Damage factors of stratospheric ozone depletion on human health impact with the addition of nitrous oxide as the largest contributor in the 2000s

Stratospheric ozone (O3) depletion caused by O3-depleting substances (ODSs) remains an unsolved issue. The leakage of older ODSs in the atmosphere continue to affect stratospheric O3, and nitrous oxide (N2O) remains the largest contributor to stratospheric O3 depletion. The purpose of this study was to update the damage factors of stratospheric O3 depletion on human health impacts, particularly skin cancers and eye cataracts, for the years 2010 and 2015 by adding N2O. The framework to derive damage factors followed that of our previous study; the marginal increase in total incidence per unit ODS emission was estimated using the following terms: ground surface emission, tropospheric chlorine loading, equivalent effective stratospheric chlorine (EESC), total O3 in the air column, ultraviolet-B (UV-B) at the ground surface, incidence due to erythemal UV-B exposure, standardized age structure, population, and ODS atmospheric lifetime. By multiplying the disability-adjusted life years (DALYs) per incidence by the marginal increase in total incidence per unit emission, the damage factor was obtained as the DALY per unit emission. The following update was made in this study: the addition of N2O and revisions of the relationship between EESC and total O3, ODS lifetime, population, and DALY per incidence. Damage factors of all ODSs regulated by the Montreal Protocol and of N2O were calculated for melanoma, non-melanoma skin cancers, and eye cataracts. The total damage factors of N2O were 2.1 × 10–5 and 2.2 × 10–5 DALY per kg nitrogen (N) in 2010 and 2015, respectively. These values were smaller than those of chlorofluorocarbons and halons; however, the global effect of N2O on stratospheric O3 depletion was approximately 170,000 DALYs or 3.9 billion USD in 2010, accounting for 48% of the total damage. The damage factor of N2O on climate change was estimated, based on existing literature, to be 27 times higher than that for stratospheric O3 depletion estimated in this study. N2O is currently the largest contributor to stratospheric O3 depletion, which accounted for approximately 50% of the total health impact induced by all ODSs in 2010. Although another important impact of N2O, i.e., climate change, was demonstrated to be 27 times more damaging than stratospheric O3 depletion, this means that N2O emissions contribute to two global environmental issues simultaneously. Thus, efforts to reduce N2O emissions should be increased.


