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Article

PhotoChem Reference Chemical Database for the Development of New Alternative Photosafety Test Methods

by
Ga-Young Lee
1,
Jee-Hyun Hwang
1,
Jeong-Hyun Hong
1,
Seungjin Bae
1,* and
Kyung-Min Lim
1,2,*
1
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
2
Graduate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul 03760, Republic of Korea
*
Authors to whom correspondence should be addressed.
Toxics 2025, 13(7), 545; https://doi.org/10.3390/toxics13070545
Submission received: 26 May 2025 / Revised: 24 June 2025 / Accepted: 25 June 2025 / Published: 28 June 2025
(This article belongs to the Special Issue New Approach Methodologies for Agrochemicals and Food Toxicology)
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Abstract

Photosafety assessments are a key requirement for the safe development of pharmaceuticals, cosmetics, and agrochemicals. Although in vitro methods are widely used for phototoxicity and photoallergy testing, their limited applicability and predictive power often necessitate supplemental in vivo studies. To address this, we developed the PhotoChem Reference Chemical Database, comprising 251 reference compounds with curated data from in vitro, in vivo, and human studies. Using this database, we evaluated the predictive capacity of three OECD in vitro test guidelines—TG 432 (3T3 NRU), TG 495 (ROS assay), and TG 498 (reconstructed human epidermis)—by comparing the results against human and animal data. Against human reference data, all three test methods showed high sensitivity (≥82.6%) and strong overall accuracy: TG 432 (accuracy: 94.2% (49/52)), TG 495 (100% (27/27)), and TG 498 (86.7% (26/30)). In comparison with animal data, sensitivity remained high for all tests (≥92.0%), while specificity varied: TG 432 (54.3% (19/35)), TG 495 (63.6% (7/11)), and TG 498 (90.5% (19/21)). TG 498 demonstrated the most balanced performance in both sensitivity and specificity across datasets. We also analyzed 106 drug approvals from major regulatory agencies to assess real-world application of photosafety testing. Since the mid-2000s, the use of in vitro phototoxicity assays has steadily increased in Korea, particularly following the 2021 revision of the MFDS regulations. Test method preferences varied by region, with 3T3 NRU and ROS assays most widely used to evaluate phototoxicity, while photo-LLNA and guinea pig tests were frequently employed for photoallergy assay. Collectively, this study provides a valuable reference for optimizing test method selection and supports the broader adoption of validated, human-relevant non-animal photosafety assessment strategies.

1. Introduction

Photosafety testing primarily aims to evaluate two major aspects: phototoxicity and photoallergy. In pharmaceuticals, photosafety assessment refers to an integrated process that includes photochemical characterization, nonclinical testing, and human safety information, as outlined in the ICH S10 guideline (Photosafety Evaluation of Pharmaceuticals) [1]. The objective of a photosafety evaluation is to minimize the potential risks of chemicals caused by concomitant light exposure to humans. Phototoxicity is defined as a nonimmunologic skin reaction that occurs when reactive chemicals and sunlight interact simultaneously. Such reactions occur shortly after concomitant exposure to photoreactive chemicals and light and often resemble moderate to severe sunburns. In contrast, photoallergy is an acquired immune-mediated reaction in which a photoactive substance activated by sunlight forms an allergenic hapten. This reaction is triggered by either antibody-mediated (immediate) or cell-mediated (delayed) immune responses. Unlike phototoxicity, photoallergy can occur with significantly lower energy exposure. When induced by exogenous substances, it almost exclusively manifests as delayed-type hypersensitivity (type IV). Additionally, this reaction requires an induction period before clinical symptoms appear [2]. This reaction requires a sensitization phase before clinical symptoms manifest [3]. Clinically, photoallergic reactions commonly present as erythema, pruritus, and vesicular lesions, often accompanied by skin lichenification or desquamation. These responses may resemble urticarial or lichenoid eruptions. In particular, flat-topped, keratinized lesions are a characteristic feature of such reactions.
The photoreactive potential of a chemical can be identified by evaluating its absorption in the ultraviolet (UV) spectrum. To elicit a phototoxic or photoallergic response, a chemical must exhibit sufficient light absorption (≥1000 L/mol·cm) within natural sunlight (290–700 nm) [1].
The term photosensitization is often used as a general descriptor for all light-induced tissue responses. However, to ensure clarity between phototoxicity and photoallergy, ICH S10 discourages the use of this term. Accordingly, this study will exclusively focus on the evaluation of phototoxic and photoallergic responses. When a chemical is identified as photoreactive, it is assessed using specific toxicological test methods designed to evaluate both phototoxicity and photoallergy. Key considerations for identifying a photosafety hazard include (1) light absorption within the natural sunlight spectrum (290–700 nm), (2) the generation of reactive oxygen species upon UV–visible light exposure, and (3) adequate distribution to light-exposed tissues (e.g., skin and eyes). If a compound does not meet at least one of these criteria, it is unlikely to pose a direct photosafety concern. Although indirect mechanisms may increase photosensitivity (e.g., metabolic activation), they are not currently addressed due to the lack of established test methods [3]. Currently, in vitro photosafety assessments are primarily focused on phototoxicity and ROS evaluations as specified in OECD and ICH guidelines replacing in vivo phototoxicity tests. However, photoallergy evaluation still requires in vivo experiments, as summarized in Table 1.
While in vitro photosafety tests considerably reduced the use of in vivo tests, comprehensive photosafety assessments still need in vivo tests due to the limitation of in vitro tests in the applicability domain and predictive capacity, demanding novel photosafety testing methods capable of accurately identifying chemicals that induce phototoxic or photoallergic reactions. Here, we compiled a comprehensive reference chemical database of 251 reference chemicals, including 59 phototoxic, 26 non-phototoxic, and 4 photoallergenic substances verified in humans, for the development and evaluation of alternative methods for phototoxic and photoallergy tests.

2. Materials and Methods

2.1. Construction of Phototoxicity Reference Substance Database

To support the research and validation of new phototoxicity test methods, a phototoxic reference chemical database was established. Each chemical was documented with key identifiers such as CAS numbers, physicochemical properties, and UV absorption parameters. To facilitate the development of testing methods across diverse chemical categories, information on their usage classification—pharmaceuticals, cosmetics, industrial chemicals, and agrochemicals—was also included. Both in vitro and in vivo data were collected. Importantly, test results from the OECD Test Guidelines (TGs) and human patch tests were incorporated to evaluate the predictive power and consistency between testing methodologies.

2.2. Phototoxicity Testing Methods Used for Pharmaceuticals

The phototoxicity testing methods used in the nonclinical stages of pharmaceutical development were investigated through searching regulatory approval documents and assessment reports from the U.S. FDA, Japan’s PMDA, the EMA, and South Korea’s MFDS.

