
Ni. Adolescents still suffer from atopic dermatitis and the risk of developing allergic contact dermatitis seems to be large. [25] Allergic contact stomatitis induced by contaminated drinking water and/or food must also be taken in consideration, as well as other chemically neighbourhood metals like cobalt, mercury, and chromium [28] The influence of atopy on delayed type hepersensitivity still remains unclear, and it is suggested that both T helper lymphocyte-
1 (Thl) and T helper lymphocyte-2 (Th2) type cytokines are involved in the immunopathogenesis of contact allergy. But no significant differences between nonatopics and atopies could be elucidated after Ni challenge. [34,18] Threshold values were calculated in accordance of patch test experiments using 5 % Nickel chloride solution. (Tab.Ill) Pyrethrum/Pyrethroids. Improper use of pyrethroid insecticides in supermarkets, schools, kindergarten, aeroplans, and private dwellings lead to the specific pyrethroid syndromes Type I and II. [15] These effects can be aggravated by its synergist piperonyl butoxide and other combinated chemicals. [11,12, 15] Long-term effects may influence the immune system and transmembrane signal-transduction affecting transcriptional nuclear factors. (Diel et al. 2000) Atopies seem to be more sensitive to pyrethroids than nonatopics. [9,10] Threshold values 3 mg/kg are estimated based on the predicted NOELs in the range 10 - 1000 mg/kg which effective in human blood lymphocyte tests ex vivo. (Tab. Ill)
Terpenes. Terpenes are relevant indoor air pollutants emitted by different sources and building materials. Mainly d-limonene, d-3-carene, a-terpinene, and a-pinene were investigated to cause especially chronic effects on the airways. However, oxidative processes like ozone/terpene reactions may occure and can be a significant source of sub-
Table III. INDECES FOR ALLERGENES IN BUILDING MATERIALS*
Allergene Building substance Index (for atopies)
Formaldehyde Acryl-, Phenyl-resin chipboards etc. 30 pg/m3 (0,025 ppm) [22] 30 pg/m3 (0,025 ppm)
Ni and other colour-metal alloys drinking-water pipes free or 10 mg/kg Material 10 mg/kg Material
Pyrethrum/Pyrethroids wood textile carpets 3 mg/kg [3] 3 mg/kg
Terpenes wood fixatives max. 30 pg/m3 [33] max. 30 (jg/m3
Isocyanates PU-foams Polyurethane-fittings 0,14 pg/m2 (0,02 ppb) [35] 0,14 pg/m2 (0,02 ppb)
* first recommendations
micron particles in indoor air.[36] Although terpene exposures up to 214 mg/ m3 did not cause any changes in lung function [13], the threshold level of 30mg/ m3 - that is one fifth of the Swedish OEL (150 mg/ m3) is recommended [33].
Isocyanates: The derivatives of isocyanates have been reported to be potent chemical sensitizers Specific and unspecific (irritant) responses are important in allergic asthma diseases. The most important source of building materials which release isocyanates are epoxy resins. On the other hand isocyanates are not volatile. Therefore, the recommendation of indoor air threshold concentrations seems to be difficult. [14,35] Based on current investigations the index of 0.14 m/m3 is recommended. (Tab. Ill)
IV. Procedure of the allergenity assessment of building materials
The allergenity tests of building-materials are performed as follows:
1 Relevance of function and exposition
2 Availability of data and substance characteristics
(safety data sheet etc.)
3 Tests of allergenity:
allergotox - IV 1
immunological ex vivo - IV 2
contact-allergological potential - IV 3
immunological in vivo - IV 4
The procedure of the indoor assessment is described in various works. [6] The testing institute notes the contaminations in reference to the manifold of the allergens, as well as the mitogenity or adjuvant characteristics of carrier materials (e.g. house dust). This can lead to a devaluation of the building material. Metabolites of the incorporated allergens must be included in the assessment following the rules of good laboratory practice. This may be true for split off of formaldehyde or paranitrophenyls from resins or other inhaled antigens. The same is true for known combination responses if any synergist, e.g. piperonyl bu-toxide in pyrethoid treated wood-materials exists. As in different sectors, structure-response analytical assessments have to be performed, as well as toxicokinetic and toxico-dynamic tests.
