化学物質管理専門家養成講習テキスト
公益社団法人 日本作業環境測定協会

まえがき

i

まえがき
令和 4 年 5 月の労働安全衛生規則等の改正で新たに「化学物質管理専門家」が導入され、作業環境測定士としての業務経験が 6 年以上の者は、厚生労働省労働基準局長が定める講習を修了すればこれに該当することとされました。
その後、通達により講習のカリキュラムや講習実施者などが示されました。
本書は、通達で示されたカリキュラムに則して、当該講習のテキストとして編集したものです。当協会では、わが国におけるオキュペイショナルハイジニストの養成のため平成20 年から認定オキュペイショナルハイジニスト養成事業を実施してきました。今回通達で示された「化学物質管理専門家」養成のためのカリキュラムは、分野が極めて多岐にわたっていますが、このハイジニスト養成事業のカリキュラムの一部を基に組み立てられたものと聞いています。
このため、当協会では、この講習テキストの編集にあたり、オキュペイショナルハイジニスト養成事業のこれまでの経験を活かして、それぞれの章の内容ができるだけ有機的につながり全体として理解しやすいものとなるように努めました。
本書が「化学物質管理専門家」を目指す測定士の皆様の化学物質リスク管理にかかるさらなる専門知識の習得あるいは整理に役立つものとなれば幸いに存じます。

令和 5 年 9 月
公益社団法人日本作業環境測定協会

ii 目次目次

第1章

有害物質の体内動態（ばく露，吸収及び分布，代謝）と生体影響，有害性試験 ······11.1

化学物質等による毒性総論 ········································································································· 11.1.1

化学物質等による毒性 ··········································································································· 1

1.1.2

標的臓器の医学，機能と生理学 ························································································· 71.2

毒性物質の体内動態 ···················································································································· 111.2.1

化学物質の生体内動態，吸収，分布，代謝，排泄 ···················································· 11

1.2.2

化学物質の細胞レベルの酵素反応と毒性の発現機序 ················································ 181.3

化学物質等の人体への作用形態とばく露限界値等の設定 ·············································· 37

1.3.1

化学物質の人体への作用形態 ···························································································· 37

1.3.2

職業性がんの歴史·················································································································· 38

1.3.3

発がん物質 ······························································································································· 39

1.3.4

化学発がん ······························································································································· 40

1.3.5

ヒト発がん性物質·················································································································· 43

1.3.6

職業性がん（職業がん） ···································································································· 45

1.3.7

毒性試験の意義と種別 ········································································································· 47

第2章

化学物質等の人体への作用形態とばく露限界等···································································· 53

1

量－影響関係と量－反応関係 ······································································································ 542

閾値とばく露限界の設定の仕方 ·································································································· 582.1

閾値とばく露限界 ····················································································································· 58

2.2

ばく露限界値の設定 ················································································································· 59

3

ばく露限界値と集団の中の健康影響の現れ方········································································ 634許容濃度と TLV ································································································································ 645欧州化学物質庁が推奨する UF その他の考え方 ···································································· 66

6発がん性とばく露限界 ··················································································································· 69

目次iii

7農薬のばく露限界値 ························································································································ 71

8エキスパート判断における配慮事項 ························································································· 71

9ばく露限界値の現状とこれからの在り方 ················································································ 72

第3章
1

化学物質の危険性及び有害性の情報並びに表示等 ······························································· 73

ハザード情報とその区分 ··············································································································· 73
1.1

労働環境のハザード ················································································································· 73

1.2

ハザード分類の世界的な統一の動き ·················································································· 74

1.3

国連 GHS 勧告とハザードクラス（化学物質の健康有害性と危険性の分類） ····· 75

1.3.1

日本の化学物質管理法と国連 GHS 勧告との関係 ··················································· 75

1.3.2

国連 GHS 勧告と SDS およびラベルの関係 ······························································· 77

1.3.3

国連 GHS 勧告の分類（クラス）と区分（カテゴリー：等級）_第 9 版 ·········· 78

1.4GHS ラベル，SDS の作成，更新の作成 ············································································· 82

1.4.1

2022 年 5 月 31 日施行の「労働安全衛生法規則等の一部を改正する省令」による SDS の変更点·········································································· 82

1.4.2

日本における国連 GHS 勧告に基づくモデル SDS およびラベルの現状 ········· 83

1.4.3

ハザード（危険性・有害性）クラスごとの特徴····················································· 90

第4章

労働環境における化学物質のリスク評価・リスクとばく露管理 ································· 95

1はじめに ·············································································································································· 95

2

ばく露限界値と管理濃度 ··············································································································· 96

3

ばく露評価の方法 ·························································································································· 100
3.1

NIOSH の方法 ··························································································································· 100

