Dipotassium tetrachloroplatinate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonable-quality study (on read-across surrogate), not performed to OECD guideline, but it appears to have been well-conducted, matches the guideline in some important respects, and has been adequately reported.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

No mention of guideline in publication, but a similar methodology was employed

Deviations:

yes

Remarks:

Numerous - see "Any other information on materials and methods incl. tables", below

Principles of method if other than guideline:

Local lymph node (auricular lymph node; ALN) assay to detect primary immune response.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: University of Dusseldorf
- Age at study initiation: 6-8 weeks
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): standard diet (not further specified) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Vehicle:

other: acetone

Concentration:

5%.
[Results for "lower concentrations" of the test compound were briefly cited in the publication, but no further details were given.]

No. of animals per dose:

5

Details on study design:

Topical treatment (25 ul) to the dorsum of both ears on 4 consecutive days. Lymph node cells analysed around 48-hours after the last exposure.

End-point: ALN index (cell count from treated group divided by cell count from vehicle control); global ALN cell count (the former is a more sensitive parameter, presumably for measuring immume/sensitisation response.

Controls were treated with vehicle alone [no further details given].

Experiment repeated in triplicate.

Positive control substance(s):

other: oxazolone, 1% in acetone, single application around 48 hours before ALN cell analysis

Statistics:

Results were analyzed for significance emplpying the U-test of Mann-Whitney.

Positive control results:

The positive control caused a 16.5-fold increase in number of proliferating cells compared to the control.

Key result

Parameter:

other: ALN cell yield

Remarks:

x 1,000,000 cells

Value:

16.9

Variability:

Standard deviation +/- 3.7

Test group / Remarks:

Mean

Remarks on result:

other: 4-Fold increase in global ALN cell yield per animal compared to control (4.3 E6 cells).

Remarks:

p<0.01

Compared to controls, the test substance caused a 23-fold increase in number of auricular lymph node (ALN) proliferating cells (ALN index = 22.8), and there was a 4-fold increase in global ALN cell yield per animal (mean global ALN cell yield +/- SD, 16.9 +/- 3.7 vs 4.3 +/- 1.5 (x 1,000,000 cells), p<0.01). The response was said to be comparable to that obtained following a single dose of the potent skin sensitiser oxazolone.

At lower concentrations of test compound [not specified and no further details given], no such increase observed (ALN index <2); the vehicle elicited an ALN index of <1.5 (i.e. reported as no reactivity).

The proliferative response detected in the ALN following skin exposure to sodium hexachloroplatinate was said to provide suggestive evidence for the predominant activation of CD4+ T lymphocytes.

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

In a study broadly comparable to the local lymph node assay in mice, disodium hexachloroplatinate induced a proliferation of auricular lymph node (ALN) cells consistent with a potential to cause skin sensitisation.

Executive summary:

In a study broadly comparable to the local lymph node assay (LLNA), groups of 5 mice were subjected to local applications, on both ears, of 5% disodium hexachloroplatinate on each of 4 consecutive days. Around 48 hours after the last exposure, the auricular lymph nodes cells were analysed.

The test substance caused a 23-fold increase in number of ALN (auricular lymph node) proliferating cells, and a 4 -fold increase in global ALN cell yield per animal compared to vehicle controls. This response was comparable to that seen in the positive control, indicating that disodium hexachlorplatinate has skin sensitisation potential.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