Introduction
Stratospheric ozone (O 3 ) depletion is a serious global environmental issue caused by the anthropogenic emissions of O 3 -depleting substances (ODSs), which increases ultraviolet intensity at the ground surface (ultraviolet-B [UV-B] in particular) and has harmful impacts on human health. Skin cancer, especially in fair-skinned individuals, and eye cataracts are important human health problems attributed to long-term UV-B exposure (WMO 2018). Major ODSs are artificial substances such as chlorofluorocarbons (CFCs) and halons. They are stable in the troposphere but release halogens in the stratosphere through their decomposition by strong ultraviolet in solar radiation, which causes catalytic and chain destruction of stratospheric O 3 (WMO 2018). The Montreal Protocol adopted in 1987 tackled the phase-down of ODS Communicated by Mark Huijbregts. production and consumption in a stepwise manner (UNEP 2022) and was effective in reducing the use of strong ODSs, such as CFCs and halons. Consequently, total ODS emissions equivalent to the O 3 -depletion potential (ODP), i.e., a relative index of O 3 destruction using CFC-11 as a reference substance (ODP of CFC-11 = 1.0), peaked at the end of the 1980s and has decreased since then (Ravishankara et al. 2009;WMO 2018). This represents a success story in addressing global environmental issues; however, once created and stored after the phase-out, stable ODSs continue to leak into the atmosphere, and once emitted into the atmosphere, have a long atmospheric lifetime, causing O 3 destruction (WMO 2018).
Nitrous oxide (N 2 O) is a potent greenhouse gas (IPCC 2013(IPCC , 2021 and an ODS (Ravishankara et al. 2009;WMO 2018). The ODP-equivalent emission of N 2 O has increased its relative contribution alongside the phase-out of strong ODSs, and N 2 O has been the highest contributing ODS since 2005 (Ravishankara et al. 2009). N 2 O is not a target substance under the Montreal Protocol because it does not contain halogens. The ODP of N 2 O is small, 0.017 as estimated by Ravishankara et al. (2009), and it was revised to 0.015 as of 2000 (WMO 2018). However, the global anthropogenic N 2 O emission in 2010, which was approximately 13 Tg year -1 (Tian et al. 2020), was 200 times that of CFC-11 emission (65 Gg year -1 ) (WMO 2018). Global N 2 O emissions have continued to increase in the twenty-first century, primarily owing to the ongoing increases in agricultural emissions (Tian et al. 2020). Thus, stratospheric O 3 depletion by N 2 O is a future concern. Notably, the O 3 -destruction ability of CFC-11 and ODP of N 2 O are subject to greenhouse gas concentrations and global warming. Higher carbon dioxide (CO 2 ) levels induce cooling of the stratosphere, which increases the chemical destruction of nitrogen oxides (NO x ) and reduces the efficiency of O 3 destruction by N 2 O (Stolarski et al. 2015). High methane (CH 4 ) levels result not only in slowing down of NO x -driven O 3 loss but also in increasing a value of N 2 O ODP. This is because increased CH 4 reduces the efficiency of CFC-11 at destroying O 3 , and CFC-11 is used as a reference gas in the ODP concept (Revell et al. 2015(Revell et al. , 2017. Accordingly, the ODP of N 2 O (0.015 in 2000) will change in future corresponding to the Representative Concentration Pathways (RCPs; IPCC 2013, 2021) as follows: 0.015 in RCP2.6, 0.017 in RCP4.5, 0.0174 in RCP6.0, and 3.0 in RCP8.5 (WMO 2018).
The authors developed the damage factors of stratospheric O 3 depletion for ODS, except N 2 O, utilizing around the year 2000 as their base (Hayashi et al. 2000;2006), which consisted of the life cycle impact assessment (LCIA) method based on endpoint modeling (LIME) (Inaba and Itsubo 2018;Murakami et al. 2022). Struijs et al. (2010) estimated the global human health toll due to ODS emissions in 2007 to be 500,000 disability-adjusted life years (DALYs); however, N 2 O was not involved in their estimation. Brink et al. (2011) estimated the effects of N 2 O on human health due to stratospheric O 3 depletion, around 2010, to be 24.2 DALY per Gg of N 2 O based on the results of Struijs et al. (2010). Therefore, the global health loss in this case corresponds to approximately 112,000 DALYs using the mean global anthropogenic N 2 O emissions during 2007-2016, i.e., 7.3 Tg N year -1 (Tian et al. 2020). Then, we have the following questions: What were the damage factors of stratospheric O 3 depletion for all ODSs, including N 2 O, in 2010 and 2015? What were the global damages to human health in 2010 and 2015 due to N 2 O emissions when calculated using our LCIA method?
The purpose of this study was to update the damage factors of stratospheric O 3 depletion for the years 2010 and 2015, by adding N 2 O that was not included in previous studies (Hayashi et al. 2000;2006). Although stratospheric O 3 depletion has various impacts on human health, social assets, and terrestrial and aquatic ecosystems (Hayashi et al. 2006), this study prioritized human health impact on skin cancer and eye cataracts, because the skin and eyes are the organs exposed to UV-B; these impacts have been the biggest concern of stratospheric O 3 depletion, particularly for fair-skinned populations (Lucas et al. 2015). The years 2010 and 2015 were selected considering the data availability to calculate damage factors. The updated damage factors were used to compare the health impacts between 2000 and 2010 or 2015, as well as to the damages induced by N 2 O as an ODS and greenhouse gas. Finally, the potential improvements and solutions to the damaging effects that could be achieved in future research were discussed.

