Cyanamide

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

For priciples of method see below.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cyanamide

EC Number:

206-992-3

EC Name:

Cyanamide

Cas Number:

420-04-2

Molecular formula:

CH2N2

IUPAC Name:

cyanamide

Test material form:

other: aqueous solution

Details on test material:

- Test substance: Cyanamide
- Appearance: Solid
- Purity: 99.5%

Radiolabelling:

no

Test animals

Species:

other: human

Sex:

male

Details on test animals or test system and environmental conditions:

-The same group of 6 volunteers from the study with oral intake of cyanamide participated in this subsequent dermal absorption study

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Duration of exposure:

6 hours

Doses:

The same dose that was applied in the oral study, 20 mg (10 mg cyanamide were applied to each forearm). The dosage was applied to the skin by a gauze patch that was charged with 1 mL of a 1 % aqueous cyanamide solution.

No. of animals per group:

6 human volunteers

Control animals:

yes

Remarks:

Urine samples collected before the Cyanamide application served as controls.

Details on study design:

- Cyanamide was applied on the skin by fixing a gauze patch under a watertight rubber foil on the inner side of each of the two forearms (2 patches per person). Each gauze was charged with 1 mL of a 1 % aqueous cyanamide solution for a period of 6 hours.
- The urine samples were collected over a period of 48 hours in 12 hours aliquots beginning immediately after the dermal application of cyanamide. Urine samples collected before the cyanamide application served as controls. Another urine sample was collected six days after cyanamide application
- After removal of the patches the contaminated skin areas were rinsed with water and wiped dry.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

Under the experimental conditions of the study the absorbed dose of cyanamide after dermal application was estimated to be between 0.87 and 3.53 % (see table below in "Remarks on results")

Conversion factor human vs. animal skin:

Not needed, the presented skin absorption study was performed in human

Any other information on results incl. tables

Absorbed quantity of Cyanamide after dermal administration of 20 mg cyanamide for six hours (human volunteers):

Volunteer No	Cyanamide absorption 0 to 48 hours ( %)
1	2.04
2	3.20
3	0.87
4	1.14
5	2.06
6	3.53

 

 

- The N-acetylcyanamide concentration in the urine of the test persons, except volunteer No 1 and 3 before and 6 days after the dermal application of the test material were below the limit of quantification. N-acetylcyanamide values of these two volunteers were very close to the above limit of quantification. It may be concluded that the values are caused by methodical variations at the limit of quantification. However, the urinary excretion of N-acetylcyanamide was completed for the most part after 24 hours.

- Dermal absorption figure was calculated by taking into account the excretion of N-acetylcyanamide of each human volunteer after oral administration of 20 mg cyanamide/person. As it is known that cyanamide is quantitative absorbed after oral administration the dermal absorbed dose can be determined.

Applicant's summary and conclusion

Conclusions:

The results of the dermal absorption study in human confirmed that N-acetylcyanamide is the main urinary metabolite of cyanamide. Cyanamide is absorbed through human skin and its excretion is efficient. The degree of dermal absorption of a 1 % aqueous cyanamide solution for a period of 6 hours exposure was found to be between 0.87 and 3.53 %.

Executive summary:

The aim of the study (Gloxhuber, C., 1989, Doc. No. 512-004) was to elucidate differences in metabolism and excretion of hydrogen cyanamide in rats and humans. The present study record describes a part of this study, the one which was conducted in human and examined the dermal absorption of cyanamide.

The same group of 6 volunteers from the study with oral intake of cyanamide participated in a subsequent dermal absorption study. The inner sides of the forearms were chosen as application site. 10 mg cyanamide were applied to each forearm (20 mg per person). A gauze patch was charged with 1 % aqueous cyanamide solution and applied to the skin by an occlusive dressing for 6 hours. The urine samples were collected over a period of 48 hours in 12 hours aliquots beginning immediately after the dermal application of cyanamide. Urine samples collected before the cyanamide application served as controls. Another urine sample was collected six days after cyanamide application. After removal of the patches the contaminated skin areas were rinsed with water and wiped dry. The used patches were analysed for residual cyanamide to demonstrate that cyanamide was not decomposed during the application period.

The study results confirmed the results of the other two parts of the study (rat and human; oral), showing that N-acetylcyanamide is the main urinary metabolite of cyanamid. The excretion of cyanamide is efficient in human after dermally administered cyanamide as by orally administered cyanamide in rats and human, however, the dermal absorption is considerably delayed compared to the oral one. The degree of dermal absorption of a 1 % aqueous cyanamide solution for a period of 6 hours exposure was found to be between 0.87 and 3.53 %.