There is evidence that halogenated platinum salts are skin sensitizers. WHO (2012) notes that urticaria (Type I immediate hypersensitivity) and contact dermatitis are reported as symptoms of platinum-specific allergic sensitization in numerous case reports and occupational studies that identify health effects in workers exposed to halogenated platinum salts (Hunter et al. 1945; Marshall 1952; Pepys et al. 1972; Pepys 1984; Merget et al. 1988, 1999, 2000; Baker et al. 1990; IPCS 1991; Bolm-Audorff et al. 1992; Calverley et al. 1995, 1999; Merget 2000; WHO 2000; Cristaudo et al. 2005). However, most of these reports do not include exposure data and there is also a lack of information on the role of the dermal route versus inhalation exposure to allow quantification of the dermal exposure to particular halogenated platinum salts. Cristaudo et al. (2005) report that 2 of the 153 workers in a catalyst manufacturing and recycling factory had a positive patch test to hexachloroplatinic acid, and 22 had a positive skin prick test (SPT) indicative of IgE antibody involvement to the same substance. The patch test was performed with 15 µl of hexachloroplatinic acid at a single concentration of 10^-2mol/l. The patch test in these individuals provides a single concentration that is associated with elicitation of the sensitized state but, as no exposure data were reported, there is insufficient information with which to evaluate sensitization. Merget et al. (2000) describes a prospective cohort study among 275 new and current German catalyst production workers who were tested at baseline for allergic sensitivity to halogenated platinum salts, with reassessment after five years of follow-up. Conversion to a positive SPT to hexachloroplatinic acid was used as an indicator of allergic sensitization to halogenated platinum salts. For the exposure assessment, workers were assigned to different exposure categories (high, low, no exposure) based on job title and location within the plant. Atopic individuals and workers with a positive SPT at the start of the study were excluded from the analyses. Of the 115 workers in the high-exposure category [arithmetic mean soluble platinum concentration 52.9 ng/m³(pooled)], 13 (11.3%) developed a positive SPT response by the end of the 5-year follow-up period. No positive SPT responses were reported in the other exposure categories. Qualitative evaluation of these data would suggest that halogenated platinum salts are potent or strong skin sensitizers (WHO, 2012).

 

Two published laboratory animal studies (Schuppe et al. 1997; Dearman et al. 1998) provide support that halogenated platinum salts are dermal sensitizers. Schuppe et al. (1997) reported a significant positive reaction in BALB/c mice exposed to 5% sodium hexachloroplatinate in a LLNA (adapted to avoid the use of radioactive labels) as well as a modified ear swelling test (MEST). At that single test concentration, the Stimulation Index (SI) exceeds 3 [the level used to differentiate sensitizers from non-sensitizers]. If that value were to be used as the EC₃[the effective concentration required to produce a 3-fold increase in the proliferation of lymph node cells compared with vehicle-treated controls], then the potency category for this halogenated platinum salt would be in the moderate range [CLP Sub-category 1B]. However, given that no lower doses were tested, a potency category of strong or extreme [Sub-category 1A] cannot be excluded.Dearman et al. (1998) reported substantial production of interleukin (IL-10) [a response profile characteristic, in fact, of respiratory sensitizers] for both diammonium hexachloroplatinate and diammonium tetrachloroplatinate when applied to the ears of BALB/c mice at exposure concentrations down to 0.25%, an exposure that would indicate a potency category of strong [Sub-category 1A]. However, Dearman et al. (1998) only evaluated cytokine release, and the experiment did not include LLNA or development of EC₃values. In addition, it should be noted that both the LLNA and MEST in isolation are unable to differentiate between immediate (Th2 type) and delayed (Th1 type) hypersensitivity responses. The available published laboratory animal data suggest that the potency category for some halogenated platinum salts would be moderate or strong (WHO 2010). However, there are significant data gaps, and published data are not available at lower exposure levels to evaluate the possibility that some halogenated platinum salts may be classified as strong or extreme sensitizers.

 

