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Ecotoxicology of dyestuffs—A joint effort by industry
ECOTOXICOLOGY
AND
ENVIRONMENTAL
Ecotoxicology
3, 59-74 (1979)
SAFETY
of Dyestuffs -A
Joint Effort by Industry’
R. ANLIKER~ P.O.
Box
CH-4005,
Received
Basle.
August
Switzerland 16, 1978
Within the dyestuff industry it was realized that the ecotoxicological problems ahead could be tackled more effectively by the deployment of the large but nonetheless limited scientific and technical resources on a collaborative basis. This led to the formation of an international association, ETAD (Ecological and Toxicological Association of the Dyestuffs Manufacturing Industry) in 1974. An outline of its organization and modus operandi is given. ETAD’s activities are mainly directed at ensuring the safety of commercial synthetic organic dyestuffs and pigments. Besides the determination of the ecotoxicological properties of specific dyestuffs ETAD also deals with more fundamental problems. Its current and completed studies include a widely accepted safety data sheet, development of test methods, analysis of exposure potential, and the formulation of viewpoints concerning testing requirements and legislation.
ETAD-FORMATION
AND OBJECTIVES
In the 1960s a number of prominent people in the dyestuffs industry came to realize that the large, but nevertheless limited scientific and technical potential in the individual companies could be used more effectively on a coordinated basis to solve any ecotoxicological problems ahead. After thorough legal and administrative preparatory work, an international association, ETAD,3 was formed in 1974. The primary objectives, as stated by the bylaws, are to coordinate and unify the efforts of manufacturers of synthetic organic dyestuffs and synthetic organic pigments to minimize any possible damage to the environment arising from the use and application of the products, to provide the best possible and practicable protection for the users and consumers of these products, and to aid and cooperate with government departments and agencies and any other public institution concerned with the ecotoxicological impact of the products. It is important to note that the bylaws refer to lowering the impact, they do not refer to eliminating all impact. ETAD is trying to maintain a balanced view. It is not possible to legislate all hazard out of existence, as some new laws which are being promulgated would have us believe. There is no point in ETAD pretending that the products of our industry have a zero effect, and equally no point in govern1 This paper was presented at the Symposium “Scientific Basis for the Ecotoxicological Assessment of Environmental Chemicals,” August 16- 18, 1978, Vienna. 2 Executive Secretary of ETAD. a Ecological and Toxicological Association of the Dyestuffs Manufacturing Industry. At present the following companies are members of ETAD: ACNA (Italy), Amar Dye-Chem, Indian Dyestuffs Ind. (India); BASF, Bayer, Hoechst (Germany); Ciba-Geigy, Rohner, Sandoz, (Switzerland); Hodogaya Chem., Mitsubishi, Mitsui Toatsu, Nippon Kayaku, Sumitomo (Japan); ICI, Yorkshire Chem. (Great Britain); Koge Chem. (Denmark); Ugine Kuhlmann (France). 59
0147-6513/79/010059-16$02.00/O Copyright 0 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
60
R. ANLIKER
(U.S,A) DETO DYES ENVIRONMENTAL AND TOXICOLOGY ORGANIZATION, INC.
DETO-ETAD LIAISON -----COFiMITTEE
-_---
ETAD US ADVISORY COMMITTEE
TOXICOLOGICAL SUBCOMMITTEE FIG.
-
TECHNICAL COMMITTEE
ECOLOGICAL SUBCOMMITTEE
1. Organization
structure
PIGMENTS ADVISORY COMMITTEE
-
ANALYTICAL SUBCOMMITTEE
..
REGIONAL ANALYTICAL SUBCOMMITTEE JAPAN
of ETAD.
mental legislators assuming that the benefits of the dyestuffs industry can be made available to the public at large, with zero risk. Activities in environmental protection are based on the realization that many features of our modern civilization are in conflict, often unavoidably, with nature. We all wish to enjoy the best quality of life both now and in the future, and unless we are prepared to forego the undoubted benefits that modern technology makes available, it is necessary to seek a compromise and to accept certain risks. It is in the complex problem area of defining the balance between risk and benefit that ETAD is involved. ORGANIZATION
OF ETAD
The ETAD members represent about 80% of world-wide dyestuff production (excluding Comecon and China). The primary authority is the General Assembly (Fig. 1) in which the various member companies are entitled to exercise one, two, or three votes depending on their annual sales of dyestuffs. The annual membership fees4 are determined by the need to cover the costs of the Secretariat, traveling expenses of committee members, and studies contracted externally. The majority of the project work is, however, carried out within the member firms and the costs involved are borne directly by them. The governing powers of the Association are vested in the Board of Directors which is elected by the General Assembly from senior managers of the dyestuffs divisions of the member companies. This ensures, in a most effective way, that studies undertaken by the Technical Committee and the various subcommittees 4 The annual fee is at present Sfr. 20,000 per vote. An associate introduced recently to encourage small companies to join ETAD.
membership
with
reduced
fees,
was
ECOTOXICOLOGY
OF DYESTUFFS
61
proceed promptly. The Technical Committee, at whose meetings the Chairmen of the subcommittees participate, coordinates activities, proposes future projects for Board approval, and sets priorities, etc. This committee consists of seven senior departmental managers delegated by the member firms. The Regional Analytical Subcommittee in Japan coordinates the activities of the Japanese member companies and, in particular, deals with any problems specific to Japan. Problems relating specifically to pigments are dealt with by the Pigments Advisory Committee in collaboration with the other scientific committees. Uncertainties about the possible complications arising from membership of American companies in ETAD led to the formation of the Dyestuffs Environmental and Toxicology Organization (DETO) in the United States in 1977. DETO is affiliated to the Synthetic Organic Chemical Manufacturers Association, Inc. (SOCMA) and has essentially the same objectives as ETAD. Whereas ETAD covers both dyestuffs and pigments, DETO deals with dyestuffs only, because the pigments manufacturers were already represented by the Dry Color Manufacturers Association (DCMA). Responsibility for ensuring close cooperation between DETO and ETAD lies with the DETO/ETAD Liaison Committee and the ETAD-U.S. Advisory Committee. The latter committee consists of representatives of United States-based manufacturing subsidiaries of European ETAD member companies. The ETAD Executive Secretary, a full-time operating executive, is responsible, among other matters, for assisting and advising the Board and committees, for contact with regulatory authorities, industrial associations, and environmental organizations, and for the preparation of official ETAD responses to various legislative proposals on environmental matters affecting the dyestuffs industry. The President, who presides at all meetings of the General Assembly and the Board, is elected each year. Those committee members who belong to the same company as the President, also take over the chairmanship of the corresponding committees for his year of office. This procedure facilitates a close contact between the President and the committee chairmen and has proved to be very beneficial. ACTIVITIES
OF ETAD
Within the framework of its objectives, ETAD attaches particular importance to: Harmonization of international environmental legislation, and the avoidance of unnecessary inhibition of innovation by overregulation. ETAD supports the principle of industrial freedom with the State having power to intervene when appropriate, and absolutely rejects the destructive principle of prohibition unless consent has been conferred by the State. Essential for the necessary environmental protection and the retention of a healthy industry, is a high degree of self-responsibility by industry, which legislation should support rather than cripple (Bretscher et al., 1978). Objective expert evaluation and judgement of ecotoxicological matters. 5 See, e.g., report on lecture given by G. Hartkop (1978). Ministry of Interior Bonn, RegierungsvorstelIungen zur Umweltspolitik des Bundes unter Beriicksichtigung der Textilindustrie. Texfilryredlung 13, 280.
62
R. ANLIKER TABLE 1 HIGHEST
IMPURITY
LEVELS
OF METALS
Metal
Impurity level (wm)
As Ba Cd co Cr (total CY+) cu Fe
50 100 50 500 500 250 2500
IN DYESTUFFS~
Metal
Impurity level @pm)
Hg Mn Ni Pb Sb Se Sn Zn
25 1000 250 250 50 50 250 5000
n These limits do not apply to metal complex dyestuffs. Highest impurity levels are those maximum metal contents of dyestuffs which, in a 2% dyeing and with a total dilution of the effluent of 1:2500 related to the dyestuff used, satisfy the currently known legal requirements.
The development and standardization of the necessary analytical, ecological, and toxicological methods. The provision of the physicochemical and ecotoxicological information which is necessary for the safe handling and use of the products. The continuing extension of our understanding of the ecotoxicological behavior of dyestuffs in order to identify any undesirable properties. The activities of ETAD are best illustrated by mentioning the work already completed and by outlining the scope of some current projects. Safety Data Sheet (SDS)
The ETAD-SDS was designed to provide the users of dyestuffs with basic information to enable safe handling of the product. Detailed explanatory notes concerning the meaning and interpretation of the data are also provided (Raab, 1978). It has been introduced widely and has influenced the formats adopted by other organizations. The requirements of the various chemical industry sectors differ but it would be beneficial if individual versions could at least achieve a basic uniformity of layout: Individualization on a national basis is unnecessary and should be avoided. Methods
Recommended
by ETAD
The use of clearly defined, standardized methods, which give reproducible results, is essential if meaningful and comparable data are to be obtained. Methods already accepted by the scientific community and the authorities are used whenever possible. Existing, as well as modified or newly developed, methods are subjected to critical appraisal, involving round-robin tests in the laboratories of the member companies, before they are recommended by ETAD. If satisfactory, the methods are used by the member companies and also made available to authorities.
