As a starting point to discussing organic pigments, it should be noted that the specific physicochemical, toxicological and ecological properties of these compounds present an uncommonly small risk potential. Pigments are not only by definition ‘practically insoluble’, but insolubility in water and organic media is a prerequisite for any application of a pigment. So in this respect, organic pigments differ from all other organic chemicals. An attempt to dissolve an organic pigment by applying extreme solvents such as dimethyl sulfoxide or hexamethylphosphoric triamide leads – if at all successful – to dyes or to decomposition.
The analysis of any substance or product that is to be marketed requires not just identification of its technical and application properties. Toxicological and ecological considerations have become a primary concern in today's industry. The pigment industry is no exception. Manufacturers, processors and customers are always faced with the question of whether the production or use of a specific product might present an unacceptably high toxicological or ecological risk for man or environment. The problem of eliminating or at least reducing these risks to legally acceptable levels is a very urgent one. The question of acceptability is not only based on one's responsibility, but criteria must be developed for each individual case with respect to legal provisions.
It is of paramount importance to evaluate the physical, chemical, toxicological and ecological properties of a pigment in order to be able to assess its influence on the environment and to estimate whether a given product presents a toxicological or ecological risk [1]. It is important also to consider the type of handling and use that a pigment is likely to undergo, the extent of human exposure that might be expected, and the amounts involved. Chemicals are typically assessed on the basis of a limited body of data, a task that is normally assigned to a specialist. More complex cases will even be judged by an interdisciplinary group of experts.
Prime considerations in pigment manufacture and use, as with any other chemical, include personnel safety, air emission and wastewater quality, and appropriate waste removal. Although basic information is supplied by the pigment manufacturer, it is the processor who is responsible for safe handling and use. The processor is also responsible for solving internal safety problems.
It has become increasingly common to provide information on safe pigment handling and use in concentrated form on safety data sheets. Apart from listing physical and chemical parameters and information as to safety and precautionary measures, fire and flammability data, first aid after contamination and accidents, and waste disposal, these sheets also provide toxicological and ecological parameters.
Without exceeding the scope of this book, we focus on the legal situation, which may also affect organic pigments [2].
The following list includes the chemical inventories of the EU and the most industrialized countries of the world:
New Chemical Inventories are expected to be released from more countries (Status Feb. 2015):
Malaysia is preparing an Environmental Hazardous Substance Notification and Registration scheme (EHSNR) (2016). The Malaysia Department of Environment has yet to finalize regulations. There is a road map of the final implementation that may last until 2017. The Authorities have committed to providing a two-month notice before the law takes effect.
These regulations, which also affect pigments, demand that all new products be registered. Various toxicological test results have to be presented, depending on the country. The discussed legal requirements are supplemented by many other more or less specific environmental acts, not only in the countries thus mentioned, but also in practically all other industrialized nations.
In recent years, the number of laws providing protection during the manufacture, use and storage of chemicals has risen worldwide. The same is true for regulations concerning environmental affairs, in particular waste removal (air emission, wastewater, solid waste) (see Table 5.1).
Table 5.1 Important principal chemical laws and ordinances.
Law | Country |
• European Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, (last amended 2015) | EU |
• Commission Regulation (EC) No 790/2009 as Amendment to 1272/2008. | EU |
• European Chemicals Agency. REACH: List of Pre-Registered Substances (2008) | EU |
• Directive 2003/105 (Major Accident Hazards, Seveso II, December 2005) | EU |
• EU Cosmetics Regulation (EC) No 1223/2009) | EU |
• Chemikaliengesetz (Chemicals Act, 2013) | CH |
• Umweltschutzgesetz (Environmental Protection Law, December 2015) | CH |
• Chemikaliengsetz (Chemicals Act, 2006), last amended 2017 | DE |
• Gefahrstoffverordnung (Dangerous Substances Ordinance, July, 2013), last amended 2017 | DE |
• Verbotsverordnung (20.01.2017) | DE |
• French National Nutritional and Health Program (2015) | FR |
• The Chemicals (Hazard Information and Packaging for Supply) Regulation (2009 No.716, March 2009) and Amendments | UK |
• Control of Substances Hazardous to Health (COSHH) (2017) | UK |
• Chemical Substance Control Law as amended (October 2011) | JA |
