Methylphosphonic acid, compound with amidinourea (1:1)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

12/1995-03/1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Pre-guideline method, but data comprehensible and scientifically acceptable. (GLP: Yes) Bronaugh, R.L., R.F. Stewart and E. R. Congdon (1982) Methods for in vitro percutaneous absorption studies II. Animal Models for Human Skin Toxicology and Applied Pharmacology 62, 481-488

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

GLP compliance:

yes (incl. QA statement)

Test type:

other: single 24 hours exposure skin penetration test

Test material

Test material information

Constituent 1

Reference substance name:

Methylphosphonic acid, compound with amidinourea (1:1)

EC Number:

282-758-4

EC Name:

Methylphosphonic acid, compound with amidinourea (1:1)

Cas Number:

84402-58-4

Molecular formula:

C2H6N4O.CH5O3P

IUPAC Name:

Phosphonic acid, P-methyl-, compd. with N-(aminoiminomethyl)urea (1:1)

Test material form:

other: solution

Details on test material:

technical product

Test animals

Species:

pig

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

The test article FLOVAN CGN was assessed for its potential to permeate through porcine skin.
The assay was performed in two independent experiments over a time scale of 0 to 24 hours. The test article was tested at the following concentration (a.i):
Experiment I and II: 0.94 mg/ml in water. Samples were drawn from the receptor chambers following a fixed schedule:
Exp. I and II: 0.0; 0.5; 1.0; 2.0; 4.0, 6.0; 8.0 and 24 hours following the application of the test article.
The samples (0.5 ml each) were labelled and transferred to the sponsor's facilities for subsequent analysis.

Specimens of a pig ear skin penetration study were separated by reversed phase HPLC follwed by UV-detection at 200 nm. The separated and detected FLOVAN
CGN a.i. was quantified by an external calibration function. The bottom quantification limit of the practical work amounted to 1.28 µg/mL FLOVAN CGN a.i. in aqueous solution. By means of a serial connection of two analytical HPLC-columns penetrated FLOVAN CGN a.i. in the specimens of the 24 h sampling interval were quantified. Within 24 hours less than 5 % (mean value) of the amount of FLOVAN CGN applied to the test system penetrated*. Within 8 hours no MPAAU were detected in the receptor chamber.

*) test substance applied to the test system: 212.44 µg FLOVAN CGN a.i.; 452.00 µg FLOVAN CGN
5 % of the test substance: 10.62 ug FLOVAN CGN a.i.; 22.60 ug FLOVAN CGN

Discussion: Since permeation of the test article through porcine skin was very low a graphical evaluation of the analytical data was impossible. The concentration of the permeated test article did not exceed the lower limit of detection prior to 8 hours after start of experiments.

In conclusion, it can be stated that FLOVAN CGN showed very low penetration through the skin of porcine ears. Within 8 hours no MPAAU were detected in the receptor chamber. Within 24 hours less than 5 % (mean value) of the amount of FLOVAN CGN applied to the test system penetrated.