Opinion on "Assessment of the risks to human health posed by certain chemicals in textiles", WS Atkins, Final report - Opinion adopted at the 17th CSTEE plenary meeting, Brussels, 5 September, 2000.

Context

The Commission's attention has been drawn, by the German Government, to the possible need for restrictions on the use of certain chemicals in textile clothing in close contact with the skin, notably sensitising dispersive dyes and trichlorobenzene. The aim of the study by WS Atkins on the risks posed by the substances identified by the German Government is to provide a basis for discussions on the need for restrictions on the marketing and use of these substances.

Terms of reference

The Committee on the basis of examination of the following report

- Assessment of the Risks to Human Health Posed by Certain Chemicals in Textiles, WS Atkins, Final Report, chapters 1 to 6

is to answer the following two questions

1) is the reported degree of risk sufficiently justified by the study

2) is the study of a good quality

Opinion

a) Is the reported degree of risk sufficiently justified by the study?

The Report is restricted solely to the assessment of the sensitisation and cancer risks for workers and consumers posed by 8 specific textile dyes, and risks for consumers and the environment posed by trichlorobenzene.

The risk assessment from textile dyes carried out in the Report is based on very limited toxicological and other data, especially for carcinogenesis, for which no data at all appear to exist for 6 of the 8 dyes. This does not allow a valid risk assessment to be conducted for these 6 dyes.

As regards the degrees of risk calculated in the Report, there are serious deficiencies in the assessment

i) For the consumers, the conclusion that cancer risks from skin contact are likely to be within acceptable levels for textiles with dye fastness 4 or more can only be applied to Disperse Blue I and Disperse Yellow 3. No conclusions can be drawn regarding the remaining dyes because of lack of relevant data. Furthermore, the important question of cancer risks from oral ingestion (through mouth contact with textiles) of any of the 8 dyes is not addressed in the Report.

The conclusion in the Report that the risk of skin sensitisation is likely to be low for textiles with dye fastness 4 or more is not based on scientifically sound methodology. The currently available evidence raises some concern that an unacceptably high level of risk may exist.

ii) As for workers, skin exposure is calculated through modelling to be above the level leading to an unacceptably high cancer risk for Disperse Blue I, although this conclusion is not clearly stated in the Report. While it is recognised that modelling may overestimate exposure, the possibility that an unacceptably high level of risk exists cannot be excluded. These conclusions apply only to the above-mentioned dye and cannot be extended to any of the other seven dyes because no appropriate data are available. Furthermore, the question of cancer risks from dye inhalation by workers is not addressed in the Report.

In the case of consumers, the quantitative calculations leading to the Report's conclusion that the risk of skin sensitisation is likely to be low for textiles with dye fastness 4 or more is not based on scientifically sound methodology. However, the very limited available epidemiological evidence suggests that such risks are indeed low.

For the assessment of risks from trichlorobenzene, the Report's focus on risks to consumers experiencing dermal exposure, and the conclusion that risks are likely to be low, is justified.

b) Is the report of a good quality?

There are serious deficiencies regarding the overall quality of the Report. It is noted for example that

i) No information on: the chemical structures, the physicochemical properties or the impurities of the dyes is given, even though such information is available, at least for some of the dyes in question; such an omission is totally unacceptable;

ii) Despite the scarcity of carcinogenicity data, no use of genotoxicity data, structure-activity relationships (SAR) or other important supporting experimental data is made to aid with the assessment of the carcinogenic potential of the dyes. Moreover, cancer risk estimates based on data for one specific dye are generalised to all the other dyes, something which is not scientifically justified.

iii) Information on endpoints other than sensitisation and carcinogenicity has not been addressed. This is only appropriate if there is evidence that these are the only endpoints of concern for each dye.

iv) The report only considers the toxicity of the dyes through dermal contact: the scenario of young children sucking or chewing dyed textiles is not addressed.

A. DYES

1. Introduction

The Report addresses the question of risks for human health (specifically for workers and consumers) posed by 8 disperse dyes used on fabrics, namely Disperse Blue 1, 35, 106 and 124, Disperse Red 1, Disperse Yellow 3 and Disperse Orange 3 and 37. These dyes are bound to the fabric by physical forces only. The Report focuses only on risks of sensitisation and carcinogenicity, apparently after consultation with EU authorities, on the basis of these effects being the main concerns.