2.3. Comparison of In Vivo and In Vitro Data of Phototoxicity Reference Chemicals

To evaluate the predictive performance and reliability of in vitro phototoxicity test methods, a comparative analysis was conducted using 252 reference chemicals with available in vivo or human data. The in vitro test methods were based on three internationally validated OECD guidelines (Table 2).
Only chemicals for which both in vitro and in vivo test results were available were included in the comparative analysis. Each compound was classified as either phototoxic (PT) or non-phototoxic (NPT) based on the outcomes of both test types. The sensitivity, specificity, and accuracy were calculated to assess the performance of each in vitro method.

2.4. Photochemical Properties

To evaluate the potential for light-induced reactivity, the primary criterion was whether the chemical absorbs light within the 290–700 nm wavelength range. A chemical was considered unlikely to cause direct phototoxicity if it exhibited a molar extinction coefficient (MEC) of less than 1000 L/mol·cm in this range. That is, if the chemical had an MEC value below 1000 L/mol·cm between 290 and 700 nm and lacked additional supportive data, it was deemed not to pose a photosafety concern in humans, according to ICH S10 guidelines [1].

3. Results

3.1. Analysis of Reference Chemicals in the PhotoChem Database

A total of 251 reference chemicals were collected and classified based on their photo-toxicity and photosensitization profiles. These compounds are widely used in various industries, including pharmaceuticals, cosmetics, and agriculture, where photoreactivity under ultraviolet (UV) exposure plays a significant role in safety evaluation.
For each chemical, various physical properties were recorded, including physical state; molar absorbance (ε); maximum UV absorption wavelength (λmax); and test results across human, animal, and in vitro models.
To better understand the material characteristics, the physical states of all 251 chemicals were analyzed. As shown in Table 3, the majority of the chemicals were in solid form (n = 218, 86.9%), followed by liquids (n = 26, 10.4%). Gels accounted for two chemicals, and viscous or oil-based chemicals, categorized as “Other,” also accounted for two chemicals (0.8%), while three chemicals were labeled as “Unknown” due to the absence of a definitive classification (1.2%).

3.2. Human vs. Animal Test Results for Reference Test Chemicals

To assess the phototoxic potential of the reference chemicals in human models, available in vivo test data were categorized by their respective outcomes. Figure 1 illustrates the comparative distribution of test results from human and animal studies for 251 chemicals.
A total of 103 chemicals out of the PhotoChem DB have human test results: 59 chemicals were identified as phototoxic (PT); 26 chemicals were categorized as non-phototoxic (NPT); 8 chemicals were reported as inconclusive; 4 chemicals were given a PT/NPT; 3 chemicals were labeled as photosensitive (PS); and a single case each was observed for mild phototoxicity (mild PT), non-photosensitization (NPS), and PS (photo patch) testing, with each indication a specialized or rare response type.
Animal model studies were also reviewed to evaluate the phototoxicity potential of the 251 reference chemicals. These models provide complementary data for human studies and are particularly important when human testing is ethically or practically limited.
As depicted in Figure 1, the animal testing results reveal the following distribution: 70 chemicals were classified as non-phototoxic (NPT), 60 chemicals showed a positive phototoxicity (PT), 12 chemicals received mixed classifications (NPT/NPS), 4 chemicals were marked as non-photosensitive (NPS), 3 chemicals were classified as PT/NPT, 2 chemicals were classified as PT/PS, and 1 chemical was confirmed as photosensitive (PS).

3.3. Correlation of Human Test Data with In Vivo or In Vitro Tests

The classification results for phototoxicity and photosensitization from human and animal studies showed substantial agreement, although some variation in sensitivity was observed. Out of 251 total chemicals, those lacking paired results across test types were excluded from the analysis. Sensitivity, specificity, precision, and accuracy were evaluated accordingly (Table 4 and Table 5).
Table 5 presents the predictive performance of three OECD test methods (TG 432 (3T3 Neutral Red Uptake phototoxicity test), TG 495 (Reactive Oxygen Species assay), and TG 498 (Reconstructed Human Epidermis model)) against human or animal tests. These results indicate that while the classification of non-phototoxic chemicals aligns with some in vivo data, inconsistencies across untested or conflicting chemicals (e.g., PT and PT/NPT) highlight the need for comprehensive and standardized in vivo testing to improve the reliability of non-phototoxic classifications.
Overall, the findings emphasize the importance of integrating both human and animal data to achieve more accurate and reliable assessments of phototoxicity and photosensitization. Leveraging the strengths of each model can enhance predictive performance and improve overall safety evaluation strategies.

