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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Reference
Reference Type:
publication
Title:
Biochemistry, histopathology and treatment of phosphorus burns. An experimental study
Author:
Ben-Hur N & Appelbaum J
Year:
1973
Bibliographic source:
Isr J Med Sci 9: 40-48

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study investigated the systemic effects caused by acute phosphorus burns, only target organs were evaluated.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Elemental phosphorus is often referred to as yellow phsophorus

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
The animals were male rats weighing 250 g. Rats were housed in metabolic cages during the experiment.

Administration / exposure

Route of administration:
other: intradermal burns
Vehicle:
unchanged (no vehicle)
Details on exposure:
Rats were anaesthetised with pentobarbital sodium i.p. then 25 mg of white phosphorus was introduced into the inguinal region by means of a 1.5 cm incision through the epidermis and dermis. The phosphorus was ignited by touching it with hot metal and allowing it to burn for 4 minutes by alternately closing and opening the wound. Following he burn the wound was sutured.
Doses:
25 mg white phosphorus
No. of animals per sex per dose:
96 rats (divided into 12 groups of 8 all identically treated) exposed to white phosphorus, and 48 rats (divided into 12 groups of 4 rats all indentically treated) were sham-exposed.
Control animals:
yes
Details on study design:
Rats were anaesthetised with pentobarbital sodium i.p. then 25 mg of white phosphorus was introduced into the inguinal region by means of a 1.5 cm incision through the epidermis and dermis. Controls were subject to the same procedure with the exception of the introduction of phosphorus. Urine was collected in the metabolism cages, and blood was collected from the tail vein for urinalysis and blood chemistry. Rats were sacrificed at intervals up to and including 72 hours post-burn for histopathological examination of the kidneys and liver.
Statistics:
No information given

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
25 other: mg
Mortality:
50% of the rats died within 3-4 days of receiving the phosphorus burn
Clinical signs:
Not reported
Body weight:
Not reported
Gross pathology:
Not reported
Other findings:
In most of the phosphorus treated animals, the burned area began to smoke when the wound was opened. The burn surface was necrotic and yellowish, smelled of garlic for 2 days and glowed in the dark. The wound did not demonstrate any tendency to heal for six days following the burn.
The biochemical changes 72 hours post-burn are shown in Table 1.

Any other information on results incl. tables

Biochemical results taken from all experiments 72 hours after the burn

Parameter

Control rats

Rats subjected to phosphorus burns

Water intake (ml/24 hr)

15 - 18

40 - 50

Urinary output (ml/24 hr)

10 - 12

30 - 40

Serum phosphorous (mg/100 ml)

4 - 5

9 - 11

Serum urea (mg/100 ml)

10 - 20

90 - 110

Serum Na (mEq/L)

135 - 140

125 - 130

Serum K (mEq/L)

4 - 5

7 - 9

SGPT (units/ml)

9 - 11

90 - 110

Serum osmolarity (mOsm/L)

284 - 300

340 - 360

Urine osmolarity (mOsm/L)

2000 - 2200

680 - 720

Creatinine clearance (ml/min)

1.2 - 1.3

0.7 - 0.8

The differences between treated and control rats were significant at P < 0.01.

Applicant's summary and conclusion

Conclusions:
50% of the rats died within 3-4 days of receiving the phosphorus burn
Executive summary:

50% of rats died within 3-4 days of receiving a phosphorus burn. Alterations in serum phosphate, sodium and potassium levels and 72 hours after the burn were throught to correspond to renal failure, further backed up by the high urine output and decrease in creatinine clearance. Histology results were not reported for these animals, although the authors summarise that the burns resulted in primary renal damage followed by functional alterations, diffuse liver changes and severe changes in blood and urine composition. They conclude that early death is likely to be caused by primary renal alterations and cardiac arrest from potassium intoxication.