ECOTOXICOLOGY
OF DYESTUFFS
63
Levels of Heavy Metals in Dyestuffs
The ETAD members ensure that the heavy metal content of their products is kept below agreed levels which enable the user to satisfy readily the current legal requirements regarding effluents (Table 1). The figures given are periodically reviewed and, if necessary, adapted to new situations. Assessment
of Ecotoxicological
Properties
of Dyestuffs
The dyestuffs industry is constantly faced with the question of the safety of its products. There is already an extensive literature on this subject (Anliker, 1977). Most dyestuffs, if properly handled and used, present no unreasonable risk. However, one must recognize that in this industry’s sector, which involves thousands of products and intermediates, one can always find substances which may present an ecotoxicological risk, and thus require special handling precautions, a limitation in use, or a switch to other products. ETAD gives high priority to the identification of specially hazardous products and to the setting up of appropriate precautionary measures. However, it must be made very clear, that any attempt to discredit whole product classes by unscientific generalizations, by one-sided and unqualified interpretations of results and by unwarranted extrapolations on the basis of similarities of chemical structures must be rejected.6 The title of a recent publication “Textile dyes are potential hazards” (Jenkins, 1978) or statements such as “Azo dyes are often found to be carcinogenic” (Sax, 1975) or “Die meisten Farbstoffe sind mehr oder wenig giftig” (Rompp, 1973) may illustrate the point. The limited space available does not permit such articles to be dealt with in detail, but perhaps the difficulty can best be illustrated by briefly describing the current situation concerning azo dyestuffs. The availability of a wide variety of aromatic azo and coupling components permits the synthesis of a very large number of azo compounds. It is estimated that more than half of all known dyestuffs (i.e., more than 50,000 aromatic azo compounds and more than 2000 commercial dyestuffs contain one or more azo groups). Azo compounds are found in almost every dyestuff application class. It is scientifically not tenable to make the generalization that these compounds represent an especially high carcinogenic risk only because compounds containing azo groups have been found to be carcinogenic in animal tests; e.g., one of the first was Butter Yellow (N,N-dimethylaminoazobenzene)’ and recently some benzidine dyes8 (DHEW, 1978). On the other hand a wide variety of azo compounds, both dyestuffs (e.g., WHO, 1966, 1974, 1975; Gaunt, 1974; Radomski, 6 For example. an expert opinion has been expressed by D. Schmahl (1977) Toxicol. Cancer Res. Inferdiscpl. Sci. Rev. 2, 305-311: “This, however. should not mislead one into thinking that, for example, each aromatic amine or polycyclic hydrocarbon must be carcinogenic. These are highly specific chemical compounds which may lose their carcinogenicity by the slightest variation in structure.” ’ For more details on carcinogenicity of azo compounds see, e.g., J. C. Acres and M. Acres, Chemical carcinogens, Prog. Drug Res. 4,407-582, E. Jucker, (ed.), Birkhauser Verlag, Basel, 1962. D. B. Clayson and R. C. Garner, Carcinogenic aromatic amines and related compounds, In Chemical Carcinogens Ch. E. Searle, (ed.). ACS Monograph 173, pp. 366-461, 1976. * The carcinogenic action may arise from different causes. In the case of benzidine dyes the activity can be attributed mainly to the metabolic formation of benzidine from the dyestuff (Rinde and Troll, 1975).
64
R. ANLIKER HUMAN
EXPOSURE
MEASURES
TAKEN
TO
REDUCE
EXPOSURE
EXPOSURE RATING
PRODUCTION WORKERSETC.
IMPROVED GOOD
PRODUCTION
IMPROVED
PHYSICAL
PERSONAL
HYGIENE
PROPER
WI.4
I
EN”*RONmNTI
FORM AND
AND
OF
IN
COLOR
EFFECTIVE
EFFLUENT
I
PROCESS
IMPROVEMENTS
.
ORDERLY
DISPOSAL
(NON
DUSTY
ADEQUATE
INFORMATION
REDUCTION
PUBLIC
TECHNOLOGY
CONDITIONS AND HANDLING FACILITIES
WORKING
PRODUCTS)
LAUNDRY
EDUCATlON
OF
FACILITIES PERSONNEL
EFFLUENT TREATMENT
OF
WASTE
PROCESSING DYERS. PRINTERS
ETC.
USE
OF
GOOD
PROPER
WORKING
APPLICATION
TMPRCVED
PHYSICAL
PERSONAL
HYGIENE
PROPER
INFORMATION
REDUCTION
OF
++
TECHNOLOGY
CONDITIONS FORM AND
ADEQUATE
AND
LAUNDRY
EDUCATION
COLOR
IN
WASTE
WATER
OF
FACILITIES PERSONNEL
EFFLUENT
I
EFFECTIVE
’
IMPROVED APPLICATION PROCESSES (E.G. BETTER EXHAUSTION OF DYES)
TREATMENT
+
1974; DFG, 1977, 1978; Drake et al., 1978; Holmes et al., 1978) and pigments (DHEW, 1977; Leuschner, 1978) have been shown in long-term animal tests to be noncarcinogenic. Furthermore, a distinction must be made between dyes which are commercial products and others prepared solely for scientific purposes. For example, out of about 300 azo compounds listed by NIOSH as being suspected carcinogens in animals only 36 are commercial dyestuffs in the United States. At present the scientific soundness of the supporting data is being checked. On many occasions attention has been drawn to the many damaging consequences of such unqualified and unjustified statements and judgements: Among other things, they distort the sense of proportion, and as a consequence lead to the setting up of wrong priorities, senseless deployment of scarce testing resources, and overregulation. The number of chemicals used today is estimated to be many tens of thousands, far beyond currently available testing capacities for a full-scale testing program. With a current world capacity for about 500 long-term tests, the investigation of say 20,000 compounds would take 40 years. This clearly explains the necessity of a stepwise procedure and the setting of priorities for the chemical industry as a whole. In the setting of priorities the important factors in the assessment of risk are: exposure pattern, ecotoxicological profiles, and production volume. The parameters which are relevant to evaluating the ecotoxicological profile of a chemical and a summary of the important problem areas in the dyestuff industry have been published previously (Anliker, 1977). Exposure assessment. The exposure assessment not only provides the basis for the pinpointing of problem areas but also for the extremely important measures
ECOTOXICOLOGY UMAN XPOSURE
USE
65
OF DYESTUFFS MEASURERS
TAKEN
TO
REDUCE
EXPOSURE RATING
EXPOSURE
l
END USE i3NSUMER
TEXTILES LEATHER
INCL.
USE
OF
BEST
USE
OF
PRODUCTS
PAPER NAPKINS FOOD PACKAGING NEWSPRINT
DITTO
PLASTICS
APPLlCATION
PAINTS AND INKS GENERAL ARTISTS' PAINTS FINGER PAINTS
INSTRUCTIONS
FOODSTUFFS
AVAILABLE
APPLICATION
WITH
BEST
TECHNOLOGY
FASTNESS
0 (+) 0
+ OF
THE
FOR
NON-MIGRATION
PROPER
PRINCIPLE
O...r^_
_I
+ + EXPOSURE
IS
PRODUCTS
REQUIRE
++
INEVITABLE RIGOROUS
TOXICOLOGICAL +++
,NVESTlGATION
++
TOYS
LEGISLATIVE
DO-IT-YOURSELF PRODUCTS
ADEQUATE
SAFETY
WITH
ORDER
__“r.e._a^.
. --_
0
USE
COSMETICS
f
0
PROPERTIES
..^_.
LOW
CONTROL,
NON-MIGRATION
INSTRUCTIONS, OF
PRINCIPLE USE
OF
PRODUCTS
0 +
TOXICITY.
-._-.z.-__.
to minimize the exposure. It must be accepted that extensive animal and even human toxicological information on all chemicals cannot be made available in the near future. It is often overlooked that the reduction of dangerous and also unnecessary exposure is still one of the most effective and immediate measures to eliminate unreasonable risks.g The objective of a current project of ETAD is the qualitative and quantitative assessment of the exposure pattern of dyestuffs. Figures 2 and 3 give a summary of the qualitative exposure pattern including an exposure rating. The figures also indicate measures already taken or to be taken to lower the exposure. Figure 4 displays schematically the exposure potential in the main areas of production, processing, and consumer use. To illustrate the scope of this project, a study to assess the trace amounts of dyestuff which may be transferred from a dyed fabric to the skin can be mentioned. The extractability of the dyestuffs from dyed fabrics is determined using the alkaline and acid perspiration stimulants defined in the standard 10s method.‘O The amount of dyestuff which is eluted from deep-shade dyed fabric samples is measured spectrophotometrically. From this value is calculated the amount which would be extracted from an area of 500 cm2. It is generally accepted that an area of 500 cm2 of sweat-moistened material remains in contact with the skin for any length of time and the maximum daily dermal exposure per person may be assumed to be the amount of dyestuff which is extracted from this area of dyed fabric. The study y Similar views have been expressed, for example, in his recommendation J. H. Weisburger (1977), Cancer prevention, Chemtech. 7, 734-740. lo Method ISO/R 105/N-1968. Colour Fastness to Perspiration.
of cancer
prevention
by
66
R. ANLIKER Exposure
Number Exposed
of Persons
Ease of Control of Exposure Production
Processing
consumer
FIG. 4. Exposure potential to dyestuffs.
includes all the main fibers and important representatives of the various dyestuff classes. The results for two disperse dyes on polyester fabric are given in Table 2.” In this case, the dermal exposure was shown to be less than 0.25 pg/person daily. Preliminary results with water-soluble dyestuffs on hydrophilic fibers show somewhat higher values in the lower microgram range. Toxicological assessment. The factors to be considered in the assessment of risk for a chemical include: the total exposure potential, the seriousness of the toxic effect, and the fact or the probability of its occurrence. The complexity of assessing evidence of toxicity and specially carcinogenicity dictates that the evaluation of the potential human hazard of a given agent must be individualized in terms of the chemical and metabolic aspects of that specific agent, its intended uses, the data available at the time that the decision must be made, and other factors pertinent to the case under consideration. Each case must be considered on its own and the criteria appropriate for one agent may not necessarily apply to another. One can distinguish the following principal groups of chemicals with regard to test requirements: pharmaceuticals (including drug dyes), food additives (including food dyes), agrochemicals, cosmetics (including hair and cosmetic dyes), chemicals for food packaging materials and toys (including selected dyestuffs and pigments), chemicals in large, medium, and small volumes (including technical dyestuffs and pigments), chemicals for research purposes only. A rational and exhaustive treatment of the many controversial issues of cancer risk assessment has recently been published by the American Industrial Health Council (AIHC, 1978). Acute toxicity. It has already been mentioned that due to the limited testing facilities, the great number of dyestuffs and intermediates to be tested, and the need to set meaningful priorities, the toxicological investigation can and will only proceed stepwise. The ETAD members agreed, as a first step, to determine systematically the physicochemical and ecotoxicological basic data necessary for the safe handling of their products. The data are made available to the users in form of the safety data sheet mentioned previously. The project has now been almost completed, ‘I The author thanks Dr. L. Yamauchi and Dr. T. Ohshima, Research Department, Chemical Co. Ltd, Osaka, Japan, for their kind permission to quote these results.
