Enclosure 

FCSE INTERIM STAFF GUIDANCE ISG-14, REVISION 0 

ACUTE URANIUM EXPOSURE STANDARDS FOR WORKERS

Prepared by 

Division of Fuel Cycle Safety, Safeguards, and Environmental Review 

Office of Nuclear Material Safety and Safeguards 

A. Introduction 

This interim staff guidance identifies acute uranium intake quantities that the staff finds 

acceptable as proposed quantitative standards used to classify the chemical 

(i.e., nonradiological) consequences of worker acute uranium exposure accidents analyzed in 

licensee’s or applicant’s Integrated Safety Analysis (ISA) which is an essential element of the 

safety program required by Title 10 of the Code of Federal Regulations (10 CFR) Section 70.62. 

These standards are required by Subpart H, “Additional Requirements for Certain Licensees 

Authorized To Possess a Critical Mass of Special Nuclear Material,” of 10 CFR Part 70, 

“Domestic Licensing of Special Nuclear Material.” 

This guidance may be used when evaluating licensee- or applicant-proposed quantitative 

standards for categorizing an acute uranium exposure event when such an exposure event is 

established as credible in an ISA. The licensee- or applicant-proposed quantitative standards 

are required by 10 CFR Paragraph 70.65(b)(7) as an element of an ISA summary and support 

the demonstration of compliance with the performance requirements of 70.61(b)(4) and (c)(4). 

B. Discussion 

The 2013 Toxicological Profile for Uranium issued by the Agency for Toxic Substances and 

Disease Registry (ATSDR), which is part of the U.S. Department of Health and Human 

Services, provides an overview of uranium toxicity and a summary of the information that 

supports the agency’s assessment of uranium toxicity (ATSDR, 2013). This ATSDR document 

notes that no human fatalities have been reported as a result of uranium toxicity. It also 

includes a discussion of uranium transport through the body describing how uranium can enter 

the body through multiple routes of exposure (e.g., inhalation, ingestion) with most of the 

inhaled and ingested uranium leaving the body in the feces. The ATSDR document also points 

out that the fraction of the uranium that is absorbed into body fluids leaves the body through the 

urine, potentially causing damage to the kidney tubular cells as it exits the body. Any damage 

caused to the critical organ, the kidney, following an acute uranium exposure event depends on 

the mass of uranium that enters the body, the route of exposure (e.g., inhalation, ingestion), and 

the chemical form of uranium. Inhalation exposure results in a higher fraction of uranium 

adsorption into the body fluids and, therefore, results in more damage to the kidney than does 

the ingestion of the same amount of the same uranium compound. A higher fraction of more 
2 

soluble uranium compounds (e.g., uranyl nitrate, uranium hexafluoride) is absorbed into the 

body fluids and, therefore, results in more damage to the kidney than does an intake of the 

same mass of a less soluble uranium compound (e.g., uranium oxide). 

Determining the acute uranium intake quantities that would be acceptable for use as a 

“proposed quantitative standard” as required by 10 CFR 70.65(b)(7) and consistent with the 

definition of high and intermediate acute chemical exposure consequences established in 

10 CFR 70.61(b)(4) and (c)(4) requires a detailed review of uranium toxicity information, 

particularly information on intakes that are expected to result in effects that approximate the 

effects identified in 10 CFR 70.61(b)(4) and (c)(4). These are (1) life endangerment or (2) 

irreversible or other serious, long-lasting effects. 