General descriptions
The target ODSs in the present study were N 2 O and all ODSs regulated by the Montreal Protocol. The procedure to derive the damage factors followed that of previous studies (Hayashi et al. 2000;2006), except for N 2 O which was not considered in the previous studies. The damage factors of the following 13 ODSs were calculated directly using the scheme shown in Fig. 1: chlorofluorocarbon (CFC)-11, CFC-12, CFC-113, Halon-1211, Halon-1301, carbon tetrachloride (CCl 4 ), methyl chloroform (1,1,1-trichloroethane), hydrochlorofluorocarbon (HCFC)-22, HCFC-123, HCFC-124, HCFC-141b, HCFC-142b, and methyl bromide. The damage factors of the other ODSs (except N 2 O) were obtained by converting the directly calculated damage factor of the chemically representative ODS into that of the target ODS using the ratio of their ODP values (correspondences are shown in Table S1 Supplementary file1). Damage factors for N 2 O were derived using the scheme shown in Fig. 1. The relationship between the N 2 O 1 3 emission at the ground surface and a marginal increase in stratospheric N 2 O as the equivalent effective stratospheric chlorine (EESC) was estimated by converting that of CFC-11 using the ODPs and lifetimes of N 2 O and CFC-11, as explained in Sect. 2.2.
For each step shown in Fig. 1, the following describes the steps used in a previous study (Hayashi et al. 2006; Supplementary file2 for details) that were updated in this study.
• The relationship between ground surface emission and an increase in tropospheric chlorine loading (TCL) for the 13 ODSs. • The relationship between an increase in TCL and an increase in EESC for the 13 ODSs. • The relationship between ground surface emission and an increase in EESC for N 2 O was calculated in this study using the ODPs and atmospheric lifetimes of N 2 O and CFC-11 (Sect. 2.2). • The relationship between the total EESC and total O 3 was revised in this study (Sect. 2.3). • The relationship between total O 3 and UV-B at the ground surface. • The correction of the ground-level UV-B into erythemal UV-B. • The correction of the atmospheric lifetimes of ODSs, updated in this study (Sect. 2.4). • The incidence rates of skin cancer and eye cataracts tied to erythemal UV-B exposure, which denote the rate to unit emission per 100,000 individuals. The skin cancer types were divided into malignant melanoma and non-melanoma skin cancer for fair, medium, and dark skin colors. • The global latitudinal population was updated in this study for 2010 and 2015. The population distinguishing the three skin colors (fair, medium, and dark) was estimated for each 10° latitudinal belt (Sect. 2.5). • An increase in the total incidence of each disease per unit emission of ODSs was calculated using the abovementioned relationships. • DALYs per incidence of melanoma, non-melanoma skin cancer, and eye cataracts were updated in this study for 2010 and 2015 (Sect. 2.6).
It should be noted that the damage factor does not necessarily represent the real damage in the future; instead, it expresses an indicative impact owing to an additional emission of the target ODS in the base year. This concept agrees to the description in the Eco-indicator 99: "it is an indicator aimed at showing the approximately correct direction for designers who want to analyze and minimize the environmental load of product systems" (Goedkoop and Spriensma 2001). The incidence rates of diseases, population, and DALY per incidence values were fixed to those of the base year (2010 or 2015) in this study. The baseline EESC has been decreasing since the phase-out of strong ODSs (WMO 2018), whereas the global population has been increasing steadily (UN 2019). The DALY value can change depending on the medical condition. Original framework in Hayashi et al. (2000Hayashi et al. ( , 2006 which was updated in this study. ODS, ozone depleting substance; UV-B, ultraviolet-B; TCL, tropospheric chlorine loading; EESC, equivalent effective stratospheric chlorine; and DALYs, disability-adjusted life years 1 3

Relationship between surface N 2 O emission and EESC
The ODP of N 2 O was estimated to be 0.017 (Ravishankara et al. 2009) and re-assessed as 0.015 (WMO 2018) and that of CFC-11 as the reference substance is 1.0 (UNEP 2022). This study applied the N 2 O-ODP of 0.015, corresponding to the RCP2.6 scenario, the lowest forcing level (IPCC 2013;WMO 2018). The ODP of an ODS is a function of its O 3 destruction rate and stratospheric lifetime. Therefore, the relationship between the unit emission at the ground surface and the increasing rate of EESC for CFC-11 [dEESC(CFC-11)], i.e., 0.048 pptv Gg -1 (Hayashi et al. 2006), was converted to that for N 2 O [dEESC(N 2 O)] using the following equation: where F LT (X) denotes the lifetime term for the ODS species X. This term was modified considering that it takes an average of 3 years for ODS to be transported from the troposphere to the stratosphere (WMO 1995;Hayashi et al. 2006). Therefore, F LT (X) is expressed as: where LT is the lifetime of the ODS species X (year). F LT (N 2 O) and F LT (CFC-11) were determined to be 106 and 49.1 years, respectively, using the N 2 O lifetime of 109 years (Forster et al. 2021), and the CFC-11 lifetime of 52 years (SPARC 2013;WMO 2018). Finally, the dEESC(N 2 O) value was obtained using Eq. (1) as 0.000333 pptv Gg -1 N 2 O and further converted to 0.000524 pptv Gg -1 N using the weight ratio of nitrogen (N) per N 2 O molecule (i.e., 28/44). We used the value per N rather than that per molecular N 2 O because N forms not only on N 2 O but also on other various compounds environmentally important. Therefore, a damage factor per unit N emission is more advantageous than that per N 2 O for consistency with other accounting systems, such as national N budgets (e.g., Hayashi et al. 2021) because they express the weight of N compounds as the weight of N to comprehensively handle various commodities containing N, such as food, goods, and materials. Although EESC expression is not suitable for N 2 O as a halogen-free molecule, a value corresponding to EESC was used in this study for convenience. The O 3 destruction by N 2 O affects the total O 3 observed at the ground surface. Therefore, a regression equation with the total O 3 as the objective variable and EESC baseline as the explanatory variable as shown below contains the effect of N 2 O on O 3 destruction. The EESC baseline in the Southern Hemisphere is approximately 3000 pptv (NASA 2022), whereas the marginal increase in EESC due to unit emission of N 2 O is relatively very small, 0.0005 pptv Gg -1 N as calculated above. Thus, we judged that the method for calculating the effect of N 2 O on O 3 destruction using the EESC equivalent value might not be the best way but an acceptable method to estimate the marginal impact due to an additional emission.