• Industrial Safety and Health Law (ISHL, 2008) | JA |
• Frank R. Lautenberg Chemical Safety for the 21st Century Act (2016) | US |
• Osha Hazard Communication Standard (2012) | US |
• Emergency Planning and Chemistry Right-to-Know Act (SARA Title III, 1986) | US |
• Canadian Environmental Protection Act (February 2014) | CA |
• Canada EPA List of Toxic Substances (March 2018) | CA |
• Industrial Chemicals (Notification and Assessment) Act (Amendments 2006) | AU |
• Measures on the Environmental Management of new Chemical Substances (2003) | CN |
• Regulation on the Control over Safety of Dangerous Chemicals (March 2011) | CN |
• Safety Rules for Classification, Precautionary Labelling and Precautionary Statements of Chemicals (2006) | CN |
• Chemicals Control Act (1 Jan.2015) | KR |
AU: Australia; EU: European Union; KR: Republic of Korea; CA: Canada; CN: China; UK: United Kingdom; CH: Switzerland; FR: France; US: USA; DE: Germany; JA: Japan. |
The most important changes of the politics of chemicals have been generated by the introduction of two comprehensive international legal frameworks, namely:
The UN GHS aims to ensure that information on the hazardous properties of chemicals is available throughout the world to enhance the protection of human health and the environment during the handling, transport and use. The UN GHS also aims to provide a structure for countries that do not yet have a classification and labelling system. The UN anticipates that once fully implemented, the GHS will:
The 2002 UN World Summit on Sustainable Development agreed that the GHS should be implemented worldwide. This commits countries to make the necessary laws to require suppliers of chemicals within their territories to adopt the UN GHS. The UN work programmes continue to be developed and refine the UN GHS in biennial work programmes. GHS supersedes the relevant European Union and United States of America standards.
Within the Europe Union, Member States asked the European Commission to prepare a proposal for a Regulation that would implement the UN GHS criteria in all EU Member States. The European Parliament together with the Council released the European Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures. It is known as the CLP Regulation. The CLP Regulation was published in the European Union's Official Journal on 31 December 2008 and entered into legal effect on 20 January 2009, subject to a lengthy transitional period. The proposed Regulation together with its Amendment Commission Regulation (EC) No 790/2009 is direct-acting, requiring no national transposition. Its provisions was phased to be in over a period of 7½ years up to 1 June 2015. This is intended to help suppliers and users of chemicals change from the current EU classification and labelling system to the new GHS-based system.
From 2010 the Globally Harmonized System (GHS) replaced the EU Dangerous Substances Directive 67/548/EEC, (see Annex 1 of 67/548/EEC under REACH).
The main aims of REACH Regulation, which came into force on 1 July 2007, are to ensure a high level of protection of human health and the environment from the risks that can be posed by chemicals, the promotion of alternative test methods, the free circulation of substances on the internal market and enhancing competitiveness and innovation. REACH makes industry responsible for assessing and managing the risks posed by chemicals and providing appropriate safety information to their users. In parallel, the European Union can take additional measures on highly dangerous substances, where there is a need for complementing action at EU level.
With the REACH Regulations the following laws have been repealed:
The Dangerous Preparations Directive (1999/45/EC) has been amended by Directive 2001/60/EC and Directive 2006/8.
Annex 1 of the Directive 67/548/EEC that listed substances which have been officially classified as dangerous is now replaced by the CLP-Regulation 1272/2008 in Annex VI Part 3 with the Table 3.2: ‘The list of harmonized classification and labelling of hazardous substances from Annex I to Directive 67/548/EEC’.
No organic pigment is included in Table 3.2 of the Regulation 1272/2008.
Section 8 REACH regulation details the restriction on certain dangerous substances, and preparations or articles which are manufactured, used and placed on the EU market. Any substance could be restricted in EU, as long as the use of the substance poses an unacceptable risk to human health or the environment.
Currently, there are 59 categories of restricted substances in REACH Annex XVII, involving more than 1000 substances. These hazardous substances have specific restrictions, and as such certain chemical substances in the specific product are not allowed to be used, so as to avoid any unnecessary testing. Typical hazardous substances that are restricted in products include lead, Azo dyes, DMF, PAHs, Phthalates, PFOS, the nickel release and so on.
Since the XVII of REACH regulation took into force in 2009, the following directives have been replaced:
“Azocolourants” concern Aromatic amines, s. Table 5.2
Table 5.2 List of carcinogenic aromatic amines referred to in Reach Annex XVII, Appendix 8, Point 43c).