3.4. Analysis of Photosafety Testing Used in Drug Approvals

In recent decades, phototoxicity and photosensitization testing have gained increasing importance in pharmaceutical safety assessments. To examine how these tests are implemented in regulatory practice, we analyzed drug approvals from major regulatory agencies including the United States Food and Drug Administration (U.S. FDA), Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), the European Medicines Agency (EMA), and South Korea’s Ministry of Food and Drug Safety (MFDS). Based on compiled data from approved drug dossiers, we assessed the frequency, testing strategies, and adoption trends of photosafety evaluations.
The analysis revealed a growing adoption of photosafety testing across all agencies. In particular, data from Korea’s MFDS showed that photosafety test results were not consistently included in approval documents prior to the revision of its regulatory guidelines on 11 November 2021. At that time, certain nonclinical safety assessments, including photosafety tests, were exempted for specific categories of drugs. However, following the regulatory revision, phototoxicity and photosensitization testing became mandatory components of nonclinical safety evaluations. This regulatory shift highlights the increasing importance placed on photosafety assessments in Korea and aligns with the global trend toward comprehensive photoreactivity risk management.
Following this, we further analyzed a total of 106 approved pharmaceutical products that included photosafety assessments, focusing on their annual adoption patterns and the specific test methods used. To visualize this trend, we generated a yearly distribution graph showing the implementation of phototoxicity and photosensitization testing over time (Figure 2). In addition, test method utilization was analyzed by regulatory authority, including the FDA, PMDA, EMA, and MFDS, to assess differences in test preferences among countries (Figure 3).
The analysis revealed a notable increase in the application of phototoxicity tests beginning in the mid-2000s, followed by a gradual rise in photosensitization testing in more recent years. Regionally, the PMDA and FDA showed the highest number of total test submissions, while MFDS data showed a steep increase post-2021. Across agencies, 3T3 NRU, ROS assays, and RHE-based models were most commonly used for phototoxicity, whereas LLNA and guinea pig-based protocols were predominantly used for photosensitization.
Figure 2 illustrates the annual trend in phototoxicity and photosensitization testing from 1979 to 2024, based on data extracted from 106 approved pharmaceutical products that included photosafety evaluations. During the early years of the dataset, reports of both phototoxicity and photosensitization testing were infrequent or absent, likely due to the absence of standardized regulatory requirements or test guidelines during that time.
A notable shift occurred beginning in the mid-2000s, with a steady increase in phototoxicity test implementation. This upward trend culminated between 2018 and 2021, during which over 18 phototoxicity assessments were recorded in a single year. This surge may be attributed to the widespread regulatory adoption of OECD TG 432 and increased emphasis on nonclinical photosafety data in global drug development and review processes.
In contrast, photosensitization testing exhibited a more gradual increase, with a relatively small number of cases—typically fewer than five per year—reported since 2010. This modest rise suggests that photosensitization assessments are applied more selectively, potentially limited to compounds with specific structural alerts, photoreactive moieties, or UV absorption profiles. The overall pattern reflects a growing awareness of photosafety considerations and regulatory alignment over time, particularly for phototoxicity.
Figure 3 presents a cumulative analysis of photosafety testing conducted by regulatory authority across four countries: the United States (the FDA), Japan (the PMDA), the European Union (the EMA), and South Korea (the MFDS). The data shows a distinct pattern in how each country has adopted and implemented phototoxicity and photosensitization testing in their regulatory processes over time.
The PMDA and FDA demonstrated relatively early adoption, with consistent test submissions reported since the mid-2000s. In contrast, data from the EMA showed a gradual increase, reflecting more selective application based on compound characteristics or risk assessment strategy. The most prominent change was observed in Korea’s MFDS, where a sharp rise in test submissions occurred after 2021, coinciding with the regulatory amendment that made photosafety testing mandatory for new drug applications.
This country-specific breakdown illustrates differing timelines and regulatory emphases in adopting photosafety tests, highlighting the importance of harmonized global guidelines and the evolving role of photoreactivity evaluation in drug approval pathways.
Figure 4 and Figure 5 present a comparative overview of phototoxicity and photosensitization test methods employed by four major regulatory agencies: the EMA, FDA, PMDA, and MFDS. These pie charts illustrate how each country distributes its use of test strategies for photosafety assessments based on approved pharmaceutical dossiers.
In phototoxicity evaluations (Figure 4), the 3T3 NRU test method was the most frequently applied across all agencies, particularly by the PMDA (58.67%) and EMA (34.40%). The FDA showed more diversified usage, including the clinical test, UV spectrum analysis, and hemoglobin oxidation methods. The MFDS primarily relied on in vivo studies and the 3T3 NRU test, reflecting its recent emphasis on incorporating alternative methods.
In contrast, photosensitization testing (Figure 5) exhibited greater heterogeneity across agencies. The FDA and MFDS predominantly used in vivo tests and clinical tests, while the PMDA applied a wider range of methods, including in vivo tests, Photo-LLNA, and photopatch testing. The EMA utilized a more balanced mix of in vivo, in vitro, and clinical approaches. These results suggest differences in regulatory preferences and test accessibility, as well as varying degrees of reliance on traditional versus alternative methods.
Figure 6 provides a comparative overview of the relative proportion of phototoxicity and photosensitization tests conducted by four regulatory agencies: the EMA, FDA, PMDA, and MFDS. Across all countries, phototoxicity assessments represented the dominant form of photosafety testing, reflecting its broader regulatory adoption and the availability of validated test guidelines such as OECD TG 432.
Among the agencies, the MFDS reported the highest proportion of phototoxicity testing (86.4%), which may reflect its more recent enforcement of standardized safety requirements and a preference for phototoxicity evaluation during initial risk screening. In contrast, the EMA exhibited the greatest use of photosensitization tests (26.7%), indicating a relatively broader application or heightened regulatory interest in photoallergy assessments. The FDA and PMDA showed similar test ratios, with phototoxicity accounting for approximately 77% of their total photosafety submissions. These findings suggest that approaches to photosafety assessment vary among regulatory agencies.

4. Discussion

This study highlights the need for a harmonized and scientifically robust approach to photosafety evaluation by providing a comprehensive overview of current trends and challenges and by establishing a curated database of reference substances with a comparative analysis of validated in vitro methods against in vivo outcomes. Through the development of the PhotoChem Reference Chemical Database, we compiled detailed information on 251 substances, including phototoxic, non-phototoxic, and photosensitization classifications. Our database includes cosmetics [159], pharmaceuticals [48], and industrial and agricultural chemicals [54] for which photosafety assessment is required. It also integrates CAS numbers, physicochemical data, UV absorbance characteristics, and test results from the literature and drug approval dossiers across four major regulatory regions: the United States, Europe, Japan, and South Korea.
An evaluation of three key OECD in vitro test methods, namely TG 432, TG 495, and TG 498, revealed that all three in vitro test methods demonstrated high sensitivity and accuracy when compared to human and animal classifications. These results suggest strong potential for these methods to serve as alternatives to traditional animal-based testing. However, the notably lower specificity observed in TG 432 and TG 495 (54.3% and 63.6%, respectively) compared to TG 498 highlights an important limitation of current cell-based models. These methods are designed to maximize sensitivity to minimize false negatives, but this often leads to an increased incidence of false positives, reducing overall specificity. In contrast, TG 498, which employs reconstructed human epidermis models, demonstrated superior performance in both sensitivity and specificity despite having fewer data points. This suggests that 3D reconstructed human skin-based models may better mimic in vivo conditions, and their use in photosafety testing is likely to expand in future regulatory frameworks. The observed differences in specificity underscore the need for continued refinement and novel photosafety testing methods suited to particular regulatory contexts.
To further address these limitations and enhance the precision of in vitro models, quantitative structure–activity relationship (QSAR) models and artificial intelligence (AI)-based prediction systems may offer promising complementary approaches. QSAR models can prescreen compounds based on structural alerts and physicochemical properties, while AI models trained on multi source data including UV spectrum, historical assay results, and chemical fingerprints can provide integrated, quantitative predictions of phototoxic potential. Importantly, the PhotoChem DB developed in this study provides a robust foundation for building and validating such predictive models, suggesting that our study may contribute to the evolution of more accurate and human relevant non-animal assessment strategies.
An analysis of 106 pharmaceutical approvals from the FDA, PMDA, EMA, and MFDS revealed an increasing emphasis on phototoxicity evaluation across jurisdictions. A notable increase in test submissions to the MFDS was observed following the 2021 revision of its regulatory guidelines. Moreover, the distribution of test method preferences varied by country, with the 3T3 NRU and ROS assays commonly used for phototoxicity evaluation, while photo-LLNA and guinea pig assays were frequently applied for photosensitization.
Together, the curated database and comparative method analysis reinforce the importance of developing scientifically validated and internationally aligned nonanimal testing strategies. These findings also demonstrate the value of integrating physicochemical and UV-reactive properties to enhance predictive toxicology and support regulatory decision making.