Update of relationship between EESC and total O 3
The regression equation of the total O 3 as the objective variable and EESC baseline as the explanatory variable for each 10° latitudinal belt (18 zones between the north and south poles) and each season (December-February, March-May, June-August, September-November) was obtained using available data. The slope (regression coefficient) was used as a factor that indicates the marginal decrease in total O 3 due to a marginal increase in EESC. The EESC baseline was obtained from NASA (2022) as an estimation in the Southern Hemisphere. The previous studies (Hayashi et al. 2000;2006) used the total O 3 observational dataset provided by McPeters and Beach (1996) that contains data from 1978 to 1993. In this revision, another dataset covering a period from 1970 to 2021 provided by GSFC (2022) was also used. As the latter dataset has no data for latitudes higher than 80°, the two datasets were combined to create the regression equations (Supplementary file2).

Update of atmospheric lifetime of ODSs
A previous study (Hayashi et al. 2006) referred to WMO (1999) to obtain the lifetimes of 13 ODSs. These values were then updated in WMO (2018) ( Table 1). Using Eq. (2), the original lifetime was converted to the F LT value for each ODS species, and an ODS with a lifetime less than 3 years can partly flow into the stratosphere, as shown for HCFC-123 and methyl bromide (Table 1).

Update of global latitudinal population
The population of each country and region in 2010 and 2015 was obtained from the World Population Prospects (UN 2019). The world was divided into latitudinal belts with a width of 10°. The population of each country was allocated to the corresponding latitudinal belts, principally using the area in the latitudinal belt as the weight. The population ratio of skin colors (fair, medium, and dark) in each country was estimated using information on ethnic groups (CIA 2021), assuming a common ratio regardless of the latitudinal belts within the country. The total population and population of each skin color in each latitudinal belt were estimated (Supplementary file2).

Update of DALYs for skin cancer and eye cataract
The years of life lost due to premature mortality (YLLs) and years of healthy life lost due to disability (YLDs) of malignant melanoma and non-melanoma skin cancers in 2010 and 2015 were obtained from the Global Burden of Disease Study 2019 (IHME 2020). For each cancer type, the summation of YLL and YLD as the world total loss in the year was divided by the number of incidences in the same year to estimate the DALY per incidence.
Eye cataract is treated as a non-fatal disease in IHME (2019), which provides only the total YLDs in a target year and does not specify the number of incidences in the year (IHME 2020). Therefore, the YLDs per incidence of eye cataracts for eight world regions (i.e., established market economies, formerly socialist economies of Europe, India, China, other Asia and islands, Sub-Saharan Africa, Latin America and the Caribbean, and Middle Eastern Crescent including North Africa) estimated by Struijs et al. (2010) were used. The population of each of the eight regions in 2010 and 2015 was obtained using the World Population Prospects (UN 2019), and the global mean (weighted-mean) YLD per incidence of eye cataracts was calculated using the population in each region as the weight. Table 2 summarizes the estimated DALYs per incidence, including those in a previous study (Hayashi et al. 2006). We suggest that each user decides the monetary cost per DALY according to one's purpose of use. As a reference, the monetary cost of 23,000 USD per DALY was provided in this study as the weighted-mean of G20 countries using population as the weight (Murakami et al. 2022). A European study provided a value of 40,000 euro per DALY (Brink et al. 2011).

