Use of Selected Surfactants To Reduce Dermal Toxicity of Insecticides

Chapter 12

Use of Selected Surfactants To Reduce Dermal Toxicity of Insecticides Ronald L. Morgan, Marius Rodson, and Herbert B. Scher

Downloaded by CORNELL UNIV on October 11, 2016 | http://pubs.acs.org Publication Date: June 24, 1988 | doi: 10.1021/bk-1988-0371.ch012

ICI Americas, 1200 South 47th Street, Richmond, CA 94804 Microencapsulation has proven to be a useful technique to reduce the dermal toxicity of insecticides. However, often in order to reduce dermal toxicity to the extent desired, the rate of release from the microcapsules needs to be reduced to the point where insecticidal activity falls below an acceptable value. A class of surfactants has been discovered which when solubilized in the aqueous phase of an insecticide microcapsule dispersion can form a second barrier in addition to the microcapsule wall. It is speculated that this second barrier forms at the skin-water interface. By the addition of the surfactant the desired dermal toxicity reduction can then be achieved without lowering the release rate from the microcapsules to the extent where insecticidal activity falls below an acceptable value. An example will be shown where this dermal toxicity reduction technique is applied to a Dyfonate microcapsule dispersion. Percutaneous absorption represents an important route of exposure for agricultural and household pesticides. It has been shown that deposition on skin is 20-1700 times the amount that may be inhaled (l). Chemicals exposed to the skin may absorb from 0.2% to greater than 50% of the applied dose into systemic circulation. For example, three common insecticides, Malathion, Parathion, and Carbaryl, are absorbed at 8.2%, 9.7%, and 73.9% of the total applied topical dose (I). Washing of the skin cannot reliably prevent the dermal absorption of insecticides or other materials. For example, a solution of polychlorinated biphenyls was applied to guinea pig skin and immediately washed with water and acetone. After this procedure, only 59% of the applied dose was actually removed from the skin (2). With these results and the fact that the skin is the most important route of exposure to most pesticides, protection of the skin from exposure is vitally important. 0097-6156/88/0371-0131$06.00/0 ° 1988 American Chemical Society

Cross and Scher; Pesticide Formulations ACS Symposium Series; American Chemical Society: Washington, DC, 1988.


132

PESTICIDE FORMULATIONS: INNOVATIONS AND DEVELOPMENTS

The skin is the largest organ in the human body and accounts for approximately 10% of the total body weight (3). This organ consists of two fundamental layers, the epidermis and dermis (Figure 1). The thinner portion, the epidermis, accounts for the major portion of biochemical transformations that occur in the skin; however, it constitutes approximately 5 to 10 percent of the total mass of human skin. The epidermis and dermis are approximately 0.1 millimeter and 2 to 4 millimeters thick, respectively. The outermost layer of the epidermis is the stratum corneum. This layer consists primarily of dead, keratinized epithelial cells. These form horny scales that are constantly worn away and replaced by the living cells underneath. This layer forms the primary protection against foreign materials from penetrating into the systemic circulation. The living cell layer below the stratum corneum is avascular and serves as a secondary level of defense. Absorption into the systemic circulation occurs in the dermis, which is highly vascular. One method used to reduce dermal toxicity of insecticides is microencapsulation. With this technique, the rate of release from the microcapsules can be controlled to the extent that dermal toxicity can be reduced considerably. However, in order to produce this type of toxicity reduction, the rate of release may need to be reduced to the point where insecticidal activity falls below an efficacious value. A class of surfactants has been found which further reduces acute dermal toxicity when used in conjunction with insecticide microcapsules. It is speculated that this class of surfactants forms a barrier at the skin surface to protect against absorption of lipophilic insecticides. The formulation technique in this paper consists of combining a hydrophilic surfactant with microencapsulated Dyfonate (a registered trademark of ICI Americas Inc.) to further reduce its dermal toxicity without changing the release rate from the microcapsules so that insecticidal activity does not fall below an acceptable level. Materials and Methods Microencapulation. A Dyfonate microcapsule suspension was prepared using Stauffer Chemical Company interfacial polymerization technology. Electron micrographs of the microcapsules are shown in Figures 2 and 3. The Stauffer microencapsulation process is based on in situ interfacial condensation polymerization of polyisocyanate monomers (4). This process is unique because the monomers reside only in one phase (organic dispersed phase). This process has been used to produce pesticide microcapsule formulations containing 4-5 lbs of active ingredient per gallon. The first step of the Stauffer microencapsulation process consists of dispersing an organic pesticide phase (contining isocyanate monomers) into an aqueous phase containing an emulsifier and a protective colloid. The isocyanate monomers used in the process are polymethylene polyphenylisocyanate (PAPI) and toluenediisocyanate (TDI) (Figure 4). The wall-forming reaction is initiated by heating the batch to an elevated temperature at which point the isocyanate monomers are hydrolyzed at the interface to form amines which, in turn, react with unhydrolyzed isocyanate monomers to form the polyurea microcapsule wall (Figure 5).