Insufficient data are available to evaluate the elicitation potency of halogenated platinum salts in humans or laboratory animals by the dermal or inhalation routes. As noted above, two workers in a catalyst manufacturing and recycling factory gave positive patch tests to hexachloroplatinic acid [15 μl at a concentration 10⁻²mol/l] (Cristaudo et al. 2005) and this provides a single concentration that is associated with elicitation. The clinical symptoms reported (rhinitis, asthma, urticaria and eczema) for individuals positive by SPT or patch test suggest that the positive patch test may have been related to eczema; among workers with a positive response, the only two workers with eczema had positive patch test results (Cristaudo et al. 2005). Although data from patch tests are limited, WHO (2012) notes that published occupational data are available on challenge doses associated with a positive SPT response to halogenated platinum salts. Brooks et al. (1990) and Biagini et al. (1985) reported that the lowest exposure concentration of halogenated platinum salts required to elicit a positive SPT ranged from 10⁻⁹to 10⁻³g/ml (six orders of magnitude) among individuals previously sensitized to halogenated platinum salts. Conclusions for the elicitation dose for halogenated platinum salts based on the occupational exposure data and SPT data would suggest that halogenated platinum salts are at the higher end of sensitizers—that is, potent or strong sensitizers with potent or strong associated elicitation (WHO 2010). Overall, there are insufficient data on dermal exposure to fully evaluate the elicitation dose for halogenated platinum salts and little information to inform a qualitative evaluation. The low doses and large variation (six orders of magnitude) for elicitation in the SPT suggest that halogenated platinum salts may have a strong dermal elicitation potency.

 

As indicated above, assays such as LLNA and MEST cannot differentiate between Th2 and Th1 immune responses and therefore in the case of the chloroplatinates positive responses do not necessarily indicate that delayed contact hypersensitivity has been induced. There is significant published evidence (e.g. Dearman et al., 1998), and unpublished data within the industry sector, which strongly suggests that the Th2 arm is preferentially induced on skin exposure to chloroplatinate salts and related Pt compounds. Extensive accumulated industrial experience from health surveillance systems in the platinum group metal sector indicates that exposure to complex halogenated salts of platinum, typified by soluble hexa- and tetra-chloroplatinates, results in the preferential induction of Th2 (IgE mediated) responses in sensitization reactions. These data encompass a sector historical record of more than 50 years, involving over 10 companies.

 

These chloroplatinate induced Th2-type responses involve activation of specific subsets of T lymphocytes and the cytokine products of these cells can be tracked with cytokine fingerprinting in both experimental toxicology studies and human clinical investigations. The end result of such activation is allergen-specific IgE antibody production, and the predominant reaction in symptomatic workers is respiratory sensitisation and/or allergic rhinoconjunctivitis, with contact urticaria being less commonly observed. In contrast, allergic contact dermatitis (ACD) as a result of non-IgE mediated mechanisms (i.e. Th1 based responses) has been rarely observed, particularly in terms of its occurrence in isolation from immediate hypersensitivity responses. It is estimated that ACD incidence accounts for <1% of symptomatic cases in sensitised worker populations.

 

Proprietary data on a guinea pig maximisation test (GPMT) (van Huygevoort 2003a) on hexachloroplatinic acid is available. The intradermal induction concentration was 0.02%, and a number of animals responded on challenge. However, the nature of the reactions in the test group are difficult to interpret since erythema was not seen in all responding animals, rather there was the presence of dermal scaliness, which was not seen in control animals. Taking into account extensive human industrial experience of exposure to this substance where skin contact does not routinely result in allergic contract dermatitis (but can cause Th2 immediate hypersensitivity), the weight of evidence indicates that classification as Sub-category 1B is appropriate for this substance (personal communicaton Johnson Matthey).

 

In summary, there is sufficient evidence both from human case reports and occupational studies, and from laboratory animal experiments, that halogenated platinum salts can induce skin sensitization responses. As for respiratory sensitization, there is often a lack of information from published case reports and occupational studies with regards to the particular compounds involved. There is also a lack of exposure data, in particular to quantify the extent of dermal involvement versus inhalation exposure. As discussed previously there is extensive evidence that these human skin responses can be mediated by Th2-type responses and this is supported by cytokine release profiles, SPT responses, and industry data indicative of IgE involvement. Therefore it can be concluded that available evidence is not supportive of the chloroplatinates having potent delayed contact hypersensitivity potential, and that the weight of evidence indicates the chloroplatinates should be classified as Sub-category 1B (low to moderate frequency of occurrence).

 

References

 

Baker Det al. (1990). Cross-sectional study of platinum salts sensitization among precious metals refinery workers.American Journal of Industrial Medicine18, 653–664 (cited in WHO, 2012).

