Phosphine

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Remarks:

combined repeated dose and carcinogenicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Literature reference, not able to review full data set.

Data source

Reference

Reference Type:

publication

Title:

Nutritional and Toxicological Effects of Long-Term Ingestion of Phosphine-Fumigated Diet by the Rat.

Author:

Cabrol-Telle, A.M., G. de Saint Blanquat, Derache, R., Hollande, E., Periquet, B, and Thouvenot, J.P.

Year:

1985

Bibliographic source:

Food Chem. Toxic. Vol 23, No. 11, pp 1001-1009.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Deviations:

yes

Principles of method if other than guideline:

Study examines the effect of phosphine residue on diet.

GLP compliance:

no

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:

Diet was stored with 2000 ppm phosphine for at least 6 months, then earated for 48 hours before being fed to the rats.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Housed individually with free access to diet and water.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Dietary exposure

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Average level of phosphine in the test diet was 5 ppb.

Duration of treatment / exposure:

From weaning (rats were ~ 50g, so would be about 3 21 days old) for a 2 year period with sacrifices at 1 and 2 years

Frequency of treatment:

continuous

Doses / concentrations

Remarks:

Doses / Concentrations:
5 ppb
Basis:
nominal in diet

No. of animals per sex per dose:

60 males and 60 females (20 of each sacrificed after 1 year)

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

Bodyweight and food consumption were measured. Haematology and clinical chemistry were conducted every 3 months from 10 males and 10 females in each group.

Sacrifice and pathology:

Necropsy included organ weights and histological evaluation was conducted on 10 males and 10 females .

Other examinations:

Carcasses were analysed for water, ash, lipid and nitrogen content.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Effect level:

5 other: ppb

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

Following exposure to diet with a 5 ppb phosphine reside from 3 weeks of age for up to 2 years, there were no clinical or pathological effects in male or female rats.