Phosphine

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-described study, results well-documented with tables and figures.

Data source

Reference

Reference Type:

publication

Title:

Evaluation of phosphine genotoxicity at occupational levels of exposure in New South Wales, Australia.

Author:

Barbosa A. and Bonin A.M

Year:

1994

Bibliographic source:

Occupational And Environmental Medicine 51(10):700-705

Materials and methods

Type of study / information:

cohort study (prospective) on fumigant workers. The endpoints were micronuclei in peripheral blood lymphocytes, urine mutagenicity and haematology parameters.

Endpoint addressed:

genetic toxicity

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

No guideline required : human data

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Phosphine

EC Number:

232-260-8

EC Name:

Phosphine

Cas Number:

7803-51-2

Molecular formula:

H3P

IUPAC Name:

phosphane

Details on test material:

Phosphine exposure depending on the techniques fumigation used. There are 8 types of fumigation.

Method

Ethical approval:

confirmed and informed consent free of coercion received

Remarks:

(The project was approved by the Sydney Univeristy Human Ethics Committee)

Details on study design:

31 fumigators working with phosphine and 21 control subject working in the same sites as grain handler, clerks and mechanics volunteered and were matched by sex, age and smoking habit.
Details were obtained on chronic and acute illnesses, use of medication, diagnostic exposure to X rays in the past 12 months and exposure to potential mutagens. Subject with a history of having medication or exposure to X rays were subdivided into a separate group.
Genotoxicity variables were evaluated: micronuclei in peripheral blood lymphocytes and urine mutagenicity.
In parallele, all fumigators and 17 controls were evaluated for full haematology, multiple biochemical analysis, whole blood organochlorines and whole blood and serum cholinesterase.
Micronuclei were scored in nonulceated cells by the criteria: diameter between 1/16 to 1/3 that of the main nuclei, non refractile, not linked to the main nuclei, morphologically identical to but smaller than the main nuclei.
50 urine extracts were tested with appropriate positive and negative controls in Salmonella typhimurium strains TA100 and TA98 (+/-S9).
The haematology variables were evaluated: haemoglobin, red cell counts, packed cell volume, mean cell volume, mean cell haemoglobin concentration, platelet counts, whole blood counts, differential white cell counts and erythrocyte sedimentation rate.
Two special test were performed for biochemistry : whole blood organichlorines and serum and whole blood cholinesterase activity.

Exposure assessment:

measured

Details on exposure:

Phosphine concentration in the breathing zone of fumigators was recorded during 8 fumigations with phosphine badges with detection (Dräger) limits ranging from 0.01 to 2.4 ppm/h depending on the duration of the measurement (30 mn-8 hours).
Fumigators had worked with phosphine for a mean of 11.6 years (range 1.5 - 32 years)
Just before phosphine release, each fumigator involved in a specific fumigation procedure placed a badge at the front of the collar as close as possible to the breathing zone. On the back of each badge was recorded the date, name of the user, fumigation technique and times of start and finish of the operation.
To detect short term peak concentrations, a phosphine tubes attached to a gas detector pump with detection limits of 0.1 to 40 ppm were used.

Results and discussion

Results:

The result of micronuclei showed no significant differences between fumigators and controls (P=0.88)
Measurement of urine mutagenicity did not show any significant difference between fumigators (56% had mutagenic activity) and controls (53% had mutagenic activity).
All haematological and biochemical variables were within normal ranges except for some non-specific changes in biochemistry.

The result of micronuclei detected a strong association between age and increased frequency of micronuclei (P=0.001)
Measurement of urine mutagenicity did show increased excretion of mutagen in smokers (100% of the fumigators and 83% of the controls who smokedexcreted mutagenic urine).

Applicant's summary and conclusion

Conclusions:

No increase was observed in clastogenicity or aneuploidy in lymphocytes of 31 long-term phosphine fumigators compared to a group of 21 matched controls. Sporadic phosphine exposure ranged from 0.1 to 2 ppm (0.14 to 2.84 mg/m3) for an average of 11.6 years.

Executive summary:

A small cohort of 31 fumigators who had worked with phosphine for a mean of 11.6 years (range = 1.5-32 years) was examined. Phosphine concentration in the breathing zone of fumigators was recorded during eight fumigations, with the highest level recorded being 2.4 ppm/hour, although more typical concentrations were <0.1 ppm/hour. These workers and 21 controls matched by sex, age, and smoking habit had hematological profiles, whole serum and blood cholinesterase activities, and several clinical biochemistry measures monitored. No significant effects were seen in any parameter monitored, including genotoxic endpoints.