5. Conclusions

In this study, we assessed the phototoxic potential of a range of chemical compounds using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU PT), along with other validated in vitro methods. Several test substances exhibited significant responses upon UVA exposure, underscoring the importance of early stage photosafety screening, particularly for substances likely to be simultaneously exposed to skin and light. The 3T3 NRU PT method proved to be a reliable and reproducible tool for identifying phototoxicity, supporting its continued use in safety assessments. When benchmarked against human and animal data, TG 495 and TG 498 also showed excellent predictive performance, further validating the role of in vitro alternatives in regulatory applications. Furthermore, the PhotoChem Reference Chemical Database developed in this study serves as a valuable platform for advancing research, regulatory alignment, and method innovation. By combining chemical characteristics, UV absorption profiles, and cross-platform results, the database enables an integrated and data-driven analysis of photoreactivity risk.
Future research should aim to improve the precision of in vitro models, deepen mechanistic understanding, and adopt computational tools such as quantitative structure activity relationship (QSAR) models and artificial intelligence-based prediction systems. These approaches will facilitate scientifically rigorous and ethically responsible photosafety evaluation while reducing reliance on animal testing. In addition, the PhotoChem DB is expected to evolve as a dynamic, expandable resource by incorporating newly identified reference compounds, mechanistic data, and test results. Its continued development will also support the creation and validation of QSAR and AI-driven models, contributing to more precise, efficient, and human relevant safety assessments.

Author Contributions

Conceptualization, G.-Y.L., S.B. and K.-M.L.; methodology, G.-Y.L., J.-H.H. (Jee-Hyun Hwang), J.-H.H. (Jeong-Hyun Hong), S.B. and K.-M.L.; formal analysis, G.-Y.L., J.-H.H. (Jee-Hyun Hwang) and J.-H.H. (Jeong-Hyun Hong); investigation, G.-Y.L., J.-H.H. (Jee-Hyun Hwang) and J.-H.H. (Jeong-Hyun Hong); resources, K.-M.L.; data curation, G.-Y.L., J.-H.H. (Jee-Hyun Hwang), J.-H.H. (Jeong-Hyun Hong) and K.-M.L.; writing—original draft preparation, G.-Y.L.; writing—review and editing, S.B. and K.-M.L.; supervision, K.-M.L.; project administration, K.-M.L.; funding acquisition, S.B. and K.-M.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by grants (RS-2024-00396737 and MFDS2024-290) from the Ministry of Food and Drug Safety Korea.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available from the corresponding author on request.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
OECDThe Organization for Economic Co-operation and Development
ICHInternational Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use
FDAU.S. Food and Drug Administration
PMDAJapan Pharmaceuticals and Medical Devices Agency
EMAEuropean Medicines Agency

