應用與建議

SN 為目前世界各國職業衛生管理機構用以警示並管理作業環境中 可透過皮膚吸收造成健康危害化學毒物的主要工具，但各國間制定過程 與作為制定基礎科學準則間之差異使其功能受限。欲有效改善作業環境 中勞工因化學毒物皮膚暴露面臨的威脅，首先必須改善 SN 的制定，使 其成為有效的皮膚暴露危害辨識與警示工具，此亦為本論文的研究核 心。本研究的發現與成果當可循以下二方向應用：

(1) 本論文發現傳統動物實驗所獲得之急性毒性實驗數值 dermal LD₅₀ 並無法確切反應化學物經皮吸收致毒的危害潛能。目前已有 SN 的 化學物應當就其 SN 制定之科學基礎逐個分析，若基礎為 dermal

LD₅₀時，該化學物應重新評估，確認授與SN 是否適當。

(2) 預測性數學模式適合用以作為制定 SN 之科學準則。以 TSCA ITC 模式為例，經由預測模式推估之化學物經皮暴露危害潛能可適當反 應化學物之皮膚危害等級，且可信度高於dermal LD₅₀。另外其應用 將可有效降低目前 SN 制定時缺乏充足科學數據之缺陷，是理想的 SN 制定替代性工具。

此外經分析工業化學毒物現有毒理學數據以及利用數學模式推論皮 膚暴露危害潛能之預測功能後，本研究建議未來的相關研究可針對以下 議題進一步研究：

(1) SN 之制定目前為定性化的皮膚暴露危害辨識，但 TSCA ITC 皮膚暴 露危害潛能預測模式及在本研究中所修正之替代模式均能提供量 化的危害潛能預測值，且該預測值已可適切反應如 solvents 類化學 物之皮膚危害等級；未來之研究似可嘗試量化利用模式預測值，如 建立危害分級系統(hazard ranks)；

(2) 在修定 TSCA ITC 模式中可能造成呼吸劑量誤差之因子後，模式之 預測效能仍無法有效提升；建議後續研究可針對模式中用以估計皮 膚劑量指標之 Kp 值進行修正，以實驗數據 Kp 值取代本研究所使

表2-1 世界主要職業衛生政策發展機構對皮膚標記符號之定義 ^a

顯著增加其整體暴露量 (overall exposure)者，須授予皮膚標記符 號，以“SN”表示；經科學實證為「產生重大皮膚吸收」之化學物應 蘭、瑞典: European Center for Ecotoxicology and Toxicology of Chemicals

(ECETOC), 1998

⁽¹⁸⁾

b

NIOSH: National Institute for Occupational Safety and Health; ACGIH: American Conference of Governmental Industrial Hygienists.

c

英國、德國、荷蘭、及瑞典之皮膚標記符號制定機構分別為英國衛生暨安全執

行委員會(United Kingdom Health and Safety Executive)、德國作業環境化學物健 康危害調查委員會(Commission for the Investigation of Health Hazards of

Chemical Compounds in the Work Area, Germany)、荷蘭職業標準專家委員會

(Dutch Expert Committee on Occupational Standards)、與瑞典國家職業安全衛生

暴露限制值委員會(Swedish National Board of Occupational Safety and Health on

Occupational Exposure Limit Values)；瑞典之定義亦為北歐三島國家(Nordic

Group)含芬蘭與挪威之共同定義。

表3-1 評估制定皮膚標記符號科學準則所須之標的化學物化性/毒性 數據與建立 TSCA ITC 模式預測值所須參數資料來源

化學物特性 資料庫

Rodent dermal LD₅₀^a

NIOSH Registry of Toxic Effects of Chemical Substances (RTECS^®) Database^b

Log K_OW^a, molecular weight and water solubility

Syracuse Research Corporation (SRC) PhysProp Database^c

OEL^a Time-Weighed Average (TWA)