Information on uranium intakes that produce effects that approximate the high and intermediate 

consequence events defined in 10 CFR 70.61, “Performance Requirements,” is sparse. The 

Royal Society (Royal Society, 2002) and U.S. Army (U.S. Army, 2004) have reviewed and 

analyzed the limited uranium exposure information and developed information on the 

relationship between uranium concentrations in the kidney and effects on the kidney. The Royal 

Society studies primarily used biokinetic models based on the following International 

Commission on Radiological Protection (ICRP) publications to estimate the uranium intake and 

peak renal concentration associated with 14 historical exposure events: 

• Publication 66 (ICRP 1994a), “Human Respiratory Tract Model for Radiological 

Protection” 

• Publication 69 (ICRP 1995), “Age-Dependent Doses to Members of the Public from 

Intake of Radionuclides—Part 3 Ingestion Dose Coefficients” 

• Publication 78 (ICRP 1997), “Individual Monitoring for Internal Exposure of Workers” 

The Royal Society studies proceeded to investigate the relationship between the predicted peak 

renal concentration and observed physiological kidney effects. This approach of using 

biokinetic models to estimate peak renal concentration allowed the investigators to use data 

from uranium exposure events that involved different exposure routes and different uranium 

compounds as they developed their understanding of the relationship between peak renal 

concentration and physiological effects on the kidney. 

The Royal Society analysis concluded that renal concentrations greater than about 50μg 

(microgram) uranium per gram kidney (μg U/g kidney) are likely to lead to acute kidney failure 

that would be lethal in the absence of appropriate medical intervention. 

The sparse information on human exposure events that result in noticeable health effects was 

re-examined by the U.S. Army. The U.S. Army effort reviewed the 14 cases analyzed by the 

Royal Society, along with 13 additional cases described by Fisher, et. al. (Fisher 1990). The 
3 

U.S. Army used this information to develop a range of relationships between renal concentration 

and physiological effects (referred to as renal effects groups). The information was presented 

and discussed in the 2004 U.S. Army report, “Depleted Uranium Aerosol Doses and Risks: 

Summary of U.S. Assessments.” The National Research Council documented its review of 

these U.S. Army renal effects groups in its 2008 report, “Review of Toxicologic and Radiologic 

Risks to Military Personnel from Exposure to Depleted Uranium During and After Combat.” The 

National Research Council committee endorsed the renal effects groups for the highest renal 

concentrations, the relationships that are considered most relevant for this effort. 

The U.S. Army’s highest renal effects group associated a renal concentration of greater than 

18 μg U/g kidney with “possible severe clinical symptoms of renal dysfunction” and the predicted 

outcome of “likely to become ill.” The next highest renal effects group associated a renal 

concentration of 6.4 to 18 μg uranium per gram kidney with “possible protracted indicators of 

renal dysfunction” and the predicted outcome of “may become ill.” 

The specific uranium exposure events analyzed by the Royal Society and the U.S. Army are 

summarized in Table 1. The table shows the different exposure events considered by the Royal 

Society and U.S. Army studies. The table shows that when both organizations examined the 

same exposure events, they had similar estimates of intake and peak renal concentration and 

similar characterization of renal effect severity. 

Figure 1 shows a graphical presentation of this information and lists acute uranium intake and 

renal concentration estimates for the various reconstructed exposure events. The right side of 

the figure shows the renal physiological effects, including the Royal Society estimate of 

50 μg U/g kidney that would lead to acute kidney failure and would be lethal without appropriate 

medical intervention, as well as the two upper renal effects groups identified by the U.S. Army 

and endorsed by the National Research Council. The figure also illustrates the limited data that 

supports these higher physiological effects estimates. 

The staff compared the definition of high and intermediate consequence exposure events in 

10 CFR 70.61 with the phrases reported by the Royal Society and the U.S. Army for relevant 

renal concentration ranges. The first comparison was for a high consequence exposure event, 

which is defined in 10 CFR 70.61(b)(4) with the phrase, “could endanger the life of a worker.” 

