Dipotassium tetrachloroplatinate

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

5 years (between December 1989 and July 1995)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not a guideline study, but data are scientifically acceptable

Data source

Reference

Reference Type:

publication

Title:

Exposure-effect relationship of platinum salt allergy in a catalyst production plant: conclusions from a 5-year prospective cohort study

Author:

Merget R et al

Year:

2000

Bibliographic source:

Journal of Allergy and Clinical Immunology, 105, 364-370

Materials and methods

Type of sensitisation studied:

respiratory

skin

Study type:

survey

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Prospective cohort study. "To assess both the exposure to [platinum] and the incidence of sensitization to [platinum] salt in a catalyst production plant in a 5-year prospective cohort study and to possibly define a threshold value for sensitization."

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexachloroplatinic acid

EC Number:

241-010-7

EC Name:

Hexachloroplatinic acid

Cas Number:

16941-12-1

Molecular formula:

Cl6Pt.2H

IUPAC Name:

hexachloroplatinic acid

Details on test material:

CAS 16941-12-1

Method

Type of population:

occupational

Ethical approval:

confirmed, but no further information available

Remarks:

Study was accepted by the ethics committee of "the university" [possibly Ruhr University, Bochum, Germany]

Subjects:

Workers in a catalyst production plant. Production process involved preparation of platinum salt solution in a closed system, immersion of various substrates in the solution by robots in the encapsulated impregnation area, reduction in a furnace.

Total population: total number of persons in cohort from which the subjects were drawn - 222 exposed subjects; 86 control subjects

10 subjects from the catalyst department (6%), 11 craftsmen with frequent jobs in the catalyst department (20%) and 30 controls (35%) refused to complete the study; 23 catalyst department subjects (14%), 9 craftsmen (17%) and 15 controls (17%) left the plant during the study; 4 catalyst department subjects (2%) had a positive response to the skin prick test with hexachloroplatinic acid at the initial assessment and were excluded from the study.

Total number of subjects in study:
209 exposed subjects: 159 from the catalyst department, 50 craftsmen with frequent jobs in the catalyst department.
66 control subjects from the canteen, administration, security staff at the plant and newly-employed blue-collar workers from other departments at the plant.

Participation rate: 95% of catalyst department subjects, 93% of craftsmen with frequent jobs in the catalyst department, 77% of controls.

High exposure: total n=115; 104 catalyst department workers, 11 craftsmen; mean age 32 years (95% confidence interval 30-34); 115/115 (100%) male; 53 smokers, 38 ex-smokers, 24 non-smokers, mean of 9 pack-years (95% CI 7-11)

Persistent low exposure: total n=51; 51 catalyst department workers; mean age 32 (95% CI 29-35); 48/51 (94%) male; 16 smokers, 12 ex-smokers, 23 non-smokers, mean of 6 pack-years (95% CI 4-8)

Intermittent low exposure: total n=61; 4 catalyst department workers, 38 craftsmen, 19 controls; mean age 39 years (95% CI 36-42); 60/61 males (98%); 18 smokers, 19 ex-smokers, 24 non-smokers, mean of 9 pack-years (95% CI 6-12)

No exposure: total n=48; 1 craftsman, 47 controls; mean age 38 years (95% CI35-41); 41/47 males (85%); 16 smokers, 16 ex-smokers, 16 non-smokers, mean of 11 pack-years (95% CI 7-15)

Atopy occurred with similar frequency in all groups

Clinical history:

Prerequisite of study participation: skin-prick test to hexachloroplatinic acid did not elicit a reaction

Controls:

See "Subjects", above

Route of administration:

other: Presumably dermal and inhalation

Details on study design:

Questionnaire (including work history and subjective symptoms), skin prick test, lung function test, bronchial hyperresponsiveness, serum IgE, enzyme allergosorbent test.