Documentation of the TLVs^® and BEIs^® with Other Worldwide Occupational Exposure Values^d

Rodent LC50 and LCLo^a

NIOSH Registry of Toxic Effects of Chemical Substances (RTECS^®) Database^b

a

LD

50

: lethal dose 50%; log K

OW

: logarithm of octanol-water partition coefficient;

OEL: occupational exposure limit; LC

50

: lethal concentration 50%; LCLo: lowest observed lethal concentration.

b

資料來源：NIOSH, 2001

⁽¹⁹⁾

.

c

資料來源：SRC, 2007

⁽³⁵⁾

.

d

資料來源：ACGIH, 2006

⁽¹¹⁾

.

表3-2 美國國家醫學圖書館危害物質職業暴露資料庫(Haz-Map)對工業 化學毒性物質的分類與化學物範例

Haz-Map 化學物分類 化學物範例 金屬(Metals) 砷(arsenic)

氮化物(Nitrogen compounds) 聯苯胺(benzidine)

農藥(Pesticides) 環氧乙烷(ethylene oxide) 1,3-丁二烯(1,3-butadiene)、

塑料及橡膠(Plastics and rubber)

氯乙烯(vinyl chloride)

有機溶劑(Solvents) 苯(benzene)、三氯甲烷(chloroform) 毒性氣體與蒸氣(Toxic gases and

vapors)

丙烯腈(acrylonitrile)、氯(chlorine)

資料來源：National Library of Medicine, 2007

⁽¹⁰⁾

表4-1 不同 SN 數目群組具有之化學物數目與各群組中 dermal LD₅₀, log K_OW,及TSCA ITC 模式 SI ratio 等三項數據有效使用度

(availability)^a

Availability (%)

SN group

Chemical (n)

Dermal LD₅₀ log Kow SI ratio

7 SNs

16 81% 94% 75%

6 SNs

30 53% 100% 77%

5 SNs

48 75% 100% 83%

4 SNs

51 67% 98% 73%

3 SNs

40 58% 93% 75%

2 SNs

70 46% 91% 63%

1 SNs

225 26% 80% 46%

Total

480

Mean±Std.

Dev.

57.9±18.8 93.7±6.8 70.2±12.2

a

SN: skin notation (皮膚標記符號);

Rodent dermal LD

50

: dermal lethal dose 50% (囓齒類動物皮膚半致死劑量);

log K

OW

: logarithm of octanol-water partition coefficient (正辛醇─水分配係數對數值);

SI ratio: ratio of skin dose to inhalation dose as estimated by the OEL-based predictive model developed by the US Toxic Substances Control Act Interagency Testing

Committee (TSCA ITC) and described in Eq. 3-1 (循 Eq. 3-1 TSCA ITC 原型模式推導

而得之化學物皮膚暴露危害潛能預測值).

表4-2 具四個以上 SN 化學物之 rodent dermal LD₅₀, log K_OW,及依TSCA ITC 模式所產生 SI ratio 等三項數據之分佈^a

Rodent dermal LD

50

Log Kow SI ratio SN group

Median 75% 25% median 75% 25% median 75% 25%

≧ 6 SNs 1,000.0 4,740.0 143.3 0.83 1.87 -0.31 0.83 1.87 -0.31

5 SNs

150.0 900.0 40.5 1.65 2.96 0.44 0.64 12.36 0.04

4 SNs

300.5 1,770.0 90.0 1.46 3.12 0.45 0.24 10.11 0.01

a SN: skin notation (皮膚標記符號);

Rodent dermal LD50: dermal lethal dose 50% (囓齒類動物皮膚半致死劑量);

log KOW: logarithm of octanol-water partition coefficient (正辛醇─水分配係數對數值);

SI ratio: ratio of skin dose to inhalation dose as estimated by the OEL-based predictive model developed by the US Toxic Substances Control Act Interagency Testing Committee (TSCA ITC) and described in Eq. 3-1 (循 Eq. 3-1 TSCA ITC 原型模式推導而得之化學物皮膚暴露危害 潛能預測值).