 

Biagini REet al. (1985). The diversity of reaginic immune responses to platinum and palladium metallic salts.Journal of Allergy and Clinical Immunology76(6), 794–802 (cited in WHO, 2012).

 

Bolm-Audorff Uet al. (1992). Prevalence of respiratory allergy in a platinum refinery.International Archives of Occupational and Environmental Health64, 257–260 (cited in WHO, 2012).

 

Brooks SMet al. (1990). Cold air challenge and platinum skin reactivity in platinum refinery workers: bronchial reactivity precedes skin prick response.Chest97, 1401–1407 (cited in WHO, 2012).

 

Calverley AEet al. (1995). Platinum salt sensitivity in refinery workers: incidence and effects of smoking and exposure.Occupational and Environmental Medicine52, 661–666 (cited in WHO, 2012).

 

Calverley AEet al. (1999). Allergy to complex salts of platinum in refinery workers: prospective evaluations of IgE and Phadiatop® status.Clinical and Experimental Allergy29, 703–711 (cited in WHO, 2012).

 

Cristaudo Aet al. (2005). Occupational hypersensitivity to metal salts, including platinum, in the secondary industry.Allergy60, 159–164 (cited in WHO, 2012).

 

Dearman Ret al. (1998). Selective induction of type 2 cytokines following topical exposure of mice to platinum salts.Food and Chemical Toxicology36,199–207 (cited in WHO, 2012).

 

Hunter Det al. (1945). Asthma caused by the complex salts of platinum.British Journal of Industrial Medicine2, 92-98 (cited in Ravindraet al., 2004; WHO, 2012; US EPA, 2009).

 

IPCS (1991). Platinum. Environmental Health Criteria 125. International Programme on Chemical Safety. World Health Organisation. Geneva. [available at:http://www.inchem.org/documents/ehc/ehc/ehc125.htm]

 

Marshall J (1952). Asthma and dermatitis caused by chloroplatinic acid.South African Medical Journal26(1), 8–9 (cited in WHO, 2012).

 

Merget Ret al. (1988). Asthma due to the complex salts of platinum—a cross-sectional survey of workers in a platinum refinery.Clinical Allergy18(6), 569–580 (cited in WHO, 2012).

 

Merget Ret al. (1999). Outcome of occupational asthma due to platinum salts after transferral to low-exposure areas.International Archives of Occupational and Environmental Health72, 33–39 (cited in WHO, 2012; US EPA, 2009).

 

Merget R (2000). Occupational platinum salt allergy. Diagnosis, prognosis, prevention and therapy. In: Zereini F, Alt F, eds. Anthropogenic platinum-group element emissions: their impact on man and environment. New York, NY, Springer Verlag, pp. 257–265 (cited in WHO, 2012; US EPA, 2009).

 

Merget Ret al. (2000). Exposure–effect relationship of platinum salt allergy in a catalyst production plant: conclusions from a 5-year prospective cohort study.Journal of Allergy and Clinical Immunology105, 364–370 (cited in WHO, 2012).

 

Pepys Jet al. (1972). Asthma due to inhaled chemical agents—complex salts of platinum.Clinical Allergy,2(4), 391–396 (cited in WHO, 2012).

 

Pepys J (1984). Occupational allergy due to platinum complex salts. In: Clinics in immunology and allergy. Vol. 4. London, W.B. Saunders, pp. 131–158. (cited in WHO, 2012).

 

Ravindra Ket al. (2004). Platinum group elements in the environment and their health risk.The Science of the Total Environment318, 1-43.

 

Schuppe Het al. (1997). Contact hypersensitivity to disodium hexachloroplatinate in mice. Toxicological Letters93(2-3), 125–133 (cited in WHO, 2012; US EPA, 2009).

 

US EPA (2009). Draft: Toxicological review of halogenated platinum salts and platinum compounds. In support of summary information on the Integrated Risk Information System. EPA/635/R-08/018. January 2009. [available at:http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=203203#Download]

 

van Huygevoort AHBM (2003). Assessment of contact hypersensitivity to dihydrogen hexachloroplatinate(IV)-solution in the albino guinea-pig (Maximisation-test). Report no. 362025.

