# Presentation: 919456

## RDRC Radiation Dose Limits

**Orhan H Suleiman**
**MS, Ph.D., FAAPM**
**Senior Science Policy Advisor**
**Presented at FDA Public Meeting**
**November 16, 2005**

## Why do we need to revisit radiation dose limits?

- Based on 1975 occupational dose limits
- Evolving Metrics
- New radiation risk concepts - E
- New scientific data
- New pediatric human research regulations
- 				E, effective dose

## RDRC Radiation Dose Limits*

_**Organ or System**_**	****	****     **_**Single Dose**_**	****	**_**Annual and Total Dose**_** **
**Whole body****	****	**** 0.03 Sv  (3 Rem) ****	****	****     0.05 Sv (5Rem)**
**Active blood-forming **
**organs**** ****	****	****	**** 0.03 Sv  (3 Rem)****	****	****      0.05 Sv (5 Rem)**
**Lens of the eye****	****	****0.03 Sv   (3 Rem)****	****	****      0.05 Sv (5 Rem)**
**Gonads****	****	****	****0.03 Sv   (3 Rem)****	****	****      0.05 Sv (5 Rem)**
**Other organs**** ****	****	****0.05 Sv   (5 Rem)****	****	****      0.15 Sv (15 Rem) ****	**
**For research subjects under 18 years of age at his last birthday, the radiation dose does not exceed 10 percent of adult dose.**
**Radiation doses from x-ray procedures that are part of the research study shall also be included.**
**	**
**	****	****	****	****	****	****	**
**	****	****	****	****	****	****	*****21 CFR 361.1 (b) (3)**

## Rationale for adopting Occupational Dose Limits

- “An informed potential research subject is able to make a decision...and assume a risk in the same sense as does a radiation worker.”
- “...that the radiation dose, even though it is within the limit, should be the smallest amount needed to carry out the study”* (ALARA – as low as reasonable achievable)
-  			*Federal Register 31298 Volume 40 Number 144 (July 25, 1975)

## RDRC Radiation Experience*

- Organ doses are the limiting constraint, not whole body limits.
- Reports suggest general compliance with radiation dose limits.
**	****	****	**
**	****	****	****	***** Review of RDRC Annual reports**

## Evolving Metrics

**1975****	**** RDRC Dose limits- rem**
**1977****	**** ****ICRP***** promulgates effective dose equivalent, H.**
**1980’s rad to Gray; rem to Sievert; mCi to MBq.**
**1991****	**** ****NRC****** adopts H for radiation dose**
**1991****	**** ****ICRP**** replaces H with effective dose, E.**
**1993    ****NCRP******* adopts E. **
**2004 ****	**** ****ICRP**** proposes modification of E.**
**	****	****	****	**** **
**	****	****   *****International Commission on Radiological Protection**
**	****	****  ******Nuclear Regulatory Commission **
**	****      ******* National Council on Radiation Protection and                                ****	****	****Measurements****	**

## Effective dose (E): A homogenized single metric of radiation risk

**Risk based metric, relating partial body irradiations (individual organ or tissue, limited x-ray field) to uniform whole body irradiation.**
**The effective dose (E) is the sum of the weighted equivalent doses in all the tissues and organs of the body.**
***E***** ****= ****Σ****T**** *****W******T******H******T***
*	**	**	**	*WT  is the weighting factor  for  tissue T, and
- 				HT   is the individual tissue or organ dose for tissue T
**	****	****	****	*****International Commission on Radiological Protection **
**	****	****	****	**** ****ICRP Report  60, (1991)**
** **

## 		      Effective Dose (E)		        Tissue Weighting Factors (wt)      	                                 ICRP 26    ICRP 60    ICRP-DRAFT       Organ (Tissue)	       	         1977    	  1991       2004

| Gonads | 0.25 | 0.20 | 0.05 |
| --- | --- | --- | --- |
| Breast | 0.15 | 0.05 | 0.12 |
| Red BM, lung | 0.12 | 0.12 | 0.12 |
| Thyroid | 0.03 | 0.05 | 0.05 |
| Bone surfaces | 0.03 | 0.01 | 0.01 |
| Colon, stomach | NC | 0.12 | 0.12 |
| Bladder, liver, esophagus | NC | 0.05 | 0.05 |
| Skin | NC | 0.01 | 0.01 |
| Salivary glands, brain | NC | NC | 0.01 |
| Remainder | 0.30 | 0.05 | 0.10 |