表 4-3 各 SN 數目群組中化學物之 LC₅₀/LCLo 數據有效使用度(availability)及依 LC₅₀/LCLo 修正模式產生 SI ratio 之分佈^a

SI ratio (LC

50

) SI ratio (LCLo)

Number of SN

Chemical

(n) (n) Availability (%) median 75% 25% (n) Availability (%) median 75% 25%

7

16 10 63 0.01217 0.01569 0.00158 8 50 0.01069 0.01454 0.00389

6

30 16 53 0.01886 0.15345 0.00042 14 47 0.01239 0.08370 0.00002

5

48 23 48 0.00355 0.09403 0.00021 17 35 0.00162 0.02612 0.00016

4

51 28 55 0.00257 0.05566 0.00027 16 31 0.00122 0.03923 0.00019

3

40 13 33 0.00240 0.00835 0.00036 11 28 0.00152 0.00256 0.00050

2

70 28 40 0.00234 0.07029 0.00019 20 29 0.00217 0.02883 0.00025

1

225 51 23 0.01167 0.07979 0.00151 36 16 0.00165 0.01121 0.00048

Total

480 169 35.2 122 25.4

Mean±Std.

Dev.

44.8±13.9 33.6±11.7

a SN: skin notation (皮膚標記符號);

LC50: inhalational lethal concentration 50% (呼吸半致死濃度);

LCLo: Inhalational Lowest Observed Lethal Concentration (最低呼吸致死濃度);

SI ratio: ratio of skin dose to inhalation dose as estimated by the LC50-/LCLo-based predictive model as described in Eq. 3-3 (循 Eq. 3-3

表 4-4 具四個以上 SN 化學物以 LC₅₀/LCLo 修正模式預測之 SI ratio 分佈^a

SI ratio (LC

₅₀

) SI ratio (LCLo) SN group

median 75% 25% median 75% 25%

≧ 6 SNs 0.0122 0.1313 0.0006 0.0107 0.0703 0.0005

5 SNs

0.0036 0.0940 0.0002 0.0016 0.0261 0.0002

4 SNs

0.0026 0.0557 0.0003 0.0012 0.0392 0.0002

a SN: skin notation (皮膚標記符號);

LC50: inhalational lethal concentration 50% (呼吸半致死濃度); LCLo: Inhalational Lowest Observed Lethal Concentration (最低呼吸致死濃度);

SI ratio: ratio of skin dose to inhalation dose as estimated by the LC50-/LCLo-based predictive model as described in Eq.

3-3 (循 Eq. 3-3 LC50/LCLo 修正模式推導而得之化學物皮膚暴露危害潛能預測值).

表4-5 具四個以上 SN 化學物據 TSCA ITC 原型與修正模式產生之 SI ratio 與 SN 個數之對數線性迴歸關係(化學物經皮暴露之危害潛能 等級依化學物所具有之SN 個數區分為四級；依序為等級七、六、

五及四) ^a

Chemicals with 4 or more SNs SI ratio

(OEL-based model)

^a

SI ratio

(LC

50

-based model)

^a

SI ratio

(LCLo-based model)

^a Intercept -2.285 -3.685 -4.437

Slope 0.430 0.275 0.371

r ² 0.897 0.730 0.817

a

TSCA ITC 原型模式：predictive model estimating skin exposure hazard potential of chemical using occupational exposure limit (OEL) as the reference concentration in inhalation dose derivation, also referred to in the table as OEL-based model;

TSCA ITC 修正模式：predictive model using inhalational lethal concentration 50%

(LC

50

) or lowest observed lethal concentration (LCLo) in inhalation dose derivation, also referred to as LC

50

- or LCLo-based model;

SI ratio: ratio of skin dose to inhalation dose as described in Eqs. 3-1 and 3-3 (循 Eqs.

