Pirimiphos-methyl

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 Sep 1996 to 06 Sep 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pirimiphos-methyl

EC Number:

249-528-5

EC Name:

Pirimiphos-methyl

Cas Number:

29232-93-7

Molecular formula:

C11H20N3O3PS

IUPAC Name:

O-2-(diethylamino)-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate

Radiolabelling:

no

Administration / exposure

Doses:

- Nominal doses: 503.7 g/L; 4.5 g/L
- Dose volume: 25.4 µL (10 µL/cm2, 2.54 cm2 application area)
- Rationale for dose selection: The two doses were prepared to mimic the commercial formulation

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: Human
- Preparative technique: Epidermal membranes were prepared from human whole skin by immersion in water at 60°C for 40-45 seconds and the epidermis teased off the dermis.
- Membrane integrity check: The integrity of the membranes was checked by measurement of the electrical resistance across the skin. Only those membranes with an acceptable resistance, thereby showing that they were intact, were used on the study.

PRINCIPLES OF ASSAY
- Diffusion cell: Measured using glass diffusion cells in which the epidermis formed a horizontal membrane and provided an application area of 2.54 cm2.
- Receptor fluid: The receptor chambers of the cells were filled with a recorded volume of receptor fluid (50% v/v ethanol in water) and placed in a water bath maintained at 30 ± 1°C. A pre-treatment sample (0 5mL) was taken from each receptor chamber for analysis by gas-liquid chromatography (GLC). An equal volume of fresh receptor fluid was added to each receptor chamber to replace the volume removed.
- Test temperature: Throughout the experiment the receptor fluid was stirred and the epidermal membranes were maintained at a normal skin temperature of 30 ± 1°C in a water bath.
- Occlusion: Unoccluded

Results and discussion

Percutaneous absorption

Percutaneous absorption 1

Key result

Time point:

24 h

Dose:

4.5 g/L

Parameter:

percentage

Absorption:

8.46 %

Percutaneous absorption 2

Time point:

6 h

Dose:

4.5 g/L

Parameter:

percentage

Absorption:

1.9 %

Percutaneous absorption 3

Time point:

10 h

Dose:

4.5 g/L

Parameter:

percentage

Absorption:

3.4 %

Percutaneous absorption 4

Time point:

6 h

Dose:

503.7 g/L

Parameter:

percentage

Absorption:

0.11 %

Percutaneous absorption 5

Time point:

10 h

Dose:

503.7 g/L

Parameter:

percentage

Absorption:

0.22 %

Percutaneous absorption 6

Time point:

24 h

Dose:

503.7 g/L

Parameter:

percentage

Absorption:

0.56 %

Any other information on results incl. tables

Table 1. Summary of the test substance 500 g/L absorption through human epidermis

Application of Test Materials	Mean Absorption Rates		Mean Amount and Percentage of Dose Absorbed
	Time period (h)	Absorption rate (µg/cm^2/h±SEM)	Time (h)	Amount (µg/cm^2)	Percentage absorbed
Concentrate Formulation	0.5 - 54	1.17+0.097
(503.7 g a.i/L)			6	5.72	0.11
10 µL/cm^2(5037 µg ai/cm^2)			8	8.32	0.17
Unoccluded			10	10.9	0.22
Duration of exposure: 54h			24	28.4	0.56
n = 5
0.9:100 v/v aqueous spray diln	0.5 – 54	0.155 +0.028
(4.536 µg a.i/L)			6	0.883	1.9
10 µL/cm^2(45.36 µg ai/cm^2)			8	1.20	2.6
Unoccluded			10	1.53	3.4
Duration of exposure: 54h			24	3.84	8.5
n = 6

 

Applicant's summary and conclusion

Conclusions:

The results obtained in this study demonstrate that the absorption of the test substance through human epidermis is slow when compared with the absorption rates of other penetrants measured using this in vitro technique (Dugard et al, 1984; Dugard and Scott, 1984). These data predict that the dermal absorption of the test substance from normal exposure to this 500g/L formulation would be low and the percentage of absorption would be 8.46 % in the worst case scenario.

Executive summary:

The absorption of the test substance from a nominal 500g/L formulation (actual content 504 g test substance/L) has been measured in vitro through human epidermis. The formulation was applied as the concentrate formulation and as a 0.9:100 v/v (4.54 g test substance/L) spray strength dilution of the formulation in water. The concentrate formulation and the spray strength dilution were applied to the epidermal membranes at a rate of 10 µL/cm2; all applications were left unoccluded throughout the entire exposure period. These applications were designed to simulate potential human dermal exposure to the formulation during normal use. 

Absorption of the test substance from both the concentrate and spray strength dilution maintained essentially constant rates over the entire exposure period (54 h). The absorption rate measured from the spray dilution (mean 0.155 µg/cm2/h) was approximately 8 times less than the rate obtained from the concentrate (1.172 µg/cm2/h). Mean amounts of the test substance absorbed during typical working day periods from the concentrate varied from 5.72 µg /cm2 (0.11% of dose) at 6 h to 10.9 µg/cm2 (0.22% of dose) at 10 h. This increased to 28.44 µg /cm2 (0.56% of dose) after 24 h exposure. The amounts absorbed from the spray dilution varied from 0.883 µg /cm2 (1.9% of dose) at 6 h to 1.53 µg/cm2 (3.4% of dose) at 10 h. This increased to 3.84 µg /cm2 (8.46% of dose) after 24 h exposure.

The results obtained in this study demonstrate that the absorption of the test substance through human epidermis is slow when compared with the absorption rates of other penetrants measured using this in vitro technique (Dugard et al, 1984; Dugard and Scott, 1984).  These data predict that the dermal absorption of the test substance from normal exposure to this 500g/L formulation would be low and the percentage of absorption would be 8.46 % in the worst case scenario.