What Do Animal Toxicology Studies Tell Us About PBO?
Numerous toxicology studies have been conducted over the past 40 years on PBO examining the full range of potential toxic effects. These studies were conducted in accord with regulatory requirements put forth by the U.S. EPA or other international agencies. When possible, the studies were conducted following U.S. EPA Good Laboratory Practices (GLPs), a system of processes and controls to ensure the consistency, integrity, quality, and reproducibility of laboratory studies conducted in support of pesticides registration. The following types of studies have been conducted in support of PBO registration:
Acute Toxicity Studies
Acute toxicity studies are designed to identify potential hazards from acute exposures. The studies usually employ a single or few high doses over a short time frame. The data are used for the development of appropriate precautionary statements for pesticide product labels. Acute studies identify:
- Dermal Toxicity
- Eye Irritation
- Inhalation Toxicity
- Oral Toxicity
- Skin Irritation
- Skin Sensitization
PBO has a low acute toxicity by oral, inhalation and dermal routes. It is minimally irritating to the eyes and skin. It is not a dermal sensitizer.
Sub-chronic and Chronic/Carcinogenicity Studies
Sub-chronic and chronic studies examine the toxicity of longer term, repeated exposure to chemicals. They may range from 90 days for sub-chronic studies, to 12-24 months for full lifetime chronic studies, designed to determine potential for carcinogenesis. They are also intended to identify any non-cancer effects as well as a clear No Observable Adverse Effect Level (NOAEL) that is used for risk assessment. Studies conducted on PBO include:
- 90 day inhalation toxicology study
- 18 month chronic toxicity/carcinogenicity study in mice
- 24 month chronic toxicity/carcinogenicity study in rats
NOAELs were derived for PBO from both sub-chronic and chronic studies. These NOAELs are used by EPA to conduct risk assessments for all individual uses of PBO to ensure that all registered products with PBO pose a reasonable certainty of no harm used according to the label directions.
PBO caused an increase in liver tumors in mice that ingested high levels of PBO in the diet for their entire lifetime. The scientific identification and analysis of the key events leading to the formation of the mouse liver tumors suggests that the events are not likely to occur in humans.
Reproduction and Fertility Study
This study examines the potential of the pesticide to alter the reproductive performance and function of the male and female rats over two generations. This is includes a comprehensive assessment of effects on gonadal function, estrus cycles, mating behavior, conception, birth, lactation, and weaning. These studies are essential to assess the potential of increased sensitivity to younger animals.
Studies have shown that PBO does not cause reproductive toxicity.
Developmental Toxicity Studies
Once referred to as “teratogenicity” studies, these studies assess the potential for a pesticide to affect the developing embryo and fetus in the pregnant female (rabbit and rat) during organogenesis, the time in which the body’s organs are forming and developing. As with the Reproduction and Fertility Study, these studies are conducted to assess the potential of increased sensitivity to younger animals.
Studies have shown that PBO does not cause harm to the developing fetus.
These studies test for the ability of a chemical to cause mutations and chromosomal changes as well as the competency of DNA repair mechanisms. Genotoxicity studies where the chemical shows a genotoxic effect are also seen as indicators that a chemical may have a high probability of causing cancer in chronic animal studies.
The HIARC (U.S. EPA’s Hazard Identification Assessment Review Committee) concluded that there is not a concern for mutagenicity resulting from exposure to piperonyl butoxide.