3-1 及 3-3 所述模式推導而得之化學物皮膚暴露危害潛能預測值);

SN: skin notation (皮膚標記符號).

表4-6 具四個以上 SN 化學物據 TSCA ITC 原型與修正模式產生之 SI ratio^a與SN 個數之對數線性迴歸關係(化學物經皮暴露之危害潛能 等級依SN 個數 7/6、5、4 區分為高、中及低三危害等級) ^a

All chemicals with 4 or more SNs SI ratio

(OEL-based model)

^a

SI ratio

(LC

50

-based model)

^a

SI ratio

(LCLo-based model)

^a Intercept -3.038 -4.009 -4.916

Slope 0.592 0.338 0.472

r ² 0.972 0.898 0.847

a

TSCA ITC 原型模式：predictive model estimating skin exposure hazard potential of chemical using occupational exposure limit (OEL) as the reference concentration in inhalation dose derivation, also referred to in the table as OEL-based model;

TSCA ITC 修正模式：predictive model using inhalational lethal concentration 50%

(LC

50

) or lowest observed lethal concentration (LCLo) in inhalation dose derivation, also referred to as LC

50

- or LCLo-based model;

SI ratio: ratio of skin dose to inhalation dose as described in Eqs. 3-1 and 3-3 (循 Eqs.

3-1 及 3-3 所述模式推導而得之化學物皮膚暴露危害潛能預測值);

SN: skin notation (皮膚標記符號).

表 4-7 七 SN 數目群組之標的化學物經 Haz-Map 系統分類產生之八種化學物類別及各類別個數^a

Number of SNs 7 6 5 4 3 2 1 Total

Solvents

9 8 8 12 11 19 18 85

Nitrogen compounds

3 11 11 11 7 12 28 83

Pesticides

0 3 16 10 5 11 18 63

Toxic gases and vapors

2 3 4 6 1 6 14 36

Plastics and rubber

0 1 1 3 2 2 11 20

Other chemicals

1 0 5 7 9 7 26 55

Biological agents

0 0 0 0 0 0 1 1

Metals

1 3 2 1 0 4 6 17

Unknown

0 1 1 1 5 9 103 120

Total

16 30 48 51 40 70 225 480

a SN: skin notation (皮膚標記符號);

Haz-Map: US National Library of Medicine Occupational Exposure to Hazardous Agents Database (美國國家醫學圖書館危害物質 職業暴露資料庫).

表 4-8 所有類別化學物^a與主要暴露途徑含皮膚暴露化學物^b依據TSCA ITC 原型與修正模式產生之 SI ratio 分佈比較

SI ratio (OEL) SI ratio (LC

₅₀

) SI ratio (LCLo) Median

All

^a

Skin-relevant

^b

All

^a

Skin-relevant

^b

All

^a

Skin-relevant

^b

7 SNs

^c

3.6710 3.3864 0.0122 0.0118 0.0107 0.0107

6 SNs 3.7031 3.7031 0.0189 0.0426 0.0124 0.0245

5 SNs 0.6370 0.5463 0.0036 0.0009 0.0016 0.0012

4 SNs 0.2430 0.2430 0.0026 0.0072 0.0012 0.0015

Wilcoxon -1.342 -0.73 -0.535

P(T≦t) 雙尾 0.18 0.465 0.593

non-significant non-significant non-significant

a All: all chemicals selected as target compounds in this study, including those classified as “solvents,” “Nitrogen compounds,” “pesticides,” “toxic gases and vapors,” “plastics and rubber,” “Other chemicals,” “biologicl agents,”

“metals,” and “unknown” according to the US National Library of Medicine Occupational Exposure to Hazardous Agents database classification (Haz-Map) system (含本研究中所有類別化學物);

b Skin-relevant: chemicals for which skin exposure is considered a relevant route of exposure, including those classified as

“solvents,” “Nitrogen compounds,” “pesticides,” and “toxic gases and vapors” by Haz-Map (含 Haz-Map 分類系統中 solvents、Nitrogen compounds、pesticides 及 toxic gases and vapors 四類化學物).