Sumitomo
ECOTOXICOLOGY
67
OF DYESTUFFS
TABLE 2 EXTRACTION
OF DISPERSE DYES BY PERSPIRATION FROM POLYESTER FABRICS”
SIMULANTS
C.I. Disperse Blue 301 Dyestuff (100% active ingredient) (% 0.w.f.) Fastness to perspiration (1 = lowest, 5 = highest fastness) Recovery rate (%) Limit of detection (Fg) Extractability (Fg/SOOcm’ of fabric)” Alkaline perspiration simulant Acid perspiration simulant
C.I. Disperse Orange 30
1.5
1
5 >95 0.5
5 >95 0.7
co.2 co.2
co.25 co.25
‘1 Sixteen grams of fabric (106 g/m’) was treated with 800 ml of perspiration removed was extracted with chloroform and determined spectrophotometrically. 500 cm2 of fabric was 5.3 g.
simulant.
The dyestuff The weight of
and has involved the testing of over 5000 commercial dyestuffs during the last 5-7 years. The costs of carrying out this agreed toxicological minimum testing program, i.e., acute oral toxicity on the rat (LD,,) and eye and skin irritation tests on the rabbit, are well over 20 million Sfr. Within the individual companies supplementary toxicological data have been collected on many products. The analysis of the LD,, data (Table 3) available in August 1977, did not uncover any recognizable structure-toxicity relationship. The products with values below 250 and 250-2000 mg/kg belong to a wide variety of different structures (Table 4). The classification of these compounds according to the Color Index (Table 5) revealed a higher incidence of the basic dyestuffs, in the two lower groups, which is not surprizing. Within this group there was no frequent occurrence of any specific structure. This survey indicates that from the 4461 commercial products tested only 15 dyestuffs with different chemical structures showed LDso values of less than 250 mg/kg, all values lying in the range of 100 to 250 mg/kg. This group of products will undergo further studies. TABLE 3 DETERMINATION
OF SINGLE (COMMERCIAL
ADMINISTRATION BRANDS) BY
ETAD
TOXICITY OF DYESTUFFS MEMBERS~
Irritation No. of dyes tested
No. of dyes tested
No. of dyes with LD,, values (mg/kg) ~250
250-2000
2000- 5000
>5000
Eye
Skin
4461 ( 100)b
44 (1)
314 (7)
434 (9.7)
3669 (82.3)
4573
4614
n Acute oral toxicity LD,, in rats and effects safety data sheets up to August 1977. * The values in parentheses are percentages.
on the skin and eyes.
Only
data published
in the ETAD
68
R. ANLIKER TABLE ANALYSIS
OF LDso VALUES LOWER THAN 2000 mg/kg BY CHEMICAL
Chemical type
14
Monoazolquaternary Disazo Trisazo Phthalocyanine Diphenylmethane Triphenylmethane Xanthene Oxazine Methine Anthraquinone Indigoid Stilbene azo Miscellaneous
16
TYPES
No. of products with L&O (mgkg)
Total No. of products
Monoazo
Total
4
c250 1(125) : (199, 200, 240, 200)
20
251-2000 13
16 16
1
0
1
2
0
2
1
0
13 6 4 20 3
1 (1W 2 (220, 250)
1 11 114
4 (133, 213, 222, 224) 0
0 1 (150) 1 (221)
1 1 10
1 (210)
2
1 12 4 3 16 3
15
99
” Criteria for analysis: 1. Mixture products were omitted. 2. Azoic diazo components (28) were not included. 3. Where products with the same basic structure, as identified by Color Index No., have been tested by different member firms, only the lowest LD,, value was used. 4. Where LD,, values were quoted as a range, the lower value has been used for classification. By this procedure the number of 358 of tested commercial products was reduced to 114 products with different structures.
The survey confirms the generally low acute toxicity of dyestuffs. It also emphasises the particularly low toxicity of pigments in terms of LD,,, (Table 5), skin and eye irritation, presumably due to their very low solubility. Chronic toxiciry. The possible chronic effects attracting most attention at present are carcinogenicity and to a lesser extent sensitization. Technical dyestuffs,12 properly handled and used, are only taken up in small traces, if at all. The available evidence indicates that these trace quantities present no unreasonable risk. However, a risk situation could arise due to improper handling or use should a product be a potent carcinogen. This is a main reason for ETAD’s continuing effort to identify any such product. At present it is generally agreed that unless epidemiological data are available only long-term tests on animals give sufficiently reliable results to serve as a basis for assessment of a carcinogenic risk. Considerable hopes were therefore attached to the short-term bacteria/mammalian microsome assay (AMES test). The present situation is best described by a comment of the subcommittee on Environmental Carcinogenesis of National Cancer Advisory Board (NCAB, 1977): I* Excluding food, hair, cosmetic, and drug dyestuffs.
ECOTOXICOLOGY TABLE
69
OF DYESTUFFS 5
ANALYSIS OF THE LD,, VALUESLOWERTHAN 2000 mg/kg BY COLORINDEX CLASSIFICATION Total
Dyestuff class Acid Basic Direct Disperse Ingrain Mordant Reactive Solvent Vat Pigment Total
No. of
No. products with LDso W&kg)
products
G250
9 64 12 10 5 1 2 9 1 1
1 8 2 2 1 0 0 0 0
8 56 10 8 4 1 2 8 1 1
114
15
99
1
251-2000
“At present none of the short-term tests can be used to establish whether a compound will or will not be carcinogenic in humans or experimental animals. Positive results obtained in these systems suggest extensive testing of the agent in long-term animal bioassays, particularly if there are other reasons for testing. Negative results in a short-term test, however, do not establish the safety of the agent”.13 “This subcommittee is enthusiastic about the possible future use of in vifro tests as part of a screening system for potential carcinogens and believes that their future development and validation deserve high priority”. ETAD is currently studying the behavior of various dyestuffs belonging to different dyestuff classes in the Salmonellalmammalian microsome test. Ecological assessment. The ecological minimum program of the ETAD SDS provides data about the biological elimination, fish toxicity and toxicity to bacteria in effluent. Bioelimination and biodegradation. Extensive testing indicates that dyestuffs are generally adsorbed to the extent of 40-80% by the biomass and are thus partially eliminated in sewage treatment plants: Practically no biodegradation of the dyestuff itself takes place. At first sight this may seem a drawback but on closer examination it may be considered an advantage. The large dyestuff molecules have a high affinity for various materials, and some are only very sparingly water soluble. Provided they are intact, they are largely eliminable from effluents in the biological and chemical stages of sewage treatment plants. But if they were partly degraded the degree of elimination of smaller molecules formed would be likely to be unsatisfactory. This could lead to heavy contamination of the treated water and complicate subsequent purification stages if potable water were required. ” This also means that at present such tests are of limited value for decisions on the future of a product and provide no basis for regulatory action. See, e.g., J. Ashby and J. A. Styles (1978), Does carcinogenic potency correlate with mutagenic potency in the Ames assay?(London) Nature 271,452-455. The topic is still under debate: B. N. Ames (1978). Eur. Chem. Nents, March 31, p. 23.
70
R. ANLIKER
Hydrolysis
Rlrther Biodegradation Mineralisation FIG. SO,H,
5. Degradation COOH, OH,
of azo dyes. Schematic NO,, NH*, NH-, N=,
model. N=N--,
Each R is any of various Alkyl, Halogen).
sabstituents
(typically
Bioaccumulation and persistence. Dye accumulation in rivers and sediments is becoming less of a problem, chiefly as a result of continuing, extensive cleaning campaigns. The same also applies to buildup in aquatic organisms. Fish accumulation studies, which are required, e.g., by MIT1 for newly introduced products in Japan, so far indicate little or no tendency to accumulate in fish. Current biological projects of ETAD include studies of aerobic and anaerobic biodegradation. Studies by ADMI (1973) already indicated that under anaerobic conditions the dyes tested were at least partly biodegraded. It has been shown that one important metabolic pathway of azo dyes is the reductive cleavage to aromatic amines (e.g., Fonts et al., 1957; Dieckhus, 1961; Radomski et al., 1962; Larsen and Tarding, 1976; Idaka and Ogawa, 1978; Rinde and Troll, 1975) (Fig. 5). Strongly hydrophilic amines, e.g., the sulfonated amines, can be regarded as being detoxified. However, problems could arise by formation of lipophilic toxic aromatic amines, e.g., the carcinogenic benzidine. To determine the biodegradability of such compounds they have been included in ETAD’s current investigations. However, it seems that there is no serious environmental hazard involved because experience so far indicates that such amines biodegrade at a greater rate (k2) than the dyestuff (k,) (k, % k,). As a consequence there is no buildup and the concentration of the amines remains extremely small. In this context the recent findings (Tabak and Barth, 1978) that benzidine is biodegradable under aerobic conditions are of considerable interest. Fish toxicity. Most of the dyestuffs sold by ETAD members have been shown to be of low toxicity to fish. A survey of these data is currently being prepared. Other investigations. The valuable research work of the American Dye Manufacturers Institute (ADMI, 1973) on the effects of dyes on the environment is being continued under the direction of DETO. An extensive study14 is currently under way to evaluate several treatment techniques for a series of 20 dye-bath wastes (Horning, 1977). I4 Work
in progress,
EPA
Grant
No.
R 803174-01-0,
R. H. Horning,
Grant
Director.