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Toxics 13 00545 g001
Figure 1. Comparison of photosafety results from human and animal tests in the PhotoChem DB. This figure shows the photosafety results for reference chemicals based on human and animal test data. In animal studies, most compounds were clearly categorized as either non-phototoxic (NPT) or phototoxic (PT). In contrast, human data included a broader range of outcomes such as inconclusive results, mild reactions, or photosensitization (photopatch), reflecting the complexity of clinical assessments.
Figure 1. Comparison of photosafety results from human and animal tests in the PhotoChem DB. This figure shows the photosafety results for reference chemicals based on human and animal test data. In animal studies, most compounds were clearly categorized as either non-phototoxic (NPT) or phototoxic (PT). In contrast, human data included a broader range of outcomes such as inconclusive results, mild reactions, or photosensitization (photopatch), reflecting the complexity of clinical assessments.
Toxics 13 00545 g001
Toxics 13 00545 g002
Figure 2. Annual trend of phototoxicity and photosensitization testing among approved pharmaceutical products (n = 106). The graph illustrates the increasing frequency of photosafety testing over the years, particularly for phototoxicity since the mid-2000s.
Figure 2. Annual trend of phototoxicity and photosensitization testing among approved pharmaceutical products (n = 106). The graph illustrates the increasing frequency of photosafety testing over the years, particularly for phototoxicity since the mid-2000s.
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Toxics 13 00545 g003
Figure 3. Number of phototoxicity and photosensitization tests conducted by country and year. The chart displays the test method distribution across four regulatory authorities: the FDA, PMDA, EMA, and MFDS.
Figure 3. Number of phototoxicity and photosensitization tests conducted by country and year. The chart displays the test method distribution across four regulatory authorities: the FDA, PMDA, EMA, and MFDS.
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Figure 4. Distribution of phototoxicity test methods used in pharmaceutical approvals by country. The chart compares the types of phototoxicity test methods adopted by four major regulatory authorities (the EMA, FDA, PMDA, MFDS), illustrating differences in testing strategies and preferences for alternative versus traditional approaches.
Figure 4. Distribution of phototoxicity test methods used in pharmaceutical approvals by country. The chart compares the types of phototoxicity test methods adopted by four major regulatory authorities (the EMA, FDA, PMDA, MFDS), illustrating differences in testing strategies and preferences for alternative versus traditional approaches.
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Figure 5. Distribution of photosensitization test methods used in pharmaceutical approvals by country. This figure highlights the diversity of test types adopted for photosensitization assessment across the EMA, FDA, PMDA, and MFDS, indicating variation in clinical, in vivo, and alternative testing practices.
Figure 5. Distribution of photosensitization test methods used in pharmaceutical approvals by country. This figure highlights the diversity of test types adopted for photosensitization assessment across the EMA, FDA, PMDA, and MFDS, indicating variation in clinical, in vivo, and alternative testing practices.
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Figure 6. Distribution of photosafety test types submitted to four regulatory agencies (the EMA, FDA, PMDA, MFDS). Phototoxicity tests accounted for the majority of evaluations across all agencies, with the MFDS showing the highest proportion (86.4%). In contrast, the EMA reported the highest relative use of photosensitization tests (29%), indicating varying emphasis on test types among regulatory bodies.
Figure 6. Distribution of photosafety test types submitted to four regulatory agencies (the EMA, FDA, PMDA, MFDS). Phototoxicity tests accounted for the majority of evaluations across all agencies, with the MFDS showing the highest proportion (86.4%). In contrast, the EMA reported the highest relative use of photosensitization tests (29%), indicating varying emphasis on test types among regulatory bodies.
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Table 1. Phototoxicity and Photoallergy test methods.
Table 1. Phototoxicity and Photoallergy test methods.
Test CategoryTest StrategyMethod
PhototoxicityIn vitroIn vitro 3T3 Neutral Red Uptake
Phototoxicity Test (OECD TG 432)		Cell viability before and after UV exposure
The Reactive Oxygen Species (ROS)
Assay (OECD TG 495)		Measurement of ROS generation after light exposure, potentially causing cellular damage
The Reconstructed Human Epidermis
Phototoxicity Test (OECD TG 498)		Tissue viability test on reconstructed human epidermis after chemical exposure with or without UV exposure
In vivoPigmented ratsAssessment of photoirritation responses in the skin and eyes after systemic administration of chemicals with or without UV exposure
The Guinea Pig phototoxicity TestAssessment of photoirritation responses in the shaved skin of guinea pigs after topical administration of chemicals with or without UV exposure
PhotoallergyIn vivoThe Photo-LLNA
(Local Lymph Node Assay)		A modified LLNA protocol measuring increased lymph node cell proliferation after UV exposure
The Guinea Pig Photoallergy TestA modified version of the Guinea Pig Maximization Test (GPMT) designed to evaluate allergic responses following UV sensitization
Abbreviations: TG = Test Guideline; ROS = Reactive Oxygen Species; LLNA = Local Lymph Node Assay; GPMT = Guinea Pig Maximization Test.
Table 2. Criteria for phototoxicity prediction according to OECD Test Guidelines.
Table 2. Criteria for phototoxicity prediction according to OECD Test Guidelines.
Test MethodPrediction of Phototoxicity
OECD TG 432 [4]
