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epidemiological data
Type of information:
other: clinical field study in workers
Adequacy of study:
weight of evidence
other: Reliability was not assessed, because the publication was considered acceptable due to the fact that it served as a basis for OEL setting.

Data source

Argyria:clinical implications of exposure to silver nitrate and silver oxide.
Rosenman, K.D.; Moss, A.; Kon, S.
Bibliographic source:
J. Occup. Med. 21, 430-435

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
repeated dose toxicity: inhalation
Principles of method if other than guideline:
The clinical field study reports the clinical findings in a work force of 30 individuals who were exposed to silver nitrate and silver oxide. Six individuals had argyria and 20 had argyrosis. Measurements of blood silver levels were included as part of examination.
GLP compliance:

Test material

Constituent 1
Reference substance name:
human study on workers exposed to silver nitrate and silver oxide
human study on workers exposed to silver nitrate and silver oxide
Details on test material:
- Name of test material (as cited in study report): silver nitrate and silver oxide (are produced and handled in the plant)
- Molecular formula (if other than submission substance): AgO and AgNO3


Type of population:
Ethical approval:
not applicable
Details on study design:
Type: Questionnaire / Work history / Clinical tests
Details: all participants were examined on the same day at a special clinic; the examination consisted of:
- Physical examination and ophthalmological study (which included slit lamp and fundus examination, tonometry, and testing for visual acuity);
- Pulmonary function testing (FVC, FEV1, FEF50, FEF75, MMEF) and chest x-ray for all over 40 years;
- 5 questionnaires (past medical history, occupational history, ophthalmologic history and symptoms, respiratory symptoms, and work-related symptoms);
- Laboratory tests (CBC, automated blood chemical analyses, occult blood in stool);
- Urinalysis with microscopic examination and 24-hour urine collection for potassium, calcium and creatine); some workers also had their urine analyzed for amino acids and quantitative protein excretion;
- Silver in blood was determined by flameless atomic absorption (the sensitivity of the procedure was such that silver concentrations less than 0.6 µg/100 mL were regarded as negative); no silver was detected in the blood of hospitalised controls.

SETTING: a small plant in New York

- All present and former employees who worked in a small plant in New York for more than two years were invited to participate.
- 29 current employees and one former worker were examined including office and laboratory personnel (all males except one office worker); 16 had worked for more than 5 years and 14 had been employed for shorter periods;
- All workers were white and the average age was 34.6 years.

- Type: control or reference group.
- Details: hospitalised controls' blood.

Exposure assessment:
Details on exposure:
- 4 months before examination, 6 production workers wore personal air samplers during two separate eight-hour workdays.
- Time weighed averages ranged from 0.039 mg/m3 to 0.378 mg/m3 by atomic absorption spectrometry.
- The two highest values were exposure levels experienced by two workers in the silver oxide production building.
- All values were above the present OSHA standard of 0.01 mg/m3.
- No historic exposure measurements were available, although both the company and the workers state that working conditions had much improved.
Statistical methods:
not stated

Results and discussion

Clinical symptoms:
- The majority of workers complained about eye, upper (nose and throat) and lower respiratory tract irritation (cough, wheezing and chest tightness).
- 60% of workers had nose bleeding.
- 90% of workers had experienced burns of the skin and 1 of 24 had ocular burns resulting from multiple contacts with silver nitrate.
- Complains about nausea, headache, nervousness and tiredness did not increase with exposure duration and were not related to blood silver levels.
- Complains (10 subjects) of abdominal pain were significantly associated with blood silver levels (p<0.25).
- Changes in skin colour (13 of 30) and eye colour (19 of 30) were reported by individuals of which 76.9% and 89.5% showed objective evidence of silver deposition in skin and eyes, respectively.
- Ten workers with silver deposition in the eyes complained about decreased night vision

Physical findings:
- Results were generally normal, except for skin discoloration.
- Six workers showed generalized bluish-gray discoloration of their skin (more marked in light-exposed areas of the face, neck, arms and hands).
- In two other workers, skin changes were noted only in light exposed skin areas.
- Ten workers showed scarring secondary to sliver nitrate burns.
- The average length of exposure was 15.9 years in these workers, and five of five workers with longer than 10 years exposure revealed generalized argyria.

Ophthalmoscopic findings:
- No changes in visual function attributable to silver deposition were found.
- Slit lamp microscopy examination revealed deposition of silver particles in the conjunctivae of 20 out of 30 workers, and corneal deposition was seen in 50%.
- Prevalence of silver deposition was shown to increase with duration of employment.
- Four workers with limited changes in their lenses were exposed longer than 10 years with an average employment of 19 years.
- Ten workers had corneal scars and had corneal dystrophy and glaucoma.

Other findings:
- None of the workers had evidence of restrictive pulmonary disease.
- Some revealed a minimal degree of pulmonary obstruction not associated with years of employment and was most common in smokers and ex-smokers.
- Twelve of 30 workers had blood silver level in the range 1.1-8.4 µg/100 cc (median: 1.95 mg/100 cc).
- One worker had an elevated creatinine level and hyperkalemia.
- Complete blood counts were normal with one exception: elevated hemoglobin.
- Despite isolated findings on clinical biochemistry parameters, only increased alkaline phosphatase levels in 8 workers appeared to have a relationship to duration of exposure and silver blood levels.
- Neither of the urinary findings were associated with the duration of exposure or silver blood levels, and no evidence of a syndrome of renal tubular damage were found.
- Creatinine clearance was less than 10% of predicted in 5 workers of which 4 had generalized argyria.

Applicant's summary and conclusion

Six out of 30 workers exposed to silver nitrate and silver oxide were reported to have argyria and 20 had deposition of silver in the eyes (argyrosis). In general, the results of the investigation supported the benign nature of argyria in terms of an absence of overt adverse effects related to functional deficits, or morphological changes of pathological consequence.