表 4-9 具四個以上 SN 且主要暴露途徑含皮膚暴露之化學物依據 TSCA ITC 原型與修正模式產生之 SI ratio^a與SN 個數之對數線性迴歸關 係(化學物經皮暴露之危害潛能等級依化學物所具有之 SN 個數區 分為四級；依序為等級七、六、五及四)

Skin-relevant chemicals

^b

with 4 or more SNs SI ratio

(OEL-based model

^a

)

SI ratio

(LC

50

-based model

^a

)

SI ratio

(LCLo-based model

^a

)

Intercept -2.290 -3.376 -4.443

Slope 0.426 0.229 0.384

r ² 0.876 0.185 0.596

a

TSCA ITC 原型模式：predictive model estimating skin exposure hazard potential of chemical using occupational exposure limit (OEL) as the reference concentration in inhalation dose derivation, also referred to in the table as OEL-based model;

TSCA ITC 修正模式：predictive model using inhalational lethal concentration 50%

(LC

50

) or lowest observed lethal concentration (LCLo) in inhalation dose derivation, also referred to as LC

50

- or LCLo-based model;

SI ratio: ratio of skin dose to inhalation dose as described in Eqs. 3-1 and 3-3 (循 Eqs.

3-1 及 3-3 所述模式推導而得之化學物皮膚暴露危害潛能預測值);

SN: skin notation (皮膚標記符號).

b

Skin-relevant chemicals: chemicals for which skin exposure is considered a relevant route of exposure, including hose classified as “solvents,” “Nitrogen compounds,”

“pesticides,” and “toxic gases and vapors” by Haz-Map (含 Haz-Map 分類系統中

solvents、Nitrogen compounds、pesticides 及 toxic gases and vapors 四類化學物).

表 4-10 主要暴露途徑含皮膚暴露化學物^a與主要暴露途徑為皮膚暴露化學物^b依據TSCA ITC 原型與 修正模式產生之SI ratio 分佈比較

SI ratio (OEL) SI ratio (LC

₅₀

) SI ratio (LCLo) Median

Skin-relevant

^a

Skin-dominant

^b

Skin-relevant

^a

Skin-dominant

^b

Skin-relevant

^a

Skin-dominant

^b

7 SNs 3.3864 2.8620 0.0118 0.0078 0.0107 0.0076

6 SNs 3.7031 1.4016 0.0426 0.0189 0.0245 0.0124

5 SNs 0.5463 0.5463 0.0009 0.0007 0.0012 0.0008

4 SNs 0.2430 0.2286 0.0072 0.0013 0.0015 0.0010

Wilcoxon -1.604 -1.826 -1.826

P(T≦t) 雙尾 0.109 0.068 0.068

non-significant non-significant non-significant

a Skin-relevant: chemicals for which skin exposure is considered a relevant route of exposure, including those classified as

“solvents,” “Nitrogen compounds,” “pesticides,” and “toxic gases and vapors” by Haz-Map (含 Haz-Map 分類系統中 solvents、Nitrogen compounds、pesticides 及 toxic gases and vapors 四類化學物);

b Skin-dominant: chemicals for which skin exposure is considered the dominant route of exposure, including those classified as “solvents,” “Nitrogen compounds,” and “pesticides” by Haz-Map (含 Haz-Map 分類系統中 solvents、Nitrogen compounds、及 pesticides 三類化學物).

