Animal Chemical Containment Levels

ACCL-1 is the lowest containment level for very low-risk materials that are considered non-hazardous to researchers, CCM staff, or the environment during drug preparation, administration, or post- administration.

ACCL-1 Chemicals

• Chemicals whose Safety Data Sheet states "not a hazardous substance or mixture". These chemicals have no GHS pictogram assigned.
• FDA-approved drugs for use in humans or animals that are commercially available
• Foods used in research
• Biodegradable, commercial nanoparticles
• Examples: Milk, fruits, sugar, phosphate-buffered saline (PBS), sodium chloride (NaCl), citric acid, Poly(lactide-co-glycolide) (PLGA), or hydrogel scaffolds

Standard Practice

PPE

• In the lab: Lab coat, nitrile gloves, safety eyewear, and mask during administration or post-administration if required by IACUC policy for animal allergy protection.
• In CCM: Standard Conventional or Standard Barrier PPE

Hazardous Waste

• These chemicals do not fall under the EPA definitions for hazardous waste. Contaminated animal bedding does not need to be collected as hazardous waste.

There are no additional controls beyond what is required by CCM staff to work at the approved Animal Biosafety Level (ABSL).

ACCL-2 materials pose a mild risk to researchers, the environment, or aquatic life during preparation and administration to animals but do not present a hazard post-administration.

ACCL-2 Chemicals

• Chemicals whose Safety Data Sheet states "a hazardous substance or mixture" with an assigned GHS pictogram (e.g., toxic, carcinogen, mutagen) that are not excreted or shed from animals after administration
• Chemotherapeutic drugs with a treatment total amount less than the human dose. Research Safety can help with dose calculation.
• FDA-approved drugs for use in humans or animals that require preparation from powder, but based on Safety Data Sheet information, these drugs are considered hazardous.
• Examples: BrdU (Bromodeoxyuridine), EdU (5-ethynyl-2’-deoxyuridine), Tamoxifen (with dosing less than human dose)

Routes of Exposure

During administration, exposure may occur through accidental inhalation, inoculation, ingestion, or splatter to mucous membranes or exposed skin. Because of these risks, researchers are required to use additional controls during animal treatment.  

Standard Practice

PPE

• In the lab: Lab coat, nitrile gloves, safety eyewear, and mask during administration or post-administration if required by IACUC policy for animal allergy protection.
• In CCM: Standard Conventional or Standard Barrier PPE

Engineering Controls

• Chemical fume hood
• Class II Type 2 biosafety cabinet
• Animal transfer station (used in CCM for husbandry and veterinary cage manipulations)

Hazardous Waste

• If a hazardous chemical solution spill has occurred, and it has contaminated the bedding or cage, contaminated bedding must be collected and disposed as hazardous waste.
• If there is a small spill of hazardous materials outside the cage, incidental spill procedures should be followed. Spill clean-up materials should be disposed as hazardous waste.
• If a hazardous chemical agent is delivered through drinking water or experimental diet, the water or diet must be collected and disposed as hazardous waste.

Post-administration, no additional controls are needed beyond what is required based on the risk assessment performed by Research Safety and the Institutional Biosafety Committee to work at the approved ABSL, as there is no significant risk of excretion or shedding from the animal and/or all known metabolites are characterized as non-hazardous.

ACCL-3 materials pose a moderate risk to researchers, CCM personnel, the environment, or aquatic life during preparation, administration, and post-administration. This level of risk can be due to the chemical mechanism of action and/or the type of administration (e.g., in drinking water or food).

ACCL-3 Chemicals

• Chemicals whose Safety Data Sheet states "a hazardous substance or mixture" with an assigned GHS pictogram (e.g., toxic, carcinogen, mutagen) that are excreted or shed from animals after administration
•  Examples: Azoxymethane (AOM), N, N-diethylnitrosamine (DEN), Heavy metals (Lead acetate), and newly synthesized chemicals or toxins without Safety Data Sheets or known metabolite data.
• Based on information provided by the Principal Investigator for unknown or newly synthesized chemicals, Research Safety can perform a risk assessment. Chemical safety level may be raised to a higher ACCL based on the risk assessment.