Available animal toxicity data appear to be limited to results of tests on the sensitising potential of all 8 dyes, carcinogenicity data for two, and acute toxicity data for four dyes. No information on the chemical structures, physicochemical properties, composition and impurities of the considered dyes is contained in the Report, apparently because of difficulties related to the use of Colour Index nomenclature. The CSTEE notes that such information is available at least for some of the dyes, and its omission from the Report very seriously weakens the toxicological assessment that follows, particularly in view of the limited amount of toxicity data available. For the same reason, the complete absence from the Report of any reference to genotoxicity test data (which is certainly available for at least some of the dyes) constitutes a serious omission.

2. Sensitisation: Hazard assessment and dose-response relationships

Only skin sensitisation is considered. Results from 4 different animal sensitisation tests show that all the dyes considered are positive in at least 2 tests, leading to the conclusion that they all have a sensitisation potential. However, the absence of dose-response information from these tests makes the identification of a NOEL impossible and complicates any attempt at a risk assessment. One approach to overcoming the problems inherent in the risk assessment of sensitising agents, suggested by ETAD and adopted in the Report, utilises the relatively detailed quantitative information available in animals and humans for the strong sensitiser Kathon CG (a microbiocide). Dose-response studies with large numbers of human volunteers suggest a threshold for the induction of skin sensitisation by Kathon CG of 1.43 microg/cm2 in man, while analogous studies in animals suggest a threshold of 2.5 microg/cm2. By comparison, the animal thresholds for the considered dyes are said to be between 0.23 mg/cm2 and 25 mg/cm2, i.e. the dyes appear to be 100-1000 times less potent than Kathon CG as initiators of skin sensitisation. The potential of the dyes to elicit a response in individuals with pre-existing sensitisation to the same or related chemicals is not addressed. Based on this limited information, it is concluded that human exposures to the considered dyes below the NOEL for Kathon CG are unlikely to present any risk to most people.

In the absence of adequate data, the above argument may serve as a pragmatic approach for the estimation of relative risks within a homologous series of compounds. However, its use with structurally unrelated chemicals (Kathon CG is a thiazolinone derivative, completely unrelated to anthraquinone- or azo- dyes) and without any information on the mechanisms by which the chemicals being compared bring about their effects, entails a high degree of uncertainty and cannot be considered as scientifically sound.

An additional weakness of the above argument is related to the estimation of the animal sensitisation potency of the dyes. The sensitisation potential of the dyes was assessed typically in maximisation tests involving a single dose level. Where multi-dose level tests were employed, responses were sometimes observed even at the lowest level employed, i.e. they were above the no-effect threshold. Hence the estimation of dye potency relative to Kathon may not be valid.

3. Carcinogenicity: Hazard assessment and dose-response relationships

Some of the dyes are stated to be azo- or anthraquinone dyes. The chemical names and structures are not set out in the Report. However, it is the CSTEE's understanding that none of them belongs to the group of azo dyes capable of releasing carcinogenic amines. As already mentioned, carcinogenicity bioassay data are available only for 2 of the considered dyes. Disperse Yellow 3 (an azo dye) has been considered by IARC in 1990 to show limited evidence of carcinogenicity in animals (induction of liver nodules and adenomas in female rats and mice, respectively, in an NTP bioassay) and classified in Group 3 (not classifiable as to its carcinogenicity in humans). A poorly reported study has suggested that the dye is mutagenic in bacteria.

Disperse Blue I (an anthraquinone derivative) has been classified by IARC as a Group 2B carcinogen (sufficient evidence of carcinogenicity in animals, possibly carcinogenic in humans) on the basis of clear induction of rat bladder tumours in an NTP bioassay. These tumours were induced only at the highest dose (5,000 ppm in diet) and correlated with the appearance of bladder calculi, suggesting a possible non-genotoxic origin. On this basis a calculation of a threshold for man at 45-56 microg/kg.day (including a safety factor of 1000) was made. On the other hand, the dye is clearly mutagenic in bacteria and for this reason the possibility of a genotoxic mechanism of cancer induction cannot be excluded. For this reason it would seem prudent to employ a linearised multistage model for carcinogenic risk assessment, although a mechanism as yet unproven of calculi formation resulting in possible erosion and cell proliferation could imply non-linearity. The linearised multistage approach has been employed by the USEPA, which has calculated lifetime risks of 10-5 and 10-6 for exposures of 3.9 and 0.39 microg/kg.day, respectively.