Photoallergic sensitization must also be considered, as well as the specific cross-reactivity potentials of allergens.
In case of doubt assessments have to be carried out in accordance to the chemical laws such as the German ChemG.
IV. 1. Allergotoxical Test
Generally the allergological tests are carried out in standardized test chambers. In total, about 200 single compounds are determined. From these, 50 show allergen and/or pseu-
do-allergen potential. The measurements are related to the following groups of contaminants:
1 Olfactometrical determinations
2 V0C and SVOC (in the standardized test chamber)
3 Glycols and other polar compounds
4 Aldehydes and ketones
5 Chemical additives
Assessments in regard to the TVOC-concept under particular consideration related to allergens and pseudo-allergens
6 Heavy- and colour-metals (from the solid samples)
7 Selected biocides
The test chamber method is performed in reference to CEN/TC 264 Air Quality - Indoor Air Quality. The substances are resorbed in special resorption tubes at different air exchange rates in 100 L- and 250 L-high-grade steel test chambers. After resorption, they are separated and analysed on GC-MS (gas chromatography - mass spectrometry). Depending on the sample material metals are determined by ICP-MS (inductively coupled plasma), AAS (atomic absorption spectrometry) or polarography (if there are toxicologically relevant oxidation levels e.g. Cr).
The toxicological values are reported in reference to the recommendations of the AGÖF (Arbeitsgemeinschaft Ökologischer Froschungsinstitute) as well as ChemG (Chemikaliengesetz v. 1982), GefStoffV (Gefahrstoffverordnung v. 1986), TRGS (German technical guidelines for hazards) and the relevant reports of the LMBG (Lebensmittel- und Bedarfsgegenständegesetz) ff. respectively.
IV.2. Immunological tests ex vivo
Immunological tests are performed for the allergotoxi-cological assessments using blood cell fractions of atopies and non-atopics in incubates and primary cell cultures. These ex v/vo-methods are publicated in peer reviewed international journals. [11,12]. These include
1 the histamine-liberation-test HLT (which mimicks the anaphylactic and anaphylactoid immediate reaction)
2 the lymphocyte-vitality-test (testing the lymphocyte proliferation, “MTT-test” after stimulation using different mitogens like PHA - phytohemagglutinin, LPS -lipopolysaccharide, Con A - concanavalin A etc.)
3 the basophile-degranulatlon-test (panoptical determination of the degranulated basophils from atopies and non-atopics. This is to recognize the challenge of basophils in atopies and non-atopics.)
