US Federal Regulations/Criteria

The original HHS Mandatory Guidelines for Federal Workplace Drug Testing Programs (1988) included measures to be taken by the collector to ensure that a specimen was not adulterated, diluted, or substituted during collection. Although certified laboratories were allowed to perform tests to determine the validity of urine specimens submitted for testing, the 1988 Guidelines did not include specific requirements for such testing

Drug-testing laboratories implemented procedures to address the types of adulterants seen in their laboratories and reported in the scientific literature, and to identify urine specimens with characteristics (i.e., low urine creatinine and specific gravity values) indicative of a dilute or substituted specimen. In 1993, HISS issued guidance to certified laboratories on reporting of specimens identified as “dilute” based on creatinine and specific gravity tests.

HHS revised the Mandatory Guidelines in 1994 to incorporate revisions based on the experience of US federal workplace programs. The Guidelines were clarified to state that certified laboratories were allowed to conduct dilution and/or adulteration testing to determine specimen validity, but such testing remained optional. The individual laboratories determined which specimen validity tests to perform and what cutoffs were used to determine dilution, substitution, or adulteration.

The l994 Guidelines revisions included additional measures to ensure that a specimen was not adulterated or diluted during the collection process. Additional guidance was provided on what constituted a reasonable amount of water to be given if a donor could not urinate during the collection process. In addition, the acceptable temperature range specified for urine specimens were widened slightly, the original range of 90. 98 °F was changed to 90 100 °F.

As the number of abnormal specimens submitted to certified laboratories increased, HHS and DOT worked with the drug-testing experts of HHS Drug Testing Advisory Board DTAB to review the scientific and medical literature and establish criteria to identifier adulterated, dilute, and substituted specimens Between 1995 and 1999, HHS issued program guidance to certified laboratories on handling, testing, and reporting such specimens. This guidance was to ensure that the procedures used by certified laboratories for specimen validity testing were scientifically acceptable and provided forensically defensible results, and to ensure consistency among the certified laboratories. Also, on September 28, 1998, DOT issued a DOT Memorandum MRO Guidance for interpreting Specimen Figure 5.1 Validity Test Results to be used in conjunction with HHS guidance. This document specified the actions that Medical Review Officers MROs and employers were to take when a laboratory reported a specimen as dilute, adulterated, or substituted.

A study in 1998 by Urry et al. Ace) was especially relevant to the development of criteria to identify urine specimens adulterated with nitrite, a common adulterant that also can be present in human urine due to natural sources. The study included a literature search to identify the natural sources of nitrite in human urine, testing of clinical specimens positive for nitrite to associate nitrite concentrations with natural sources, testing of workplace testing specimens suspected to the adulterated with nitrite, and testing of specimens adulterated with a commercial adulterant product containing nitrite. The authors compared the observed nitrite concentrations from adulteration i.e., the workplace specimens suspected and known to be adulterated with nitrite) with the concentrations from natural sources i.e., reports in the literature and testing of clinical specimens. The natural sources of nitrite were identified as endogenous formation, pathological conditions E.g., sepsis, asthma, rheumatoid arthritis) urinary tract infections, air, food, water, occupational exposure, medicines that metabolize to nitrite, and medicines that stimulate the in vivo production of nitrite. The highest concentration from the clinical specimen testing portion of the study was 129 mcg/mL (urinary tract infection), and the highest nitrite concentration found in the literature that was associated with pathological conditions was 48 mcg/mL. The authors concluded that it was possible to establish a scientifically valid and forensically defensible cutoff concentration for nitrite to distinguish nitrite added as an adulterant from naturally occurring nitrite.

Studies in other fields have been done which are  (E.g., public health) relevant to another common oxidizing adulterant, chromate. In addition to occupational exposure, people may be exposed to low levels of chromium in soil, tap water, and air. Some studies used urine testing to assess levels of chromium in exposed populations, and others determined chromium concentrations after ingestion of trivalent chromium (Cr[III]) and hexa-valent chromium (Cr[IV]). Information from such studies was useful to drug-testing laboratories implementing test methods for chromium adulterants, and for regulatory agencies establishing an appropriate cutoff for chromium adulteration.

From October to December 2000, OHS directed special NLCP inspections of all certified laboratories that performed specimen validity testing to ensure compliance with program guidance. The inspectors reviewed laboratory procedures, observed practice, and reviewed specimen records. As of November 2000, NLCP inspection documents have included a section addressing specimen validity testing. This ensures that specimen validity test procedures, laboratory practice, and specimen records are thoroughly reviewed during the initial inspections of applicant laboratories and the routine periodic inspections of certified laboratories. Beginning in January 2001, HHS included NLCP PT samples designed to challenge certified laboratories’ ability to perform specimen validity testing.