The staff determined that this effect is slightly less severe than the effect the Royal Society 

associates with a renal concentration of greater than 50 μg U/g kidney, which is characterized 

by the phrase, “likely to lead to acute kidney failure that would be lethal in the absence of 

appropriate medical intervention.” The staff concluded that a renal concentration of 

approximately 50 μg U/g kidney or more would result in a high consequence exposure event as 

defined in 10 CFR 70.61(b)(4), but the staff also considers there to be limited conservatism in 

this conclusion.
4 

The second phrase the staff compared was for an intermediate consequence exposure event, 

which is defined in 10 CFR 70.61(c)(4) as “could lead to irreversible or other serious, longlasting effect.” The staff concluded that this effect is more severe than the effect that the 

U.S. Army associates with Renal Effect 3, greater than 18 μg U/g kidney. The U.S. Army 

characterizes the effects of this level of exposure with the phrases, “possible severe clinical 

symptoms of renal dysfunction, may become ill.” Based on the available information, the staff 

concluded that a renal concentration of 18 μg U/g kidney could conservatively be described as 

an intermediate consequence exposure event. This position is supported by the U.S. Army 

study, which reported that the available uranium toxicity information suggests that acute renal 

toxicity from uranium does not necessarily lead to chronic toxicity, and by the National Research 

Council, which concluded that the question of whether uranium exposure can cause chronic or 

irreversible renal disease is still open. 

The staff developed estimates of uranium intake quantities that would result in kidney uranium 

concentrations of 50 μg U/g kidney and 18 μg U/g kidney by using conversion factors derived 

from the current ICRP biokinetic models for uranium (Leggett, et. al., 2012). The biokinetic 

models used in developing the conversion factors were ICRP Publication 66 (1994a), ICRP 

Publication 100 (2006), “Human Alimentary Tract Model for Radiological Protection,” ICRP 

Publication 68 (1994b), and ICRP 69 (1995). The conversion factors are based on conservative 

assumptions about uranium intake methods (i.e., inhalation) and uranium solubility class 

(i.e., Type F)1

. Using the conversion factors, the uranium intake quantity associated with a renal 

concentration of 50 μg U/g kidney is 480 milligrams (mg) of Type F uranium and the uranium 

intake quantity associated with a renal concentration of 18 μg U/g kidney is 173 mg of Type F 

uranium. 

The staff reduced the calculated value of 480 mg to the round number of 400 mg to account for 

the differences between the terms of 10 CFR 70.61(b)(4)(i) and the Royal Society 

characterization of the effects following an exposure that resulted in a renal concentration of 

greater than 50 μg U/g kidney, which was considered to be slightly more severe than the effects 

escribed in 10 CFR 70.61(b)(4)(i). The limited number of historical exposure events that have 

resulted in renal concentrations near 50 μg U/g kidney supports the staff’s conservatism in 

developing an acceptable quantitative standard for a high consequence event as defined in 

10 CFR 70.61. The 173 mg value was rounded down to 150 mg, consistent with the precision 

of the underlying information. As a result, an intake of 400 mg was identified as a quantity that 

would be acceptable for defining a “high” consequence acute uranium exposure event for a 

worker and an intake of more than 150 mg (but less than 400 mg) would be acceptable for 

defining an “intermediate” consequence acute uranium exposure event for a worker. 

 

1

 Biokinetic models allow for three generic absorption types in their analysis: Type F, representing 

fast dissolution and a high level of adsorption to blood; Type M, representing a moderate rate of 

dissolution and an intermediate level of absorption to blood; and Type S, representing slow 

dissolution and a low level of adsorption to the blood (Leggett, el. al., 2012). 
5 

C. Regulatory Basis 

According to 10 CFR 70.65(b)(7), ISA summaries are required to include a description of the 

proposed quantitative standards used to assess the consequences to an individual from acute 

chemical exposure to licensed material or chemicals produced from licensed materials. 

D. Technical Review Guidance 

The staff will accept the use of 400 mg as an acute intake quantity standard for a high 

consequence event for a worker and 150 mg as an acute intake quantity standard for an 

intermediate consequence event for a worker. 