The catalogue of allergens in the MAK- BAT-lists of the DFG (Deutsche Forschungsgemeinschaft)-Senatskommis-sion serves as a basis for the assessments. In this case mainly inhalative (contact-) allergens are reported. (Table IV)
Table IV. ALLERGENS IN THE GERMAN MAK- UND BAT- VALUE LISTING (DFG 2000)
Acrylnitril [107-13-1] (Sh)
1-Allyloxy-2,3-epoxypropan [106-92-3] (Sh)
0-Aminoazotoluol [97-56-3] (Sh) a-Amylase (Sa)
1.2-Benzisothiazol-3(2H)-on [2634-33-5] (Sh)
Bisphenol A (4,4'-Isopropylidendiphenol) [80-05-7] (SP) Bisphenol-A-diglycidylether [1675-54-3] (Sh)
Bithionol [97-18-7] (SP)
2-Brom-2-(brommethyl)pentandinitril (l,2-Dibrom-2,4-dicyanbutan) [35691-65-7] (Sh)
Butanonoxim [96-29-7] (Sh)
1-n-Butoxy-2,3-epoxypropan [2426-08-6] (Sh)
1-tert-Butoxy-2,3-epoxypropan [7665-72-7] (Sh) n-Butylacrylat [141-32-2] (Sh)
N-Carboxyanthranilsäureanhydrid [118-48-9] (Sh)
2-Chlor-10-(3-(dimethylamino)propyl)phenothiazin (Chlorpromazin) [50-53-3] (SP)
1-Chlor-2,4-dinitrobenzol [97-00-7] (Sh)
Chloressigsäuremethylester [96-34-4] (Sh) 5-Chlor-2-methyl-2,3-dihydroisothiazol-3-on [26172-55-4] und
2-Methyl-2,3-dihydroisothiazol-3-on [2682-20-4]
Gemisch im Verhältnis 3:1 (Sh)
Chlorthalonil [1897-45-6] (Sh)
Chrom(VI)-Verbindungen [18540-29-9] (Sh)
Cobalt [7440-48-4], seine Legierungen und wasserlöslichen Salze (Sah) Colophonium [8050-09-7] (Sh)
4,4'-Diaminodiphenylmethan [101-77-9] (Sh)
1.3-Dichlorpropen [542-75-6] (cis- und trans-) (Sh) Diglycidylresoreinether [101-90-6] (Sh)
1.1-Dimethylhydrazin l9) [57-14-7] (Sh)
1.2-Dimethylhydrazin l9)[540-73-8] (Sh) Diphenylmethan-4,4'-diisoeyanat [101-68-8] (Sah)
Disulfiram ,7) [97-77-8] (Sh)
Ethylacrylat [140-88-5] (Sh)
Ethylenglykoldimethacrylat [97-90-5] (Sh)
2-Ethylhexylacrylat [ 103-11 -7] (Sh)
Ethylmethacrylat [97-63-2 (Sh)
Formaldehyd [50-00-0] (Sh)
Getreidemehlstäube (Sa):
Roggen
Weizen
Glutardialdehyd [111-30-8] (Sh)
Glycerylmonothioglykolat [30618-84-9] (Sh) Glycidyltrimethylammoniumchlorid [3033-77-0] (Sh)
Glyoxal [107-22-2] (Sh)
Gummiinhaltsstoffe:
Dithiocarbamate (Sh) p-Phenylendiamin Verbindungen (Sh)
Thiazolgruppe (Sh)
Thiurame (Sh)
Hexahydrophthalsäureanhydrid [85-42-7] (Sa) Hexamethylendiisocyanat [822-06-0] (Sah)
Hexamethylentetramin [100-97-0] (Sh)
1,6-Hexandioldiacrylat [13048-33-4] (Sh)
Hölzer:
Acacia melanoxylon R.Br. (Sh), tropische Akazie Brya ebenus DC. (Sh), Cocusholz, westindisches Grenadillholz Chlorophora excelsa (Welw.) Benth. & Hook (Sh), Iroko, Kambala Dalbergia latifolia Roxb. (Sh), ostindischer Palisander Dalbergia melanoxylon Guill. et Perr. (Sh), afrikanisches Grenadillholz:
Dalbergia nigra Allem. (Sh), Rio Palisander Dalbergia retusa Hemsl. (Sh), Cocobolo Dalbergia stevensonii Standley (Sh), Honduras Palisander Distemonanthus benthamianus Baill. (Sh), Ayan, Movingui Grevillea robusta A.Cunn. (Sh), australische Silbereiche Khaya anthotheca C.DC. (Sh), Acajou blanc, afrikanisches Mahagoni Machaerium scleroxylon Tul. (Sh), Jacaranda pardo,
Santos Palisander Mansonia altissima A.Chev. (Sh), Be Paratecoma peroba (Record) Kuhlm. (Sh),
Peroba do campo, Peroba jaune
