2.01.08

Safety Review: Ingredients in Checkmate LBAM-F

[DRAFT - authors' names have been removed pending final edits and review]

Checkmate LBAM-F is a biochemical pesticide designed for mating disruption of the light brown apple moth (LBAM). In early November 2007 aerial spraying of the pesticide was conducted over residential areas in Santa Cruz County as part of an ongoing ìeradicationî program. Aerial sprayings in Monterey County in September, October and November of 2007 included the use of a similar pheromone pesticide Checkmate OLR-F. Neither product is registered with the EPAís Office of Pesticides for residential use. According to a spokesperson for the product manufacturer Suterra, Checkmate OLR-F is registered for use on California vineyards, but this is the first time Checkmate LBAM-F has been used in California or elsewhere (Renner 12/5/07).

The Checkmate LBAM-F formulation includes two types of synthetic moth pheromones, as well as a variety of ìinertî ingredients. Though safety data sheets for the inert ingredients in the formulas have raised many serious health and safety concerns, materials presented by the CDFA (CDFA 2007; DPR/OEHHA 2007) have consistently focused on the safety of only the pheromone constituents, failing to address the preponderance of known toxicity data for the inerts. A 2007 CDFA Questions and Answers document on the LBAM states that ìthe ingredients in the formulation are water and biodegradable elements used to delay the release of the active ingredientî and that ìthe basic biodegradable building block is urea, a normal constituent of the human body that is derived from the breakdown of proteins that we eat.îÝ However a review of the available research data as well as the MSDS sheets (Material Safety Data Sheets) for these chemicals indicates a high level of toxicity for many of the inerts.

The word ìinertî as used on a pesticide label is commonly mistaken to mean inactive or benign. However the EPA states that ìalthough the term ìinertî may connote physical, chemical or biological inactivity, use of the word ìinertî to describe a component in a pesticide product means only that the substance is not intended to exert a pesticidal effect Ö in that product. The ìinertî ingredient may have biological activity of its own, it may be toxic to humans, and it may be chemically activeî (EPA 2002). Though typical pesticide formulations are comprised largely of inerts (a review of 100 agricultural pesticide products found that the formulations contained on average 50% inert ingredients, with many containing 90% or more ìinertsî; NCAP 2006) the majority of safety tests required to register a pesticide are performed with the active ingredient alone, not the complete formulation (Cox & Surgan 2006).Ý

Numerous studies have shown that inerts can increase the toxicity of pesticides to body systems such as the nervous, cardiovascular, and hormonal systems, the mitochondria, and genetic material. Inerts can also interact with other chemicals in pesticide formulations, to increase human exposure levels to the pesticide. Additionally, inerts have been shown to raise the ecotoxicity of pesticide formulations; increasing the severity of toxic effects to plants, animals, and non-target microorganisms (Cox & Surgan 2006).Ý

A comparison of potential health effects listed for the inert ingredients in the Checkmate formulas, with the actual adverse effects reported following the sprayings, indicates a remarkable consistency between the two. In fact a DPR/OEHHA (2007) consensus document provided by the CDFA states the following:

… ìThe toxicity data on the pheromone active ingredients as well as on microencapsulated pheromone product formulations suggest that exposure to a high dose of airborne Checkmate microcapsule particles could cause eye, skin, or respiratory irritation.î

… ìThe toxicological information on the Checkmate product indicates that exposure to high levels of the applied material would be consistent with many of the reported symptoms. However, because the application rate was extremely low, it is likely that exposure occurred at levels below those that would be expected to result in health effects.î