表4-11 具四個以上 SN 且主要暴露途徑為皮膚暴露之化學物依據 TSCA ITC 原型與修正模式產生之 SI ratio^a與SN 個數之對數線性迴歸 關係(化學物經皮暴露之危害潛能等級依化學物所具有之 SN 個 數區分為四級；依序為等級七、六、五及四)

Skin-dominant chemicals

^b

with 4 or more SNs SI ratio

(OEL-based model

^a

)

SI ratio

(LC

50

-based model

^a

)

SI ratio

(LCLo-based model

^a

)

Intercept -2.111 -4.565 -4.634

Slope 0.370 0.380 0.383

r ² 0.997 0.538 0.677

a

TSCA ITC 原型模式：predictive model estimating skin exposure hazard potential of chemical using occupational exposure limit (OEL) as the reference concentration in inhalation dose derivation, also referred to in the table as OEL-based model;

TSCA ITC 修正模式：predictive model using inhalational lethal concentration 50%

(LC

50

) or lowest observed lethal concentration (LCLo) in inhalation dose derivation, also referred to as LC

50

- or LCLo-based model;

SI ratio: ratio of skin dose to inhalation dose as described in Eqs. 3-1 and 3-3 (循 Eqs.

3-1 及 3-3 所述模式推導而得之化學物皮膚暴露危害潛能預測值);

SN: skin notation (皮膚標記符號).

b

Skin-dominant chemicals: chemicals for which skin exposure is considered the dominant route of exposure, including those classified as “solvents,” “Nitrogen compounds,” and “pesticides” by Haz-Map (含 Haz-Map 分類系統中 solvents、

Nitrogen compounds、及 pesticides 三類化學物).

表4-12 具四個以上 SN 之 solvent 類化學物依據 TSCA ITC 原型與修正 模式產生之 SI ratio^a與 SN 個數之對數線性迴歸關係(化學物經 皮暴露之危害潛能等級依化學物所具有之 SN 個數區分為四 級；依序為等級七、六、五及四)

Solvents with 4 or more SNs SI ratio

(OEL-based model)

^a

SI ratio

(LC

50

-based model)

^a

SI ratio

(LCLo-based model)

^a Intercept -4.185 -6.112 -5.823

Slope 0.683 0.609 0.507

r ² 0.976 0.988 0.996

a

TSCA ITC 原型模式：predictive model estimating skin exposure hazard potential of chemical using occupational exposure limit (OEL) as the reference concentration in inhalation dose derivation, also referred to in the table as OEL-based model;

TSCA ITC 修正模式：predictive model using inhalational lethal concentration 50%

(LC

50

) or lowest observed lethal concentration (LCLo) in inhalation dose derivation, also referred to as LC

50

- or LCLo-based model;

SI ratio: ratio of skin dose to inhalation dose as described in Eqs. 3-1 and 3-3 (循 Eqs.

3-1 及 3-3 所述模式推導而得之化學物皮膚暴露危害潛能預測值);

SN: skin notation (皮膚標記符號).

圖1-1 本論文研究之研究架構與預設進程(SN：皮膚標記符號；LD₅₀： 皮膚半致死劑量；log K_OW：正辛醇─水分配係數對數值；LC：

呼吸致死濃度；TSCA ITC 預測模式：皮膚暴露危害預測模式；

圖1-2 本研究使用箱型圖(Box-Plot)中各百分位數之區間表示

90%

95%

50%

25%

10%

5%

75%

圖 2-1 美國 ACGIH (US)與丹麥(DK)、荷蘭(NL)、德國(DE)、波蘭(PL) 及斯洛伐克(SLO)等五國間 SN 之差異⁽⁸⁾

圖2-2 用於判斷化學物是否為皮膚暴露危害因子之臨床及動物實驗數 據⁽⁹⁾

結構–活性 關係分析

單次暴露急性系統毒 初級皮膚刺激及侵蝕

局部傷害 經皮吸收系統毒

皮膚暴露毒害鑑識之科學數據

癌症或標的器官/

生物系統健康效應 皮膚刺激(臨床案例)

皮膚過敏

亞慢性及慢 性系統毒 重複暴露(亞急性)系統毒

圖2-3 NIOSH 授予 SN 化學物經由皮膚接觸所引發之主要負面健康效 應⁽⁹⁾

0 10 20 30 40 50

急性毒 (高)