Estimated damage for major ODSs
The increases in the total incidence per unit emission of each of the 13 ODSs and N 2 O are shown in Table 3. The estimated values denoted that 1-Gg emission of halons and CFCs causes approximately one dozen to several hundred cases of melanoma, one to twelve thousand cases of nonmelanoma skin cancers and eye cataracts, respectively. CCl 4 has similar effects to CFCs. The impact of unit emission of N 2 O was less than 3% of CFC-11; however, it was less than 2% when using the same denominator, i.e., Gg of the compound instead of Gg N.
The pattern of latitudinal impacts due to a unit emission of an ODS is similar regardless of the ODS species, because the regression equation expressing the variation in total O 3 in each latitudinal belt to a marginal increase in EESC is common regardless of the ODS species. Here, the latitudinal pattern is shown using the impact of 1-Gg N emission of N 2 O as an example (Fig. 2). The global population is

Sources of uncertainty
Many processes are involved in the impact of stratospheric O 3 depletion from ODS emissions on human health. Struijs et al. (2010) discussed the uncertainty in LCIA of stratospheric O 3 depletion. We aimed to add information of the possible uncertainties to determine the damage factors for stratospheric O 3 depletion.

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On ODS emissions, the total ODP-weighted emissions for all CFCs in 2016 was estimated to be 110 Gg year -1 CFC-11-equivalent, with a possible uncertainty of ± 30 Gg year -1 CFC-11-equivalent (WMO 2018). The global N 2 O budgets based on a wide variety of top-down and bottom-up methods have various sources of uncertainty such as the inversion of atmospheric N 2 O measurements into its emissions in topdown approaches and the differences in model configuration and parameterization of each N 2 O emission process in bottom-up approaches (Tian et al. 2020). Transportation of atmospheric constituents from the troposphere to the stratosphere and O 3 destruction in the stratosphere fluctuate spatially and seasonally (WMO 2018). The pace of O 3 destruction in the stratosphere is affected by the greenhouse gas levels and climate change as explained in the Introduction (Stolarski et al. 2015;Revell et al. 2015;WMO 2018). The atmospheric lifetime of ODSs is subject to changes in atmospheric chemistry and therefore has a certain degree of uncertainty (WMO 2018; IPCC 2021). EESC also changes greatly depending on the setting of the attenuation curve (Newman et al. 2007). Only the optical depth of total O 3 was considered in this study to calculate the UV-B intensity at the ground surface. Nonetheless, clouds also attenuate UV-B (Estupiñán et al. 1996), whereas snow and ice cover increase UV-B exposure via their surface reflection (Moehrle 2008).
UV-B intensity at the ground surface does not always equal the UV-B exposure of individuals. For example, there are lifestyles that reduce UV-B exposure, such as not going out during the mid-day, and those that increase UV-B exposure, such as utilizing tanning salons (Lucas et al. 2015). Estimating the proportion of skin color in the population was difficult because changes in skin color are continuous, not discrete, and pigmentation of skin, i.e., change in color, can happen as a result of stresses such as UV-B exposure (Costin and Hearing 2007). There are also individual differences in damage caused by UV-B exposure (Heenen et al. 2001). Although the DALYs of skin cancer and eye cataracts in this study were calculated as the world mean values, and the suggested monetary value of DALY corresponded to the G20-weighted mean value, DALYs and their monetary values are subject to medical and economic conditions as well. Additionally, human health impacts of UV-B exposure are not limited to skin cancer and eye cataracts, but also involve solar keratoses, sunburn, photoaging, and photoimmunosuppression (Struijs et al. 2010;Lucas et al. 2015).

Sensitivity analysis
To identify the contribution of each parameter to the damage factor of stratospheric O 3 depletion, the damage factor response to a 10%-increase in each parameter was investigated. This sensitivity analysis was performed for the damage factor of N 2 O for skin cancer in 2010. As explained in Sect. 2.2, the marginal EESC increase in CFC-11 per unit emission was converted to that of N 2 O using the ODPs and lifetimes of CFC-11 and N 2 O to calculate the damage factor of N 2 O. Certain parameters related to CFC-11 were also used for this sensitivity analysis. As shown in Table 5, the most effective parameter was the slope (regression coefficient) of total O 3 to EESC that showed an effect of more than 10% to its increase in 10%. The second was the lifetime of CFC-11. The lifetime of N 2 O showed no effect because an increase in N 2 O lifetime reduced the parameter of dEESC(N 2 O) (Eq. 1), but this effect was canceled by multiplying the F LT (N 2 O) by the initial impact to estimate the total damage. The ODP, UV-B irradiance at the top of the atmosphere, and total population showed a 1:1 effect on the damage factor. The relatively high effect of the ratio of fair-skinned populations is ascribed to their high risks of skin cancer. Notably, an increase in fair-skinned populations by the 10%-increase in its ratio in a latitudinal belt was compensated for by reducing the medium and dark-skinned populations using their population ratios as the weight not to change the total population. dEESC(CFC-11) showed a near 1:1 effect on the damage factor. In addition, dEESC(N 2 O) is the objective variable being estimated using dEESC  and ODPs and lifetimes of CFC-11 and N 2 O (Eq. 1), and therefore, it was excluded from the sensitivity analysis. The correction factor of erythemal UV-B (300-310 nm) was effective; however, that of the shortest wavelength of UV-B (290-300 nm) was fixed at 1.0 in definition (CIE 1987), and therefore was left unchanged in this analysis. The effectiveness of DALY and incidence rate factor (fair-skinned populations) for non-melanoma skin cancer is attributable to the increase in non-melanoma skin cancer per unit emission, approximately 60 times larger than that of melanoma (Table 3). The parameters described here will be the subject of future improvement.