643 adverse reactions reported following the sprayings in Monterey and Santa Cruz counties (and documented by various governmental agencies and citizen groups) included the following:

v asthma attacks

v bronchial irritation

v lung congestion and soreness

v difficulty breathing and shortness of breath

v coughing or ìwheezingî

v skin rashes (sometimes severe)

v vision blurred

v eye irritation

v sore throats

v nasal congestion

v sinus bleeding

v chest pains and tightness

v heart arrhythmia and tachycardia (irregular and rapid heartbeat)

v headaches (sometimes debilitating)

v an inability to concentrate and focus

v dizziness

v muscle aches

v body tremors

v intestinal pain and diarrhea

v nausea

v swollen glands and lymph nodes in neck and under arms

v feelings of lethargy and malaise

v menstrual cramping, an interruption to menstrual cycles, and in some cases a recommencement of menstrual cycles after menopause

(HOPE 1/3/08)

The particle size of the microcapsule shell is another issue that has raised serious health concerns. A consensus document provided by the CDFA in regard to the microencapsulated spray lists the particle size as 25 micrometers (microns) or larger (DPR/OEHHA 2007), however a UC Davis study on the spray discovered a wide range of particle sizes down to the 10 micron size (Werner et al 2007). The EPA classifies particles 10 microns in size or smaller as ìparticle pollutionî, cautioning that this size particle can get deep into the lungs and cause or aggravate a variety of health problems including coughing, difficulty breathing, asthma, and other respiratory symptoms (EPA website). The sprayings in Monterey and Santa Cruz counties were followed by numerous reports of mild to severe respiratory and asthma-like symptoms (HOPE 1/03/08). Ý

Checkmate LBAM-F

Product Description

• an aqueous suspension of pheromone containing micro-bead/dispensers (Suterra MSDS)
• a biochemical for mating disruption of the Light Brown Apple Moth (Epiphyas postvittana) (Suterra LBAM-F label)

Toxicity

As stated on Suterra MSDS Product Sheet: the toxicity of the product is determined by the toxicity of the pheromone active ingredient. The toxicity of this pheromone will be similar to the toxicity of other lepidopteran pheromones, ie:

• oral (rat), LD₅₀: >5000 mg/Kg (Suterra MSDS)
• dermal (rabbit), LD₅₀: >2000 mg/Kg (Suterra MSDS)
• acute inhalation (rat), LC₅₀: >5 mg/L (Suterra MSDS)
• primary eye irritation (rabbit): mildly irritating (Suterra MSDS)
• primary skin irritation (rabbit): moderately irritating (Suterra MSDS)

Potential Health Effects (Warnings)

• ingestion - may cause upset stomach in large doses (Suterra MSDS)

• inhalation ñ due to product form exposure not expected (Suterra MSDS)
• eye ñ may cause transient irritation (Suterra MSDS)
• skin ñ may cause transient irritation (Suterra MSDS)
• ingestion ñ may cause upset stomach in large doses (Suterra MSDS)
• chronic ñ long-term studies on the active ingredients have not been done, however, no adverse effects expected (Suterra MSDS)
• recommended exposure limits ñ none established (Suterra MSDS)
• listed as carcinogen ñ no (Suterra MSDS)
• other health effects ñ no known adverse effects expected (Suterra MSDS)
• health hazard categories ñ EPA Toxicity Category III ñ Caution (Suterra MSDS)

Ecological Toxicity

• none listed on Suterra MSDS
• Suterra product information states the following:

ENVIRONMENTAL HAZARD

For terrestrial uses: For purposes of this Section 18 use only, this product may be applied in Riparian habitats, over water that is covered or partially covered by tree canopies, or over uncovered water that is close to such water bodies. Otherwise, do not apply directly to water, or to areas where surface water is present, or to intertidal areas below the mean high water mark. Do not contaminate water when cleaning equipment or disposing of equipment washwaters or rinsate.

(E)-11-Tetradecenyl Acetate

(E)-11-Tetradecen-1-YL Acetate (As Listed on Checkmate LBAM-F MSDS)

CAS Number - 33189-72-9

Class

• use type ñ pheromone (PAN Database)
• chem class ñ pheromone (PAN Database)

Toxicity

• no available weight-of-the-evidence summary assessment (PAN Database).