3T3 Neutral Red Uptake Phototoxicity Test		Classification as phototoxic was assigned when the Photoirritation Factor (PIF) was ≥5 or the Mean Photo Effect (MPE) was ≥0.15.
OECD TG 495 [5]
Reactive Oxygen Species Assay		Positive results were determined by the significant generation of reactive oxygen species (ROS) following UV exposure compared to non-irradiated controls.
OECD TG 498 [6]
Reconstructed Human Epidermis Phototoxicity Test		Phototoxic if the UVA-exposed group(s) exhibit a 30% decrease in viability relative to the corresponding dark-exposed group.
Table 3. List of reference chemicals in the PhotoChem DB.
Table 3. List of reference chemicals in the PhotoChem DB.
No.ChemicalCAS No.Physical StateMolar Extinction Coefficient
(M1 cm−1)		UV λmaxHumanAnimalTG432
(3T3)		TG495
(ROS)		TG498
(RhE Model)		OthersReferences
1Chlorpromazine hydrochloride69-09-0Solid30,000–32,000254PTPTPTPTPT [7,8,9,10,11,12,13,14]
2Promethazine60-87-7Solid21,000250PTPTPT PT [10,13,15,16,17,18,19,20]
35-Methoxypsoralen
(5-MOP or Bergapten)		484-20-8Solid15,000305PTPTPT PT [8,13,15,16,19,20,21,22,23]
48-Methoxypsoralen
(8-MOP or Methoxsalen)		298-81-7Solid18,400300PTPTPTPTPT [8,9,11,13,14,15,16,18,19,22,23,24,25]
5Para-aminobenzoic acid (PABA)150-13-0Solid14,000268PS
(photopatch)		 NPTNPTNPT [11,13,14,15,16,20,21,26,27]
6Benzophenone-3131-57-7Solid1150288PTNPTPT NPT [13,15,16,19,20,21,26]
7Octyl methoxycinnamate5466-77-3Liquid22,500310PT/NPTNPTNPTNPTNPT [12,13,14,15,19,26]
8Ecamsule (Mexoryl SX)92761-26-7Solid32,000344NPT NPT NPT [12,13,15,16]
96-Methylcoumarin92-48-8Solid9500326PTPTPTPTNPT [11,13,14,15,19,20,21,23,28,29]
104-tert-Butyl-3-methoxy-2,6-dinitrotoluene(Musk ambrette)83-66-9LiquidNANAPTNPTPT NPT [12,13,15,16,19,20,30]
11Demeclocycline hydrochloride64-73-3Solid13,400270PTPTPT NPT [8,12,13]
12Bithionol97-18-7Solid20,000258PTPTPTPTPT [11,12,13,14,15,19,20,21,22,31]
13Bergamot oil8007-75-8LiquidNANAPTPTPT PT [8,13,15,16,19,20,23,30,31,32]
14Acridine hydrochloride17784-47-3Solid11,800355PTPTPTPTPT [12,13,14,20]
15Anthracene120-12-7Solid19,300251PTPTPTPTPT [12,13,14,15,19,20,23]
16Neutral red553-24-2Solid8000530PTPTPTPTPT [11,13,15,19,20,21,30]
17Tetracyline60-54-8Solid27,000276-PT-PTPT [13,14,21]
18Penicillin G61-33-6Solid1700264NPTNPTNPT NPT [10,13,15,19,30]
19Sodium lauryl sulfate (SDS)151-21-3SolidNANANPTNPTNPTNPTNPT [8,10,11,12,13,14,15,18,19,20,21,23,29,30]
20Octyl salicylate118-60-5Liquid900–1500307NPTNPTNPTNPTNPT [12,13,14,15,30,32]
21Benzylidene Camphor Sulfonic Acid56039-58-8Solid28,000310NPTNPTNPT [12,13]
224-Methylbenzylidene camphor (3-(4-Methylbenzylidene)camphor)36861-47-9Solid27,000303PT/NPTNPTNPTNPTNPT [10,12,13,15,19,30]
23Benzalkonium chloride139-07-1LiquidNANA NPTNPT NPT [15,33]
24Acridine260-94-6Solid11,800355PTPTPT PT [14,15,19,20,23,30]
25Amiodarone1951-25-3Solid25,000242PTPTPT PT [11,12,15,19,20]
26Chlorhexidine
dihydrochloride		3697-42-5Solid10,000255 NPTNPT [11,20]
27Chlorpromazine50-53-3Solid3500–4500256PTPTPT PT [15,16,17,19,20,29,30,34]
28Demeclocycline127-33-3Solid1200350PTPTPT [19,20]
29Fenofibrate49562-28-9Solid9800290–310PT PTPT [8,14,19,20]
30Furosemide54-31-9Solid2300273PT PT/NPTPT [8,9,14,19,20,29,35]
31Hexachlorophene70-30-4Solid12,000–14,000270–290PT/NPTNPTNPTPT [14,15,17,19,20,31,36]
32Ketoprofen22071-15-4Solid2000–3000260–280PTPT/NPTPTPT [8,9,12,14,19,20]
33Nalidixic acid sodium salt3374-05-8Solid5000–7000270–280PTPTPTPT [14,20]
34Nalidixic acid389-08-2Solid7500276PTPTPTPT [14,19,20]
35Norfloxacin70458-96-7Solid8000–10,000277–278PTPTPTPT [9,14,15,19,20,35]
36Ofloxacin82419-36-1Solid8000–10,000293PTPTPTPT [8,14,19,20,29]
37Penicillin G sodium salt69-57-8Solid1000–2000230–250NPTNPTNPTNPT [8,11,20,21]
38Protoporphyrin IX553-12-8Solid80,000400–430PTPTPT PT [15,19,20]
39Protoporphyrin IX
disodium salt		50865-01-5Solid80,000–90,000405–410PTPTPT [12,20]
40Xantryl(Rose Bengal (sodium salt)(1:2))632-69-9Solid70,000550PTNPTPTPTPT [11,14,20,21,23]
41Tiaprofenic acid33005-95-7Solid4000–5000270PTPTPT [8,19,20]
42Benzylidene camphor15087-24-8Solid22,000–24,000300NPT NPT [12]
432-(Methylthio)phenol(o-(Methylthio)-phenol)1073-29-6LiquidNANA PT [32,37]
44Polyacrylamidomethyl benzylidene camphor113783-61-2Solid NPT NPT [12]
45Sulisobenzone
(Benzophenone-4)		4065-45-6Solid20,000–30,000290–360NPTNPTNPTNPTNPT [9,11,12,14,15,19,29,35]
46Methyl-2-[(3,5,5-
trimethylhexylidene)
amino]benzoate		67801-42-7SolidNANANPT PT NPT [32,37]
47Promethazine hydrochloride58-33-3Solid21,000257PT PT PT [8,11,12,14,21]
48Lime oil8008-26-2Liquid 315PTPT [19,31,38]
49Lemon oil8008-56-8Liquid PTPTPT/NPT PT [15,31,33]
50Orange oil8028-48-6Liquid PTPTPT/NPT PT [15,31,33]
51Rue oil8014-29-7Liquid PTPT [22,31]
52Cumin oil8014-13-9Liquid PTPT [22,31]
53Angelica root oil8015-64-3Liquid PTPT [22,31]
54Methylene blue61-73-4Liquid74,000665PT [31]
55Eosin Y Disodium17372-87-1Solid44,000515PT [31]
56Disperse blue 3512222-75-2SolidNA450–600PT [31]
57Bengal rose
(Rose bengale)		11121-48-5Solid>5000500–600PTPTPT PT [10,13,15,19,31]
583,3′,4′,5-Tetrachlorosalicylanilide (TCSA)1154-59-2SolidNANAPTPTPT [11,19,31]
59Tribromsalan(3,5,4′-Tribromosalicylanilide,TBS)32055SolidNANANPT [31]
60Buclosamide(n-Butyl-4-chloro-2-hydroxybenzamide)575-74-6Solid PT [19,31]
61Doxycycline hydrochloride10592-13-9Solid20,000270–280PTPTPTPTPT [9,11,14,19]
62Tetracycline hydrochloride64-75-5Solid10,000270–280PTPT/NPTPT PT/NPT [11,13,15,19,23]
63Piroxicam36322-90-4Solid4000350PTPTNPTPT [11,14]
64Cinnamaldehyde104-55-2Liquid6000280PSNPTNPT NPT [11,15,25,39]
65L-Histidine71-00-1Solid13,000210NPTNPTNPTweak PRNPT [8,11,12,14,15,19,21]
66Thiocarbamide(Thiourea)62-56-6Solid7000210PS NPT [11,19]
67Carprofen53716-49-7Solid2000254PTPT [17,19]
68Fenticlor97-24-5Solid1000250 PT [17,19]
697-Acetyl-1,1,3,4,4,6-
hexamethyltetra
Hydronaphthalene		21145-77-7Solid PT [22]
70Galaxolide(4,6,6,7,8,8-Hexamethyl-1,3,4,6,7,8-hexahydrocyclopenta[g]isochromene)1222-05-5LiquidNANA PT [22]
71Celestolide(4-Acetyl-6-tert-butyl-1,1-dimethylindane)13171-00-1SolidNANA NPT [22]
72Phantolide15323-35-0SolidNANA NPT [22]