No carcinogenicity data on the remaining dyes are available. No review of genotoxicity or other supporting data is included in the Report, nor is any attempt at using SAR made.

4. Other health effects

LD50 values are available for four of the considered dyes. All are over 2000 mg/kg, indicating a low acute toxicity. No other data appear to be available.

5. Occupational exposure and disease data

Only dermal exposure is assessed in the Report. It is noted that inhalation is a likely route of worker exposure during dye manufacture, and the possible risks associated with it cannot be ignored, particularly in view of the carcinogenic potential of at least some of the dyes.

No occupational exposure measurements or monitoring data appear to be available from the dye manufacturing or textile dyeing industries. Consequently, exposures have been calculated using the EASE model and, for both industries, dermal exposures in the range 0.1-1 mg/cm2.day are estimated. While such exposures are likely to be a serious overestimate, (the EASE model does not take into consideration the use of personal protective equipment), comparison with the USEPA carcinogenicity unit risk estimate for Disperse Blue 1 suggests that some carcinogenicity risks might be present. This conclusion only applies to that particular dye and there is no basis for extending it to the remaining dyes. No occupational epidemiology data related to the carcinogenicity of the considered dyes appear to be available.

No reliable assessment of the corresponding sensitisation risks can be made. If the comparison with the sensitisation NOEL of Kathon CG, adopted in the Report, is made, it leads to the conclusion that a significant risk for workers may exist. On the other hand, occupational disease data from industry surveys and an occupational skin disease database indicate that cases of occupational dermatitis associated with the manufacture and application of textile dyes are rarely reported from which the report concludes that no significant sensitisation risk exists. Although airborne dispersal of these dyes may occur in the workplace no consideration is given in the Report to possible respiratory sensitisation.

6. Consumer exposure and disease data

Although consumer exposure to textile-associated dyes may be dermal and oral, the Report discusses only dermal exposure because of the dyes' low acute toxicity. The CSTEE notes that oral exposure of children sucking dyed garments might result in substantial oral exposures, and, in view of the possible carcinogenicity and other risks. It is therefore essential that this route be considered.

The main factors determining dye release from textiles to the skin, include the type of dyed textile, contact with other substrates (skin, other textiles), "dye depth" (amount of dye mix per mass of garment) and number of previous washings. Quantitative release data from studies carried out by ETAD are presented in the Report, without a critical assessment of the methodology used for their generation. Two exposure scenarios are considered:

a) A "sufficient fastness" scenario assumes a new and previously unwashed, close-fitting garment with a dye perspiration fastness of 4 (considered in the textile industry to be a good level of fastness, apparently achieved by all the considered dyes on all commonly employed textiles). Based on experimental release data, this scenario predicts a release to the skin of 0.03 microg/cm2 (the time period over which this release takes place is not clarified but appears to correspond to the time of normal daily use of a garment, i.e. per day). In the absence of suitable quantitative data, it is not possible to assess the skin sensitisation risk which this exposure presents.

For the calculation of carcinogenic risks, a figure of 0.007 microg/cm2.day, based on ETAD tests of dye extractability from textiles, is used as the average skin exposure arising from the use of a garment of fastness 4 over its lifetime. Assuming full absorption of the dye, this corresponds to a systemic exposure of 1 microg/kg.day for a 70 kg adult, which is roughly fiftyfold lower than the assumed threshold level (45-56 microg/kg.day) and fourfold lower than the 10-5 risk level (3.9 microg/kg.day) for Disperse Blue 1.

b) A "worst case" scenario assumes a close-fitting nylon garment (a material with relatively poor fastness properties) dyed heavily to a "dye depth" of 8 (in contrast to the more usual 1% which is associated with fastness 4). This scenario leads to a predicted exposure of 6.1 microg/cm2.day which suggesting that garments with dye depth above 8 (corresponding to fastness level below 4) may pose carcinogenic risks.

