Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (1-2:1)

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

HEDP salts and acid are members of HEDP Category, therefore read-across among Category members is justified. Please see attached justification for read-across.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

dermal absorption in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The substance was applied to the shaved back skin of rats. The animals were housed in metabolic cages to collect urine and faeces. After 48 h the rats were euthanised and the substance was measured in urine and faeces, in the skin of the application area and in the remaining body.

GLP compliance:

no

Radiolabelling:

yes

Remarks:

14C

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

weight: 220-260 g
caging in open metabolic cages at a room temperature of 20 °C
feed (Altromin 1324) and water ad libitum

Type of coverage:

other: glass capsule with holes, allows gas exchange but prevents the rats to lick off the substance

Vehicle:

water

Duration of exposure:

48 h

Doses:

0.2 g of a 1 % solution

No. of animals per group:

10

Control animals:

no

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Total recovery:

81.5 %

Dose:

0.1 %

Parameter:

percentage

Absorption:

0.46 %

Remarks on result:

other: 48 h

The absorbed radioactivity was mostly eliminated via faeces (0.082 %), while a minor part was eliminated via urine (0.025 %). Elimination via faeces was similar in both collection periods (0 - 24 h and 24 - 48 h), while elimination via urine was predominantly found in the first collection period. After 48 h a mean of 0.339 % of the applied radioactivity could be found in the remaining carcass.

Conclusions:

The absorption of sodium HEDP is very low (0.46 %).

Executive summary:

Cutaneous absorption and elimination of sodium HEDP was determined in male rats. The measurements were performed with ¹⁴C labelled CA 2. The radioactive substance was applied as a 1 % solution to the shaved back skin of rats. Absorption and elimination was measured after 48 h. After this time, 0.46 % of the applied radioactivity was absorbed. This shows that sodium HEDP is absorbed poorly. The main route of elimination was via faeces. Most of the absorbed amount (0.34 %) could be found in the remaining carcass (excluding the skin of the application area) at the end of the test. This may suggest a delayed elimination and probably an accumulation in the bones.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

trisodium hydrogen (1-hydrogen phosphonato-1-hydroxyethyl)phosphonate hydrogen (1-hydroxy-1-phosphonoethyl)phosphonate

EC Number:

701-237-9

Molecular formula:

HEDP-1Na C2H7NaO7P2 HEDP-2Na C2H6Na2O7P2

IUPAC Name:

trisodium hydrogen (1-hydrogen phosphonato-1-hydroxyethyl)phosphonate hydrogen (1-hydroxy-1-phosphonoethyl)phosphonate

Test material form:

not specified

Results and discussion

Percutaneous absorption

Time point:

48 h

Dose:

0.1%

Parameter:

percentage

Absorption:

0.46 %