HHS began investigations in April 2001 into technologies and instruments new to federally regulated workplace drug-testing programs for use in specimen validity testing (e.g., refractometers that measure urine specific gravity to 4 decimal places for application of the HHS criteria for substituted specimens).

Moreover, in April 2001, HHS began studies in which commercial adulterant products were obtained and tests were performed to determine the effects on samples that contain the drugs of interest, evaluate the effects of the adulterant on drug tests, evaluate the effectiveness of certified laboratories’ methods for their detections and identify their composition. An important part of this ongoing work consists of monitoring Internet websites for adulterant and substitution products to keep abreast of available products purported to alter drug test results. To date, 30 products have been obtained and analyzed by the NLCP.

HHS, in consultation with the DOT, first provided guidance to certified laboratories with the definitions and test cutoffs for Dilute,” Substituted, and adulterated” specimens on September 28, 1998. As knowledge in the area of specimen validity testing has increased through both the practical experience of the drug-testing industry and scientific research, HHS and the DOT have developed and refined their criteria for reporting dilution, adulteration, or substitution.

The 1998 HHS program guidance defined specimens with creatinine <20.0 mg/dL and specific gravity <1.003 as “Dilute”. (Then, as now, a dilute finding is reported in conjunction with the positive or negative drug test result) Specimens were reported as “substituted” when the creatinine was ≤5.0 mg/dL and the specific gravity was ≤1.001 or ≥1.020. In February 2000, HHS issued an “NLCP State of the Science Updates” explaining the scientific literature review that was the basis for the creatinine and specific gravity criteria. A controlled hydration study performed in 2002 to evaluate the HHS/DOT criteria supported that the program cutoffs correctly identified specimens as dilute or substituted.

There were challenges from a few aviation industry employees whose specimens were reported as substituted, leading to further evaluation of the workplace program criteria. In February 2003, the Federal Aviation Administration FAA, whose drug-testing program falls under the DOT Regulations, sponsored a conference to discuss the issue Information from a Congressional mandated scientific study was presented to the attendees, who included toxicologists, nephrologists, MROs, officials from HHS and DOT, and aviation industry employees.

Based on this updated information, the DOT amended its regulations to minimize the possibility that an individual could be misidentified as providing a substituted specimen. While laboratories continued to report specimens as substituted using the creatinine cutoff of 5.0 mg/dL, DOT specified different MRO actions for specimens reported as substituted. Those with creatinine values ≤2.0 mg/dL were reported by the MRO to the employer as substituted; those with creatinine values <5.0 mg/dL but >2.0 mg/dL were reported to the employer as negative and dilute, with instructions to recollect immediately under direct observation.

In the 2004 revision of the Mandatory Guidelines for Federal Workplace Drug Testing Programs to include specimen validity test requirements, HHS lowered the creatinine cutoff for substitution from 5.0 mg/dL to 2.0 mg/dL. The DOT subsequently amended portions of its Regulations to be consistent with the US Guidelines, including the revised creatinine cutoff for substitution. The DOT has retained its requirement for a directly observed recollection when a specimen is reported negative and dilute with creatinine between 2.0 and 5.0 mg/dL and specific gravity <1.0030. Both HHS and the DOT have provisions allowing the donor to demonstrate to the MRO the ability to produce a urine specimen meeting substitution criteria.

When revising the Mandatory Guidelines, used information gathered from the experience of regulated drug-testing entities (e.g. laboratories, MROs & other federal agencies), demographic information obtained through the NLCP, and data from the HHS-directed studies investigating products available for drug test subversion and technologies available for specimen validity test. Although, it is not possible to address all substances that may be used to adulterate a urine specimen, the program requirements address oxidizing adulterants in general as well as some specific chemicals known to be used as adulterants. The HHS requirements are designed to ensure that analytical specimen validity tests and laboratory reporting of the test results are consistent with good forensic laboratory practice. The effective date of the revised Guidelines was November 1, 2004.

HHS also updated the HHS Collection Handbook and HHS MRO Manual effective November 1, 2004. These documents include detailed information for collectors on the procedures for preventing and/or identifying specimen tampering during collections and for MROs’ interpretations of specimen reports based on specimen validity testing.

At the time of this writing, under the DOT Regulations, specimen validity testing is authorized but not required. However, the DOT has issued proposed revisions requiring specimen validity testing of specimens submitted for drug testing under the DOT Regulations.

The Appendix is a summary of the HHS Mandatory Guidelines’ requirements for certified laboratories concerning specimen validity testing and reporting of dilute, adulterated, substituted, and invalid specimens.

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