73Versalide88-29-9SolidNANA NPT [22]
74Ichthammol8029-68-3Liquid PTPT PT [15,40]
755-Aminolevulinic acid106-60-5Solid28,000400 PTPT PT [15]
767-Methylcoumarin2445-83-2SolidNANA PTPT PT [15]
77Tetrachlorosalicylanilide2018517SolidNANA PTPT PT [15]
78Deterpenated lemon (-) NANA PT/NPTPT/NPT PT [15,41]
79Litsea cubeba oil68855-99-2LiquidNANA NPTPT NPT [15,41]
80ichthyolic acid, sodium salt1340-06-3SolidNANA NPTPT NPT [15]
81Avobenzone70356-09-1Solid30,000–40,000320–400PT/NPTNPTPTPTNPT [10,14,15,23,28,37,39,41,42,43,44]
82Dimethyl sulfoxide67-68-5LiquidNANA NPTNPT NPT [15]
83Ethanol64-17-5LiquidNANA NPTNPT NPT [15,18]
84Eucalyptus oil8000-48-4LiquidNANA NPTNPT NPT [15]
85Coumarin91-64-5Solid16,000–18,000275NPTNPTNPT [8,15]
86Titanium (IV) oxide13463-67-7Solid~100,000320–350 NPT [15,39,43]
87Cadmium sulfide1306-23-6Solid58,000450 PT NPT [7]
88Cadmium selenide1306-24-7Solid~100,000560 NPT NPT [7]
89Mercury(II) sulfide1344-48-5Solid NPT NPT [7]
90Chromium oxide11118-57-3Solid10,000–40,000visible region NPT NPT [7]
91Carbazole86-74-8Solid6000–7000290 PT PT [7]
92Cobalt aluminum oxide13820-62-7Solid 500–700 NPT NPT [7]
93Benoxaprofen51234-28-7Solid 320PTPT [19]
94Naproxen22204-53-1Solid19,300330PTPT [19]
95Suprofen40828-46-4Solid 244PT [19]
96Triclosan3380-34-5Solid4200280PT [19]
97Ciprofloxacin85721-33-1Solid33,000278PTPT [19,25]
98Fleroxacin79660-72-3Solid25,000–35,000278 [19]
99lomefloxacin98079-51-7Solid27,000–30,000287PTPT [8,19]
100Bergaptol486-60-2Solid 290–320 NPT (V79 micronucleus assay)[45]
101Isopsoralen523-50-2Solid15,000–20,000300–320PT [8,19]
1024,5′,8-Trimethylpsoralen
(trioxsalen)		3902-71-4Solid10,000–20,000300–320PT [19]
1035-Fluorouracil51-21-8Solid8200266 NPTNPT [9,14,24,35,46,47]
104Amiodarone hydrochloride19774-82-4Solid 290–350PTPTPTPT [9,14,19,35]
105Diclofenac sodium15307-79-6Solid11,000–13,000276PTPTPTPT [9,14,19,35,48]
106Levofloxacin100986-85-4Solid16,000292PTPTPTPT [14,25,49,50,51]
107Omeprazole73590-58-6Solid18,000–22,000302PT PT/NPTPT [9,14,35,49,52]
108Quinine hydrochloride130-89-2Solid5460350PTNPTPTPT [9,14,19,35,53]
109Rosiglitazone122320-73-4Solid PT [14]
110Bumetrizole729335Solid 300–400 NPTNPT [14]
111Camphor sulfonic acid1450959Solid NPTNPT [14]
112Cinnamic acid140-10-3Solid8000–10,000260 NPTWeak PT [14]
113Drometrizole2440-22-4Solid 290–320 NPTNPT [14]
114Octrizole3147-75-9Solid 290–320 NPTNPT [14]
1152-(2H-Benzotriazol-2-yl)-6-dodecyl-4-methylphenol125304-04-3Liquid 290–400 NPT [14]
116Aspirin50-78-2Solid15,000–20,000265 NPTNPT [14,35]
117Benzocaine34584Solid9000–11,000260 NPTNPT [35]
118Erythromycin114-07-8Solid8000–10,000230NPTNPTNPTNPT [35,54,55]
119Penicillin G potassium113-98-4Solid 203 NPTNPT [14,35]
120Phenytoin57-41-0Solid4500–6500254 NPTWeak PT [14,35]
121Chlorhexidine55-56-1Solid1200–1400260NPT Weak PT/NPT [8,14,19]
122Octyl methacrylate93878Liquid 210–220 NPTNPT [14]
123Ethyl vanillin121-32-4Solid11,000–13,000270(inconclusive)NPTPT NPT [32,37]
124Vanillin isobutyrate20665-85-4Liquid 270–280(inconclusive)NPTPT NPT [32,37]
125Methyl 2,4-dihydroxy-3-methylbenzoate33662-58-7Solid 270–300(inconclusive)NPTPT PT [32,37]
12610H-Phenothiazine92-84-2Solid 255–265 PTPT PT [32,56]
1274-Acetoxy-3-ethoxybenzaldehyde72207-94-4Solid 250–300(inconclusive) PT NPT [32,37]
1281-phenyl-3-(4-propan-2-ylphenyl)propane-1,3-dione63250-25-9- 250–300PT [19,26]
129Minocycline10118-90-8Solid7700350NPT [19]
130Chlordiazepoxide58-25-3Solid 250–260 PT [19]
131Diflunisal22494-42-4Solid 252 PT [19]
132Griseofulvin126-07-8Solid 290 PT [19]
133Chloroquine19851Solid7000–12,000260 NPT [19]
134Chlortetracycline57-62-5Solid8500–12,000270 NPT [19]
135chlorothiazide58-94-6Solid 260 NPT [19]
136Clomocycline1181-54-0- 270–280 NPT [19]
137Cyclamic acid100-88-9Solid 250–260 NPT [19]
138Fenoprofen29679-58-1Solid 270–280 NPT [19]
139Flurbiprofen5104-49-4Solid 247–260 NPT [19]
140Ibuprofen15687-27-1Solid 264 NPT [19]
141Indoprofen31842-01-0Solid 250–280 NPT [19]
142Methacycline914-00-1Solid 270–280 NPT [19]
143Oxytetracycline79-57-2Solid 270 NPT [19]
144Tolbutamide64-77-7Solid 230–240 NPT [19]
145Vanillin propylene glycol acetal68527-74-2Liquid 270–280(inconclusive) PT NPT [19,37]
1464′-Hydroxy-3′-methoxyacetophenone(acetovanillone)498-02-2Solid 280–300(inconclusive) PT NPT [19,37]
147Vanillin121-33-5Solid15,000–18,000270 PT NPT [37]
1482-Methoxycinnamaldehyde1504-74-1Solid 270–290(inconclusive) PT NPT [37]
1495-Methylquinoxaline13708-12-8Liquid 260–300(inconclusive) PT PT [37]
150Capmatinib1029712-80-8Solid PSPT [57]
151Fosdenopterin hydrobromide2301083-34-9Solid PTPT [58]
152Berdazimer sodium1846565-00-1gel NPT(UV spectrum)[59]
153Tretinoin302-79-4Solid NPT [60]
154Sabizabulin1332881-26-1Solid PT [61]
155Rezafungin acetate1631754-41-0Solid PTPT [62]
156Viloxazine hydrochloride35604-67-2Solid56.62290 NPT(UV spectrum)[63]
157ESTRADIOL50-28-2Solid NPT [64]
158Oxybutynin5633-20-5Solid NPT [65]
159Darolutamide1297538-32-9Solid23,100–22,500290–320 NPT NPT(UV spectrum)[66,67]
160Berotralstat Hydrochloride1809010-52-3Solid NPT [68]
161Esflurbiprofen51543-39-6Solid NPT [69]
162Fosravuconazole L-lysine ethanolate914361-45-8Solid NPT [70]
163Quizartinib950769-58-1Solid NPT [71]
164Entrectinib1108743-60-7Solid PTPT [72]
165Filgotinib Maleate1802998-75-9Solid NPTPT [73]
166Riociguat625115-55-1Solid 290–720 NPTPT/NPT [74]
167Dabrafenib Mesylate1195768-06-9Solid PT [75]
168Encorafenib1269440-17-6Solid PT [76]
169Trametinib Dimethyl Sulfoxide1187431-43-1Solid>1000290–700 PTPT [77,78]
170Suvorexant1030377-33-3Solid NPT [79]
171Molnupiravir2349386-89-4Solid>1000290–700 NPT NPT(UV spectrum)[79]
172Gefapixant1015787-98-0Solid 290–350 NPT NPT(UV spectrum[80]
173Bictegravir sodium1807988-02-8Solid NPTPT [81]
174Lenacapavir sodium-Solid NPT [82]
175Doravirine1338225-97-0Solid NPTNPT [83]
176Eltrombopag olamine496775-62-3Solid NPTNPTPT [84]
177Bisoprolol66722-44-9Solid PT/PS [85]
178Binimetinib606143-89-9Solid PTPT [86]
179Ibandronate Sodium138844-81-2Solid NPSPT [87]
180Ledipasvir1256388-51-8Solid NPT [88]
Sofosbuvir1190307-88-0Solid
181Dolutegravir sodium1051375-19-9Solid NPT [89]