 

WHO (2000). Air quality guidelines for Europe, 2^nded. WHO Regional Publications, European Series, No. 91. World Health Organisation Regional Office for Europe, Copenhagen. Platinum, pp. 166-169 [available at:http://www.euro.who.int/__data/assets/pdf_file/0005/74732/E71922.pdf

 

WHO (2012). Guidance for immunotoxicity risk assessment for chemicals. Harmonization Project Document. Case-study 3: assessment of sensitization and allergic response to halogenated platinum salts. World Health Organisation. Geneva. [available at:http://www.who.int/ipcs/methods/harmonization/areas/guidance_immunotoxicity.pdf]

Migrated from Short description of key information:
There is evidence that halogenated platinum salts are skin sensitizers. Urticaria (Type I immediate hypersensitivity) and contact dermatitis are reported as symptoms of platinum-specific allergic sensitization in numerous case reports and occupational studies that identify health effects in workers exposed to halogenated platinum salts. Supporting data from laboratory animal studies are available. See full discussion below.

Justification for selection of skin sensitisation endpoint:
Well-conducted study on a read-across compound. This study informs the health precautionary classification of this compound as a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The development of allergic sensitization following exposure to halogenated platinum compounds via the inhalation route is a well-established human health hazard associated with occupational exposure, and has been the subject of a number of comprehensive expert reviews (IPCS, 1991; Ravindraet al., 2004; US EPA, 2009; WHO, 2000; WHO, 2012). The following brief summary is based largely on information cited in these reviews and is focussed on the key information to indicate an appropriate classification category under the revised sensitization criteria of Regulation (EC) No. 1272/2008, as amended by Commission Regulation (EU) No. 286/2011, of 10 March 2011.

Adverse occupational health effects following exposure to complex salts of platinum were apparently first reported as far back as 1911 (Karasek & Karasek, 1911). Hunteret al. (1945) reported that 52 out of 91 (57%) precious metal workers in four British platinum refineries had symptoms of sneezing, wheezing and shortness of breath when exposed to occupational levels of between 0.9 and 1700 µg/m³. Ravindraet al. (2004) reported that approximately 50% of exposed refinery workers were likely to develop immediate-type respiratory hyper-sensitivity reactions following exposure to platinum salts such as ammonium tetrachloroplatinate(II) and ammonium hexachloroplatinate(IV), used in the production of industrial catalysts (Hughes, 1980; Roberts, 1951). Latency from the first contact with platinum salts to the development of symptoms was said to vary from a few months to six years. WHO (2000) notes that following the adoption of an occupational exposure limit with a threshold limit value (TLV) for soluble platinum salts of 2 µg/m³as an 8-hour time-weighted average, the incidence of platinum salt sensitivity had fallen, although several epidemiological studies found increased prevalences of workers with allergic sensitization in chloroplatinate–contaminated workplaces with estimated air concentrations below this 2 μg of soluble platinum/m³limit (Bakeret al., 1990; Bolm-Audorffet al., 1992; Linnett & Hughes, 1999; Mergetet al., 2000).

The adverse health effects associated with platinum exposure in the workplace were attributed to halogenated salts based on an understanding of the processes utilized in the refining of platinum (US EPA, 2009). The work environment of a platinum refinery or platinum catalyst production plant where individuals become sensitized to platinum compounds evidently primarily involves exposure to halogenated platinum salts, mainly chloroplatinates (e.g. ammonium hexachloroplatinate, sodium hexachloroplatinate, potassium hexachloroplatinate, and hexachloroplatinic acid) (Merget, 2000; Mergetet al., 1999; Parrotet al., 1969; Hunteret al., 1945).