12.

MORGAN ETAL.

Reduction of Dermal Toxicity

133

Figure 1: Structure of skin.

Figure 2: Electron micrograph of a microcapsule on filter paper (lOOOx).



134


Figure 3: Electron micrograph of microcapsules on soil (lOOOx).

NCO TDI

Figure 4: Structures of the isocyanate monomers, PAPI and TDI that are used in wall formation.


12.

MORGAN E T A L .

Reduction ofDermal Toxicity

135


The release rate of this microcapsule system can be varied by varying microcapsule particle size (i.e. total surface area per pound of pesticide), wall thickness (weight percent isocyanate monomers in organic phase) and wall permeability. The wall permeability can be varied by varying the crosslink density of the polyurea (ratio of PAPI to TDI), by varying the wall microporosity (solvent effect), by limiting crosslinking (ammonia addition) and by varying the isocyanate monomer chemical composition. In addition, mixtures of microcapsules with different wall thickness and wall permeability can be produced by this process by sequential dispersion of different organic phases into the same aqueous phase Surfactants. Igepal DM-970 and Igepal CO-990 were obtained from General Aniline and Film Corp. The structures are shown in Figure 6. (Igepal is a registered trademark of 6AF Corp.) Animal Test Method. Acute dermal toxicity testing was performed according to the OECD guidelines (6J. The test animal used was Stauffland albino rabbits, 5 of each sex per dose, (a cross between New Zealand and Florida white strains, Phillips Rabbitry, Soquel, California). The abdominal areas of the rabbits to be dosed were shaved 24 hours prior to treatment. A dosage of test material was pipetted onto a piece of rubber damming, and the area of the rubber damming containing the test material was placed directly on the shaved area of the rabbit. This rubber damming was then secured to the rabbit with surgical tape and covered with gauze. The gauze and the damming were removed 24 hours after the test material application. The dose site was wiped with gauze and rinsed with distilled water to remove the remaining test material. The abdomen of the rabbit was then rewrapped with clean gauze to prevent the rabbit from grooming the dose site and ingesting any residual material. A group of four rabbits were sham-treated and served as controls for each dose level. All test animals were observed for up to 14 days and mortalities were recorded. The median lethal dose (LD50) values for each test material were calculated using the method of Litchfield and Wilcoxon (_7). Results and Discussion Dose-mortality plots for the acute dermal toxicities of Dyfonate microcapsule dispersions are shown in Figure 7. From these plots the LD50 value for each formulation was determined and listed in Table I. A concentration of 3% Igepal CO-990 or DM-970 in the dispersion approximately doubled the LD50 value. Potency ratios (i.e. LD50 value for the microcapsule dispersion with Igepal divided by the LD50 value for the dispersion without Igepal) were calculated for each microcapsule dispersion and shown in figure 8. No significant protective effect of Igepal CO-990 was observed at a 2% concentration, however, a 3% concentration of either Igepal CO-990 or Igepal DM-970 produce a significant decrease on acute dermal toxicity (i.e. an increase in potency ratio).


136


H - NCO + H 0 2

—»

0

- N - C - OH —>

Isocyanate

- NCO + - NH —> 2

Isocyanate


Figure 5:

- NH + C0 T 2

Carbamlc Acid

Amine

2

Amine

H 0 H I H I - N - C - C Polyurea

Microcapsule wall forming reaction.