Classification as carcinogen | ||||
Aromatic amine | CAS-No. | EU (Annex1) | IARC | MAK III |
o-Anisidinea) | 90-04-0 | Cat. 2 | 2 | |
2-Naphthylamine | 91-59-8 | Cat. 1 | Group 1 | 1 |
3,3′-Dichlorobenzidine | 91-94-1 | Cat. 2 | Group 2B | 2 |
4-Aminodiphenyl | 92-67-1 | Cat. 1 | Group 1 | 1 |
Benzidine | 92-87-5 | Cat. 1 | Group 1 | 1 |
o-Toluidine | 95-53-4 | Cat. 2 | Group 2B | 2 |
4-Chloro-o-toluidine | 95-69-2 | Cat. 2 | Group 2A | 1 |
4-Methyl-1,3-phenylenediamine | 95-80-7 | Cat. 2 | Group 2B | 2 |
o-Aminoazotoluene | 97-56-3 | Cat. 2 | Group 2B | 2 |
5-Nitro-o-toluidine | 99-55-8 | b) | Group 3 | 2 |
4,4′-Methylene-bis(2-chloraniline) | 101-14-4 | Cat. 2 | Group 2A | 2 |
4,4′-Methylenedianiline | 101-77-9 | Cat. 2 | Group 2B | 2 |
4,4′-Oxydianiline | 101-80-4 | b) | Group 2B | 2 |
p-Chloraniline | 106-47-8 | Cat. 2 | Group 2B | 2 |
3,3′-Dimethoxybenzidine | 119-90-4 | Cat. 2 | Group 2B | 2 |
3,3′-Dimethylbenzidine | 119-93-7 | Cat. 2 | Group 2B | 2 |
p-Cresidine | 120-71-8 | b) | Group 2B | 2 |
2,4,5-Trimethylaniline | 137-17-7 | b) | Group 3 | 2 |
4,4′-Thiodianiline | 139-65-1 | b) | Group 2B | 2 |
4-Methoxy-m-phenylenediamine | 615-05-4 | b) | Group 2B | 2 |
4,4′-Methylenedi-o-toluidine | 838-88-0 | Cat. 2 | Group 2B | 2 |
4-Aminoazobenzene | 60-09-3 | Cat. | Group 3 | |
a) The application is banned to carpets and to articles that may come into contact with the oral cavity and to toys containing leather or textiles. b) EU classification pending. c) 4-Amino-3-fluorphenol and 6-Amino-2-ethoxynaphthalin are not listed in Table 5.2, because no Azo dyes are known, which could split to these amines. |
Over the next decade the REACH regulation will assemble a large body of information on the properties of chemical substances produced or imported in quantities in excess of 1 ton per year. This complex regulation, with major constraints on industrialists, is a fundamental tool for the public powers and civil society to improve the long-term wellbeing of the population in terms of health and the environment.
The implementation of REACH entails three real challenges:
Important legal regulations for pigments are primarily connected with food packaging, consumer goods and toys. In this context two general principles must be considered [5]:
The primary concern of regulations that pertain to pigments in particular is to define upper limits for impurities such as traces of heavy metals, traces of aromatic amines, polychlorobiphenyls, polychlorinated dibenzodioxins/-furans (‘dioxins’). These limits, which are defined differently by individual countries, should not be exceeded. This is of paramount importance in pigment applications that involve particularly high potential human exposure, for instance in colours for the artists' market or for children's finger paints. The same is true for low exposure applications (pigments are incorporated in coatings or plastics and thus largely protected from human contact) but, however, affect a large number of persons. This is particularly important in areas such as toys or food packaging. In Germany, for instance, the use of colourants for consumer goods is described by Recommendation IX of the Federal Institute for Risk Assessment at the Federal Health Agency (Bundesgesundheitsamt), which stipulates that no colourant may enter food at all, not even in traces [6].
Examining the ‘curriculum vitae’ of a pigment consists of the following steps:
The single most important factor in evaluating the toxicological and ecological properties of an organic pigment is its extreme insolubility in water and in the application media.
Pigments are therefore processed largely as solids, crystalline, and consequently are physiologically inert materials.
Since organic pigments are commonly combined with other materials, a pigmented system typically contains only a small percentage of actual pigment. It is therefore likely that other components, such as binders, solvents and various agents may more severely affect the ecological and toxicological properties of the applied product.
Table 5.3 below lists the specific legislation primarily concerning organic pigments.
Table 5.3 Legislation concerning organic pigments.