These uranium intake values were developed from specific renal concentrations of uranium 

based on assumptions about the nature of uranium intake (i.e., inhalation) and the solubility 

class of the uranium (i.e., Type F) and a renal concentration of less than 50 μg U/g of kidney for 

a high consequence event and a renal concentration of less than 18 μg U/g of kidney for an 

intermediate consequence event. The staff may accept other acute uranium intake values 

based on other assumptions if the assumptions are justified. 

E. Recommendation 

This ISG should be used as an addendum to NUREG-1520, “Standard Review Plan for the 

Review of a License Application for a Fuel Cycle Facility,” to supplement information in 

Section A.2. 

F. References 

Agency for Toxic Substances and Disease Registry, “Toxicological Profile for Uranium,” 

February 2013. 

Fisher, D.R, M.J. Swint, and R.L. Kathren, “Evaluation of Health Effects in Sequoyah Fuels 

Corporation Workers from Accidental Exposure to Uranium Hexafluoride,” NUREG/CR-5566, 

United States Nuclear Regulatory Commission, Washington D.C., May 1990. 

International Commission on Radiological Protection (ICRP, 1994a), “Human Respiratory Tract 

Model for Radiological Protection,” ICRP Publication 66, Annals of the ICRP 24 (1-3), Elsevier 

Science Ltd: Oxford, 1994. 

ICRP (1994b) “Dose Coefficients for Intake of Radionuclides by Workers,” ICRP Publication 68, 

Annals of the ICRP 24 (4), Elsevier Science Ltd: Oxford, 1994.
6 

ICRP (1995), “Age-Dependent Doses to Members of the Public from Intake of Radionuclides—

Part 3 Ingestion Dose Coefficients,” ICRP Publication 69, Annals of the ICRP 25 (1), Elsevier 

Science Ltd: Oxford, 1995. 

ICRP (1997), “Individual Monitoring for Internal Exposure of Workers,” ICRP Publication 78, 

Annals of the ICRP 27 (3-4), Elsevier Science Ltd: Oxford, 1997. 

ICRP (2006), “Human Alimentary Tract Model for Radiological Protection,” ICRP 

Publication 100, Annals of the ICRP 36 (1-2), Elsevier Science Ltd: Oxford, 2006. 

Leggett, R.W., et. al., “Controlling Intake of Uranium in the Workplace: Applications of Biokinetic 

Modeling and Occupation Monitoring Data,” Oak Ridge National Laboratory, TM-2012/14, 

January 2012. 

National Research Council, Committee on Toxicologic and Radiologic Effects from Exposure to 

Depleted Uranium During and After Combat, Committee on Toxicology, “Review of Toxicologic 

and Radiologic Risks to Military Personnel from Exposure to Depleted Uranium During and After 

Combat,” 2008. 

Nuclear Energy Institute, “Acute Chemical Toxicity of Uranium with Application to 

10 CFR 70.61,” Revision 1, Ronald L. Kathren, the Kathren Group, Inc., May 22, 2009 

(Agencywide Documents Access and Management System Accession No. ML091490747). 

Royal Society, “The health hazards of depleted uranium munitions: Part II,” 2002. 

U.S. Army, “Depleted Uranium Aerosol Doses and Risks: Summary of U.S. Assessments,” 

Attachment 3, “Human Health Risk Assessment of Capstone Depleted Uranium Aerosols,” 

October 2004. 
7 

Table 1 Acute Uranium Exposure Events Analyzed in Developing Relationship between 

Peak Renal Concentration and Renal Effects 

Royal Society U.S. Army 

Reference Intake route Uranium 

form 

Subjects Intake, 

mg 

Peak renal 

concentration 

μg U/g kidney 

Effect 

severity 

Intake, 

mg 

Peak renal 

concentration 

μg U/g kidney 

Effect 

severity 

Pavlakis, 

et al, 1996 

ingestion acetate 1 8500 100 +++ 8500 100 +++ 

Zhao and 

Zhao, 1990 

dermal 

(burn) 

