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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
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 hours, 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:

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
EC Number:
Molecular formula:
HEDP-2Na C2H6Na2O7P2 HEDP-3Na C2H5Na3O7P2
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
Test material form:
not specified

Test animals

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
Water: ad libitum

Administration / exposure

Type of coverage:
other: glass capsule with holes, allows gas exchange but prevents the rats to lick off the substance
Duration of exposure:
48 h
0.2 g of a 1 % solution
No. of animals per group:
Control animals:
Details on study design:
Possible contamination of animals with radioactivity was measured in urine and faeces which were collected over 24 hours prior to the experiment.
0.2 g of a 1 % solution of the test substance was applied to an 8 cm² area on the back of the rats which had been shaven 24 hours prior to the administration. The application area was covered with a glass capsule with holes to ensure gas exchange but to prevent the rats from licking the substance off the skin. The animals were housed in open metabolic cages and urine and faeces were collected in two fractions (0 -24 hours and 24-48 hours). After 48 hours, the rats were euthanised using CO2 and the skin of the application area was dissected and dissolved with a tissue solubiliser. The remaining body was homogenised using an electric mincer. Radioactivity of the different samples was measured in a scintillation counter as follows:
- dissolved skin - neat solution.
- urine - mixed with water and scintillation fluid
- faeces or remaining body - lyophilised, homogenised and combusted. Combustion products were absorbed and mixed with scintillation liquid
glass capsule - stirred in water/methanol (50/50 v/v) and the extract was mixed with scintillation liquid.
The exhaled air was not used for radioactivity measurements as in previous experiments, no radioactive CO2 could be found in exhaled air after parenteral administration of HEDP.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Total recovery:
81.5 %
Percutaneous absorption
0.1 %
0.46 %
Remarks on result:
other: 48 h

Any other information on results incl. tables

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 hours and 24 - 48 hours), while elimination via urine was predominantly found in the first collection period. After 48 hours, a mean of 0.339 % of the applied radioactivity could be found in the remaining carcass.

Applicant's summary and conclusion

In a dermal absorption study, not conducted according to any OECD Test Guideline and pre-GLP, a solution of 1% of HEDP (2-3Na) with 14C labelled CA 2 was applied to the shaved back skin of male rats. Following 48 hours, 0.46 % of the applied radioactivity was absorbed, indicating a poorly absorption. 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.