The WHO (2012) evaluation cites a large number of case reports and occupational studies that identify the health effects in workers exposed to halogenated platinum salts as asthma, rhinitis and conjunctivitis (Hunteret al., 1945; Marshall, 1952; Pepyset al., 1972; Pepys, 1984; Mergetet al., 1988, 1999, 2000; Bakeret al., 1990; IPCS, 1991; Bolm-Audorffet al., 1992; Calverleyet al., 1995, 1999; Merget, 2000; WHO, 2000; Cristaudoet al., 2005). This review notes that additional reports provide support for one or more of the above effects, consistent with respiratory sensitizers: asthma (Brookset al., 1990; Mergetet al., 1991, 1994, 1995, 1996), respiratory difficulties (Karasek & Karasek, 1911), inflammatory changes in the respiratory tract (Roberts, 1951; Mergetet al., 1996), bronchospasms (Calverleyet al., 1999) and bronchial hyperactivity (Biaginiet al., 1985; Brookset al., 1990; Mergetet al., 1991). A similar extensive list of relevant reports is provided in US EPA (2009). Individuals with halogenated platinum-salt allergic sensitization apparently show progression to moderate or severe asthma with continued exposure (Mergetet al., 1999); the effects of work-related allergic sensitization may be severe and disabling (Friedman-Jimenezet al., 2000). Severe cases of allergic sensitization to halogenated platinum salts have included workers with bluish skin due to insufficient oxygen in the blood, feeble pulse, and extreme difficulty breathing requiring the subject to maintain an upright position to breath (Roberts, 1951).

Data are not always available to identify the individual platinum compounds involved. No occupational studies were identified that report speciation of platinum compounds, analytical characterization of platinum compounds, or specific measurements of halogenated platinum compounds (US EPA, 2009). For most occupational studies, it is unlikely workers would be exposed to a single platinum compound. Work by Cleareet al. (1976), Cristaudoet al. (2005), and Linnett & Hughes (1999) indicate that the allergenic potential may be related to the degree of chlorination. Results from animal studies provide supportive data on the relationship of allergenic potential and the degree of chlorination (Murdoch & Pepys, 1986, 1985, 1984a,b; Schuppeet al., 1997, 1992) and together the data suggest that highly chlorinated forms of halogenated platinum salts (such as hexachloroplatinate and tetrachloroplatinate salts) may have a relatively higher potential to induce sensitization than less-chlorinated forms.

In summary, there appears to be extensive evidence from case reports and epidemiological studies that halogenated platinum salts can act as respiratory sensitizers, with a large proportion (up to approximately 50%) of the exposed workers developing symptoms if the occupational levels are sufficiently high. The symptoms can be severe and potentially disabling, particularly with continued exposure. There is a lack of information with regards the particular compounds involved, but the human data, together with supporting animal studies, indicate the more highly chlorinated forms such as hexachloroplatinate and tetrachloroplatinate are more active as respiratory sensitizers than the less chlorinated forms.

Several chloroplatinate compounds are being registered under REACH: Dipotassium tetrachloroplatinate (CASRN 10025-99-7); Dipotassium hexachloroplatinate (CAS RN 16921-30-5); Diammonium hexachloroplatinate (CAS RN 16919-58-7); Hexachloroplatinic acid (CAS RN 16941-12-1). Given the high frequency of occurrence of respiratory sensitization in workers exposed to sufficiently high occupational levels, and the severity of the symptoms that may develop, particularly if exposure is continued, the available data would indicate that for this group of substances a classification in sub-category 1A would be appropriate.

References

Baker Det al. (1990). Cross-sectional study of platinum salts sensitization among precious metals refinery workers.American Journal of Industrial Medicine18, 653–664 (cited in WHO, 2012).

Biagini REet al. (1985). The diversity of reaginic immune responses to platinum and palladium metallic salts.Journal of Allergy and Clinical Immunology76(6), 794–802 (cited in WHO, 2012).

Bolm-Audorff Uet al. (1992). Prevalence of respiratory allergy in a platinum refinery.International Archives of Occupational and Environmental Health64, 257–260 (cited in WHO, 2012).

Brooks SMet al. (1990). Cold air challenge and platinum skin reactivity in platinum refinery workers: bronchial reactivity precedes skin prick response.Chest97, 1401–1407 (cited in WHO, 2012).