Global impacts
The main purpose of using damage factors in LCIA is to assess the impacts of additional emissions of ODSs due to an industrial process; however, it is also interesting to investigate the degree of the total impact of global emissions. Global emissions of major ODSs and N 2 O in 2010 were obtained from WMO (2018) and Tian et al. (2020), respectively, as the average of the top-down and bottom-up estimations of global emissions. Given the global phase-out of the production of CFCs and halons for dispersive uses under the Montreal Protocol, their emissions to the atmosphere are expected to be due only to leakage from banks (WMO 2018). Thus, even phased-out ODSs continue to threaten stratospheric O 3 . Global emissions were obtained for 11 ODS, i.e., all in Table 1 except HCFC-123 and HCFC-124. Figure 3 shows that the global emissions of CFCs and halons ranged from several Gg year -1 to several dozen Gg year -1 , that of HCFC-22 was approximately 360 Gg year -1 , and that of N 2 O was orders of magnitude higher than other ODSs, i.e., approximately 13 Tg year -1 as N 2 O (i.e., 8 Tg N year -1 ), owing to large emissions from agriculture, fossil fuel consumption, and industry (Tian et al. 2020;Canadell et al. 2021).
The global impacts of these emissions were calculated by multiplying global emissions by the total damage factor for each substance. Although the difference in global impacts between N 2 O and other ODSs narrowed in comparison with that of global emissions (because of the smaller damage factor of N 2 O per unit emission; Table 4), the impact of N 2 O emissions accounted for 48% of the total impact (Fig. 3). Response of the damage factor to a 10% increase in each parameter Some parameters related to CFC-11 were also subject to this sensitivity analysis since they were used to calculate the damage factor of N 2 O (see the main text for details)

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However, this estimation does not cover all ODSs regulated by the Montreal Protocol. The impact of N 2 O emissions in 2010 was estimated to be approximately 170,000 DALYs, corresponding to approximately 3.9 billion USD, using a value of 23,000 USD DALY -1 (Murakami et al. 2022).

Comparison with previous studies
The damage factors of stratospheric O 3 depletion estimated by Hayashi et al. (2006) around the year 2000 were compared with those estimated in this study for the years 2010 and 2015. The difference between the two studies mainly originated from the revision of regression coefficients between EESC and total O 3 , ODS lifetimes, DALYs, and population. The 13 ODSs shown in Table 1, except N 2 O, were the targets of this comparison because N 2 O was not treated in the previous study. Figure 4 compares the damage factors (DALY per kg emission) in approximately the year 2000 to those in 2010 and 2015 for melanoma, non-melanoma skin cancers, eye cataracts, and the total. As a general trend, the damage factors obtained in this study decreased compared to those in the previous study. The damage factors of melanoma were 68% on average compared to the previous study (range: 47-115%). The damage factors of non-melanoma skin cancer and eye cataracts, and the total damage were 37% (26-63%) and 81% (54-144%), and 65% (44-113%), respectively. The general decrease of the damage factors is ascribed to the revision of the regression coefficients between EESC and total O 3 , i.e., the strongest parameter on the damage factor (Table 5), where their absolute values decreased compared to the previous study. Atmospheric lifetime is also an effective parameter to the damage factor (Table 5). The reason for the difference in decreasing trends among the ODSs is ascribed to the difference in the revision of ODS lifetimes (Table 1). For example, F LT (Eq. 2) of HCFC-123 decreased to 79% but that of CH 3 Br increased to 195% between the two studies. The DALY of melanoma increased to 104% on average between the two studies, whereas that of non-melanoma skin cancer and eye cataracts reduced to 57% and 88%, respectively. This is why the decrease in damage factors was particularly remarkable in non-melanoma skin cancer. The world population, which had the effect of increasing the overall damage factors by 1:1, increased from 6.14 billion in 2000 to 6.96 billion (113%) in 2010 and 7.38 billion (120%) in 2015; however, the decreasing effect of the regression coefficients between EESC and total O 3 seems to cancel the increasing effect of population. As mentioned previously, Brink et al. (2011) estimated the damage factor of N 2 O emissions on health impacts (skin cancer and eye cataracts) through stratospheric O 3 depletion in approximately 2010, utilizing the results of Struijs et al. (2010). Their value of 24.2 DALY per Gg of N 2 O corresponds to 38.0 DALY per Gg N = 3.8 × 10 -5 DALY kg -1 N. Our results, i.e., 2.1 × 10 -5 and 2.2 × 10 -5 DALY kg -1 N in 2010 and 2015, respectively (Table 4), corresponded to 55%-58% of their estimation.