Legislation | Country |
Regulation (EC) No 1935/2004 on materials and articles Intended to come into contact with Foodstuff (Framework) | EU |
European Norm EN 71-Part 3: Safety of Toys | EU |
Matériaux au contact des denrées alimentaire produits de nettoyage de ces | EU |
Directive 2009/48 on the Safety of Toys (June 2009), last amendment 2015 | EU |
European Council Resolution AP(89)1: Colourants in plastic materials (1989) | Council of Europe |
Matériaux, No. 1227, Direction des Journaux Officiels, Paris | FR |
Circulaire No 176 relative aux pigments et colourants des matières plastiques du 2 décembre 1959 | FR |
Matériaux mis au contact des denrées alimentaires Lettre-circulaire (1979–1985) | FR |
Projet d'arrêté relatif à la colouration des matériaux et objets en matière plastique, des vernis et des revêtements destinés à entrer en contact avec les denrées, produits et boissons pour l'alimentation de l'homme et des animaux (2010) | FR |
Entwurf zur Änderung der Bedarfsgegenständeverordnung vom 26.06.2016 | DE |
Verwaltungsvorschrift wassergefährdende Stoffe (Änderung 2011) | DE |
817.02 Lebensmittel- und Gebrauchsgegenständeverordnung (February 2016) | CH |
817.023.21 Verordnung des EDI 2005 über Bedarfsgegenstände (1 April 2013) | CH |
Self-Restrictive Requirements on food-contacting Articles made of polyolefins and certain polymers, part 2, Positive lists, Colourants. 8th edition (May 2004) | JA |
GB 9685-2008, Hygienic Standards for Uses of Additives in Food Containers and Packaging Material | CN |
FDA Regulation 21CFR 178.3297. Colourants for Polymers | USA |
Safe Handling of Colour Pigments, edited by CPMA | USA |
The European Commision has published the August 2014 version of “Addresses of European and National European Authorities” related to ‘General Health and Consumers’ as well as a list of the National Governmental Authorities in Europe.These documents can be obtained from: http://ec.europa.eu/food/food/chemicalsafety/foodcontact/auth_ref_en.pdf
Brochures on Safe Handling of Pigments have been published in the USA [7] and in Europe [8, 9] summarizing general health effects, hazard communication, environmental concern and providing information on safety data of the most important pigment classes.
Food packaging plays an important role in context of food contact. The number of regulations considering food contact materials like plastics, metals, coatings, paper and board, rubbers and others alone amounts to more than 4700 regulations worldwide, although the EU legislation has lead to a considerable unification of laws.
Materials and articles intended to come into contact with foodstuff are generally regulated in the EU by Framework Regulation (EC) No. 1935/2004/EEC. The principle underlying this regulation is that any material or article intended to come into contact directly or indirectly with food must be sufficiently inert to preclude substances from being transferred to food in quantities large enough to endanger human health.
Council Directive 89/109/EEC and Commission Directive 90/128 have been repealed.
Single Directives, laws and resolutions are released under Regulation (EC) 1935/2004, such as given below.
Regarding colourants no uniform EU regulation exists so far concerning the colouration of food packing. The European Resolution AP (89)1 [10] aims at a harmonized EU regulation. The required purity criteria for colourants to be used for the colouration of food packing materials made from plastics are:
Council of Europe Resolution AP (89) 1 (1989):
Metal | Limit (ppm) | Metal | Limit (ppm) |
As | 100 | Hg | 50 |
Ba | 100 | Pb | 100 |
Cd | 100 | Sb | 500 |
Cr | 1000 | Se | 100 |
Belgium, France, Great Britain, Germany, Greece, Portugal and Switzerland are in accordance with these limit values. Deviations exist in the Netherlands for Cd (1000) and Sb (2000) and in Spain for Ba (1000) and Cd (2000) [11].
Several non-European countries have released identical or similar regulations to the European Regulation AP (89)1 regarding the threshold limits for metals, aromatic amines, aromatic aminosulfonic acids and PCB.
Identical threshold limit values for metals with the data of the Council of Europe Resolution AP (89)1 exist in:
Country | |
Australia: | Australian Standard 2070-1999 Plastic materials for food contact use |
Japan: | Japan Hygienic PVC Association (JHPA) PVC for Food Contact Applications: for As, Cd, Hg and Pb. |
Belgium | Arrêté royal modifiant l'arrêté royal du 3 juillet 2005 relatif aux matériaux et aux objets en matière plastique destinés à entrer en contact avec les denrées alimentaires (18 September 2008). |
Germany: | Empfehlung IX. Farbmittel zum Einfärben von Kunststoffen und anderen Polymeren für Bedarfsgegenstände (01.02.2015) (Rec. IX. Colourants for Plastics and other Polymers Used in Commodities (2015)). |
United Kingdom: | Statutory instruments 2009 No. 205. The Plastic Materials and Articles in Contact with Food Regulations 2009. |
Switzerland: | Kunststoffverordnung, (June 2015). |
The Council of Europe Resolution AP (89) 1 also regulates the contents of the following substances:
Limit values for a specific country should be viewed in the corresponding listed references.