Potential Health Effects (Warnings)

• Based on low toxicity in animal testing, and expected low exposure to humans, no risk to human health is expected from the use of these pheromones. During more than 10 years of use of lepidopteran pheromones as pesticides, no adverse effects have been reported (EPA website).
• The safety record for lepidopteran pheromones has allowed the Agency to conclude that consumption of food containing residues of the pheromones presents no risk. In addition, these pheromones can be used experimentally without a permit on up to 250 acres, versus the 10-acre limit imposed on other pesticides (EPA website).
• carcinogenicity - no available weight-of-the-evidence summary assessment (PAN Database).
• developmental or reproductive toxin - no available weight-of-the-evidence summary assessment (PAN Database).
• endocrine disruptor - no available weight-of-the-evidence summary assessment (PAN Database).

Ecological Toxicity

• Adverse effects on non target organisms (mammals, birds, and aquatic organisms) are not expected because these pheromones are released in very small amounts to the environment and act on a select group of insects (EPAÝ website).
• ground water contaminant - no available weight-of-the-evidence summary assessment (PAN Database).

(E,E)-9,11-Tetradecadienyl Acetate

(E,E)-9,11-Tetradecadien-1-YL Acetate (As Listed on Checkmate LBAM-F MSDS)

CAS Number - 54664-98-1

Class

• use type ñ information not available
• chem class ñÝ information not available

Toxicity

• information not available

Potential Health Effects (Warnings)

• information not available

Ecological Toxicity

• information not available

Crosslinked Polyurea Polymer

(generic term - actual chemical name unknown. According to Checkmate manufacturer Suterra, polymethylene polyphenyl isocyanate is used to create the encapsulation polymer, however they say that the PPI starter compound is used up during the reaction [Renner 12/5/07])

CAS Number ñ information not available

Crosslinked Polyurea Polymer is a component of the microcapsule shell. A DPR /OEHHA (Department of Pesticide Regulation/Office of Environmental Health Hazard Assessment) consensus document states that the polyurea shell biodegrades into urea. Research has linked urea to the occurrence of harmful algal blooms (HABís), also known as red tides. Following the spraying, a harmful algal bloom (red tide) described by a water specialist with the Santa Cruz County Environmental Health Services as ìone of the more dramatic ones in recent memoryî, hit the Monterey Bay (Ragan 11/13/07).

Class

• use type ñ information not available
• chem class ñÝ information not available

Toxicity

• information not available

Potential Health Effects (Warnings)

• information not available

Ecological Toxicity

• A DPR /OEHHA (Department of Pesticide Regulation/Office of Environmental Health Hazard Assessment) consensus document states that the polyurea shell biodegrades into urea. A number of studies have linked urea to the occurrence of harmful algal blooms (HABís).
• research published by scientists at San Francisco State University indicates that urea fuels the growth of potentially toxic algal blooms (SFSU 2000)
• various studies have shown that urea increases levels of domoic acid (DA), a toxin occurring in several species of Pseudo-nitzschia algae (Cochlan et al. 2006, Howard et al. 2007)
• Pseudo-nitzschia australis is present in the waters of the Monterey Bay (Fire & Silver 2005)
• domoic acid has been linked to illness and mortality in a variety of species including birds, sea lions, seals, dolphins, and whales (UCSC 2001, IBRRC 2007, Cempa 2000, SFSU 2000)
• domoic acid from Pseudo-nitzschia has also been implicated in sickness/death in humans (NWFSC website).

Polymethylene Polyphenyl Isocyanate (PPI)

synonym ñ polymeric MDI (PMDI)

CAS Number ñ 9016-87-9

According to a Suterra representative, PPI is used to create the encapsulation polymer but reacts into different chemicals by the time the product is ready to use. The company maintains that the PPI starter compound is used up during the reaction (Abraham 10/18/07; Renner 12/5/07). The MSDS sheet on this chemical states that ìthe product reacts with water at the interface, forming CO₂ and a solid insoluble product with high melting point (polyurea). This reaction is accelerated by surfactants (e.g. detergents) or by watersoluble solvents.î (Pagel MSDS)