Tectona grandis L.f. (Sh), Teak
Terminalia superba Engl. u. Diels (Sa), Frake, Limba
Thuja plicata (D.Don.) Donn. (Sah), Riesenlebensbaum,
Rotzeder, Western Red Cedar Triplochiton scleroxylon K.Schum. (Sah), Abachi, Obeche Hydrazin [302-01-2] (Sh)
Hydrazinhydrat [7803-578] und Hydrazinsalze (Sh) Hydroxyethylacrylat [818-61-1] (Sh)
2-Hydroxyethylmethacrylat [868-77-9] (Sh) N-(2-Hydroxyethyl)-3-methyl-2-chinoxalincarboxamid-1,4-dioxid (Olaquindox) [23696-28-8] (SP) Hydroxypropylaerylat (alle Isomeren) [25584-83-2] (Sh)
2-Hydroxypropylmethacrylat [923-26-2] (Sh)
Isophorondiisoeyanat [4098-71-9] (Sah)
Limonen (Sh):
d,l-Limonen [138-86-3] und ähnliche Gemische, d(+)-Limonen [5989-27-5] l(-)-Limonen [5989-54-8]
Maleinsäureanhydrid [108-31-6] (Sah)
Merbromin [129-16-8] (Sh)
Mercaptobenzothiazol [149-30-4] (Sh)
Methylacrylat [96-33-3] (Sh)
N-Methyl-bis(2-chlorethyl)amin [51-75-2] (Sh)
Methylisocyanat [624-83-9] (Sh)
Methylmethacrylat [80-62-6] (Sh)
N-Methylolchloracetamid [2832-19-1] (Sh) Methyltetrahydrophthalsäureanhydrid [11070-44-3] (Sa) N-Methyl-2,4,6-N-tetranitroanilin [479-45-8] (Sh)
Methylvinylketon [78-94-4] (Sh)
Monomethylhydrazin [60-34-4] (Sh)
Naphthalsäureanhydrid [81-84-5] (Sh)
1,5-Naphthylendiisocyanat [3173-72-6] (Sa) Natriumdiethyldithiocarbamat [148-18-5] (Sh)
Naturgummilatex [9006-04-6] (Sah)
Nickel [7440-02-0], seine Legierungen und wasserlöslichen Salze (Sah) 4-(2-Nitrobutyl)-morpholin [2224-44-4] (70 Gew. %) und
4,4'-(2-Ethyl-2-nitro-l,3-propandiyl)bis-morpholin [1854-23-5] (20 Gew.%) (Gemisch) (Sh)
2-Nitro-p-phenylendiamin [5307-14-2] (Sh)
2-n-Octyl-2,3-dihydroisothiazol-3-on [26530-20-1] (Sh) 4,4'-Oxydianilin [101-80-4] (Sh)
Pentaerythrittriacrylat [3524-68-3] (Sh) o-Phenylendiamin [95-54-5] (Sh) p-Phenylendiamin [106-50-3] (Sh)
Phenylglycidylether [122-60-1] (Sh)
Phenylhydrazin [100-63-0] (Sh)
Phthalsäureanhydrid [85-44-9] (Sa)
Piperazin [110-85-0] (Sah)
Platinverbindungen (Chloroplatinate) (Sah)
„Polymeres MDI“ [9016-87-9] (in Form atembarer Aerosole) (Sah) Pyrethrum [8003-34-7] (Sh)*
Quecksilber [7439-97-6] und seine organischen Verbindungen (Sh) Quecksilberverbindungen, organische (Sh)
Rizinusproteine (Sa)
Sojabohneninhaltsstoffe (Sa)
Terpentinöl [8006-64-2] (Sh)
Thiohamstoff [62-56-6] (Sh SP)
Thiomersal [54-64-8] (Sh)
Thiram [137-26-8] (Sh)
Tierhaare, -epithelien und andere Stoffe tierischer Herkunft (Sah) Toluylendiisocyanate (Diisocyanattoluole): (Sa)
2,4-Toluylendiisocyanat [584-84-9]
2,6-Toluylendiisocyanat [91 -08-7]
Triethylenglykoldimethacrylat [109-16-0] (Sh)
Trimellitsäureanhydrid [552-30-7] (Sa)
Trimethylolpropantriacrylat [15625-89-5] (Sh)
2,4,6-Trinitrophenol [88-89-1] (Sh) N,N’,N”-Tris(ß-hydroxyethyl)-hexahydro-l,3,5-triazin [4719-04-4] (Sh)
Vinylcarbazol [1484-13-5] (Sh)
Zinkchromat [13530-65-9] (Sh)
Zirkon [7440-67-7] und seine unlöslichen Verbindungen (Sah) Zirkonverbindungen (löslich) (Sah)
(Quelle: Deutsche Forschungsgemeinschaft (Hrsg.): MAK und BAT-Werte-Liste. Verlag Wiley-VCH, Weinheim 1999)
*Only relevant for the drug and their extracts with a-Methylensesquiterpenlactone (Pyrethrosin etc.)