On a national basis, toys require compliance of limits for the same impurities as outlined under food packaging/food contact. In particular, trace metal amounts have to be considered as well as threshold limits for aromatic amines, soluble in 0.07M hydrochloric acid. The trace amount of cancerogenic amines should, depending on the various countries, not exceed 5 or 10 ppm.
Incorporation of the EU regulation into national laws has reduced the number of national laws in this field.
EU Directive 2009/48/EC [15] on the safety of toys contains a list of migration limits of 19 ‘elements’ (metals), a list of allergenic fragrances with <100 mg kg−1 and a corresponding list with >100 mg kg−1.
The following region- or nation-specific regulations apply for toys, with most of the EU countries transposed.
Country | |
Belgium: | Koninklijk besluit van 4 maart 2002 - Wijziging: Koninklijk besluit van 30 december 2009, veiligheidvan speelgoed. |
Germany: | EN/DIN 71-3: Part 3: Migration of certain elements (November 2002). |
BfR Rec. 47 [XLVII.] Toys from plastics and from paper and paperboard (2003). | |
France: | Décret no 2010-166 du 22 février 2010 relatif à la sécurité des jouets. |
Switzerland: | Verordnung über die Sicherheit von Spielzeug (2002); Änderung vom 13 January 2011. |
Country | |
Australia: | Australian Standard 1647 (1982) Children Toys, Parts 3, Toxicological Requirements, Parts 3. |
Canada: | Hazardous Products (Toys) Regulations (2007). |
Japan: | Specifications, Standards and Testing Methods for Foodstuffs, Implements, Containers and Packaging, Toys, Detergents (January 2009). |
USA: | 16 CFR 1130 Requirements for consumer registration of durable infant or toddler products (plus parts 1-9). |
Standard Consumer Safety Specification on Toy Safety: ASTM F 963-08. |
Consumer Goods are defined and regulated in Germany according to the Lebensmittel-, Bedarfsgegenstände- und Futtermittelgesetzbuch (latest version 26 January 2016) and Bedarfsgegenständeverordnung (Consumer Goods Ordinance, latest amendment 24 June 2013).
Table 5.4 Limit values of extractable impurities in mg kg−1 (ppm), but (T) is the total content.
Impurity | Europe 1a) | Europe 2b) | UK | USA | Australia (T) |
Lead | 90 (T) | 90 | 250 T | 600c) | 100 |
Arsenic | 25 (T) | 25 | 100 T | 100 | 100 |
Mercury | 60 | 25 | 100 | 100 | 100 |
Cadmium | 75 | 50 | 100 | 100 | 100 |
Selenium | 500 | 500 | — | — | 100 |
Barium | 500 | 250 | 500 | 500 | 100 |
Chromium | 60 | 25 | 250 | 250 | 100 |
Antimony | 60 | 60 | 50 | 25 | 100 |
a) Europe 1: surface coatings, polymers, paper and board, textiles, glass/ceramic/metallic materials. b) Europe 2: modelling compounds, paints, varnishes, lacquers. c) In paints. |
Annex 1 Nr.7 of the Consumer Goods Ordinance introduced a prohibition on the production, import and sale of certain garments and fabrics dyed with azo colourants that may split to cancerogenic aromatic amines. There are 24 prohibited amines in total (see TRGS 614 [17]).
Hydrazone pigments were also excluded, because by application of the official testing method none of the listed aromatic amines could be detected [18].
This German restriction inevitably stimulated similar restrictions in other EU member states, and finally a harmonization at EU level was reached through the EU Directive 2002/61/EC, now repealed and replaced by Reach Annex XVII [19]. Table 5.2 lists the 22 prohibited aromatic amines.
PCB (polychlorobiphenyl) traces may be found in two groups of organic pigments, namely, in:
Strict legal limits have been defined in several countries, because of the persistency and wide distribution of polychlorobiphenyls. These regulations have primarily been issued to protect the environment, and less so because of a direct hazard for humans.
A threshold limit value for polychlorinated biphenyls (PCBs) of 25 mg kg−1, expressed as decachlorobiphenyl, is recommended by the Council of Europe and exists, for instance, throughout the European Union, Switzerland, USA [20] and China.