Routes of Exposure

During administration, exposure may occur through accidental inhalation, inoculation, ingestion, or splatter to mucous membranes or exposed skin. Because of these risks, researchers are required to use additional controls during and post- animal treatment.

Standard Practice

PPE

• In the lab: Lab coat, nitrile gloves, safety eyewear, and mask during administration or post-administration if required by IACUC policy for animal allergy protection.
• In CCM: Standard Containment PPE

Engineering Controls

• Chemical fume hood
• Class II Type 2 biosafety cabinet

Hazardous Waste

• Contaminated bedding is required to be collected as chemical hazardous waste.

Post-administration hazardous risk includes evaluation of:

• Chemical excretion or shedding period by the animal
• Location where chemical treatment is performed
• Whether metabolites are hazardous and are excreted by the animals
• Whether metabolites and/or their amounts and routes or excretion are unknown

After treatment, animals are housed in Containment, with incubation time depending on the excretion period and location of administration. Animals can be downregulated from Containment Housing.

ACCL-4 represents the highest level of chemical hazard and containment requirements within the Animal Chemical Containment Level classification system.  These chemicals can present life-threatening hazards for lab workers or CCM personnel.  These chemical compounds require a special risk assessment evaluation from Research Safety and CCM before use in experiments, and additional containment measures may be necessary.

ACCL-4 Chemicals

• These compounds require enhanced containment because they are classified as highly toxic under the Globally Harmonized System (GHS), with hazard statements such as H300 (Fatal if swallowed), H310 (Fatal in contact with skin), and H330 (Fatal if inhaled). In addition, these compounds may be highly volatile, reactive, or readily aerosolized. Accidental needlestick injuries, dermal exposure during animal dosing, or inhalation of aerosols may present severe and immediate health risks to personnel.
•  Examples: MPTP/MPP+ (neurotoxin) which penetrates the blood-brain barrier and enters the brain cells, causing Parkinson's Disease-like symptoms.
• Based on information provided by the Principal Investigator for unknown or newly synthesized chemicals, Research Safety can perform a risk assessment. Based on the risk assessment evaluation, the chemical can be downregulated to a lower ACCL.

Routes of Exposure

During administration, exposure may occur through accidental inhalation, inoculation, ingestion, or splatter to mucous membranes or exposed skin. Because of these risks, researchers are required to use additional controls during and post- animal treatment.

Standard Practice

Because of the unique hazards associated with ACCL4 compounds, no single standard containment approach exists. Risk mitigation measures should be developed on a case-by-case basis through a comprehensive risk assessment.

Engineering Controls

In addition to standard engineering controls, such as chemical fume hoods and Class II Type B2 biosafety cabinets, enhanced controls may be necessary, including:

• Conducting procedures within a sealed dedicated room designated to protect from aerosolization within the CCM facility.
• Implementing additional ventilation or containment measures based on risk assessment.

PPE

In addition to standard containment PPE, the following additional controls may be required based on the Research Safety risk assessment:

• Additional respiratory protection to prevent inhalation exposure (e.g., a respirator).
• Disposable chemical-resistant or hazmat suits to prevent skin contact and chemical penetration during administration.
• Specialized administration devices or closed-system transfer devices, when appropriate, to minimize aerosol generation and accidental exposure during dosing procedures.

For animal housing, disposable caging systems may be used to minimize personnel exposure during cage handling, cleaning, and waste management.

Hazardous Waste

• Contaminated bedding must be collected and disposed of as chemical hazardous waste.
• Animal carcass disposal requirements should be determined based on the characteristics of the chemical and the results of the risk assessment. Carcasses may be disposed of as routine biological waste or as chemically contaminated waste, as appropriate.

Post-administration risks should be evaluated based on the following factors:

• The duration and extent of chemical excretion or shedding by the animal
• Whether hazardous metabolites are produced and excreted
• Whether the identity, toxicity, quantity, or route of excretion of metabolites is unknown