Calverley AEet al. (1995). Platinum salt sensitivity in refinery workers: incidence and effects of smoking and exposure.Occupational and Environmental Medicine52, 661–666 (cited in WHO, 2012).

Calverley AEet al. (1999). Allergy to complex salts of platinum in refinery workers: prospective evaluations of IgE and Phadiatop® status.Clinical and Experimental Allergy29, 703–711 (cited in WHO, 2012).

Cleare Met al. (1976). Immediate (type I) allergic responses to platinum compounds.Clinical Allergy6, 183-195 (cited in US EPA, 2009).

Cristaudo Aet al. (2005). Occupational hypersensitivity to metal salts, including platinum, in the secondary industry.Allergy60, 159–164 (cited in WHO, 2012).

Friedman-Jimenez Get al. (2000). Clinical evaluation, management, and prevention of work-related asthma.American Journal of Industrial Medicine37(1), 121-141 (cited in US EPA, 2009).

Hughes EG (1980). Medical surveillance of platinum refinery workers.Journal of the Society of Occupational Medicine30, 27-30 (cited in Ravindraet al., 2004; WHO, 2000).

Hunter Det al. (1945). Asthma caused by the complex salts of platinum.British Journal of Industrial Medicine2, 92-98 (cited in Ravindraet al., 2004; WHO, 2012; US EPA, 2009).

IPCS (1991). Platinum. Environmental Health Criteria 125. International Programme on Chemical Safety. World Health Organisation. Geneva. [available at:http://www.inchem.org/documents/ehc/ehc/ehc125.htm]

Karasek SR & Karasek M (1911). The use of platinum paper. Report of (Illinois) commission on occupational diseases to his Excellency Governor Charles S. Deneen, Chicago, Warner Printing Company, January 1911, p. 97 (cited in Ravindraet al., 2004; WHO 2010).

Linnett P & Hughes E (1999). 20 years of medical surveillance on exposure to allergenic and non-allergenic platinum compounds: the importance of chemical speciation.Occupational and Environmental Medicine56, 191-196 (cited in US EPA, 2009).

Marshall J (1952). Asthma and dermatitis caused by chloroplatinic acid.South African Medical Journal26(1), 8–9 (cited in WHO, 2012).

Merget Ret al. (1988). Asthma due to the complex salts of platinum—a cross-sectional survey of workers in a platinum refinery.Clinical Allergy18(6), 569–580 (cited in WHO, 2012).

Merget Ret al. (1991). Quantitative skin prick and bronchial provocation tests with platinum salt.British Journal of Industrial Medicine48, 830–837 (cited in WHO, 2012).

Merget Ret al. (1994). Nonspecific and specific bronchial responsiveness in occupational asthma caused by platinum salts after allergen avoidance.American Journal of Respiratory and Critical Care Medicine150, 1146–1149 (cited in WHO, 2012).

Merget Ret al. (1995). The sequence of symptoms, sensitization and bronchial hyperresponsiveness in early occupational asthma due to platinum salts.International Archives of Allergy and Immunology107(1–3), 406–407 (cited in WHO, 2012).

Merget Ret al. (1996). Absence of relationship between degree of nonspecific and specific bronchial responsiveness in occupational asthma due to platinum salts.European Respiratory Journal9(2), 211–216 (cited in WHO, 2012).

Merget Ret al. (1999). Outcome of occupational asthma due to platinum salts after transferral to low-exposure areas.International Archives of Occupational and Environmental Health72, 33–39 (cited in WHO, 2012; US EPA, 2009).

Merget R (2000). Occupational platinum salt allergy. Diagnosis, prognosis, prevention and therapy. In: Zereini F, Alt F, eds. Anthropogenic platinum-group element emissions: their impact on man and environment. New York, NY, Springer Verlag, pp. 257–265 (cited in WHO, 2012; US EPA, 2009).

Merget Ret al. (2000). Exposure–effect relationship of platinum salt allergy in a catalyst production plant: conclusions from a 5-year prospective cohort study.Journal of Allergy and Clinical Immunology105, 364–370 (cited in WHO, 2012).