Sa = inhalative: Sh = skin: Sah = both - sensitizing: SP = photosensitizing agents
IV.3. Contact-allergen potential Tests
No in vitro test method exists for this. Therefore one has to use the provocation tests with human beings or animals. Normally the animals used in tests are mice and guinea pigs, which are more sensitive than human beings in some cases.
Testing the improvement of the sensitizing potential in humans is forbidden (even for volunteers) in the EU with regard to ethical limits. However in the USA many results exist from relevant studies.
The following animal-tests are usable:
1 guinea pig maximisation test [26]
2 lymph node test on mice [24]
3 TINA-test on guinea pigs [37]
A substance has to be reported as sensitizing after skin contact (“Sa”) when in the presence of Freund's adjuvants > 30 % respond with sensitization of the skin (allergic contact ekzema) or typical changes of the lymph nodes respectively. The substance must then be indicated with an “R” in the working place. (GefStofiV, Anhang 1 No 1.1.2.4.10.-4)
IV.4. Immunological tests in vivo
(has to be elucidated)
As far allergens in building materials are incorporated as aerosols after rub-off or aging a devaluation has to be performed, (see at the beginning ® carriers) The recommendations and definitions in the MAK-publications have to be considered. (DFG 1999, p 157ff) Additionally the mitogenic responses of the carriers from dust, fiber rub-off, foams and emissions must be indicated as ultrafine aerosols obtaining diffusion-equivalent radius < 100 nm.
The following point-scale is recommended for use in the assessment of the allergenity of building materials (Tab. V)
Table V. POINT-SCORE ALLERGENITY OF BUILDING MATERIALS
Sen sitizing (anaphylactic)-*- other toxicity (e.g cancerogen) Basic points max 5
Sensitizing + contact allergen (Type 1 + Type IV) 4
Sensitizing (Type 1) 3
Contact-allergen (Type IV) 2
Pseudoallergenity (anaphylactoid) 1
Indirect allergenity (chapter II) 1
Other Type of the allergic responses 1
From this score the maximum number has to be selected and multiplied with the following factors dependent on exposure risk:
Factor
Inhalative and/or aerosol 2
Combination response (Synergist) 1,5
Aerosols after aging and/or rub-off 1,5
Additional main allergens 1,5
(Other the allergic symptoms supporting influences 1,5)*
*optional, if more than one of the mentioned influences exist but do not lead to be valued by the factor 1.5
In this scheme, a maximum score of 5 x 2 x 1,5 x 1,5 x 1,5 = 33,75, rounded up to 34, can be calculated. (It must be rounded up or down)
1. Example: HCHO. A formaldehyde-containing (>
00.3 ppm) chipboard with terpene (e.g. d,l-limonen) paint suffering from slight abrasion can reach the following point score: (Diel F 1993)
5 (sensitizing and chemical change of body proteins + suggestion of cancerogen activity) x 2 (inhalative) x 1.5 (aerosols after aging of the chipboard - less intensive) x 1.5 (terpenes are violent allergens) x 1.5
Total count for the wooden chipboard: 34
2. Example: Ni. A loam paste at the outer wall of a building contains > 500 mg/kg Ni as well as Cr and Co. (Schubert 1985)
2 (contact-allergen) x 1.5 (other non-unresponsive con-tact-allergens)
Total count for outside loam paste: 3
3. Example: Pyrethrum. A cotton carpet is treated with pyrethrum/PBO and fixed with SVOC emitting fixative. (Fischer et al. 2000)
3.1. Without lanolin (wool-fat allergen)
2 (weak contact-allergen) x 2 (inhaled as aerosol in house dust) 1.5 (combination response with PBO) (Witte et al. 2000)
Total count for fixed cotton carpet without lanolin: 6
3.2. With lanolin