急性毒 (臨界)

癌症 慢性毒 皮膚 刺激

重度皮膚 刺激及

侵蝕

結構–

活性 關係 負面健康效應

化學物數目佔全體SN總數百分比(%)

圖4-1 具不同數目皮膚標記符號(number of SNs)化學物之皮膚半致死劑 量(dermal LD₅₀)分佈箱型圖

Number of SNs

1 2

3 4

5 6

7

Dermal LD

₅₀

(mg/Kg)

1e-2

1e-1

1e+0

1e+1

1e+2

1e+3

1e+4

1e+5

1e+6

圖4-2 具不同數目皮膚標記符號(number of SNs)化學物之正辛醇─水分 配係數對數值(log K_OW)分佈箱型圖

Number of SNs

1 2

3 4

5 6

7

Log K

_OW

-10

-5

0

5

10

圖4-3 具不同數目皮膚標記符號(number of SNs)化學物之 TSCA ITC 原 型模式(TSCA ITC model)預測值(SI ratio)分佈箱型圖

Number of SNs

1 2

3 4

5 6

7

SI Ratio (TSCA ITC Model)

1e-5

1e-4

1e-3

1e-2

1e-1

1e+0

1e+1

1e+2

1e+3

1e+4

1e+5

Dermal LD50 availability (%)

0%

20%

40%

60%

80%

100%

7 6 5 4 3 2 1

Number of SNs

Rabbit Guinea pig Rat Mouse

圖4-4 具不同數目皮膚標記符號(number of SNs)化學物所有之皮膚半致 死劑量(dermal LD₅₀)源自兔子(rabbit)、天竺鼠(guinea pig)、大鼠 (rat)、及小鼠(mouse)等四類囓齒類動物之比例

圖4-5 具不同數目皮膚標記符號(number of SNs)化學物源自兔子(rabbit) 之皮膚半致死劑量(dermal LD₅₀)分佈箱型圖

Number of SNs

1 2

3 4

5 6

7

Rabbit dermal LD

₅₀

(mg/Kg)

1e-1

1e+0

1e+1

1e+2

1e+3

1e+4

1e+5

圖4-6 不同數目皮膚標記符號(number of SNs)化學物以呼吸半致死劑量 修正模式(LC₅₀-based model)所產生之皮膚暴露危害預測值(SI ratio)分佈箱型圖(圖中虛線值 0.0004 表依 NIOSH 對 TSCA ITC 原 型模式危害辨識恕限值推論之LC50修正模式恕限值)

Number of SNs

1 2

3 4

5 6

7

SI Ratio (LC

₅₀

-Based Model)

1e-11

1e-10

1e-9

1e-8

1e-7

1e-6

1e-5

1e-4

1e-3

1e-2

1e-1

1e+0

1e+1

1e+2

圖4-7 不同數目皮膚標記符號(number of SNs)化學物以最低呼吸致死劑 量修正模式(LCLo-based model)所產生之皮膚暴露危害預測值(SI ratio)分佈箱型圖(圖中虛線值 0.0002 表依 NIOSH 對 TSCA ITC 原 型模式危害辨識恕限值推論之LCLo 修正模式恕限值)

Number of SNs

1 2

3 4

5 6

7

SI Ratio (LCLo-Based Model)

1e-10

1e-9

1e-8

1e-7

1e-6

1e-5

1e-4

1e-3

1e-2

1e-1

1e+0

1e+1

1e+2

1e+3

0 20 40 60 80 100

7 6 5 4 3 2 1

Number of SNs

Availability of LC

50

(%)

Rodent Mouse Rat

Guinea Pig Rabbit

圖 4-8 具不同數目皮膚標記符號(number of SNs)化學物所有之呼吸半致死劑量(inhalational LC₅₀)依囓齒類動物整體 (rodent)與依兔子(rabbit)、天竺鼠(guinea pig)、大鼠(rat)、及小鼠(mouse)等四類動物區分之有效數據百分比

