Regulatory Research Agencies

DOT

Last updated: December 6, 2007

The US Department of Transportation (DOT) was established in 1966 with a mandate to “serve the United States by ensuring a fast, safe, efficient, accessible and convenient transportation system that meets our vital national interests and enhances the quality of life of the American people, today and in the future.” DOT is comprised of numerous sub-organizations, each responsible for a distinct form of national transportation (e.g., aviation, highway, railway, maritime).

In the context of regulatory toxicology, DOT’s Pipeline and Hazardous Materials Safety Administration oversees the safety of nearly one million daily shipments of hazardous materials, and is “dedicated solely to safety by working toward the elimination of transportation-related deaths and injuries in hazardous materials and pipeline transportation, and by promoting transportation solutions that enhance communities and protect the natural environment.”

 

Regulatory Authority

The Federal Hazardous Materials Transportation Law (49 USC § 5101 et seq.) states: “The Secretary [of Transportation] shall designate a material or a group or class of materials as hazardous when the Secretary decides that transporting the material in commerce in a particular amount and form may pose an unreasonable risk to health and safety or property. The Secretary shall issue regulations for the safe transportation of hazardous materials.”

US Hazardous Material Regulations are codified in Title 49, Parts 100-185 of the Code of Federal Regulations. DOT requirements with a bearing on toxicological testing fall within Part 173 concerning the classification, labeling, and packaging of hazardous substances destined for intrastate, interstate, and global commerce.

DOT’s hazard classification and labeling system closely mirrors that of the United Nations (UN) Globally Harmonized System (GHS). Depending upon a substance’s classification, it will be assigned to an appropriate UN Packing Group:

  • Packing Group I      Great Danger
  • Packing Group II     Medium Danger
  • Packing Group III    Minor Danger

The GHS identifies nine classes of hazards that must be addressed on packing labels. Most deal with the inherent physico-chemical properties of a substance and therefore are unlikely to involve any degree of in vivo testing; however, the following GHS hazard classes may involve animal testing to varying degrees:

  • Poisonous Materials (Class 6, Division 6.1; 49 CFR § 173.132): “Presumed to be toxic to humans because it falls within any one of the following categories when tested on laboratory animals….” In vivo tests cited in this section are oral and dermal LD50 (median lethal dose) studies in rats and rabbits and inhalation LC50 (median lethal concentration) studies in rats.
  • Infectious Substances (Class 6, Division 6.2; 49 CFR § 173.134): “A material known or reasonably expected to contain a pathogen … (i) Category A: An infectious substance in a form capable of causing permanent disability or life-threatening or fatal disease in otherwise healthy humans or animals when exposure to it occurs.”
  • Corrosive Materials (Class 8; 49 CFR § 173.136): “A liquid or solid that causes full thickness destruction of human skin at the site of contact within a specified period of time … [T]he packing group must be determined using data obtained from tests conducted in accordance with the 1992 OECD Guideline for Testing of Chemicals, Number 404, ‘Acute Dermal Irritation/Corrosion.'”


Alternatives Policies & Actions

In 1999, the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) endorsed the use of the in vitro membrane barrier test Corrositex® as a standalone replacement for classifying various types of corrosive substances according to UN Packing Groups. DOT subsequently issued a regulatory exemption in September 2002 authorizing the use of Corrositex® in lieu of in vivo methods as a basis for classifying the corrosivity of the following types of materials:

  • Acids, inorganic and organic
  • Acid derivatives (anhydrides, haloacids, salts, etc.), inorganic and organic
  • Acyl halides
  • Alhylamines and polyalkylamines
  • Bases, inorganic and organic
  • Chlorosilanes
  • Metal halides and oxyhalides

Also in the late 1990s, the validity of the human skin models EPISKINTM and EpiDermTM, as well as that of a rat-skin transcutaneous electrical resistance (TER) assay, was endorsed by the European Centre for the Validation of Alternative Methods (ECVAM) Scientific Advisory Committee for skin corrosivity testing. These methods have since been adopted as Organisation for Economic Cooperation and Development (OECD) Test Guidelines 431 and 430, respectively, which require that regulatory authorities in all OECD member countries accept test results generated according to these methods. However, ICCVAM has endorsed the use of these methods only as “positive screens,” whereby negative results in vitro must be subject to “confirmatory” animal testing. DOT’s position concerning the acceptability of human skin model studies for its regulatory programs is currently not available either on the DOT or ICCVAM websites.

DOT’s current involvement in 3Rs activities appears to be limited to its membership in ICCVAM.