Murdoch R & Pepys J (1984a). Immunological responses to complex salts of platinum. I. Specific IgE antibody production in the rat.Clinical and Experimental Immunology57,107–114 (cited in US EPA, 2009).

Murdoch R & Pepys J (1984b). Immunological responses to complex salts of platinum. II. Enhanced IgE antibody responses to ovalbumin with concurrent administration of platinum salts in the rat.Clinical and Experimental Immunology58, 478–485 (cited in US EPA, 2009).

Murdoch R & Pepys J (1985). Cross reactivity studies with platinum group metal salts in platinum-sensitised rats.International Archives of Allergy and Applied Immunology77,456–458 (cited in US EPA, 2009).

Murdoch R & Pepys J (1986). Enhancement of antibody production by mercury and platinum group metal halide salts. Kinetics of total and ovalbumin-specific IgE synthesis.International Archives of Allergy and Applied Immunology80, 405–411 (cited in US EPA, 2009).

Parrot Jet al. (1969). Platinum and platinosis. Allergy and histamine release due to some platinum salts.Archives of Environmental Health19(5), 685-691 (cited in US EPA, 2009).

Pepys Jet al. (1972). Asthma due to inhaled chemical agents—complex salts of platinum.Clinical Allergy,2(4), 391–396 (cited in WHO, 2012).

Pepys J (1984). Occupational allergy due to platinum complex salts. In: Clinics in immunology and allergy. Vol. 4. London, W.B. Saunders, pp. 131–158. (cited in WHO, 2012).

Ravindra Ket al. (2004). Platinum group elements in the environment and their health risk.The Science of the Total Environment318, 1-43.

Roberts AE (1951). Platinosis: a five year study of the effects of soluble platinum salts on employees in a platinum laboratory and refinery.Archives of Industrial Hygiene4, 549-559 (cited in Ravindraet al., 2004; WHO, 2012; US EPA, 2009).

Schuppe Het al. (1992). T-cell-dependent popliteal lymph node reactions to platinum compounds in mice.International Archives in Allergy and Immunology97(4), 308-314 (cited in US EPA, 2009).

Schuppe Het al. (1997). Contact hypersensitivity to disodium hexachloroplatinate in mice. Toxicological Letters93(2-3), 125–133 (cited in WHO, 2012; US EPA, 2009).

US EPA (2009). Draft: Toxicological review of halogenated platinum salts and platinum compounds. In support of summary information on the Integrated Risk Information System. EPA/635/R-08/018. January 2009. [available at:http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=203203#Download]

WHO (2000). Air quality guidelines for Europe, 2nd ed. WHO Regional Publications, European Series, No. 91. World Health Organisation Regional Office for Europe, Copenhagen. Platinum, pp. 166-169 [available at:http://www.euro.who.int/__data/assets/pdf_file/0005/74732/E71922.pdf]

WHO (2012). Guidance for immunotoxicity risk assessment for chemicals. Harmonization Project Document. Case-study 3: assessment of sensitization and allergic response to halogenated platinum salts. World Health Organisation. Geneva. [available at:http://www.who.int/ipcs/methods/harmonization/areas/guidance_immunotoxicity.pdf]

Migrated from Short description of key information:
The development of allergic sensitization following exposure to halogenated platinum compounds via the inhalation route is a well-established human health hazard associated with occupational exposure. See full discussion below.

Justification for classification or non-classification

The well known and extensive data set for halogenated platinum compounds indicates that classification for both skin sensitization and respiratory sensitization are required.

 

As discussed above, available evidence is not supportive of the chloroplatinates having potent delayed contact hypersensitivity potential, and that the weight of evidence indicates the chloroplatinates should be classified as Sub-category 1B (low to moderate frequency of occurrence) for skin sensitization.

 

Given the high frequency of occurrence of respiratory sensitization in workers exposed to sufficiently high occupational levels, and the severity of the symptoms that may develop, particularly if exposure is continued, the available data would indicate that for this group of substances a classification in sub-category 1A would be appropriate for respiratory sensitization.