## Adult Effective dose (E) 

**Radiation                       Effective  ****	****Equivalent to****	****Equivalent****	****                      Lifetime***
_**Source**_**	****                  **_**Dose (E)**_**         **_**# of chest x-rays**_**                    **_**time **_**	****           **_**Cancer Mortality Risk**_**	**
**	****	****	****	****        ****Background**
**U.S. - 1 year                3 mSv     ****	****   150****	****    ****	****1 year****	****	****1.5 10****-4**
**	****	****	****	****            ****Medical**
**Chest x-ray             0.02 mSv ****	****      1****	****                   2.4 days****	**** ****	****1.0 10****-6**
**Upper GI fl                  3 mSv****	****    150****	****	****1 year****	**** ****	****1.5 10****-4**
**CT- abdomen           10 mSv****	****    500****	****	****3.3 years****	**** ****	****5.0 10****-4**
**Tc-99m-lung perf       1 mSv****	****     50****	****	****4 months****	**** ****	****5.0 10****-5**
**Tc-99m-bone              4 mSv****	****   200****	****	****1.3 years****	**** ****	****2.0 10****-4**
**PET–FDG                  10 mSv****	****   500****	****                   3.3  years**** ****	****	****5.0 10****-4**
**	****	****	****	****     ****Regulatory Limits**
**Individual Gen pop    1 mSv    ****	****     50****	****	****4 months****	****	**** 5.0 10****-5**
**Worker****	****                50 mSv  ****	****  2500****	****	****16.7 years****	****	**** ****2.5 10****-3**
**Emergency Worker     ****500 mSv        25,000****	**** ****	****167 years****	****	**** ****2.5 10****-2**
**	**** **
**               **
**                                                                         ****RDRC  Limits**
**Whole body              50 mSv****	****  2500****	****	****16.7 years****	****	**** ****2.5 10****-3**
**RBM**  (50 x .12) =     6 mSv****	****    300****	****	****  2.0 years****	****	**** ****3.0 10****-4**
**	****	****	****	****	****	**
**	****	****	****	**
- 					*ICRP risk coefficients
- 					**RBM = Red Bone marrow; (HRBM x wt)= E

**Notes:**

Source: EU, NCRP, and FDA sources

##  We ask...

- Are current dose limits for adults still appropriate for research conducted under 361.1 ?
- If not, what dose limits are appropriate?
- Should there be different dose limits for different adult age groups?

## Pediatric Effective Dose (E) 

**Radiation                 Effective  ****	****Equivalent to****	****Equivalent****	****          Lifetime* cancer**
_**Source**_**	****                **_**Dose (E)**_**       **_**# of chest x-rays**_**            **_**time **_**	****            **_**Mortality Risk**_**	**
**	****	****	****	****Background**
**U.S. - 1 year                ****3 mSv     ****	****   150****	****    ****	****1 year****	****	****1.5 10****-4**
**	****	****	****	****Medical**
**     ****Chest**
**X-ray -child              0.02 mSv ****	****      1****	****                   2.4 days****	****	**** ****1.0 10****-6**
**PET FDG adult**          8 mSv****	****   400****	****	****2.67 years****	****	**** 4.0 10****-4**
**PET 10year old**        6.4 mSv****	****   320****	****	****2.13 years****	****	**** ****3.2 10****-4**
**PET  5 year old**        5.6 mSv****	****   280****	****                   1.87  years****	**** ****2.8 10****-4**
**	****	****	****	****Regulatory Limits**
**Individual Gen pop****	**** 1 mSv    ****	****     50****	****	****4 months****	****	**** 5.0 10****-5**
**                      ****Pediatric RDRC Limits**
**Whole body                 5 mSv****	****   250****	****	****1.67 years****	****	**** ****2.5 10****-4**
**RBM*** (5 x .12)  =    0.6 mSv****	****     30****	****	****2.4 months****	**** ****3.0 10****-5**
**	****	****	****	****	****	****	**
**	****	****	****	***ICRP risk coefficients
**	****	****	****	********Stabin MG, Gelfand MJ. Q J Nuclear Med 					1998:42:93-112.
- 				***RBM = Red Bone marrow; (HRBM x wt)= E

**Notes:**
Source: EU, NCRP, and FDA sources...

## Pediatric ethics and risks

**Pediatric Ethics* – 21 CFR Part 50 Protection of Human Subjects **
**	****Subpart D Additional Safeguards for Children in Clinical Investigations **
**Higher risk for children**
**	****“...****, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously.”****
**Noncancer risk**
**	****“****The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up.  Statistically significant increases are seen for heart disease, digestive diseases, and respiratory diseases.”****
**Work in progress**
**	****“****People exposed prior to age 20 comprise the largest portion (41%) of the cohort and most of these are still alive..”;  “Because our risk models suggest that excess rates (particularly for cancer) are highest for those exposed as children, we anticipate that 60 to 70% of the radiation-associated deaths in the LSS cohort have yet to occur.”****
**	*****66 FR 20598, April 24, 2001.**
- 	**Preston et al. Studies of Mortality of Atomic Bomb Survivors Report 13: Solid Cancer and Noncancer Mortaltiy: 1950-1997. Radiation Research 160, 381-407 (2003)

**Notes:**
Cited reference:

Preston DL, Shimuzu Y, Pierce DA et. Al. Studies of Mortality of Atomic Bomb Survivors.  Report 13: Solid Cancer and Noncancer Disease Mortality: 1950-1997.  Radiation Research 160 381-407 (2003).

## From Preston et al.  Radiat. Res. 160, 381-407 (2003)

## We ask...

- Does 361.1 provide adequate safeguards for pediatric subjects?  If yes...
- Do current radiation dose limits for pediatric subjects pose a significant risk?
- If not, what dose limits would be appropriate to ensure no significant risk?
- Should there be different dose limits for different pediatric age groups?