In many countries any content of polychlorobiphenyls in food or food packing material is banned or restricted to 0.5-2 mg kg−1, which means not detectable in this concentration range.
Hexachlorobenzene is principally treated and classified as a polychloropbiphenyl.
Starting from chlorine-containing compounds, similar to the formation of PCBs, pigment synthesis might lead to the formation of trace amounts of polychlorinated dibenzodioxins (PCDDs) and/or polychlorinated dibenzofurans (PCDFs) (‘dioxins’). Some 75 PCDD and 135 PCDF cogeners can be formed. The toxicological effect of these compound is quite different; dioxins with at least tetrachloro (or bromo) substitution in 2,3,7,8-positions are of most concern [21].
The German Hazardous Substances Ordinance (Chemikalien-Verbotsverordnung) prohibits products to be placed on the market for which very low limits of dioxin traces are exceeded [22]. Regulated substances are chlorinated and brominated dioxins. The stringent limit are detailed in Table 5.5.
Table 5.5 Limits for dibenzodioxins/dibenzofurans (‘dioxins’).
Barium pigments, which are the barium salts of 1-azo-2-hydroxy-naphthalenyl-arylsulfonic acid, are excluded from the generic classification of barium salts as ‘harmful’ [Reg. 1272/2008, Annex 1, Classification and Labelling for Hazardous Substances and Mixtures]: ‘056-002-00-7 barium salts, with the exception of…1-azo-2-hydroxynaphthalenyl aryl sulphonic acid…’. This classification for barium salts results in the non-labelling of other barium pigments [23]. Table 5.6 lists a few industrially used barium pigments.
Table 5.6 Industrially used barium pigments (1-azo-2-hydroxynaphthalenyl aryl sulfonic acid, barium salts).
CAS-No. | C.I. Pigment | Chemical name | C.I. Const. No. |
15782-04-4 | P. Orange 17 | Benzenesulfonic acid, 4-[(2-hydroxy-1-naphthalenyl)azo]-, barium salt (2 : 1) | 15510:1 |
67801-01-8 | P. Orange 46 | Benzenesulfonic acid, 5-chloro-4-ethyl-2-[(2-hydroxy-1-naphthalenyl)azo]-, barium salt (2 : 1) | 15602 |
7585-41-3 | P. Red 48:1 | 2-Naphthalenecarboxylic acid, 4-[(5-chloro-4-methyl-2-sulfophenyl)azo]-3-hydroxy-,barium salt (1 : 1) | 15865:1 |
5850-87-3 | P. Red 51:1 | Benzenesulfonic acid, 4-[(2-hydroxy-1-naphthalenyl)azo]-2-methyl-, barium salt (2 : 1) | 15580:1 |
17814-20-9 | P. Red 52:3 | 2-Naphthalenecarboxylic acid, 4-[(4-chloro-5-methyl-2-sulfophenyl)azo]-3-hydroxy-,barium salt (1 : 1) | 15860:3 |
5160-02-1 | P. Red 53:1 | Benzenesulfonic acid, 5-chloro-2-[(2-hydroxy-1-naphthalenyl)azo]-4-methyl-, barium salt (2 : 1) | 15585:1 |
17852-98-1 | P. Red 57:2 | 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4-methyl-2-sulfophenyl)azo]-, barium salt (1 : 1) | 15850:2 |
61013-97-6 | P. Red 151 | Benzenesulfonic acid, 2-[[2-hydroxy-3-[[(4-sulfophenyl)amino]carbonyl]-1-naphthalenyl]azo]-, barium salt (1 : 1) | 15892 |
Table 5.5 lists important regulations that are related to organic pigments.
The European Commission has published the July 2013 version of ‘Addresses of European and National European Authorities’ related to ‘General Health and Consumers’ as well as a list of the National Governmental Authorities in Europe. These documents can be obtained from: http://ec.europa.eu/food/food/chemicalsafety/foodcontact/auth_ref_en.pdf
Although pigments, because they are practically insoluble in water and – if at all – only sparingly soluble in common solvents, are largely biologically inert, it is the responsibility of the pigment manufacturer and producer to comply with legal requirements.
Ecological considerations include air emissions and wastewater.
Air emissions: Organic pigments are basically subject to a general limit to particulate emission: the concentration of fine dust in the air may not exceed 3 mg m−3 [24]. Although an organic pigment dust is not considered a health hazard, emission control includes filtering waste air after manufacture to remove the pigment dust. Suitable methods involve using dust filters or adsorption techniques. Generally, to avoid possible exposure to pigment dust, individuals involved in the manufacture of a pigment must wear additional protective equipment (dust mask).