Polymethylene Polyphenyl Isocyanate (PPI) is classified as harmful by inhalation, and as an irritant to the eyes, respiratory system, and skin under European classification. MSDS sheets warn against breathing the vapor or spray and caution individuals with asthma and other known respiratory problems to avoid exposure to the product. PPI is a known respiratory irritant associated with occupational asthma (Carlisle MSDS; HAZ-MAP; IRIS data sheet; Seguin et al. 1987). An EPA document from IRIS (Integrated Risk Information System) indicates that ìexposure to isocyanates is a leading cause of occupational asthma worldwideî. The document also cites a number of case reports describing occupational asthma and hypersensitivity pneumonitis, related to PMDI exposure (IRIS data sheet).

Following the sprayings in Monterey and Santa Cruz Counties there were numerous reports of respiratory symptoms including asthma, bronchial irritation, difficulty breathing, shortness of breath, coughing and wheezing, and lung congestion. Blurred vision, eye irritation, and skin rashes were also reported (HOPE 1/03/08).

Class

• use type ñ none listed (PAN Database)
• chem class ñ polymer (PAN Database)

European Classification

• hazard symbols ñ Xn (harmful), Xi (irritant) (EC Annex II; Gestis Database)
• risk phrases ñ R20 (harmful if inhaled), R36/37/38 (irritating to eyes, respiratory system, skin), R42/43 (inhalation/skin sensitization) (EC Annex III; Gestis Database)
• safety phrases ñ S(1/2) (keep locked up and out of reach of children), S23 (do not breathe gas/fumes/vapor/spray), S36/37 (use protective clothing and gloves), S45 (in case of accident or illness seek medical advice) (EC Annex IV; Gestis Database)

WHMIS Classification (Canada)

• D1A - very toxic material causing immediate and serious toxic effects (D1A classification applies to aerosol exposures. No LC50 values for vapor exposure were located. This chemical has a very low vapor pressure.) (CCOHS data sheet; CSST data sheet)
• D2A - very toxic material causing other toxic effects (CCOHS data sheet; CSST data sheet)
• D2B - toxic material causing other toxic effects (CCOHS data sheet; CSST data sheet)

WHMIS Health Effects Criteria Met by this Chemical (Canada)

• D1A - acute lethality - very toxic ñ immediate (CCOHS data sheet)
• D2A - chronic toxicity - very toxic ñ other (CCOHS data sheet)
• D2A - respiratory tract sensitization - very toxic ñ other (CCOHS data sheet)
• D2B - skin sensitization - toxic ñ other (CCOHS data sheet)

Toxicity

Acute toxicity - no available weight-of-the-evidence summary assessment (PAN Database).

• inhalation (rat), TC_Lo: 490 mg/m³ per 4 hours (respirable aerosol) (Carlisle MSDS)
• inhalation (rat), LC₅₀: 370 mg as aerosol/m³, 4,0 h of exposure (Pagel Safety Data Sheet)
• oral (rat), LD₅₀: >5000 mg/kg (Carlisle MSDS)
• oral (female rat), LD₅₀: >15000 mg/kg (Pagel Safety Data Sheet)

Potential Health Effects (Warnings)

• ingestion - single dose oral toxicity is considered to be extremely low. Can result in irritation and corrosive action in the mouth, stomach tissue and digestive tract (Carlisle MSDS)