6 (from 3.1) x 1.5 (additional allergen)
Total count for fixed cotton carpet with lanolin: 9
In Table VI the point scale is recommended:
Table VI. VALUE SCALE FOR THE ALLERGENITY OF BUILDING
MATERIALS
Points score/value
1 - 4 no or weak allergenity
5-10 relevant allergenity
11-20 increased allergenity
> 20 high allergenity
Results for the calculated examples from this assessment:
Example 1:
Formaldehyde containing chipboard “high allergenity’’
Example 2:
Colour-metal containing outside loam paste “no allergenity” Example 3:
Insecticide treated cotton carpet “relevant allergenity”
A basis point score is provided in Table V in relation to the priority in Table I. This can be explained following the generally accepted allergotoxical considerations. For the assessment of the allergy risk, which can be suffered after the use of building materials containing allergens similar to other harmful contaminants, the type and structure of the molecule is important for the choice of the basic point score. On the other hand, the individual incorporation and sensitivity of target organs is of importance. (Factor)
This can be different than other pollutants, which do not respond as much depending on the individual sensitivity, as other allergens do. The family heredity, the fact of atopy - yes or no - can definitely influence the allergotox-icological assessment scores. In extreme cases, the one and only contamination of an allergen can be relevant in one family, but irrelevant in another. Increased Ni-conatmina-tions can cause elevated chronic digestive diseases with all its complications in a family with predisposition to contact-allergen sensitivity against colour-metals. Sometimes it is difficult to make the proper diagnosis. A different family without any such predisposition may not show any symptoms. How is it possible to standardize the assessment of those building materials?
The recommended scores in the presented paper can give a rough orientation to the matter of consumer care. With long-term experiences in indoor assessment and the study of literature, it can now be suggested that the risk of suffering from an indoor disease caused by the “formaldehyde containing chipboard” is much higher than being harmfully contaminated by the “cotton carpets”. In this case, the lanolin could be crucial for increased allergic symptoms. This can only be true, if skin contact or incorporation of dust after rub-off has taken place.
The selected cases should validate the procedure for the proper choice of basic points and factors. It can be elucidated that the inspector and the inspecting institute can make their recommendation within a defined range of consideration. With this, an “after the point-precision” can be avoided. The professional inspector should obtain sufficient knowledge in chemistry, toxicology, and medicine. The al-lergotoxicological education is the main content along the way to the profession Certificated Indoor Inspector. Currently no final criteria or judgement for the allergotoxico-logical assessment of building materials or products exist. This may also be excluded because allergies naturally vary depending on age, geo-social and ethnical conditions.
The decision whether building materials can be used or how much the allergic potential can be minimized has to be
considered on the basis of environmental medical prognoses and the individual family heredity.
Acknowledgement: This work is supported by a grant from the Stiftung VERUM (München).
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поступила в редакцию 20.02.2002 принята к печати 15.09.2002