Comparison of N 2 O impacts on climate change and stratospheric O 3 depletion
Anthropogenic N 2 O emissions cause both climate change and stratospheric O 3 depletion. In this study, the impacts of N 2 O emissions on human health through climate change and stratospheric O 3 depletion were compared. Tang et al. (2018) estimated the effects of carbon dioxide (CO 2 ) emissions on human health based on the Special Report on Emission Scenarios (SRESs) of the IPCC (Nakicenovic and Swart 2000): 6.2 × 10 -7 (A2 scenario), 4.2 × 10 -7 (B2 scenario), 2.1 × 10 -7 (B1 scenario), and 2.0 × 10 -7 (A1B scenario) DALY kg -1 CO 2 . These scenarios, A1, A2, B1, B2, are called story lines, i.e., narrative scenarios, on the development of future human society. These values were converted to those of N 2 O using the global warming potential of N 2 O for 100 years of 273 (Forster et al. 2021), and a conversion factor from kg N 2 O to kg N (i.e., 44/28): 2.7 × 10 -4 , 1.8 × 10 -4 , 9.0 × 10 -5 , and 8.6 × 10 -5 DALY kg -1 N for the respective scenarios. Tang  updated this estimation for the Shared Socioeconomic Pathways (SSPs) for the scenarios SSP1, SSP2, and SSP3 (e.g., Hasegawa et al. 2015): 1.3 × 10 -6 (SSP1), 1.5 × 10 -6 (SSP2), and 2.0 × 10 -6 (SSP3) DALY kg -1 CO 2 , respectively. SSPs are also narrative scenarios but consider the socioeconomic challenges for adaptation and mitigation against climate change, where SSP1, SSP2, and SSP3 correspond to "Sustainability -Taking the Green Road," "Middle of the Road," and "Regional Rivalry -A Rocky Road" scenarios, respectively (O'Neill et al. 2017). These values, converted to those of N 2 O in the same manner, were 5.6 × 10 -4 (SSP1), 6.4 × 10 -4 (SSP2), and 8.6 × 10 -4 (SSP3) DALY kg -1 N. The damage factors obtained for the SSPs were 3-5 times higher than those obtained for the SRESs. Tang et al. (2019) interpreted that this was mainly because the relative risk per temperature increase used in a later study (WHO 2014) was higher than that used in a previous study (McMichael et al. 2004). SSP1 is the scenario with the most successful mitigation and adaptation against climate change. In addition, it is the scenario closest to achieving RCP2.6, which is the lowest radiative forcing among the RCPs. Therefore, to examine the effects of N 2 O emissions, the impact of climate change in SSP1 calculated using the results of Tang et al. (2019) and that of stratospheric O 3 depletion in RCP estimated in this study were compared. The former, 5.6 × 10 -4 DALY kg -1 N, was 27 times higher than the latter, 2.1-2.2 × 10 -5 DALY kg -1 N (Table 4).

