3-iodo-2-propynyl butylcarbamate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-03-27 to 1995-09-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: data requirement UK HSE Control of Pesticides Regulations

Version / remarks:

1986

Deviations:

yes

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

yes

Principles of method if other than guideline:

Deviations: The sampling time of the receptor fluid was 8 hours instead of 24 hours, as recommended. There is no information about the solubility of the test substance in the receptor fluid.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-iodo-2-propynyl butylcarbamate

EC Number:

259-627-5

EC Name:

3-iodo-2-propynyl butylcarbamate

Cas Number:

55406-53-6

Molecular formula:

C8H12INO2

IUPAC Name:

3-iodoprop-2-yn-1-yl butylcarbamate

Specific details on test material used for the study:

Three different comercially available formulations were investigated.
Formulation I containing 2.32 % w/w
Formulation II containing 0.604 and 0.583 % w/w
Formulation III containing 17.1 % w/w test item

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 31-83-a

RADIOLABELLING INFORMATION
- Radiochemical purity: 247 µCi (ca. 9 MBq)
- Specific activity: 962 MBq/mmol

Radiolabelling:

yes

Test animals

Species:

other: human epidermis in vitro

Administration / exposure

Vehicle:

other: the test item was applied in each of three different commercially available formulations

Duration of exposure:

8 h

Doses:

- Applied volume: 50 µL

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: abdominal autopsy skin
- Type of skin: epidermal membranes
- Preparative technique: the full thickness skin sample was immersed in water heated to ca 60 °C for ca 1 minute. On removal, the epidermis was peeled away using forceps, floated on water and picked up onto aluminium foil. The membranes were then either used immediately, or stored wrapped in foil at ca 4°C overnight.
- Membrane integrity check: yes
- Storage conditions: at -20 °C or 4 °C overnight

PRINCIPLES OF ASSAY
- Diffusion cell: automated flow-through diffusion apparatus
- Receptor fluid: 0.9 % saline solution containing ca. 1 mg/mL tetracycline hydrochloride
- Solubility od test substance in receptor fluid:
- Flow-through system: yes
- Test temperature: 30-32 °C
- Reference substance: not applicable

Results and discussion

Total recovery:

- Total recovery:
In samples treated with formulation I unabsorbed material accounted for 69-93% (mean 84%), with a further 1-17% associated with the solubilised skin sample itself. The radioactivity associated with the skin may be unabsorbed material not fully removed by die skin wash, or absorbed material within the membrane. Given the low cumulative absorption observed, the former explanation seems most likely. Radioactivity associated with die residual receptor contents was low (mean 0.13%).
As the proportion of the dose absorbed was greater for the formulation II the amount associated with unabsorbed material washed from the skin surface at 8 h was correspondingly lower than that observed for the Microtech formulation (48-69%, mean 60%). A small proportion of the applied dose was also recovered in the solubilised skin (2-4%). Again, diis may be either unabsorbed material not removed in the skin wash, or absorbed chemical within the membrane. The residual receptor fluid contents accounted for 1-2 % of the applied dose for this group of samples.
Unabsorbed material accounted for 93-100% (mean 97%) of the applied dose for die samples treated with formulation III reflecting the very low absorption observed in these samples. Correspondingly, the amount of material associated with die solubilised skin was lowest for this formulation (ca 1%), while the residual receptor contents amounted to a mean of only 0.04% of the applied dose.
- Limit of detection, LOD of LSC 30 dpm:

Percutaneous absorption

Percutaneous absorption 1

Key result

Time point:

8 h

Dose:

Formulation I

Parameter:

percentage

Absorption:

3.7 %

Percutaneous absorption 2

Key result

Time point:

8 h

Dose:

Formulation II

Parameter:

percentage

Absorption:

26.3 %

Percutaneous absorption 3

Key result

Time point:

8 h

Dose:

Formulation III

Parameter:

percentage

Absorption:

0.8 %

Any other information on results incl. tables

Table 1 In Vitro dermal Absorption

	Formulation I	Formulation II	Formulation III
Number of replicates	9	9	7
Applied radioactivity	3.75 to 3.94 mg/cm2	736 to 714 µg/cm2	32.81 to 33.12 mg/cm2
Test item concentration [%]	2.3	0.6	17.1
	[% applied dose]
Receptor fluid after 8 hours	3.66	26.25	0.80
Receptor rinse	0.13	1.29	0.04
Washings	83.85	59.71	96.79
Skin retention	6.49	3.20	0.77
Total recovery	94.12	90.45	98.40

Applicant's summary and conclusion

Conclusions:

Following application of 14C-labelled test item to human epidermis in each of three different commercially available formulations the extent of absorption on a % dose basis was found to be formulation dependent. Cumulative absorption reached 3.66%, 26.25% and 0.80% for formulation I, II and III respectively. However, when the concentration in the different formulations was taken into account, the actual quantities of 14C-labelled test item absorbed were found to be similar for the three formulations. The corresponding absolute amounts of 14C-labelled test item absorbed were 140.49, 190.27 and 262.55 µg/cm^2 respectively. The data obtained suggest that absorption of 14C-labelled test item from these commercially available formulations is dependent on the capacity of the membrane for transport of the chemical rather than the amount of test item on the skin surface.

Executive summary:

14C-labelled test item was applied to human epidermis in vitro in each of three different commercially available formulations, and absorption measured over an 8 h period, equivalent to the likely duration of worker exposure to the chemical. Three different formulations were used in this study. Following application of 14C-labelled test item in formulation I, the cumulative absorption at 8 h reached 3.66 % of the applied dose, equivalent to 140.49 µg/cm^2. Proportional absorption was greater for formulation II, reaching 26.25 % at 8 h. However, due to the lower concentration of 14C-labelled test item in this formulation, this was equivalent to absorption of a similar total amount of test item (190.27 µg/cm^2). For the formulation III, the proportional absorption was lowest, reaching only 0.80 % of the applied dose in 8 h. This was equivalent to absorption of 262.55 µg/cm^2 over the 8 h period, as the concentration of test item in this formulation was greater than in the other formulations. The results indicate that absorption of 14C-labelled test item from the commercially available formulations is limited by the skin transport capacity for the chemical, rather than the quantity of chemical available for absorption.