Wastewater: The danger of contaminating free-running water with organic pigments may be met with measures such as filtration, sedimentation, adsorption or, if necessary, with biological treatment. By means of these techniques, wastewater pollution may be practically avoided. As a result of their negligible solubility, organic pigments are probably nontoxic to fish – at least there is no evidence to the contrary. Fish toxicity is conceivable only if the receiving water cannot offer a sufficiently high dilution factor and thus accumulates such quantities of pigment as to cause gill failure.
Although the bacteria used in biological treatment are not effective in degrading organic pigments, the compounds are likely to decompose slowly under anaerobic conditions.
Legal limitations placed upon the use of all newly launched non-biodegradable chemicals in Japan require testing each product for accumulation in fish before it can be marketed. These regulations have stimulated corresponding studies about the bioaccumulation of pigments [25]. The distribution coefficient Pow between n-octanol and water may be used to indicate the tendency of a chemical to accumulate in biological systems [26].
An empirical rule, which also applies to dyes, predicts a bioaccumulation factor of <100 in fish, if the Pow is below 1000. Notably, however, this rule does not apply to organic pigments, since they are only very sparingly soluble in water and in lipids (for instance in the lipid simulant solvent n-octanol) and consist of comparatively large molecules. Although the theoretical log Pow is very high for pigments (up to 10), the compounds do not accumulate in fish [27].
Persistent organic pollutants (POPs) are characterized by their toxicity, their resistance to degradation and their capacity to accumulate in living organisms and be transported over long distances; their restriction and elimination are the subject of two international legal instruments: the Stockholm Convention 2 [28] and the POPs Protocol of the Geneva Convention (4th Meeting, May 2009), whose obligations are implemented in the EU through a specific European regulation(Commission Regulation (EC) No 465/2008).
Since the properties of most organic pigments make the possibility of their bioaccumulation very unlikely, these pigments should therefore not classified as POPs, nor as persistent, bioaccumulative and toxic (PBT) substances [29].
Toxicological studies are concerned with various aspects, primarily with the following factors:
Testing on animals may provide initial information on the effect of a possible short-term exposure on human health. Acute toxicity is defined as the toxic effect of a substance after a single oral, dermal or inhalation application. For acute oral toxicity, for instance, LD50 is defined as the amount of substance expressed in mg per kg body weight that has a lethal effect on 50% of the test animals after a single oral application. Such tests are useful in that they assess the toxicity of a material relative to that of other known compounds.
One hundred and eight organic pigments have been examined concerning their acute oral lethal dose in rats. None of the studied pigments shows a LD50 of less than 5000 mg kg−1 body weight [30].
Another publication summarizes the results of testing 194 organic pigments for toxicity. The most important chemical types were represented [31]. None of the tested specimens was found to have a LD50 value of <5000 mg kg−1, with the exception of four values, which were located in the 2000–5000 mg kg−1 range. EC Chemical Law requires substances to be labelled as harmful if the LD50, for acute oral toxicity, is below 2000 mg kg−1. For comparison, NaCl has an LD50 of 3000 mg kg−1.
Pigments are passed via the gastro-intestinal tract and not discharged via the urethra. According to the results of these studies, organic pigments show practically no acute toxicity.
Publications summarizing the results of studies on the effect of pigments on the skin and mucous membrane (conjunctiva of eyes) of rabbits describe similar observations. These sources refer to pigments as trade products that may contain auxiliaries (Table 5.7).
Table 5.7 Irritation effects caused by organic pigments.
Number of pigments | ||
Skin | Mucous membrane (conjunctiva) | |
Non-irritating | 186 | 168 |
Slightly irritating | 5 | 20 |
Moderately irritating | 1 | 1 |
Strongly irritating | 0 | 3 |
To summarize the results given above: it has been demonstrated that organic pigments exhibit very high LD50 values and only rarely cause irritations of skin or mucous membranes.
These so-called subacute or subchronic toxicity studies involve the repeated application of a test substance to animals, typically for a period of 30 or 90 days. The time pattern is thus an intermediate one between acute and chronic toxicity. To test a substance for subacute or subchronic toxicity, it is mainly applied by ingestion or inhalation. Not one out of the large number of organic pigments that have thus been tested has demonstrated any irreversible toxic effect. No toxic response was observed in rats that were fed either Pigment Yellow 1 or Pigment Yellow 57:1 for 30 days [32].
