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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 April 1974 to 31 May 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study investigated the absorption, distribution and metabolism of orally administered radiolabelled white phosphorus
GLP compliance:
no
Remarks:
: older study

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Elemental phosphorus is often referred to as yellow phsophorus
Radiolabelling:
yes
Remarks:
32P-labeled white phosphorus

Test animals

Species:
rat
Strain:
other: Charles River CD
Sex:
female
Details on test animals and environmental conditions:
Female Charles River CD rats were obtained from the Charles River Breeding Laboratories (Massachusetts). They were kept in air conditioned rooms (75±5°F) with relative humidity of 50±10%, and a photoperiod of 12 hours. They were supplied with Purina rodent chow ad libitum. The rats were acclimatised for 1 week prior to the study, and only healthy animals were used. They were housed in plastic cages with hardwood bedding. Rats weighing 175-250 g were used.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on exposure:
Each rat was fasted overnight before being given a single oral dose of 32P-labeled white phosphorus in peanut oil. The dose was approximately 10% of the LD50, spiked with 10 µi of radiolabel. A volume of 1 ml/100 g bw was administered. An additional group of rats were given 5 consecutive daily doses.
Duration and frequency of treatment / exposure:
Single oral dose or 5 days of dosing.
Doses / concentrations
Remarks:
Doses / Concentrations:
The dose was approximately 10% of the LD50, spiked with 10 µi of radiolabel.
No. of animals per sex per dose:
No information available.
Control animals:
not specified
Positive control:
Not examined.
Details on study design:
A single oral dose of radiolabelled material was adminsitered to female rats then tissues and excreta were assayed for radioactivity.
Details on dosing and sampling:
After dosing each rat was placed immediately in a metabolism cage with food and water available ad libitum. Expired CO2 and urine and faeces were collected. At the end of each experiment, the rat was anaesthetised and aoritc blood collected in a heparinised syringe. Liver, kidneys, brain, lungs, and thigh muscle were removed, weighed and representative samples taken for analysis of radioactivity. The gastrointestinal tract (GI) plus contents were removed and weighed and assayed for radioactivity.
Statistics:
None reported.

Results and discussion

Preliminary studies:
Not performed.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Total 32P absorbed reached a maximum of 60-65% of the administered radioactivity at 24 hours post-dosing. The amount of radioactivity remaining in the GI tract was 57%, 15.3% and 1.7% of the administered dose at the end of 4 hours, 1 day and 5 days, respectively. All the tissues from the rats receiving 5 daily doses contained 4.1 to 10.5 times as much radioactivity as those receiving a single dose.
Details on distribution in tissues:
The liver contained the highest amount of radioactivity, representing 16.1% of the dose at 4 hours, 16.9% at 1 day, and 6.3% at 5 days. Significant amounts of radioactivity was also found in the blood and skeletal muscle. The radioactivity in the blood represented 6.1%, 4.1% and 1.7% of the administered dose at the end of 4 hours, 1 day and 5 days, respectively. The amount in muscle averaged 4%, 5.5%, and 6% at 4 hours, 1 day and 5 days.
Details on excretion:
Most of the absorbed radioactivity was excreted in the urine, averaging 17.1% of the administered dose at 4 hours, 34.5% at 1 day, and 46.7% at 5 days. 2%, 16.6% and 33% of the radioactivity was recovered in the faeces at the end of 4 hours, 1 day and 5 days, respectively.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Thin layer chromatography of urine samples indicated the metabolites consisted of two classes of compounds, one of which corresponded to inorganic phosphate. TLC analysis of liver extracts also demonstrated two classes of metabolites with similar properties to those in urine.

Any other information on results incl. tables

At 4 hours the radioactivity levels were in the order of liver > kidneys > lungs > spleen > bone > muscle > brain.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: the results of the study indicate that the substance is incorporated into the phosphate pool
White phosphorus was moderately absorbed after oral administration in the rat and was rapidly distributed and excreted. The results of the study indicate that a proportion of the administered substance is incorporated into the phosphate pool
Executive summary:

The toxicokinetics of radiolabelled white phosphorus were investigated in the rat using gavage administration. Radioactivity was well absorbed, with absorption essentially complete in 24 hours with 60 -65% of the administered dose. Most of the absorbed radioactivity was excreted in the urine, suggesting that the substance was metabolised since white phosphorous has limited solubility in water. Chromatography of urine samples indicated the metabolites consisted of two classes of compounds, one of which corresponded to inorganic phosphate. The liver contained high amounts of radioactivity. Skeletal muscle also contained a large percentage of the dose but this was thought to be due to the high muscle mass of the body. Only small amounts of radioactivity were found in other tissues. An additional repeat dose group indicated an accumulation of radioactivity in all tissues examined. The results of the study indicate that a proportion of the administered substance is incorporated into the phosphate pool