ECOTOXICOLOGY LEGISLATOR
:
71
OF DYESTUFFS
LAW NAKING PRo”,DE
THE FRAMEWORK OF REGULATIONS
TO ENSURE
ADEQUATE PROTECTION
OF HUMANS AND ENVIRONMENT.
WITHOUT
THIS
PREJUDICING
FLEXIBILITY SPECIAL
PRIME OBJECTIVE
ADEQUATE
MUST BE EXERCISED TO TAKE ACCOUNT OF
REQUIREMENTS OF VARIOUS CLASSES OF CHEMI-
CALS AND THEIR
USES, AND OF THE DIFFERENT
INDUSTRY
SECTORS,
ENFORCEMENT OF LAWS LEGISLATOR MUST MAKE SURE THAT THE LAWS AND REGULATIONS ARE FOLLOWED BY ALL CONCERNED.
MONITORING THE ENVIRONMENT AND PUBLIC
INDUSTRY
:
HEALTH.
INVENTION PRODUCTION DISTRIBUTION ACTS ON ITS
AND
OF USEFUL PRODUCTS OWN RESPONSIBILITY
FOLLOWING
THE LAWS,
MEDICAL AND ENVIRONMENTAL SURVEILLANCE
FIG. 6. Tasks of legislator and industry.
TASKS OF LEGISLATORS
AND INDUSTRY
There is a growing understanding that the ecotoxicological problems can only be solved by a close cooperation of legislator and industry in an environment of an efficient economy and a healthy society. Although well known, the primary roles of the two bodies should be mentioned (Fig. 6). It is hoped that the testing schemes currently under consideration, which are also going to be included in new laws, will be realistic, and well adjusted to the practical requirements of industrial product development and to the technical and economic possibilities. It is sensible to proceed stepwise with such testing, but it is essential that the decisions concerning the need for more detailed testing should lie in the hands of a trained toxicology expert who takes appropriate account of exposure potential.15 ACTIVITIES
FOR SECURING
SAFETY
Can dyestuffs now be called environmental chemicals? According to definitions by Korte (1976) probably not, with perhaps the exception of a few large volume I5 A balanced view has been recently expressed by E. Langley (1978), Health and safety aspects of the proposed notification scheme for new chemicals, Chem. Ind. (London) W-507.
72
R. ANLIKER
CONTINUOUS REDUCTION OF EXPOSURE BY -
IMPROVED PRODUCTION
-
GOOD WORKING CONDITIONS
TECHNOLOGY
-
PERSONAL HYGIENE AND ADEQUATE LAUNDRY FACILITIES
-
PROPER INFORMATION
-
IMPROVED PHYSICAL
-
REDUCTION
AND HANDLING
FACILITIES
AND EDUCATION OF PERSONNEL PROPERTIES
OF DYESTUFF
OF PRODUCTS (E.G.
-
IMPROVED APPLICATION
-
USE OF BEST AVAILABLE
-
USE OF PRODUCTS WITH BEST FASTNESS PROPERTIES
-
NEW PRODUCTS
-
NON DUSTY FORMS)
IN EFFLUENTS PROCESSES AND TECHNOLOGY APPLICATION
TECHNOLOGY
INNOVATION
CONTINUOUS MONITORING
BY INDUSTRY,
GOVERNMENT & PUBLIC
-
ENVIRONMENTAL
SURVEILLANCE
-
MEDICAL SURVEILLANCE EPIDEMIOLOGY
-
SCIENTIFIC
-
GENERAL ALERTNESS OF WORKERS. EMPLOYERS,
AND TECHNOLOGICAL
SEARCH FOR CHEMICALS
INTERCOMMUNICATION SCIENTISTS
(BAD ACTORS) WHICH ARE LIKELY
TO
-
DEVELOPMENT OF NEW, SHORTER AND MORE ECONOMIC ECOTOXII SPECIALLY SHORT-TERM TESTS FOR
-
BASIC
RESEARCH ON STRUCTURE-ACTIVITY
FIG.
RELATIONSHIP.
METABOLISM
7.
products. Nevertheless the annual world-wide production of dyestuffs of roughly 650,000 tons justifies careful assessment of their overall environmental impact. It has been the aim of this paper to show how ETAD operates and to summarize the present status of ecotoxicology of dyestuffs. However substantial, ETAD’s contribution is only a fraction of the total effort being expended by the chemical industry to secure and improve safety .16These endeavors form part of a continuing and concurrent process. Since this fact is often overlooked by many, a summarizing scheme of the important simultaneous activities for securing safety is shown in Fig. 7. ACKNOWLEDGMENT The author manuscript.
thanks
I6 The extensive industry, research and internationale Berufsgenossenschaft
Dr.
E. A. Clarke
for
his critical
discussion
and
help
in preparing
the English
collaborative efforts in the field of occupational medicine and ecotoxicology by institutions, and authorities have been reviewed by A. M. Thiess (1977), Nationale arbeitsmedizinische Zusammenarbeit im Bereich der chemischen Industrie, (August), 361-371.
ECOTOXICOLOGY
OF DYESTUFFS
73
REFERENCES ADMI (1973). Dyes and the Environment, Vols. 1 and 2 American Dye Manufacturers Institute Inc., New York. AIHC (1978). AIHC Recommended Alternatives 10 OSHA’s Generic Carcinogen Proposal. American Industrial Health Council, New York. See also Chem. Eng. Netifs, Jan 30, 1978, 30-35. ANLIKER, R. (1977). Color Chemistry and the Environment. Ecotoxicol. Environ. Sufefy 1, 21 l-237. See also Rev. Prog. Coloration 8, (1977), 60-72. BRETSCHER, H., EIGENMANN, G., AND PLATTNER, E. (1978). Die Umweltsgesetzgebung: Eine Herausforderung fiir die Chemische Industrie. Chimia 32, 173-180. DFG (1977). Kosmefische Fiirbemittel. Deutsche Forschungsgemeinschaft, Farbstoff-Kommission. Harald Boldt Verlag, Boppard. DFG (1978). Lebensmittelfarbstoffe. Deutsche Forschungsgemeinschaft, Farbstoff-Kommission, Harald Boldt Verlag, Boppard. DHEW (1977). Bioassay of Diarylanilide Yelloh, for Possible Curcinogenicity. DHEW Publication No. (NIH) 77-830. DHEW (1978). Direct Black 38, Direct Blue 6, and Direct Brown 95, Benzidine Derived Dyes. U.S. Department of Health, Education and Welfare. NIOSH/NCI Joint Intelligence Bulletin No. 24, April 17. See also NCI, Technical Report Series No. 108, 1978. l3-week subchronic studies of these three dyestuffs. DIECKHUS, B. (1961). Untersuchungen zur reduktiven Spaltung der Azofarbstoffe durch Bakterien. Zentralbl.
Bakteriol.
Parasitcn.
Infektionskr.
180, 244-249.
DRAKE, J. P.. BUTTERWORTH, K. R., GAUNT, I. F., AND HARDY, J. (1978). Long-term toxicity studies of Chocolate Brown HT in mice. Toxicology 10, 17-27. FONTS, J. R., KAMM, J. J., AND BRODIE, B. B. (1957). Enzymatic reduction of Prontosil and other azo dyes, .I. Phurmacol. Exp. Ther. 120, 291-300. GAUNT, I. F., MASON, P. L., GRASSO,P., AND KISS, I. S. (1974). Long-term toxicity of Sunset Yellow FCF in mice. Food. Cosmet. Toxicol. 12, 1- 10. HOLMES, P. A., PRITCHARD, A. B., KIRSCHMAN, J. L. (1978). A one year feeding study with Carmoisine in rats. To.rico/ogy 10, l69- 183. HORNING, R. H. (1977). Characterization and treatment of textile dyeing wastewater. Text. Chemist Colorist
9, 73-76.
JENKINS, C. L. (1978). Textile dyes are potential hazards. J. Environ. Health 40, 2.56-262. IDAKA, E., AND OGAWA, T. (1978). Degradation of azo compounds by Aeromonas hydrophila var. 24B. J. Soc.Dyers Cal. 94, 91-94. KORTE, F. (1976). Global inputs and trends ofchemical residues in the biosphere. Environ. @al. Safety 5, l83- 196. LARSEN. J. C., AND TARDING, F. (1976). Studies on the metabolism of Orange RN in the pig. Acta Pharmacol. Toxicol. 39, 525-53 1. LEUSCHNER, F. (1978). Carcinogenicity studies on different Diarylanilide Yellow pigments. Toxicol. Lett.
2, 253-260.
NCAB (1977). National Cancer Advisory Board. J. Nar. Cancer Inst. 58, 463. RAAB, R. (1978). ErlLuterungen zum Sicherheitsdaten-Blatt der ETAD. Deaf. Ferber-Kalender 82, 506-514. RADOMSKI, J. L.. AND MELLINGER, T. J. (1962). The absorption, fate and excretion in rats of watersoluble azo dyes. J. Pharmacol. Exp. Ther. 136, 259-266. RADOMSKI, J. L. (1974). Toxicology of food colors. Amer. Rev. Pharmacol. 14, 127-137. RINDE, E., AND TROLL, W. (1975). Metabolic reduction of benzidine azo dyes to benzidine in the rhesus monkey. J. Naf. Cancer Inst. 55, 181-182. R~MPPS CHEMIE LEXIKON (1973). Frankh’sche Verlagshandlung Stuttgart, Bd. 2, 1083. SAX, N. I. (1975). Dangerous Properties oflndasrriul Materials, 4th ed., p. 428, Van NostrandReinhold. New York. TABAK. H. H.. AND BARTH, E. F. (1978). Biodegradability of benzidine in aerobic suspended growth reactors. J. Water Pollut. Control Fed. 50, 552-558.
74
R. ANLIKER
WHO (1%6). Sunset Yellow FCF, p. 83. Tartrazine, p. 88. WHO Food Addition Rep. Ser. No. 38B. 66.25. WHO (1974). Azorubine, pp. 47-50. Brilliant Black PN, pp. 53-56. Ponceau 4R, pp. 109-112. WHO Food
Addition
Ser.
No.
6.
WHO (1975). Amaranth, pp. 10-27. WHO
Food
Addition
Ser.
