By Pat Rizzuto
July 15 --A scientifically appropriate way the Environmental Protection Agency could base safe lifetime exposure decisions about a chemical using data from human studies that found no adverse effects is just one of the questions a scientific advisory panel is wrestling with as it develops advice on a draft agency analysis of ammonia.
How the agency can determine whether a chemical harms the body when the chemical is needed by and produced naturally within the body but also is inhaled and ingested is another issue on which the EPA's Chemical Assessment Advisory Committee will offer advice.
The committee, part of the agency's Science Advisory Board, met through July 16 to peer review the agency's draft Integrated Risk Information System (IRIS) assessment of ammonia (CAS No. 7664-41-7).
More than 11 million tons of ammonia were produced in 2012, according to figures provided to EPA by the Fertilizer Institute. The institute's members produce nearly all of the ammonia made in the U.S. for farm and other agricultural uses.
IRIS assessments examine the carcinogenic and other human health hazards of chemicals and the route (ingestion or inhalation) and dose that may cause those hazards to manifest.
The agency's water, air and other regulatory and regional offices, other federal agencies and state governments combine that information with exposure and other data to determine whether the risks from a particular exposure scenario warrant some kind of regulation or other control.
Released in 2012, the ammonia draft assessment proposes a daily inhalation concentration level of 0.3 milligram ammonia per cubic meter of air .
The level, called an inhalation reference concentration or RfC, is an estimate of the amount of ammonia a person could inhale daily that is not likely to cause harmful health effects.
The agency said it was unable to estimate a draft reference dose (RfD), or lifelong, daily ingestion rate due to inadequate data.
Similarly, there was not enough information about ammonia's carcinogenicity to assess whether or not it could increase the risk of cancer in people, the agency said.
The Chemical Assessment Advisory Committee focused much of the second day of its meeting, July 15, on the EPA's scientific rationale for its RfC.
The EPA primarily set the RfC on the basis of four human studies that examined respiratory and lung function effects that followed workers exposure to ammonia.
Among the four studies, the agency focused particular attention on one involving 58 soda ash production workers that found ammonia caused no adverse effects at all.
The workers in that study were exposed below 50 parts per million (ppm) of airborne ammonia.
The EPA derived its RfC from the lowest dose, 12.5 ppm that the researchers reported as being part of the range of their “high dose” exposure category, said Abby Li, a committee member and neurotoxicologist with the consulting firm Exponent Inc. That was among several inhalation concentrations included in the study that caused no adverse effects.
Jill Ryer-Powder, a toxicologist who addressed the committee on behalf of the Fertilizer Institute, questioned the scientific basis of the 12.5 ppm choice.
Exposures included in the same study that were higher than 12.5 ppm also did not cause adverse effects, Ryer-Powder said during a public comment period. EPA defines a no adverse effect level or NOAEL as the highest level at which there are no adverse effects, she added.
The Fertilizer Institute urged the committee to advise the EPA to use a NOAEL of 25 ppm as the basis of calculating its RfC. Many regulatory standards are based on that threshold and workers exposed to that concentration have reported no adverse effects, Ryer-Powder said.
Vincent Cogliano, acting IRIS director, told the committee the issue involved in the agency's selection of its NOAEL involves a conundrum the EPA faces as it strives to increase its use of so called “negative data.” In the IRIS context, negative data refers to research results that find no biological changes or adverse effects following exposure to a chemical.
The question is how does the agency select one exposure to be its NOAEL when there are multiple possible NOAELs, he said.
“We're interested in hearing your discussion,” Cogliano added.
Many committee members said they were not comfortable with the agency's decision to use the 12.5 ppm as the NOAEL when a mean or median dose within the high-exposure group also could have been used.
Committee Chairman Michael Dourson, a toxicologist with Toxicology Excellence for Risk Assessment, summed up the panel's recommendation.
The EPA should ask the researchers for additional data from the key study to determine whether the agency could use the additional data to calculate a more scientifically defensible NOAEL, Dourson said.
If the researchers will not provide additional data, the agency may be able to use available information to more thoroughly justify its NOAEL selection, he said.
On July 16 the committee was scheduled to discuss another issue that may affect the EPA's assessments of other endogenously produced chemicals such as formaldehyde.
Humans and other mammals produce ammonia as they make proteins and balance acidity levels in the stomach.
“Thus, tissues are normally exposed to ammonia, and external concentrations that do not alter homeostasis would not be expected to pose a hazard for systemic effects,” the EPA's draft ammonia assessment said.
Yet chronic exposure to airborne ammonia can increase the risk of respiratory irritation, cough, wheezing, tightness in the chest, and reduction in the normal function of the lung in people, the assessment said.
Studies in experimental animals suggest breathing ammonia at sufficiently high concentrations can result in effects on the respiratory system.
According to the EPA's assessment, about 80 percent of commercially produced ammonia is used in agricultural fertilizers. Ammonia also is used as a corrosion inhibitor, in water purification, as a household cleaner, as an antimicrobial agent in food products, as a refrigerant, as a stabilizer in the rubber industry, in the pulp and paper and metallurgy industries, as a source of hydrogen in the hydrogenation of fats and oils and as a chemical intermediate in the production of pharmaceuticals, explosives, and other chemicals, the EPA said.
Ammonia's beneficial commercial applications include reducing reduce nitrogen oxide emissions from combustion sources such as industrial and municipal boilers, power generators and diesel engines, according to the draft assessment.
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Information about the Chemical Assessment Advisory Committee's meeting, including presentations made by agency staff and observers, is available at http://tinyurl.com/qa2kuuk.
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