182Sofpironium Bromide1628106-94-4Solid>1000 NPT(UV spectrum)[90]
183Isavuconazonium sulfate946075-13-4Solid NPT [91]
184Ribavirin36791-04-5Solid NPTPT [92]
185Fosnetupitant Chloride Hydrochloride1643757-72-5Solid PT [93]
186Risdiplam1825352-65-5Solid NPT [94]
187Opicapone923287-50-7Solid NPSNPT [95]
188Difamilast937782-05-3Solid NPT/NPSNPT [96]
189Sirolimus((-)-Rapamycin)53123-88-9Solid NPSNPT [97]
190Momelotinib1056634-68-4Solid NPT [98]
191Siponimod1230487-00-9Solid3309260 NPT [99]
192Asciminib1492952-76-7Solid PT/PSPT [100,101]
193Artemether71963-77-4Solid PT [102]
Lumefantrine82186-77-4Solid
194Cabotegravir1051375-10-0Solid2670–20,800257 NPT(UV spectrum)[103]
195Baricitinib1187594-09-7Solid>1000290–329 NPT PT(UV spectrum)[104]
196Anamorelin249921-19-5Solid4958291 NPT(UV spectrum)[105]
197Delgocitinib1263774-59-9Solid NPT/NPSNPT [106]
198Bedaquiline fumarate845533-86-0Solid NPT/NPSPT [107]
199Nintedanib656247-17-5Solid PT [108]
200Pazopanib444731-52-6Solid NPT [109]
201Roxadustat808118-40-3Solid NPT [110]
202Selexipag475086-01-2Solid mild PT PT [111]
203Fulvestrant129453-61-8Solid NPT [112]
204Degarelix acetate934016-19-0Solid NPT [113]
205Remimazolam besilate1001415-66-2Solid NPT [114]
206Selumetinib606143-52-6Solid11,786290 NPT [115]
207Pimitespib1260533-36-5Solid NPT [116]
208Tirabrutinib hydrochloride1439901-97-9Solid NPT [117]
209Vemurafenib918504-65-1Solid 240–450 NPTPT [118,119]
210Avibactam Sodium1192491-61-4Solid NPT [120]
Ceftazidime pentahydrate78439-06-2Solid
211Dasatinib302962-49-8Solid NPTPT [121]
212Diclofenac Etalhyaluronate Sodium1398396-25-2viscous NPT [122]
213Aripiprazole129722-12-9Solid NPT [123]
214Terbinafine hydrochloride78628-80-5Solid NPTNPT/NPS [124]
215Methyl Salicylate119-36-8liquid NPT/NPS [125]
216Ivermectin70288-86-7Solid <290 UV spectrum[126]
217Docosanol661-19-8solid NPT/NPS [127]
218Butenafine hydrochloride101827-46-7solid NPT/NPS [128]
219Diclofenac sodium15307-79-6solid NPT/NPS [129]
220Avobenzone70356-09-1Solid NPT/NPS [130]
Ecamsule92761-26-7Solid32,000344
Octocrylene6197-30-4liquid
221Trifarotene895542-09-3solid NPT [131]
222Adapalene106685-40-9solid NPT [132]
223TIRBANIBUlin 1%897016-82-9solid NPT/NPS [133]
224Tazarotene118292-40-3solid NPT/NPS [134]
225Tapinarof79338-84-4solid NPT [135]
226SULFACETAMIDE SODIUM127-56-0solid NPT [136]
227SULCONAZOLE NITRATE61318-91-0solid NPT [137]
228Spinosyn A131929-60-7solid NPT [137]
Spinosyn D131929-63-0solid
229Sofpironium bromide1628106-94-4solid/gel NPT(UV spectrum)[90]
230Ruxolitinib941678-49-5oil NPTNPT [138]
231Roflumilast162401-32-3solid NPT NPT [139]
232Pimecrolimus137071-32-0solid NPTPT [140]
233Penciclovir39809-25-1solid NPTNPT NPT(UV spectrum[141]
234Ozenoxacin245765-41-7solid NPTNPT [142]
235Oxymetazoline hydrochloride151615solid NPT [143]
236Alitretinoin1241893solid PTPT(hemoglobin assay, histidine assay)[144]
237Aminolevulinic acid hydrochloride1297222solid PSPT [145]
238Benzoyl peroxide94-36-0solid NPTPT(hemoglobin assay, histidine assay)[146]
239Birch triterpenesbotanical druggel NPSNPSNPT [147]
240Brimonidine tartrate70359-46-5solid NPT [148]
241Bexarotene153559-49-0solid NPTPT(hemoglobin assay, histidine assay)[146]
242Capsaicin404-86-4solid NPT [149]
243Ciclopirox29342-05-0solid NPT [150]
244Clascoterone19608-29-8solid NPT(UV spectrum)[151]
245Dapsone80-08-0solid NPT [152]
246Econazole nitrate24169-02-6solid NPT [153]
247Efinaconazole164650-44-6solid NPT [154]
248Fluorouracil51-21-8solid 265–266 NPT [155]
249Glycopyrronium tosylate1883451-12-4solid NPT(UV spectrum)[156]
250Ivermectin70288-86-7solid NPT [157]
251Luliconazole187164-19-8solid NPT/NPS [158]
Abbreviations: PT = Phototoxic; NPT = Non-Phototoxic; PS = Photosensitization. Of the 251 reference chemicals listed above, the majority were solids (86.9%), followed by liquids (10.4%). Gels, viscous substances, and unknowns made up a minor proportion of the database.
Table 4. Predictive performance of in vivo phototoxicity tests compared with human patch tests.
Table 4. Predictive performance of in vivo phototoxicity tests compared with human patch tests.
Animal
PTNPT
HumanPT404
NPT113
Total (n) 58
Sensitivity 90.9%
Specificity 92.9%
Accuracy 91.4%
Abbreviations: PT = Phototoxic; NPT = Non-Phototoxic; n = number of substances.
Table 5. Predictive performance of in vitro phototoxicity tests compared with human test results.
Table 5. Predictive performance of in vitro phototoxicity tests compared with human test results.
TG432 (3T3 NRU)TG495 (ROS Assay)TG498 (Epiderm Model)
PTNPTPTNPTPTNPT
Human vs. in vitro phototoxic test results
PT36122 194
NPT213 5 7
Total (n) 52 27 30
Sensitivity 97.3% 100% 82.6%
Specificity 86.7% 100% 100%
Accuracy 94.2% 100% 86.7%
Animal vs. in vitro phototoxic test results
PT38117 232
NPT161947219
Total (n) 74 28 46
Sensitivity 97.4% 100% 92.0%
Specificity 54.3% 63.6% 90.5%
Accuracy 77.0% 85.7% 91.3%
Abbreviations: PT = Phototoxic; NPT = Non-Phototoxic; TG = OECD Test Guideline.
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Lee, G.-Y.; Hwang, J.-H.; Hong, J.-H.; Bae, S.; Lim, K.-M. PhotoChem Reference Chemical Database for the Development of New Alternative Photosafety Test Methods. Toxics 2025, 13, 545. https://doi.org/10.3390/toxics13070545

AMA Style

Lee G-Y, Hwang J-H, Hong J-H, Bae S, Lim K-M. PhotoChem Reference Chemical Database for the Development of New Alternative Photosafety Test Methods. Toxics. 2025; 13(7):545. https://doi.org/10.3390/toxics13070545

Chicago/Turabian Style

Lee, Ga-Young, Jee-Hyun Hwang, Jeong-Hyun Hong, Seungjin Bae, and Kyung-Min Lim. 2025. "PhotoChem Reference Chemical Database for the Development of New Alternative Photosafety Test Methods" Toxics 13, no. 7: 545. https://doi.org/10.3390/toxics13070545

APA Style

Lee, G.-Y., Hwang, J.-H., Hong, J.-H., Bae, S., & Lim, K.-M. (2025). PhotoChem Reference Chemical Database for the Development of New Alternative Photosafety Test Methods. Toxics, 13(7), 545. https://doi.org/10.3390/toxics13070545

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