Various methods are available to test a chemical for mutagenicity, that is, its effect on the genetic material. The Ames test has gained most recognition as a short-term test [33]. This is a bacterial test that allows fast performance and requires limited expense. Its correlation with the mutagenicity of mammals or even with a carcinogenic effect on mammals or humans has repeatedly been tested [34], but remains controversial.
Only two out of 25 Ames-tested organic pigments show a positive result [30].
One of the prime concerns, apart from acute and subacute toxicity, is the question of whether a product causes chronic effects. In this context, carcinogenicity studies are of cardinal importance. A possible chronic hazard may be indicated by epidemiological studies. Where such investigations are not available, experiments are performed on animals for the duration of their entire life span. The type of application depends on the exposition (perorally, dermally, per inhalation).
Dichlorobenzidine pigments have stimulated particular interest in this respect. Although reductive cleavage of the dichlorobenzidine moiety might conceivably afford 3,3′-dichlorobenzidine, this is not observed in animals. Despite the fact that all epidemiological studies produced similarly negative results [35], the pigments in question were also tested in long-term feeding studies. Pigment Yellow 12, 16, and 83 were fed to rats and mice over a period of two years. The daily dosage for mice was up to 2 g pigment per kg body weight, while rats were fed up to 0.6 g kg− per day. No carcinogenic effect was observed [36]. The results were confirmed by two independent studies on Pigment Yellow 12 [37, 38].
There is a publication that, caused by an unsuitable experimental design, erroneously claims to have found 3,3′-dichlorobenzidine in the urine of rabbits – an observation which, if true, would have pointed to metabolism of P.Y.13 [39]. The results were challenged and contradicted later by comprehensive research on rats and mice [36] and on rats, rabbits and monkeys [40].
Studies investigating the bioavailability of P.Y.17 in rats, applied not only orally but also by inhalation, in no case showed the presence of any cleavage product of the pigment (e.g. 3,3′-dichlorobenzidine or metabolites) in the urine or blood of the animals [41]. Similar studies were carried out with P.Y.13 and 174 [42, 43]. Recently, the non-bioavailability of 3,3′-dichlorobenzidine from P.Y.13 and P.Y.17 was confirmed by means of molecular dosimetry for haemoglobin and DNA adducts [44].
Table 5.8 lists pigments that have been tested for carcinogenicity [31].
Table 5.8 Chronic toxicity of organic pigments (long-term feeding studies).
C.I. Name | C.I. Constitution No. | Test animal | Result | References |
P.Y.12 | 21090 | Mouse, rat | Negative | [36–38] |
P.Y.16 | 20040 | Mouse, rat | Negative | [36] |
P.Y.83 | 21108 | Mouse, rat | Negative | [36] |
P.O.5 | 12075 | Mouse, rat | Equivocal | [45] |
P.R.3 | 12120 | Mouse, rat | Equivocal | [46] |
P.R.23 | 12355 | Mouse, rat | Negativea) | [47] |
P.R.49 | 15630 | Rat | Negative | [48] |
P.R.53:1 | 15585:1 | Mouse, rat | Negative | [49] |
P.R.57:1 | 15850:1 | Rat | Negative | [50] |
P.B.60 | 69800 | Rat | Negative | [51] |
a) Equivocal evidence of carcinogenic activity in male rats. |
Organic pigment lakes, whose free acidic functions makes them at least partially water soluble, were tested in the form of their soluble sodium salts (Table 5.9) [52].
Table 5.9 Long-term feeding studies of water soluble Na salts of pigment lakes.
C.I. Name | C.I. Constitution No. | Tested as | Test animal | Result |
P.Y.100 | (Al), 19140 | Acid Yellow 23 (Na) | Mouse, rat, dog | Negative |
P.Y.104 | (Al), 15985 | Food Yellow 3 (Na) | Mouse, rat | Negative |
P.R.172 | (Al), 45430 | Food Red 4 (Na) | Rat, dog | Negative |
P.B.24 | (Ba), 42090 | Food Blue 9 (Na) | Mouse, rat | Negative |
P.B.63 | (Al), 73015 | Food Blue 1 (Na) | Rat and others | Negative |
The insolubility and migration fastness of most organic pigments largely eliminates human health hazards. Despite this fact, the need for consumer protection and compliance with the legal regulations makes it necessary to regularly test not only the pigmented materials but also the pigments themselves. This is to ensure that no trace of pigment migrates from the printed or coloured packaging into food and that the stringent requirements, particularly regarding impurities (traces of heavy metal, aromatic amines, dioxins or PCB), are met. Several papers deal with the safe handling of colourants [53].