Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants

Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants

46 Evaluation

The critical effect of isopropyl myristate is the local effects (mainly irritation) it might cause. In animals, undiluted isopropyl myristate was moderately to severely irritating to the skin following repeated exposure and at most slightly irritating to the eyes. However, in the majority of studies with human volunteers no or minimal skin irritation has been observed following repeated dermal administration of undiluted isopropyl myristate. In one human study the highest non-irritant concentration of isopropyl myristate was 10%. After application to rabbit skin comedones formation was observed. The wheezing and coughing of monkeys exposed by inhalation to a formulation containing isopropyl myristate is probably a result of respiratory tract irritation since the monkeys had normal lung function tests and the only histological observation was a dose-related accumulation of macrophages within the lungs. In addition, results of haematology, blood chemistry and urinalysis were normal as were organ weights. The only observed effect in guinea pigs exposed by inhalation to a formulation containing isopropyl myristate was increased lung weights but no histological changes were found. It should be noted, that in the inhalation studies, isopropyl myristate has only been tested as part of a formulation and not as the pure substance.

Experimental studies with healthy volunteers and the guinea pig sensitisation test have failed to show any potential for skin sensitisation. The local lymph node assay in mice was weakly positive for skin sensitisation. One human case report of a positive patch test to isopropyl myristate indicates that the chemical might sensitise humans via the skin. A few human case reports of positive skin-prick tests to isopropyl myristate also exist.

Isopropyl myristate was of low acute toxicity to laboratory animals by the oral and dermal routes. Low systemic toxicity was observed in animals exposed by inhalation, dermally, or orally to isopropyl myristate. Only when applied in high doses in the oral or dermal studies, repeated administration produced some changes in organ weights, increased blood levels of two liver enzymes, and/or leucocytosis. Only few studies exist on the absorption of isopropyl myristate. Following inhalation, the absorption was very low (less than 1%) in monkeys exposed for 5 seconds. Autoradiography of animals exposed dermally to isopropyl myristate only showed local penetration but no penetration into the organs. The low systemic toxicity could therefore possibly be explained in a low absorption of isopropyl myristate.

Only one developmental study and one mutagenic study have been performed. None of them caused any concern. However, the value of the developmental study is limited because of the relatively low dose of isopropyl myristate and the dermal route of application.

In three carcinogenic studies with dermal application of isopropyl myristate, no significant differences in the incidence of skin or internal tumours was observed between control and exposed animals. However, the chemical did accelerate the carcinogenic activity of a known skin carcinogen, benzo[a]pyrene.

It is a cause of concern that isopropyl myristate has the ability to enhance the dermal absorption of other chemicals since it, as an inert ingredient in pesticide formulations, might alter the absorption of the active substance or of other of the inert ingredients and thus possibly alter the toxicity of these chemicals.