• inhalation ñ irritation of upper respiratory tract and lungs, respiratory sensitization with asthma-like symptoms, pulmonary edema (with severe overexposure), allergic respiratory reactions; symptoms including coughing, dryness of throat, headache, nausea, breathing difficulty, tightness in the chest; impaired lung function has been associated with overexposure to isocyanates (Carlisle MSDS); persons with known respiratory or allergy problems must not be exposed to this product (Carlisle MSDS); in case of hypersensitivity of the respiratory tract (e.g. asthma, chronic bronchitis) it is inadvisable to work with the product (Mehren Kjemi MSDS); harmful by inhalation, may cause sensitization by inhalation, irritating to respiratory system (Gestis Database)
• eye ñ irritation, inflammation, damage to sensitive eye tissue; symptoms including watering or discomfort to eyes (Carlisle MSDS); irritating to eyes (Gestis Database)
• skin ñ irritation, reddening, dermatitis, sensitization (with prolonged or repeated exposure); allergic skin reactions (Carlisle MSDS); irritating to skin (Gestis Database); skin protection preparations do not protect sufficiently against the substance, isocyanates react with skin and cause contamination that is very hard to remove (Gestis Database)
• carcinogenicity ñ lung tumors observed in lab animals exposed to aerosol droplets of MDI/Polymeric MDI (6 mg/m3) for their lifetime. Tumors occurred concurrently with respiratory irritation and lung injury. (Carlisle MSDS); unclassifiable (because the data are incomplete or ambiguous) (PAN Database); Category 3 carcinogen: substances which possibly are carcinogenic for humans and thus give cause for concern (Gestis Database); classified as a Category 4 carcinogen by the German MAK-Commission: substances which are carcinogenic with no or minor genetically toxical effects (Gestis Database)
• developmental or reproductive toxin - no available weight-of-the-evidence summary assessment (PAN Database); classified as Pregnancy Group C, by the German MAK-Commission: there is no reason to fear risk of damage to the developing embryo or fetus when MAK or BAT values are adhered to (Gestis Database); MAK-value = 0,005 ppm EPROS Safety Data Sheet; JCP MSDS)
• endocrine disruptor - no available weight-of-the-evidence summary assessment (PAN Database).

Ecological Toxicity

• classified as ìhazardous wasteî under the European Waste Catalogue Ordinance (AVV) (Gestis Database)
• decomposition ñ can polymerize vehemently in the warmth (Gestis Database); violent exothermic reaction, development of heat, development of hazardous gas or vapor with: water -> carbon dioxide (Gestis Database); isocyanates will react with water and generate carbon dioxide (Carlisle MSDS); hazardous decomposition products: isocyanate vapor and mist, carbon dioxide, nitrogen oxides, traces of hydrogen cyanide (Carlisle MSDS); reacts with water at the interface forming CO₂ and a solid insoluble product with a high melting point (polyurea). This reaction is accelerated by surfactants or by water soluble solvents (Pagel Safety Data Sheet).
• ground water contaminant - no available weight-of-the-evidence summary assessment (PAN Database); may be a hazard to drinking water sources when larger quantities get into groundwater (Gestis Database)
• aquatic ecotoxicity
• acute- fish LC₀ = > 1000 mg/l (Pagel Safety Data Sheet)
• acute- bacteria EC₅₀ =Ý > 100 mg/l (Pagel Safety Data Sheet)
• acute- daphnia EC₅₀ =Ý > 1000mg/l (Pagel Safety Data Sheet)

Butylated Hydroxytoluene (BHT)

synonym ñ 2,6-Di-tert-butyl-p-cresol

CAS Number ñ 128-37-0

Butylated Hydroxytoluene (BHT) is classified as irritating to the eyes, respiratory system, and skin under European classification. Allergic contact dermatitis and contact urticaria are associated with exposure to BHT (HAZ-MAP). It is currently listed as ìunclassifiableî in regard to itís carcinogenicity in humans (due to limited human test data), however a variety of in vitro and animal studies have shown it to have carcinogenic, tumorigenic, mutagenic, and teratogenic effects in animals as well as in human cells (Sigma-Aldrich MSDS). Studies have also confirmed BHT to have estrogenic activity (Miller et al. 2001; Wada et al. 2004) and MSDS sheets state that chronic exposure to BHT may cause reproductive and fetal effects (Acros MSDS).