The Report concludes that textiles dyed to fastness of 4 or above do not pose any significant health risks. The CSTEE notes that a) these conclusions are only likely valid for cancer risks from Disperse Blue I, and probably the less carcinogenic Disperse Yellow 3, but they cannot be extrapolated to the other dyes, and b) no quantitative estimation of the sensitisation risks is possible.

Α detailed review of the literature (case reports and incidence studies) on sensitisation appears to have been carried out by the Report's authors. According to the results of this review, during the period 1965-98, approximately 10-15 cases per year of skin sensitisation to the dyes under discussion were reported, their trend in time being relatively constant. The authors conclude that, having in mind the large number of people who probably come in contact with dyed garments, sensitisation to the specific dyes is a rare occurrence in the general population. However, it should be noted that the probability of a case of dye sensitisation, being recognised as such and considered by clinicians of sufficient interest to be published in the scientific literature, is likely to be small and that the true incidence may be much higher. This finds some support in the Report's conclusions regarding published incidence surveys, i.e. studies based on random patch-testing of subjects at dermatology clinics. A significant number of such studies report that 1-3% (sometimes as many as 10.1%) of all individuals tested give a positive skin reaction to the considered dyes, an incidence which is clearly well above the tolerable limit. The hypothesis that this reaction is the result of cross-sensitisation, i.e. that these individuals suffered primary sensitisation to another dye is suggested. P-phenylenediamine, a sensitising dye widely used in hair dyes is mentioned as a possible primary sensitiser. While such a possibility cannot be excluded, no specific evidence to support it has been put forward. Furthermore, cross-sensitisation would be expected to operate between structurally-related chemicals. The high incidence of sensitisation to the considered dyes among the general population, in combination with their known sensitising potential, raises the possibility that these dyes may present an unacceptable risk of sensitisation for consumers.

7. Conclusions

The Report concludes that

a. for workers, despite the high skin exposure calculated through modelling, sensitisation risks are likely to be within acceptable limits based on the limited evidence from occupational health surveys. This is a reasonable conclusion. The Report does not state any specific conclusion regarding cancer risks. Based on the modelled exposures, such risks would be expected to be significant for Disperse Blue I, while no conclusions can be drawn regarding the other seven dyes. Furthermore, the question of cancer risks from dye inhalation by workers is not addressed in the Report.

b. for consumers, it is assumed that no significant initiation of sensitisation or cancer risks will arise from dermal contact with textiles dyed to fastness of 4 or above. This conclusion is appropriate only for carcinogenic risks arising from Disperse Blue I, while for skin sensitisation, no quantitative estimates can be made. However, the proven sensitising potential of the dyes and the high incidence of sensitisation to them observed among the general population raises concern that such a risk may exist. The risk from the oral exposure route for young children needs to be considered.

B. TRICHLOROBENZENE

The Report reviews in a separate chapter the risks to consumer health and the environment posed by TCB in textiles. Occupational exposure is not considered because this agent is no longer used in the European textile dyeing industry.

Toxicity data are very briefly mentioned and the conclusions of the hazard and risk assessments made by other authorities (WHO, RIVM, German competent authority) are presented. WHO and RIVM concluded in 1991 that provided appropriate care is taken, health hazards are minimal. Following a "worst case" scenario exposure assessment, the German competent authority concluded in 1997 that a 2.7 safety margin exists. The Report correctly suggests that this safety margin is likely to be much higher in the case of textiles finished according to state-of-the-art technology, which are likely to have an approximately 10fold lower TCB content than that assumed in the exposure scenario. It is also pointed out, on the other hand, that this assumption may not hold for imported garments.

As regards environmental effects of TCB, based on a brief review of the literature and information from an RIVM report, PNEC values for aquatic and terrestrial organisms are derived. In view of the absence of data on TCB release from textiles to the environment, historical data on TCB concentrations in surface waters are presented which show a decreasing trend during the 1980's when TCB was more commonly used than it is nowadays. These data indicate that TCB concentrations were then below the PNEC values and it is thus suggested that they are unlikely to present any problem today.

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