No.
8.
AND
ENVIRONMENTAL
Ecotoxicology
3, 59-74 (1979)
SAFETY
of Dyestuffs -A
Joint Effort by Industry’
R. ANLIKER~ P.O.
Box
CH-4005,
Received
Basle.
August
Switzerland 16, 1978
Within the dyestuff industry it was realized that the ecotoxicological problems ahead could be tackled more effectively by the deployment of the large but nonetheless limited scientific and technical resources on a collaborative basis. This led to the formation of an international association, ETAD (Ecological and Toxicological Association of the Dyestuffs Manufacturing Industry) in 1974. An outline of its organization and modus operandi is given. ETAD’s activities are mainly directed at ensuring the safety of commercial synthetic organic dyestuffs and pigments. Besides the determination of the ecotoxicological properties of specific dyestuffs ETAD also deals with more fundamental problems. Its current and completed studies include a widely accepted safety data sheet, development of test methods, analysis of exposure potential, and the formulation of viewpoints concerning testing requirements and legislation.
ETAD-FORMATION
AND OBJECTIVES
In the 1960s a number of prominent people in the dyestuffs industry came to realize that the large, but nevertheless limited scientific and technical potential in the individual companies could be used more effectively on a coordinated basis to solve any ecotoxicological problems ahead. After thorough legal and administrative preparatory work, an international association, ETAD,3 was formed in 1974. The primary objectives, as stated by the bylaws, are to coordinate and unify the efforts of manufacturers of synthetic organic dyestuffs and synthetic organic pigments to minimize any possible damage to the environment arising from the use and application of the products, to provide the best possible and practicable protection for the users and consumers of these products, and to aid and cooperate with government departments and agencies and any other public institution concerned with the ecotoxicological impact of the products. It is important to note that the bylaws refer to lowering the impact, they do not refer to eliminating all impact. ETAD is trying to maintain a balanced view. It is not possible to legislate all hazard out of existence, as some new laws which are being promulgated would have us believe. There is no point in ETAD pretending that the products of our industry have a zero effect, and equally no point in govern1 This paper was presented at the Symposium “Scientific Basis for the Ecotoxicological Assessment of Environmental Chemicals,” August 16- 18, 1978, Vienna. 2 Executive Secretary of ETAD. a Ecological and Toxicological Association of the Dyestuffs Manufacturing Industry. At present the following companies are members of ETAD: ACNA (Italy), Amar Dye-Chem, Indian Dyestuffs Ind. (India); BASF, Bayer, Hoechst (Germany); Ciba-Geigy, Rohner, Sandoz, (Switzerland); Hodogaya Chem., Mitsubishi, Mitsui Toatsu, Nippon Kayaku, Sumitomo (Japan); ICI, Yorkshire Chem. (Great Britain); Koge Chem. (Denmark); Ugine Kuhlmann (France). 59
0147-6513/79/010059-16$02.00/O Copyright 0 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
60
R. ANLIKER
(U.S,A) DETO DYES ENVIRONMENTAL AND TOXICOLOGY ORGANIZATION, INC.
DETO-ETAD LIAISON -----COFiMITTEE
-_---
ETAD US ADVISORY COMMITTEE
TOXICOLOGICAL SUBCOMMITTEE FIG.
-
TECHNICAL COMMITTEE
ECOLOGICAL SUBCOMMITTEE
1. Organization
structure
PIGMENTS ADVISORY COMMITTEE
-
ANALYTICAL SUBCOMMITTEE
..
REGIONAL ANALYTICAL SUBCOMMITTEE JAPAN
of ETAD.
mental legislators assuming that the benefits of the dyestuffs industry can be made available to the public at large, with zero risk. Activities in environmental protection are based on the realization that many features of our modern civilization are in conflict, often unavoidably, with nature. We all wish to enjoy the best quality of life both now and in the future, and unless we are prepared to forego the undoubted benefits that modern technology makes available, it is necessary to seek a compromise and to accept certain risks. It is in the complex problem area of defining the balance between risk and benefit that ETAD is involved. ORGANIZATION
OF ETAD
The ETAD members represent about 80% of world-wide dyestuff production (excluding Comecon and China). The primary authority is the General Assembly (Fig. 1) in which the various member companies are entitled to exercise one, two, or three votes depending on their annual sales of dyestuffs. The annual membership fees4 are determined by the need to cover the costs of the Secretariat, traveling expenses of committee members, and studies contracted externally. The majority of the project work is, however, carried out within the member firms and the costs involved are borne directly by them. The governing powers of the Association are vested in the Board of Directors which is elected by the General Assembly from senior managers of the dyestuffs divisions of the member companies. This ensures, in a most effective way, that studies undertaken by the Technical Committee and the various subcommittees 4 The annual fee is at present Sfr. 20,000 per vote. An associate introduced recently to encourage small companies to join ETAD.
membership
with
reduced
fees,
was
ECOTOXICOLOGY
OF DYESTUFFS
61
proceed promptly. The Technical Committee, at whose meetings the Chairmen of the subcommittees participate, coordinates activities, proposes future projects for Board approval, and sets priorities, etc. This committee consists of seven senior departmental managers delegated by the member firms. The Regional Analytical Subcommittee in Japan coordinates the activities of the Japanese member companies and, in particular, deals with any problems specific to Japan. Problems relating specifically to pigments are dealt with by the Pigments Advisory Committee in collaboration with the other scientific committees. Uncertainties about the possible complications arising from membership of American companies in ETAD led to the formation of the Dyestuffs Environmental and Toxicology Organization (DETO) in the United States in 1977. DETO is affiliated to the Synthetic Organic Chemical Manufacturers Association, Inc. (SOCMA) and has essentially the same objectives as ETAD. Whereas ETAD covers both dyestuffs and pigments, DETO deals with dyestuffs only, because the pigments manufacturers were already represented by the Dry Color Manufacturers Association (DCMA). Responsibility for ensuring close cooperation between DETO and ETAD lies with the DETO/ETAD Liaison Committee and the ETAD-U.S. Advisory Committee. The latter committee consists of representatives of United States-based manufacturing subsidiaries of European ETAD member companies. The ETAD Executive Secretary, a full-time operating executive, is responsible, among other matters, for assisting and advising the Board and committees, for contact with regulatory authorities, industrial associations, and environmental organizations, and for the preparation of official ETAD responses to various legislative proposals on environmental matters affecting the dyestuffs industry. The President, who presides at all meetings of the General Assembly and the Board, is elected each year. Those committee members who belong to the same company as the President, also take over the chairmanship of the corresponding committees for his year of office. This procedure facilitates a close contact between the President and the committee chairmen and has proved to be very beneficial. ACTIVITIES
OF ETAD
Within the framework of its objectives, ETAD attaches particular importance to: Harmonization of international environmental legislation, and the avoidance of unnecessary inhibition of innovation by overregulation. ETAD supports the principle of industrial freedom with the State having power to intervene when appropriate, and absolutely rejects the destructive principle of prohibition unless consent has been conferred by the State. Essential for the necessary environmental protection and the retention of a healthy industry, is a high degree of self-responsibility by industry, which legislation should support rather than cripple (Bretscher et al., 1978). Objective expert evaluation and judgement of ecotoxicological matters. 5 See, e.g., report on lecture given by G. Hartkop (1978). Ministry of Interior Bonn, RegierungsvorstelIungen zur Umweltspolitik des Bundes unter Beriicksichtigung der Textilindustrie. Texfilryredlung 13, 280.
62
R. ANLIKER TABLE 1 HIGHEST
IMPURITY
LEVELS
OF METALS
Metal
Impurity level (wm)
As Ba Cd co Cr (total CY+) cu Fe
50 100 50 500 500 250 2500
IN DYESTUFFS~
Metal
Impurity level @pm)
Hg Mn Ni Pb Sb Se Sn Zn
25 1000 250 250 50 50 250 5000
n These limits do not apply to metal complex dyestuffs. Highest impurity levels are those maximum metal contents of dyestuffs which, in a 2% dyeing and with a total dilution of the effluent of 1:2500 related to the dyestuff used, satisfy the currently known legal requirements.
The development and standardization of the necessary analytical, ecological, and toxicological methods. The provision of the physicochemical and ecotoxicological information which is necessary for the safe handling and use of the products. The continuing extension of our understanding of the ecotoxicological behavior of dyestuffs in order to identify any undesirable properties. The activities of ETAD are best illustrated by mentioning the work already completed and by outlining the scope of some current projects. Safety Data Sheet (SDS)
The ETAD-SDS was designed to provide the users of dyestuffs with basic information to enable safe handling of the product. Detailed explanatory notes concerning the meaning and interpretation of the data are also provided (Raab, 1978). It has been introduced widely and has influenced the formats adopted by other organizations. The requirements of the various chemical industry sectors differ but it would be beneficial if individual versions could at least achieve a basic uniformity of layout: Individualization on a national basis is unnecessary and should be avoided. Methods
Recommended
by ETAD
The use of clearly defined, standardized methods, which give reproducible results, is essential if meaningful and comparable data are to be obtained. Methods already accepted by the scientific community and the authorities are used whenever possible. Existing, as well as modified or newly developed, methods are subjected to critical appraisal, involving round-robin tests in the laboratories of the member companies, before they are recommended by ETAD. If satisfactory, the methods are used by the member companies and also made available to authorities.
