**3. Biological manifestations of HMRE**

Two broad categories of clinical (e.g., biologic) effects of radiation, specific to the contexts of radiation therapy or accidental isotope exposure, include deterministic injuries and stochastic injuries. Deterministic injuries manifest as radiation-induced escalation of normal physiologic apoptosis resulting in increased death of essential cells with resultant tissue and organ dysfunction [27]. These types of injuries occur when large numbers of cells become damaged and, as a result, die immediately or shortly after irradiation [28]. Dermatoligic post-exposure injury can range from "local erythema" to "skin necrosis" [28]. Estimation of dosage is measured in the units of Gy, with 0–2 Gy associated with no biological effects; 2–5 Gy causing transient erythema (<2 weeks), followed by epilation (2–8 weeks) and recovery (6–52 weeks); 5–10 Gy associated with prolonged erythema (up to 8 weeks), epilation (2–8 weeks), and recovery (6–52 weeks); 10–15 Gy exposure causes transient erythema (<2 weeks), dry/moist desquamation (2–8 weeks), followed by permanent epilation (6–52 weeks) and finally atrophy (>40 weeks); and >15 Gy being associated with acute ulceration (<2 weeks), moist desquamation (2–8 weeks), dermal necrosis (6–52 weeks), and eventual surgery (>40 weeks) [28]. **Table 3** outlines the above exposure levels in a systematized fashion.

**4. Regulatory mechanisms and safety enforcement**

well-being of both patients and healthcare workers include [7, 32, 36–38]:

with caution signs

physician, the physicist, and a dosimetrist)

alternatives to ionizing diagnostics [40].

those employees who exceeded established thresholds

of origin (e.g., the hospital) and at the destination (e.g., landfill)

The first line of ensuring safety is the presence of organizational policies and procedures pertaining to HMRE as well as the handling of radioisotope-containing medical materials, both at the departmental and institutional levels [29–31]. In addition to applicable policies and procedures that are harmonized to prevailing laws and regulations, organizations also employ radiation safety experts in the role of Radiation Safety Officer (or functional equivalent thereof) to ensure the maintenance of appropriate legal and procedural compliance [31–33]. Any HMRE events that are deemed reportable to appropriate local, regional, or national authorities are handled by the Radiation Safety Officer. In addition, employees who work around radiation equipment and/or interact with medical radioisotopes must wear radiation monitoring badges that help quantify levels of healthcare worker exposure [34, 35]. Some general considerations of how appropriate policies and procedures can help protect the

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• In diagnostic radiography, the use of hardwired "safety prompts" helps facilitate doublechecking of the expected radiation dosage; also, it is important to ensure the presence of appropriate warning lights, such as "X-ray in progress" and sufficiently labeled facilities

• Ensuring that the delivery process of therapeutic radiation is appropriately structured, including thorough planning, simulated application, and the presence of built-in crosschecks (e.g., two or more experts sign-off on the final therapeutic plan, including the

• Monitoring of cumulative monthly radiation exposure and limiting further exposure for

• Protocolized monitoring of medical waste for the presence of radioactivity, both at the site

In the European Union and associated countries, the Euratom Treaty recommends that a patient examination and clinical justification are provided before a referral is made to a radiologist or a nuclear medicine expert. Moreover, nonionizing radiation is preferred whenever it will provide comparable information to that obtained by means of ionizing radiation [39]. For example, an ultrasound or magnetic resonance imaging (MRI) may provide the same desired information as a CT, without the need for ionizing radiation [40]. Additional safety enforcement strategies include: safety checklists to verify the patient and study being performed; radiation dose customization utilizing the patient's weight, age, medical history, and intended body segment to be scanned/imaged; and decision support systems which provide ordering physicians an opportunity to answer questions regarding their patients and consider

The US Food and Drug Administration (FDA) has partnered with other organizations to promote education and communication regarding radiation safety to patients and medical professionals

Stochastic effects manifest as cellular carcinogenesis and result from radiation induced mutations in genetic material of cells including germ cells [27]. For stochastic injuries, postradiation damage becomes the key determinant of clinically apparent, usually long-term manifestation [28]. Such effects also depend on the type/activity of the isotope involved. More specifically, these kinds of injuries have a linear nonthreshold dose that may lead to radiation-induced malignancy and/or heritable genetic defects [28]. Estimation of dosage from radiologic studies utilizes the units of Sieverts (Sv), with procedures such as dual-isotope SPECT (24 mSv) and CT angiography (19 mSv), carrying the highest effective radiation doses [28]. Of note, victims of the Chernobyl disaster were exposed to a maximum radioactivity of 300–450 mSv/h within a 15 km radius. The individuals that had suffered from radiation are suspected to have received a minimum of 0.8–2 Gy (80–200 Rad) dose [28].


**Table 3.** Post-exposure deterministic injury shown with radiation dose in Gray units and the typical timeline associated with the appearance of adverse effects.