nitrate 1 130 35 +++ 130 35 +++ 

Zhao and 

Zhao, 1990 

inhalation UF4 1 900 10 ++ 920 10 ++ 

Luessenhop 

et al, 1958 

injection nitrate 2 10 5 ++ 16 

11 

6 

4 

+ 

+ 

Butterworth, 

1955 

dermal 

(burn) 

nitrate 1 10 3 ++ 10 3 ++ 

Boback, 

1975 

inhalation Ore 

concentrate 

1 200 3 - 

Luessenhop 

et al, 1958 

injection nitrate 3 5 2 + 5.9 

5.5 

4.3 

2 

2 

1.5 

+ 

- 

- 

Kathren and 

Moore, 1986 

inhalation UF6 3 50-100 1-3 + 40-50 4 

4 

1.2 

+ 

+ 

+ 

Butterworth, 

1955 

ingestion nitrate 1 470 1 + 470 1 + 

Boback, 

1975 

inhalation UF6 1 20 1 - 20 1 - 

Fisher et al, 

1990 

inhalation UF6 13 24 

18 

18 

17 

15 

12 

11 

11 

8.7 

8.4 

7.4 

6 

6 

2.5 

1.9 

1.9 

1.8 

1.5 

1.2 

1.1 

1.1 

0.9 

0.87 

0.76 

0.62 

0.62 

+ 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

- 

Effect severity code: +++ = clinical symptoms severe renal dysfunction, ++ = biochemical indicators of protracted renal 

dysfunction, + = biochemical indicators of transient renal dysfunction, - = no detectable effects 

References cited in Table 1 

Boback, Michael W., "A Review of Uranium Excretion and Clinical Urinalysis Data in Accidental Exposure Cases", Conference on 

Occupational Health Experience with Uranium, April 28-30, 1975, ERDA-93 

Butterworth, A., “The Significance and Value of Uranium in Urine Analysis,” Transactions of the Association of Industrial Medical 

Officers, 5, pages 36-43, 1955. 

Fisher, D.R., M.J. Swint, and R.l. Kathren. Evaluation of Health Effects in Sequoyah Fuels Corporation Workers from Accidental 

Exposure to Uranium Hexafluoride, NUREG/CR-5566, PNL-7328, May 1990. 

Kathren R.L. and R.H. Moore, “Acute Accidental Inhalation of U: 38-Year Follow-Up,” Health Physics, Vol. 51, No 5 (November), 

pp. 609-619, 1986. 

Luessenhop, A.J., et. al., “The Toxicity in Man of Hexavalent Uranium Following Intravenous Administration”, The American Journal 

of Roentgenology, Radium Therapy, and Nuclear Medicine, Volume 79, pages 53-100, 1958 

Pavlakis, Nicholas, Carol A. Pollock, Greg McLean, and Roger Bartop, “Deliberate Overdose of Uranium: Toxicity and Treatment,” 

Nephron, 72:313-317, 1996. 

Zhao, Su Lu and Fu-Yao, “Nephrotoxic Limit and Annual Limit on Intake for Natural U,” Health Physics, Volume 58, No. 5 (May) 

pages 619-623, 1990. 
8 

acetate ingestion, Pavlakis

nitrate ingestion, Butterworth

nitrate injection, Luessenhop

nitrate dermal, Zhao and Zhao

nitrate dermal, Butterworth

UF4 inhalation, Zhao and Zhao

UF6 inhalation, Fisher

UF6 inhalation, Boback

UF6 inhalation, Kathren and Moore

UF6 inhalation, Kathren and Moore

0.1

1

10

100

1 10 100 1000 10000

Peak renal concentration, ug U/g kidney

Uranium intake, mg

Figure 1 - Relationships between uranium intake (mass, form and route) and peak 

concentration and between peak renal concentation and renal effects

> 6.4 to 1Possible p

R

> 18 μg/g severe cli> 6.4 to 1Possible p

< 2.2 μg/

> 2.2 to 6Possible tRoyal Socconcentra