0 20 40 60 80 100

7 6 5 4 3 2 1

Number of SNs

Availability of LCLo (%)

Rodent Mouse Rat

Guinea Pig Rabbit

圖 4-9 具不同數目皮膚標記符號(number of SNs)化學物所有之最低呼吸致死劑量(inhalational LCLo)依囓齒類動物 整體(rodent)與兔子(rabbit)、天竺鼠(guinea pig)、大鼠(rat)、及小鼠(mouse)等四類動物區分之有效數據百分比

圖4-10 具 4 個以上皮膚標記符號(SN)之化學物以 TSCA ITC 原型與修正 模式計算而得皮膚暴露危害預測值(SI ratio)對數值與皮膚暴露危 害等級(Hazard Level)之線性關係(屬危害等級 7、6、5 及 4 之化學 物分別具有7、6、5 及 4 SNs；SI ratio (OEL)、SI ratio (LC₅₀)、及 SI ratio (LCLo)分別為經由 TSCA ITC 原型、呼吸半致死劑量與最 低呼吸致死劑量修正模式推估之SI ratio)

Hazard level

3 4

5 6

7 8

SI Ratio

1e-5 1e-4 1e-3 1e-2 1e-1 1e+0 1e+1 1e+2

SI Ratio (OEL) SI Ratio (LC₅₀) SI Ratio (LCLo)

圖4-11 具 4 個以上皮膚標記符號(SN)之化學物以 TSCA ITC 原型與修正 模式計算而得皮膚暴露危害預測值(SI ratio)對數值與皮膚暴露危 害等級(Hazard Level)之線性關係(屬危害等級 6、5 及 4 之化學物 分別具有7 加 6、5 及 4 SNs；SI ratio (OEL)、SI ratio (LC₅₀)、及 SI ratio (LCLo)分別為經由 TSCA ITC 原型、呼吸半致死劑量與最 低呼吸致死劑量修正模式推估之SI ratio)

Hazard level

3 4

5 6

7

SI Ratio

1e-5 1e-4 1e-3 1e-2 1e-1 1e+0 1e+1 1e+2

SI Ratio (OEL) SI Ratio (LC₅₀) SI Ratio (LCLo)

0 20 40 60 80 100

7 6 5 4 3 2 1 Total

N u m b e r o f SN

SI ratio (OEL) SI ratio (LC50) SI ratio (LCLo) Pe rc e n ta g e o f SI Ra tio a b o v e

H a z a rd -R e c o g n iz in g Th re sh o ld (% )

圖 4-12 具不同數目皮膚標記符號(number of SNs)之標的化學物其 TSCA ITC 原型與修正模式皮膚暴露危害預測值 (SI ratio)高於各模式危害辨識恕限值(hazard-recognizing threshold)之比例與分佈(SI ratio (OEL)、SI ratio (LC₅₀)、及 SI ratio (LCLo)分別為經由 TSCA ITC 原型、呼吸半致死劑量與最低呼吸致死劑量修正模式推估

17.7%

17.3%

13.1%

4.2% 7.5%

11.5%

0.2%

3.5%

25.0%

Solvents

Nitrogen Compounds Pesticides

Toxic Gases & Vapors Plastics & Rubber Other Chemicals Biological Agents Metals

Unknown

圖4-13 標的化學物經由美國國家醫學圖書館 Haz-Map 資料庫系統分類後各類別化學物佔所有化學物之比例

圖4-14 屬美國國家醫學圖書館 Haz-Map 資料庫分類系統中 solvents、

nitrogen compounds、pesticides 及 toxic gases and vapors 四類、具

nitrogen compounds、pesticides 及 toxic gases and vapors 四類、具

在文檔中 制定皮膚標記符號科學準則建立與比較; Development and Comparison of Scientific Criteria for Application in Assignment of Skin Notations (頁 83-173)