ECOTOXICOLOGY
OF DYESTUFFS
63
Levels of Heavy Metals in Dyestuffs
The ETAD members ensure that the heavy metal content of their products is kept below agreed levels which enable the user to satisfy readily the current legal requirements regarding effluents (Table 1). The figures given are periodically reviewed and, if necessary, adapted to new situations. Assessment
of Ecotoxicological
Properties
of Dyestuffs
The dyestuffs industry is constantly faced with the question of the safety of its products. There is already an extensive literature on this subject (Anliker, 1977). Most dyestuffs, if properly handled and used, present no unreasonable risk. However, one must recognize that in this industry’s sector, which involves thousands of products and intermediates, one can always find substances which may present an ecotoxicological risk, and thus require special handling precautions, a limitation in use, or a switch to other products. ETAD gives high priority to the identification of specially hazardous products and to the setting up of appropriate precautionary measures. However, it must be made very clear, that any attempt to discredit whole product classes by unscientific generalizations, by one-sided and unqualified interpretations of results and by unwarranted extrapolations on the basis of similarities of chemical structures must be rejected.6 The title of a recent publication “Textile dyes are potential hazards” (Jenkins, 1978) or statements such as “Azo dyes are often found to be carcinogenic” (Sax, 1975) or “Die meisten Farbstoffe sind mehr oder wenig giftig” (Rompp, 1973) may illustrate the point. The limited space available does not permit such articles to be dealt with in detail, but perhaps the difficulty can best be illustrated by briefly describing the current situation concerning azo dyestuffs. The availability of a wide variety of aromatic azo and coupling components permits the synthesis of a very large number of azo compounds. It is estimated that more than half of all known dyestuffs (i.e., more than 50,000 aromatic azo compounds and more than 2000 commercial dyestuffs contain one or more azo groups). Azo compounds are found in almost every dyestuff application class. It is scientifically not tenable to make the generalization that these compounds represent an especially high carcinogenic risk only because compounds containing azo groups have been found to be carcinogenic in animal tests; e.g., one of the first was Butter Yellow (N,N-dimethylaminoazobenzene)’ and recently some benzidine dyes8 (DHEW, 1978). On the other hand a wide variety of azo compounds, both dyestuffs (e.g., WHO, 1966, 1974, 1975; Gaunt, 1974; Radomski, 6 For example. an expert opinion has been expressed by D. Schmahl (1977) Toxicol. Cancer Res. Inferdiscpl. Sci. Rev. 2, 305-311: “This, however. should not mislead one into thinking that, for example, each aromatic amine or polycyclic hydrocarbon must be carcinogenic. These are highly specific chemical compounds which may lose their carcinogenicity by the slightest variation in structure.” ’ For more details on carcinogenicity of azo compounds see, e.g., J. C. Acres and M. Acres, Chemical carcinogens, Prog. Drug Res. 4,407-582, E. Jucker, (ed.), Birkhauser Verlag, Basel, 1962. D. B. Clayson and R. C. Garner, Carcinogenic aromatic amines and related compounds, In Chemical Carcinogens Ch. E. Searle, (ed.). ACS Monograph 173, pp. 366-461, 1976. * The carcinogenic action may arise from different causes. In the case of benzidine dyes the activity can be attributed mainly to the metabolic formation of benzidine from the dyestuff (Rinde and Troll, 1975).
64
R. ANLIKER HUMAN
EXPOSURE
MEASURES
TAKEN
TO
REDUCE
EXPOSURE
EXPOSURE RATING
PRODUCTION WORKERSETC.
IMPROVED GOOD
PRODUCTION
IMPROVED
PHYSICAL
PERSONAL
HYGIENE
PROPER
WI.4
I
EN”*RONmNTI
FORM AND
AND
OF
IN
COLOR
EFFECTIVE
EFFLUENT
I
PROCESS
IMPROVEMENTS
.
ORDERLY
DISPOSAL
(NON
DUSTY
ADEQUATE
INFORMATION
REDUCTION
PUBLIC
TECHNOLOGY
CONDITIONS AND HANDLING FACILITIES
WORKING
PRODUCTS)
LAUNDRY
EDUCATlON
OF
FACILITIES PERSONNEL
EFFLUENT TREATMENT
OF
WASTE
PROCESSING DYERS. PRINTERS
ETC.
USE
OF
GOOD
PROPER
WORKING
APPLICATION
TMPRCVED
PHYSICAL
PERSONAL
HYGIENE
PROPER
INFORMATION
REDUCTION
OF
++
TECHNOLOGY
CONDITIONS FORM AND
ADEQUATE
AND
LAUNDRY
EDUCATION
COLOR
IN
WASTE
WATER
OF
FACILITIES PERSONNEL
EFFLUENT
I
EFFECTIVE
’
IMPROVED APPLICATION PROCESSES (E.G. BETTER EXHAUSTION OF DYES)
TREATMENT
+
1974; DFG, 1977, 1978; Drake et al., 1978; Holmes et al., 1978) and pigments (DHEW, 1977; Leuschner, 1978) have been shown in long-term animal tests to be noncarcinogenic. Furthermore, a distinction must be made between dyes which are commercial products and others prepared solely for scientific purposes. For example, out of about 300 azo compounds listed by NIOSH as being suspected carcinogens in animals only 36 are commercial dyestuffs in the United States. At present the scientific soundness of the supporting data is being checked. On many occasions attention has been drawn to the many damaging consequences of such unqualified and unjustified statements and judgements: Among other things, they distort the sense of proportion, and as a consequence lead to the setting up of wrong priorities, senseless deployment of scarce testing resources, and overregulation. The number of chemicals used today is estimated to be many tens of thousands, far beyond currently available testing capacities for a full-scale testing program. With a current world capacity for about 500 long-term tests, the investigation of say 20,000 compounds would take 40 years. This clearly explains the necessity of a stepwise procedure and the setting of priorities for the chemical industry as a whole. In the setting of priorities the important factors in the assessment of risk are: exposure pattern, ecotoxicological profiles, and production volume. The parameters which are relevant to evaluating the ecotoxicological profile of a chemical and a summary of the important problem areas in the dyestuff industry have been published previously (Anliker, 1977). Exposure assessment. The exposure assessment not only provides the basis for the pinpointing of problem areas but also for the extremely important measures
ECOTOXICOLOGY UMAN XPOSURE
USE
65
OF DYESTUFFS MEASURERS
TAKEN
TO
REDUCE
EXPOSURE RATING
EXPOSURE
l
END USE i3NSUMER
TEXTILES LEATHER
INCL.
USE
OF
BEST
USE
OF
PRODUCTS
PAPER NAPKINS FOOD PACKAGING NEWSPRINT
DITTO
PLASTICS
APPLlCATION
PAINTS AND INKS GENERAL ARTISTS' PAINTS FINGER PAINTS
INSTRUCTIONS
FOODSTUFFS
AVAILABLE
APPLICATION
WITH
BEST
TECHNOLOGY
FASTNESS
0 (+) 0
+ OF
THE
FOR
NON-MIGRATION
PROPER
PRINCIPLE
O...r^_
_I
+ + EXPOSURE
IS
PRODUCTS
REQUIRE
++
INEVITABLE RIGOROUS
TOXICOLOGICAL +++
,NVESTlGATION
++
TOYS
LEGISLATIVE
DO-IT-YOURSELF PRODUCTS
ADEQUATE
SAFETY
WITH
ORDER
__“r.e._a^.
. --_
0
USE
COSMETICS
f
0
PROPERTIES
..^_.
LOW
CONTROL,
NON-MIGRATION
INSTRUCTIONS, OF
PRINCIPLE USE
OF
PRODUCTS
0 +
TOXICITY.
-._-.z.-__.
to minimize the exposure. It must be accepted that extensive animal and even human toxicological information on all chemicals cannot be made available in the near future. It is often overlooked that the reduction of dangerous and also unnecessary exposure is still one of the most effective and immediate measures to eliminate unreasonable risks.g The objective of a current project of ETAD is the qualitative and quantitative assessment of the exposure pattern of dyestuffs. Figures 2 and 3 give a summary of the qualitative exposure pattern including an exposure rating. The figures also indicate measures already taken or to be taken to lower the exposure. Figure 4 displays schematically the exposure potential in the main areas of production, processing, and consumer use. To illustrate the scope of this project, a study to assess the trace amounts of dyestuff which may be transferred from a dyed fabric to the skin can be mentioned. The extractability of the dyestuffs from dyed fabrics is determined using the alkaline and acid perspiration stimulants defined in the standard 10s method.‘O The amount of dyestuff which is eluted from deep-shade dyed fabric samples is measured spectrophotometrically. From this value is calculated the amount which would be extracted from an area of 500 cm2. It is generally accepted that an area of 500 cm2 of sweat-moistened material remains in contact with the skin for any length of time and the maximum daily dermal exposure per person may be assumed to be the amount of dyestuff which is extracted from this area of dyed fabric. The study y Similar views have been expressed, for example, in his recommendation J. H. Weisburger (1977), Cancer prevention, Chemtech. 7, 734-740. lo Method ISO/R 105/N-1968. Colour Fastness to Perspiration.
of cancer
prevention
by
66
R. ANLIKER Exposure
Number Exposed
of Persons
Ease of Control of Exposure Production
Processing
consumer
FIG. 4. Exposure potential to dyestuffs.
includes all the main fibers and important representatives of the various dyestuff classes. The results for two disperse dyes on polyester fabric are given in Table 2.” In this case, the dermal exposure was shown to be less than 0.25 pg/person daily. Preliminary results with water-soluble dyestuffs on hydrophilic fibers show somewhat higher values in the lower microgram range. Toxicological assessment. The factors to be considered in the assessment of risk for a chemical include: the total exposure potential, the seriousness of the toxic effect, and the fact or the probability of its occurrence. The complexity of assessing evidence of toxicity and specially carcinogenicity dictates that the evaluation of the potential human hazard of a given agent must be individualized in terms of the chemical and metabolic aspects of that specific agent, its intended uses, the data available at the time that the decision must be made, and other factors pertinent to the case under consideration. Each case must be considered on its own and the criteria appropriate for one agent may not necessarily apply to another. One can distinguish the following principal groups of chemicals with regard to test requirements: pharmaceuticals (including drug dyes), food additives (including food dyes), agrochemicals, cosmetics (including hair and cosmetic dyes), chemicals for food packaging materials and toys (including selected dyestuffs and pigments), chemicals in large, medium, and small volumes (including technical dyestuffs and pigments), chemicals for research purposes only. A rational and exhaustive treatment of the many controversial issues of cancer risk assessment has recently been published by the American Industrial Health Council (AIHC, 1978). Acute toxicity. It has already been mentioned that due to the limited testing facilities, the great number of dyestuffs and intermediates to be tested, and the need to set meaningful priorities, the toxicological investigation can and will only proceed stepwise. The ETAD members agreed, as a first step, to determine systematically the physicochemical and ecotoxicological basic data necessary for the safe handling of their products. The data are made available to the users in form of the safety data sheet mentioned previously. The project has now been almost completed, ‘I The author thanks Dr. L. Yamauchi and Dr. T. Ohshima, Research Department, Chemical Co. Ltd, Osaka, Japan, for their kind permission to quote these results.