0(CH CH 0 ) 2

2

150

H

0(CH CH 0) oH 2

C H 9

Igepal DM-970

2

10

1 9

Igepal CO-995

Figure 6: Structures of Igepal CO-990 and Igepal DM-970. (Igepal is a registered trademark of 6/\F Corp.)

i

100

200

i

i

i

i

1111

400 1000 Dose, mg/kg

i

2000

r

4000

Figure 7: Log-Probit plots of acute dermal toxicity dose-mortality curves for Dyfonate microcapsule dispersions without Igepal (-), with 2% Igepal CO-990 (--), with 3% Igepal CO-990 (-.-) and with 3% Igepal DM-970 ( ). (Dyfonate is a registered trademark of ICI Americas Inc.)


12.

MORGAN ETAL.

Reduction of Dermal Toxicity

137


TABLE I: Acute Dermal LD50 Values for Dyfonate Microcapsule Dispersions with and without Igepal Acute Dermal LD50 Igepal Surfactant(a) 370 (265-460)(b) None 2% CO-990 457 (350-596) 3% CO-990 794 (585-1078) 3% DM-970 809 (564-1160) (a) The microcapsule portion was identical in each formulation. (b) Values in parenthesis are 95% confidence limits. Mammalian skin is highly lipophilic (2), and this property represents an important barrier function of the stratum corneum. Lipophilic substances like Dyfonate can easily be absorbed by the stratum corneum and transferred into systemic circulation. In an effort to reduce this absorption, the material can be microencapsulated, thus reducing the availability at the skin surface. Acute dermal toxicity of the microencapsulated material could be decreased further by increasing the thickness and/or the crosslink density of the capsule wall. In the case of the Dyfonate microcapsule dispersion, this approach caused the insecticidal efficacy to fall below an acceptable value. However, addition of Igepal to the microcapsule dispersion did further reduce the dermal toxicity without effecting the insecticidal efficacy. It is speculated that Igepal formed a secondary barrier at the skin surface. This is schematically shown in Figure 9. The lipophilic end of the Igepal molecule is adsorbed on the skin surface. Since Dyfonate is highly lipophilic, it is speculated that the secondary barrier's protection resides in the hydrophilic layer associated with the long hydrophilic chains of the surfactant. This barrier further reduces the amount of Dyfonate available at the skin's surface for absorption, thus reducing toxicity. Addition of either Igepal DM-970 and Igepal CO-990 to a Dyfonate microcapsule formulation has been shown to decrease the dermal toxicity and increase safety of the concentrated formulation. The presence of Igepal in this type of formulation provides a decrease in dermal toxicity of the concentrated formulation without altering the insecticidal efficacy of the diluted dispersion on soil.


138


No Igepal


2% Igepal CO-990

3% Igepal CO-990

3% Igepal DM-970

Potency ratio

Figure 8: Potency Ratios for the microcapsule dispersions with and without Igepal.


12.

MORGAN ETAL.

Reduction ofDermal Toxicity

139

Literature Cited 1. 2. 3. 4. 5. 6. Downloaded by CORNELL UNIV on October 11, 2016 | http://pubs.acs.org Publication Date: June 24, 1988 | doi: 10.1021/bk-1988-0371.ch012

7.

Feldmann, R. J.; Maibach, H. I. Toxicol. App. Pharmacol. 1974, 28, 126-132. Wester, R.C.; Bucks, D.A.W.; Maibach, H.I.; Anderson, J. J . Toxicol. Env. Health. 1983, 12, 511-519. Rongone, E.L. Dermatoxicology, 2nd Ed., F. N. Marzulli and H.I. Maibach (editors). Hemisphere Publishing Corp. New York, 1983; pp 2-19. Scher, H.B., U.S. Patent 4285720, 1981. Scher, H.B. Proc. Pest. Chem. IUPAC, 1983, 295-300. Acute Dermal toxicity. Organization for Economic Cooperation and Development 1981; Guideline 402. Litchfield, J.T. J r . ; Wilcoxon, F. J . Pharmacol-Exp. Therap. 1949, 95:95-113.

RECEIVED December 28, 1987


Use of Selected Surfactants To Reduce Dermal Toxicity of Insecticides

Recommend Documents