Medical examination of subjects at 6-monthly intervals in the first year, then yearly, comprising:
- questionnaire to assess personal information and symptoms, including: job descriptions (including exposure times and previous jobs); work-related symptoms (recurrent, including asthma, rhinitis, conjunctivitis, dermatitis), categorising time of onset as prior to joining plant, after joining plant but prior to study, or during study;
- skin prick test with hexachloroplatinic acid at 0.01 mol/litre (4.1 g/L) in 0.9% NaCl; also skin prick tests with environmental allergens to assess atopy;
- lung function test, measuring FEV1 with a pneumotachograph;
- bronchial hyperresponsiveness to histamine (49 tests in 47 subjects were not performed/allowed);
- total serum IgE and enzyme allergosorbent test using the same allergens as in the skin test

Results and discussion

Results of examinations:

Conversion from negative to positive skin prick test response to hexachloroplatinic acid occurred in 13 subjects in the high exposure category and 1 subject in the persisent low exposure category (although some high exposure had also been experienced by this individual); incidence was 4.1 conversions/100 person-years; for newly-employed subjects (n=10), incidence was 5.9 conversions/100 person-years; for existing employees (n=3), incidence was 2.1 conversions/100 person-years; multivariate analysis showed strong association between skin prick test conversion and exposure category (p=0.011); also statistically significant positive association for smoking (relative risk 3.9, 95% confidence interval 1.6-9.7).

Symptoms (asthma, rhinitis, conjunctivitis, dermatitis) beginning during the study occurred more frequently in the high exposure category; frequency of at least 1 of the symptoms 35/115 (33%) high exposure, 6/61 (12%) persistent low exposure, 3/61 (5%) intermittent low exposure, 4/48 (8%) no exposure

No other differences in results (total IgE, FEV1, bronchial hyperresponsiveness) between exposure groups

Applicant's summary and conclusion

Conclusions:

"[Platinum] salts represent relevant allergens in a catalyst production plant. Both [platinum] salt sensitization and new allergic symptoms were associated with the degree of exposure"; "because of the high variability of [platinum] concentrations in the high-exposure category, a valid cut-off value for occupational hygiene cannot be defined by this study. However, because no sensitization was observed in subjects with low or no exposure, maximal [platinum] concentrations in these areas (below 10 ng/m3 soluble [platinum]...) may be defined as safe."

Executive summary:

A 5 -year prospective cohort study aimed to assess both the exposure to platinum and the incidence of sensitization to platinum salt in a catalyst production plant, and to possibly define a threshold value for senstization. 209 exposed workers (42 with "Intermittent low" exposure and 1 with "no" exposure) and 66 control subjects (19 with "intermitent low" exposure) from a catalyst production plant were examined. Exposure was defined as high, persistent low, intermittent low, and no exposure. Assessment (6 -monthly for first year, then yearly) included a questionnaire, skin prick tests, lung function tests, bronchial hyperresponsiveness, serum IgE, enzyme allergosorbent test.

Conversion from negative to positive skin prick test response to hexachloroplatinic acid occurred in 13 subjects in the high exposure category and 1 subject in the persisent low exposure category (incidence 4.1 conversions/100 person-years; for newly-employed subjects (n=10), incidence was 5.9 conversions/100 person-years; for existing employees (n=3), incidence was 2.1 conversions/100 person-years); multivariate analysis showed strong association between skin prick test conversion and exposure category (p=0.011); also statistically significant positive association for smoking (relative risk 3.9, 95% confidence interval 1.6 -9.7).

Work-related symptoms (asthma, rhinitis, conjunctivitis, dermatitis) ocurring during the study were more frequently reported in the high exposure category; frequency of at least 1 of the symptoms (related to work) 15/115 (13%) high exposure; 3/51 (6%) persistent low exposure; 0/61 (0%) intermittent low exposure; 3/48 (6%) no exposure.

The investigators concluded that "[Platinum] salts represent relevant allergens in a catalyst production plant. Both [platinum] salt sensitization and new allergic symptoms were associated with the degree of exposure"; "because of the high variability of [platinum] concentrations in the high-exposure category, a valid cut-off value for occupational hygiene cannot be defined by this study. However, because no sensitization was observed in subjects with low or no exposure, maximal [platinum] concentrations in these areas (below 10 ng/m3 soluble [platinum]...) may be defined as safe."