Following the sprayings in Monterey and Santa Cruz counties, several women reported unusual menstrual symptoms including cramping, interruption of menstrual cycle, and postmenopausal recommencement of the menstrual cycle (HOPE 1/03/08). A wide variety of respiratory symptoms, as well as blurred vision and eye irritation, and skin rashes were also reported (HOPE 1/03/08).

Class

• use type ñ preservative (PAN Database)
• chem class ñ phenol (PAN Database)

European Classification

• hazard symbols ñ Xn (harmful) (EC Annex II; Chemblink data sheet)
• risk phrases ñ R22 (harmful if swallowed), R36/37/38 (irritating to eyes, respiratory system, skin) (EC Annex III; Chemblink data sheet)
• safety phrases ñS26 (in case of eye contact rinse w/ water, seek medical advice), S37/39 (use suitable gloves, eye/face protection) (EC Annex IV; Chemblink data sheet)

WHMIS Classification (Canada)

• has not yet been classified by the Service du repertoire toxicologique (Science Lab MSDS)

Toxicity

Acute toxicity ñ slight (PAN Database)

• acute oral (rat), LD_50: 890 mg/kgÝ (Science Lab MSDS)
• acute oral (mouse), LD_50: 650 mg/kgÝ (Science Lab MSDS)
• acute oral (guinea pig), LD_50: 10700 mg/kgÝ (Science Lab MSDS)

Potential Health Effects (Warnings)

• ingestion ñ acute symptoms include abdominal pain, confusion, dizziness, nausea, vomiting (NIOSH - ICSC 0841)

• inhalation ñ lung and respiratory tract irritant (Science Lab MSDS); acute symptoms include cough, sore throat (NIOSH - ICSC 0841; PAN Database)
• eye ñ irritantÝ (Science Lab MSDS); redness, pain (PAN Database)
• skin ñ irritantÝ (Science Lab MSDS); contact dermatitis, contact urticaria (diseases associated with exposure to this agent) (Haz-Map.com); redness (PAN database)
• exposure limits
• TWA: 10 (mg/m3) from OSHA (PEL) [United States] Inhalation
• TWA: 10 (mg/m3) from ACGIH (TLV) [United States] Inhalation
• TWA: 10 (mg/m3) from NIOSH [United States] Inhalation
• carcinogenicity ñ not classifiable for human; may cause cancer based on animal test data (Science Lab MSDS); unclassifiable (because the data are incomplete or ambiguous) (PAN Database); classified as a Category 4 carcinogen by the German MAK-Commission: substances which are carcinogenic with no or minor genetically toxical effects (Gestis Database)
• mutagenicity ñ may affect genetic material (mutagenic); mutagenic for mammalian somatic cells; mutagenic for bacteria and/or yeast (Science Lab MSDS); mutagenic effects have occurred in humans (Acros MSDS);
• teratogenicity ñ may cause adverse reproductive effects and birth defects (Science Lab MSDS)
• general ñ may be toxic to blood, liver, central nervous system (CNS). Repeated or prolonged exposure can produce target organs damage (Science Lab MSDS)
• developmental or reproductive toxin - no available weight-of-the-evidence summary assessment (PAN Database); classified as Pregnancy Group C, by the German MAK-Commission: there is no reason to fear risk of damage to the developing embryo or fetus when MAK or BAT values are adhered to (Gestis Database); MAK-value = 0,005 ppm EPROS Safety Data Sheet; JCP MSDS); chronic exposure may cause reproductive and fetal effects (Acros MSDS)
• endocrine disruptor - no available weight-of-the-evidence summary assessment (PAN Database); studies have shown BHT to have estrogenic activity (Miller et al. 2001).

Ecological Toxicity

• classified as a hazardous substance on California Director's List of Hazardous Substances (Science Lab MSDS)
• classified as hazardous by OSHA (Science Lab MSDS)

• harmful to aquatic organisms (NIOSH - ICSC 0841)
• ground water contaminant - no available weight-of-the-evidence summary assessment (PAN Database); may be a hazard to drinking water sources when larger quantities get into groundwater (Gestis Database)
• aquatic ecotoxicity