Sumitomo
ECOTOXICOLOGY
67
OF DYESTUFFS
TABLE 2 EXTRACTION
OF DISPERSE DYES BY PERSPIRATION FROM POLYESTER FABRICS”
SIMULANTS
C.I. Disperse Blue 301 Dyestuff (100% active ingredient) (% 0.w.f.) Fastness to perspiration (1 = lowest, 5 = highest fastness) Recovery rate (%) Limit of detection (Fg) Extractability (Fg/SOOcm’ of fabric)” Alkaline perspiration simulant Acid perspiration simulant
C.I. Disperse Orange 30
1.5
1
5 >95 0.5
5 >95 0.7
co.2 co.2
co.25 co.25
‘1 Sixteen grams of fabric (106 g/m’) was treated with 800 ml of perspiration removed was extracted with chloroform and determined spectrophotometrically. 500 cm2 of fabric was 5.3 g.
simulant.
The dyestuff The weight of
and has involved the testing of over 5000 commercial dyestuffs during the last 5-7 years. The costs of carrying out this agreed toxicological minimum testing program, i.e., acute oral toxicity on the rat (LD,,) and eye and skin irritation tests on the rabbit, are well over 20 million Sfr. Within the individual companies supplementary toxicological data have been collected on many products. The analysis of the LD,, data (Table 3) available in August 1977, did not uncover any recognizable structure-toxicity relationship. The products with values below 250 and 250-2000 mg/kg belong to a wide variety of different structures (Table 4). The classification of these compounds according to the Color Index (Table 5) revealed a higher incidence of the basic dyestuffs, in the two lower groups, which is not surprizing. Within this group there was no frequent occurrence of any specific structure. This survey indicates that from the 4461 commercial products tested only 15 dyestuffs with different chemical structures showed LDso values of less than 250 mg/kg, all values lying in the range of 100 to 250 mg/kg. This group of products will undergo further studies. TABLE 3 DETERMINATION
OF SINGLE (COMMERCIAL
ADMINISTRATION BRANDS) BY
ETAD
TOXICITY OF DYESTUFFS MEMBERS~
Irritation No. of dyes tested
No. of dyes tested
No. of dyes with LD,, values (mg/kg) ~250
250-2000
2000- 5000
>5000
Eye
Skin
4461 ( 100)b
44 (1)
314 (7)
434 (9.7)
3669 (82.3)
4573
4614
n Acute oral toxicity LD,, in rats and effects safety data sheets up to August 1977. * The values in parentheses are percentages.
on the skin and eyes.
Only
data published
in the ETAD
68
R. ANLIKER TABLE ANALYSIS
OF LDso VALUES LOWER THAN 2000 mg/kg BY CHEMICAL
Chemical type
14
Monoazolquaternary Disazo Trisazo Phthalocyanine Diphenylmethane Triphenylmethane Xanthene Oxazine Methine Anthraquinone Indigoid Stilbene azo Miscellaneous
16
TYPES
No. of products with L&O (mgkg)
Total No. of products
Monoazo
Total
4
c250 1(125) : (199, 200, 240, 200)
20
251-2000 13
16 16
1
0
1
2
0
2
1
0
13 6 4 20 3
1 (1W 2 (220, 250)
1 11 114
4 (133, 213, 222, 224) 0
0 1 (150) 1 (221)
1 1 10
1 (210)
2
1 12 4 3 16 3
15
99
” Criteria for analysis: 1. Mixture products were omitted. 2. Azoic diazo components (28) were not included. 3. Where products with the same basic structure, as identified by Color Index No., have been tested by different member firms, only the lowest LD,, value was used. 4. Where LD,, values were quoted as a range, the lower value has been used for classification. By this procedure the number of 358 of tested commercial products was reduced to 114 products with different structures.
The survey confirms the generally low acute toxicity of dyestuffs. It also emphasises the particularly low toxicity of pigments in terms of LD,,, (Table 5), skin and eye irritation, presumably due to their very low solubility. Chronic toxiciry. The possible chronic effects attracting most attention at present are carcinogenicity and to a lesser extent sensitization. Technical dyestuffs,12 properly handled and used, are only taken up in small traces, if at all. The available evidence indicates that these trace quantities present no unreasonable risk. However, a risk situation could arise due to improper handling or use should a product be a potent carcinogen. This is a main reason for ETAD’s continuing effort to identify any such product. At present it is generally agreed that unless epidemiological data are available only long-term tests on animals give sufficiently reliable results to serve as a basis for assessment of a carcinogenic risk. Considerable hopes were therefore attached to the short-term bacteria/mammalian microsome assay (AMES test). The present situation is best described by a comment of the subcommittee on Environmental Carcinogenesis of National Cancer Advisory Board (NCAB, 1977): I* Excluding food, hair, cosmetic, and drug dyestuffs.
ECOTOXICOLOGY TABLE
69
OF DYESTUFFS 5
ANALYSIS OF THE LD,, VALUESLOWERTHAN 2000 mg/kg BY COLORINDEX CLASSIFICATION Total
Dyestuff class Acid Basic Direct Disperse Ingrain Mordant Reactive Solvent Vat Pigment Total
No. of
No. products with LDso W&kg)
products
G250
9 64 12 10 5 1 2 9 1 1
1 8 2 2 1 0 0 0 0
8 56 10 8 4 1 2 8 1 1
114
15
99
1
251-2000
“At present none of the short-term tests can be used to establish whether a compound will or will not be carcinogenic in humans or experimental animals. Positive results obtained in these systems suggest extensive testing of the agent in long-term animal bioassays, particularly if there are other reasons for testing. Negative results in a short-term test, however, do not establish the safety of the agent”.13 “This subcommittee is enthusiastic about the possible future use of in vifro tests as part of a screening system for potential carcinogens and believes that their future development and validation deserve high priority”. ETAD is currently studying the behavior of various dyestuffs belonging to different dyestuff classes in the Salmonellalmammalian microsome test. Ecological assessment. The ecological minimum program of the ETAD SDS provides data about the biological elimination, fish toxicity and toxicity to bacteria in effluent. Bioelimination and biodegradation. Extensive testing indicates that dyestuffs are generally adsorbed to the extent of 40-80% by the biomass and are thus partially eliminated in sewage treatment plants: Practically no biodegradation of the dyestuff itself takes place. At first sight this may seem a drawback but on closer examination it may be considered an advantage. The large dyestuff molecules have a high affinity for various materials, and some are only very sparingly water soluble. Provided they are intact, they are largely eliminable from effluents in the biological and chemical stages of sewage treatment plants. But if they were partly degraded the degree of elimination of smaller molecules formed would be likely to be unsatisfactory. This could lead to heavy contamination of the treated water and complicate subsequent purification stages if potable water were required. ” This also means that at present such tests are of limited value for decisions on the future of a product and provide no basis for regulatory action. See, e.g., J. Ashby and J. A. Styles (1978), Does carcinogenic potency correlate with mutagenic potency in the Ames assay?(London) Nature 271,452-455. The topic is still under debate: B. N. Ames (1978). Eur. Chem. Nents, March 31, p. 23.
70
R. ANLIKER
Hydrolysis
Rlrther Biodegradation Mineralisation FIG. SO,H,
5. Degradation COOH, OH,
of azo dyes. Schematic NO,, NH*, NH-, N=,
model. N=N--,
Each R is any of various Alkyl, Halogen).
sabstituents
(typically
Bioaccumulation and persistence. Dye accumulation in rivers and sediments is becoming less of a problem, chiefly as a result of continuing, extensive cleaning campaigns. The same also applies to buildup in aquatic organisms. Fish accumulation studies, which are required, e.g., by MIT1 for newly introduced products in Japan, so far indicate little or no tendency to accumulate in fish. Current biological projects of ETAD include studies of aerobic and anaerobic biodegradation. Studies by ADMI (1973) already indicated that under anaerobic conditions the dyes tested were at least partly biodegraded. It has been shown that one important metabolic pathway of azo dyes is the reductive cleavage to aromatic amines (e.g., Fonts et al., 1957; Dieckhus, 1961; Radomski et al., 1962; Larsen and Tarding, 1976; Idaka and Ogawa, 1978; Rinde and Troll, 1975) (Fig. 5). Strongly hydrophilic amines, e.g., the sulfonated amines, can be regarded as being detoxified. However, problems could arise by formation of lipophilic toxic aromatic amines, e.g., the carcinogenic benzidine. To determine the biodegradability of such compounds they have been included in ETAD’s current investigations. However, it seems that there is no serious environmental hazard involved because experience so far indicates that such amines biodegrade at a greater rate (k2) than the dyestuff (k,) (k, % k,). As a consequence there is no buildup and the concentration of the amines remains extremely small. In this context the recent findings (Tabak and Barth, 1978) that benzidine is biodegradable under aerobic conditions are of considerable interest. Fish toxicity. Most of the dyestuffs sold by ETAD members have been shown to be of low toxicity to fish. A survey of these data is currently being prepared. Other investigations. The valuable research work of the American Dye Manufacturers Institute (ADMI, 1973) on the effects of dyes on the environment is being continued under the direction of DETO. An extensive study14 is currently under way to evaluate several treatment techniques for a series of 20 dye-bath wastes (Horning, 1977). I4 Work
in progress,
EPA
Grant
No.
R 803174-01-0,
R. H. Horning,
Grant
Director.
ECOTOXICOLOGY LEGISLATOR
:
71
OF DYESTUFFS
LAW NAKING PRo”,DE
THE FRAMEWORK OF REGULATIONS
TO ENSURE
ADEQUATE PROTECTION
OF HUMANS AND ENVIRONMENT.