Further development needed
Stratospheric O 3 depletion may be a solved problem owing to the phase-out of major ODSs; however, the contribution of N 2 O to stratospheric O 3 depletion has increased since the 1990s, with N 2 O becoming the largest contributor in the mid-2000s (Ravishankara et al. 2009;WMO 2018) and anthropogenic N 2 O emissions continuing to increase (Tian et al. 2020;Canadell et al. 2021). WMO (2018) also pointed out that strengthening the greenhouse effect enhances stratospheric O 3 depletion as shown in the increasing ODPs of N 2 O according to the RCP scenarios from RCP2.6 to RCP8.5. Accordingly, stratospheric O 3 depletion is not a solved problem. The health impacts of N 2 O emissions were evaluated to be 27 times greater due to climate change compared to stratospheric O 3 depletion (Sect. 3.6). Even though the total damage (i.e., the total amount of impact after emissions) due to stratospheric O 3 depletion caused by N 2 O emissions in 2010 amounted to 170,000 DALY, the equivalent to 3.9 billion USD (Sect. 3.4), stratospheric O 3 depletion remains an unsolved issue. In particular, refinement of the calculation scheme for N 2 O from its emission to impact is required. The method used to obtain the damage factors in this study aimed to estimate the slight increases in impacts due to the additional emissions of various ODSs as simply and Fig. 4 Comparison of damage factors between a previous study (Hayashi et al. 2006) and the present study of the following: a melanoma, b non-melanoma skin cancers, c eye cataracts, and d the total (i.e., the sum of impacts on melanoma, nonmelanoma skin cancers, and eye cataracts). DALY, disabilityadjusted life year quantitatively as possible. According to the sensitivity analysis (Sect. 3.3), the following parameters were particularly effective on the damage factors: the relationship between EESC and total O 3 , i.e., actual state of O 3 destruction in the stratosphere, atmospheric lifetimes of ODSs, ODPs, UV-B irradiance perturbed with solar activity, population distribution with the ratio of skin colors, and DALYs. As the impact of N 2 O is currently larger than that of other ODSs, a methodological development is recommended to incorporate the following schemes on stratospheric O 3 depletion into the existing Earth system models to simulate the effects of N 2 O behavior on climate change: changes in UV-B irradiance at the ground surface due to N 2 O emissions; estimation of human UV exposure considering actual lifestyle; elaborating estimation of the global population; and elaborating dose-response relationships of major diseases due to UV exposure. It is expected that a common method will enable consistent evaluation of the impacts of both climate change and stratospheric O 3 depletion due to N 2 O emissions based on common future scenarios such as SSPs.
This study focused on some of the various impacts induced by stratospheric O 3 depletion, i.e., skin cancers and eye cataracts. There are other possible impacts on human health, such as photoimmunosuppression; social assets, such as crop and timber production and material degradation; biodiversity loss in terrestrial and aquatic ecosystems; and net primary productivity of terrestrial and aquatic ecosystems (Hayashi et al. 2006). In a previous study (Hayashi et al. 2006), we attempted to estimate the damage factors of crop, timber, terrestrial, and aquatic production, in addition to those of skin cancers and eye cataracts. For re-evaluation, it is necessary to determine the precise dose-response relationships to UV-B exposure of major biological species as well as their production rates and biomass with information on spatial distribution.

Conclusions
CFCs and halons, which are artificial substances, once brought great benefits to industries and human life as useful materials; however, they have had the unexpected impact of depleting stratospheric O 3 and subsequently increasing UV-B exposure at the ground surface. These major ODSs have been gradually phased out, representing a success story in addressing global environmental issues. However, the effects of historically-created ODSs remain due to their leaking and/ or their lingering in the atmosphere, and N 2 O has emerged as the largest contributor to stratospheric O 3 depletion in addition to its effects on climate change. In this study, we evaluated the damage factors of N 2 O and re-evaluated those of all ODSs regulated by the Montreal Protocol for 2010 and 2015 on human health impacts (skin cancers and eye cataracts). The damage factors of many ODSs did not change remarkably compared to a previous study, which targeted around the year 2000. The steady increase in the global population has increased the damage factor, most of which was counterbalanced by the downward trend of the DALY per incidence in non-melanoma skin cancers and eye cataracts. The damage factors of N 2 O were estimated to be 2.1 × 10 -5 and 2.2 × 10 -5 DALY kg -1 N in 2010 and 2015, respectively. They correspond to approximately 0.5 USD kg -1 N using the coefficient of 23,000 USD DALY -1 . Although N 2 O had much smaller damage factors than CFCs and halons, which were comparable to those of other ODSs, the health impact induced by N 2 O emissions was the largest among all ODSs because it has the largest global emissions by several orders of magnitude. The total impact due to N 2 O emissions in 2010 was estimated to be 170,000 DALY, or 3.9 billion USD. Another important impact of N 2 O, i.e., climate change in the SSP1 scenario, demonstrated a damage factor 27 times larger than that of stratospheric O 3 depletion in the RCP2.6 scenario. However, N 2 O emissions affect both stratospheric O 3 depletion and climate change. Thus, efforts to reduce N 2 O emissions are efficient in simultaneously addressing both these issues.