WITHOUT
THIS
PREJUDICING
FLEXIBILITY SPECIAL
PRIME OBJECTIVE
ADEQUATE
MUST BE EXERCISED TO TAKE ACCOUNT OF
REQUIREMENTS OF VARIOUS CLASSES OF CHEMI-
CALS AND THEIR
USES, AND OF THE DIFFERENT
INDUSTRY
SECTORS,
ENFORCEMENT OF LAWS LEGISLATOR MUST MAKE SURE THAT THE LAWS AND REGULATIONS ARE FOLLOWED BY ALL CONCERNED.
MONITORING THE ENVIRONMENT AND PUBLIC
INDUSTRY
:
HEALTH.
INVENTION PRODUCTION DISTRIBUTION ACTS ON ITS
AND
OF USEFUL PRODUCTS OWN RESPONSIBILITY
FOLLOWING
THE LAWS,
MEDICAL AND ENVIRONMENTAL SURVEILLANCE
FIG. 6. Tasks of legislator and industry.
TASKS OF LEGISLATORS
AND INDUSTRY
There is a growing understanding that the ecotoxicological problems can only be solved by a close cooperation of legislator and industry in an environment of an efficient economy and a healthy society. Although well known, the primary roles of the two bodies should be mentioned (Fig. 6). It is hoped that the testing schemes currently under consideration, which are also going to be included in new laws, will be realistic, and well adjusted to the practical requirements of industrial product development and to the technical and economic possibilities. It is sensible to proceed stepwise with such testing, but it is essential that the decisions concerning the need for more detailed testing should lie in the hands of a trained toxicology expert who takes appropriate account of exposure potential.15 ACTIVITIES
FOR SECURING
SAFETY
Can dyestuffs now be called environmental chemicals? According to definitions by Korte (1976) probably not, with perhaps the exception of a few large volume I5 A balanced view has been recently expressed by E. Langley (1978), Health and safety aspects of the proposed notification scheme for new chemicals, Chem. Ind. (London) W-507.
72
R. ANLIKER
CONTINUOUS REDUCTION OF EXPOSURE BY -
IMPROVED PRODUCTION
-
GOOD WORKING CONDITIONS
TECHNOLOGY
-
PERSONAL HYGIENE AND ADEQUATE LAUNDRY FACILITIES
-
PROPER INFORMATION
-
IMPROVED PHYSICAL
-
REDUCTION
AND HANDLING
FACILITIES
AND EDUCATION OF PERSONNEL PROPERTIES
OF DYESTUFF
OF PRODUCTS (E.G.
-
IMPROVED APPLICATION
-
USE OF BEST AVAILABLE
-
USE OF PRODUCTS WITH BEST FASTNESS PROPERTIES
-
NEW PRODUCTS
-
NON DUSTY FORMS)
IN EFFLUENTS PROCESSES AND TECHNOLOGY APPLICATION
TECHNOLOGY
INNOVATION
CONTINUOUS MONITORING
BY INDUSTRY,
GOVERNMENT & PUBLIC
-
ENVIRONMENTAL
SURVEILLANCE
-
MEDICAL SURVEILLANCE EPIDEMIOLOGY
-
SCIENTIFIC
-
GENERAL ALERTNESS OF WORKERS. EMPLOYERS,
AND TECHNOLOGICAL
SEARCH FOR CHEMICALS
INTERCOMMUNICATION SCIENTISTS
(BAD ACTORS) WHICH ARE LIKELY
TO
-
DEVELOPMENT OF NEW, SHORTER AND MORE ECONOMIC ECOTOXII SPECIALLY SHORT-TERM TESTS FOR
-
BASIC
RESEARCH ON STRUCTURE-ACTIVITY
FIG.
RELATIONSHIP.
METABOLISM
7.
products. Nevertheless the annual world-wide production of dyestuffs of roughly 650,000 tons justifies careful assessment of their overall environmental impact. It has been the aim of this paper to show how ETAD operates and to summarize the present status of ecotoxicology of dyestuffs. However substantial, ETAD’s contribution is only a fraction of the total effort being expended by the chemical industry to secure and improve safety .16These endeavors form part of a continuing and concurrent process. Since this fact is often overlooked by many, a summarizing scheme of the important simultaneous activities for securing safety is shown in Fig. 7. ACKNOWLEDGMENT The author manuscript.
thanks
I6 The extensive industry, research and internationale Berufsgenossenschaft
Dr.
E. A. Clarke
for
his critical
discussion
and
help
in preparing
the English
collaborative efforts in the field of occupational medicine and ecotoxicology by institutions, and authorities have been reviewed by A. M. Thiess (1977), Nationale arbeitsmedizinische Zusammenarbeit im Bereich der chemischen Industrie, (August), 361-371.
ECOTOXICOLOGY
OF DYESTUFFS
73
REFERENCES ADMI (1973). Dyes and the Environment, Vols. 1 and 2 American Dye Manufacturers Institute Inc., New York. AIHC (1978). AIHC Recommended Alternatives 10 OSHA’s Generic Carcinogen Proposal. American Industrial Health Council, New York. See also Chem. Eng. Netifs, Jan 30, 1978, 30-35. ANLIKER, R. (1977). Color Chemistry and the Environment. Ecotoxicol. Environ. Sufefy 1, 21 l-237. See also Rev. Prog. Coloration 8, (1977), 60-72. BRETSCHER, H., EIGENMANN, G., AND PLATTNER, E. (1978). Die Umweltsgesetzgebung: Eine Herausforderung fiir die Chemische Industrie. Chimia 32, 173-180. DFG (1977). Kosmefische Fiirbemittel. Deutsche Forschungsgemeinschaft, Farbstoff-Kommission. Harald Boldt Verlag, Boppard. DFG (1978). Lebensmittelfarbstoffe. Deutsche Forschungsgemeinschaft, Farbstoff-Kommission, Harald Boldt Verlag, Boppard. DHEW (1977). Bioassay of Diarylanilide Yelloh, for Possible Curcinogenicity. DHEW Publication No. (NIH) 77-830. DHEW (1978). Direct Black 38, Direct Blue 6, and Direct Brown 95, Benzidine Derived Dyes. U.S. Department of Health, Education and Welfare. NIOSH/NCI Joint Intelligence Bulletin No. 24, April 17. See also NCI, Technical Report Series No. 108, 1978. l3-week subchronic studies of these three dyestuffs. DIECKHUS, B. (1961). Untersuchungen zur reduktiven Spaltung der Azofarbstoffe durch Bakterien. Zentralbl.
Bakteriol.
Parasitcn.
Infektionskr.
180, 244-249.
DRAKE, J. P.. BUTTERWORTH, K. R., GAUNT, I. F., AND HARDY, J. (1978). Long-term toxicity studies of Chocolate Brown HT in mice. Toxicology 10, 17-27. FONTS, J. R., KAMM, J. J., AND BRODIE, B. B. (1957). Enzymatic reduction of Prontosil and other azo dyes, .I. Phurmacol. Exp. Ther. 120, 291-300. GAUNT, I. F., MASON, P. L., GRASSO,P., AND KISS, I. S. (1974). Long-term toxicity of Sunset Yellow FCF in mice. Food. Cosmet. Toxicol. 12, 1- 10. HOLMES, P. A., PRITCHARD, A. B., KIRSCHMAN, J. L. (1978). A one year feeding study with Carmoisine in rats. To.rico/ogy 10, l69- 183. HORNING, R. H. (1977). Characterization and treatment of textile dyeing wastewater. Text. Chemist Colorist
9, 73-76.
JENKINS, C. L. (1978). Textile dyes are potential hazards. J. Environ. Health 40, 2.56-262. IDAKA, E., AND OGAWA, T. (1978). Degradation of azo compounds by Aeromonas hydrophila var. 24B. J. Soc.Dyers Cal. 94, 91-94. KORTE, F. (1976). Global inputs and trends ofchemical residues in the biosphere. Environ. @al. Safety 5, l83- 196. LARSEN. J. C., AND TARDING, F. (1976). Studies on the metabolism of Orange RN in the pig. Acta Pharmacol. Toxicol. 39, 525-53 1. LEUSCHNER, F. (1978). Carcinogenicity studies on different Diarylanilide Yellow pigments. Toxicol. Lett.
2, 253-260.
NCAB (1977). National Cancer Advisory Board. J. Nar. Cancer Inst. 58, 463. RAAB, R. (1978). ErlLuterungen zum Sicherheitsdaten-Blatt der ETAD. Deaf. Ferber-Kalender 82, 506-514. RADOMSKI, J. L.. AND MELLINGER, T. J. (1962). The absorption, fate and excretion in rats of watersoluble azo dyes. J. Pharmacol. Exp. Ther. 136, 259-266. RADOMSKI, J. L. (1974). Toxicology of food colors. Amer. Rev. Pharmacol. 14, 127-137. RINDE, E., AND TROLL, W. (1975). Metabolic reduction of benzidine azo dyes to benzidine in the rhesus monkey. J. Naf. Cancer Inst. 55, 181-182. R~MPPS CHEMIE LEXIKON (1973). Frankh’sche Verlagshandlung Stuttgart, Bd. 2, 1083. SAX, N. I. (1975). Dangerous Properties oflndasrriul Materials, 4th ed., p. 428, Van NostrandReinhold. New York. TABAK. H. H.. AND BARTH, E. F. (1978). Biodegradability of benzidine in aerobic suspended growth reactors. J. Water Pollut. Control Fed. 50, 552-558.
74
R. ANLIKER
WHO (1%6). Sunset Yellow FCF, p. 83. Tartrazine, p. 88. WHO Food Addition Rep. Ser. No. 38B. 66.25. WHO (1974). Azorubine, pp. 47-50. Brilliant Black PN, pp. 53-56. Ponceau 4R, pp. 109-112. WHO Food
Addition
Ser.
No.
6.
WHO (1975). Amaranth, pp. 10-27. WHO
Food
Addition
Ser.
No.
8.