3.2

AIHA の方法 ······························································································································ 103

3.3

欧州規格 ····································································································································· 1053.4

日本産業衛生学会のガイドラインの方法 ······································································· 1064

個人ばく露測定による管理の進め方 ······················································································· 1095

個人ばく露測定のためのサンプリング機器 ·········································································· 109

6

個人サンプリング法（C・D 測定）························································································· 113

7A・B 測定，C・D 測定の特徴とその適用対象 ····································································· 120

iv 目次8

作業環境測定のリスク判定，リスク管理への応用 ····························································· 1229

個人ばく露測定と作業環境測定の相違点と化学物質管理専門家等の必要性 ············ 124

10

生物学的モニタリング ··············································································································· 127

10.1

生物学的モニタリングとは何か？ ·················································································· 127

10.2

労働衛生行政の進展と生物学的モニタリングの歴史 ··············································· 129

10.3

ばく露評価のための基準値・指標値 ·············································································· 129

10.4

生物学的モニタリングの測定試料と測定対象 ···························································· 130

10.5

代表的な指標の例～トルエンばく露により生成する馬尿酸 ·································· 130

10.6

生物学的モニタリングの測定対象の代謝 ····································································· 130

10.7

ばく露量・気中濃度とばく露指標との関係 ································································· 131

10.8

ジクロロメタンのばく露指標 ··························································································· 134

10.9

生物学的モニタリングの実施基準 ·················································································· 134

10.10

生物学的モニタリングの一般的な実施手順 ······························································ 135

10.11

生物学的半減期と生体試料の最適採取時期 ······························································ 135

10.12

吸収・分布・代謝・排泄（ADME）に影響を与えうる要因 ································· 13610.13

測定が義務付けられている生物学的モニタリングの指標物質 ··························· 138

10.14

生物学的モニタリングの実施の例外············································································ 143

10.15

いろいろな尿試料と測定値の補正 ················································································ 144

10.16

尿中馬尿酸と尿中総三塩化物の測定例における尿比重補正とクレアチニン補正の比較·································································································· 145

10.17

極端に濃い尿・薄い尿に関する ACGIH/BEI 委員会の見解·································· 146

10.18

有機溶剤ばく露の指標としての尿中代謝物濃度の分布の区分 ··························· 147

10.19

生物学的モニタリングの結果のまとめと結果報告書 ············································· 14810.20

異なる物質のばく露により同一の代謝物が生じるとき········································· 149

10.21

生物学的モニタリングの分布区分の結果と指導 ······················································ 150

10.22

生物学的モニタリングの結果の活用············································································ 152

10.23

生物学的モニタリングの利点 ························································································· 152

10.24

生物学的モニタリングの問題点・注意点 ··································································· 153

10.25

これからの生物学的モニタリング ················································································ 154

10.26

新たなモニタリングマーカーの研究開発例 ······························································ 156

10.27

生物学的モニタリングのまとめ ···················································································· 156

目次第5章1

労働環境における化学物質のリスクの評価・リスクとばく露管理 ·························· 158

リスクの評価と手順，方法········································································································· 158
1.12v

リスクの評価・リスクの管理の手法及び手順 ······························································ 158

1.1.1

リスクの評価の 4 段階の考え方 ················································································· 158

1.1.2

簡易測定法及び推定法と適用の注意事項等 ··························································· 170

1.1.3

ばく露濃度推計モデル，ボックスモデル等 ··························································· 198

リスク管理の方法・優先順位 ···································································································· 222
2.1

リスク管理の方法の優先順位 ····························································································· 222

3

事例研究 ············································································································································ 2274

化学物質等による危険性又は有害性等の調査等に関する関係法令等 ·························· 236

第6章
12

化学物質等の危険又は有害性等の調査の結果に基づく措置等 ···································· 238

有害化学物質等の発散抑制のための工学的対策と管理 ···················································· 238
1.1

工学的対策の概要 ··················································································································· 2381.2

有害物質の製造，使用等の禁止および使用中止 ·························································· 2411.3

有害性の低い物質への転換·································································································· 2411.4

生産工程，作業方法の改良による有害物質の発散防止 ············································· 243

1.5

設備の密閉化，自動化，遠隔操作，有害工程の隔離 ················································· 244

1.6

局所排気装置 ···························································································································· 246

1.7

プッシュプル型換気装置 ······································································································ 266

1.8

局所排気装置等の定期自主検査 ························································································· 271

1.9全体換気装置 ···························································································································· 272

1.10

多様な発散防止抑制措置 ···································································································· 274

1.11

作業管理による不要なばく露の防止 ·············································································· 275

1.12

安全面の対策 ·························································································································· 277

排ガス・粉じん・廃液の処理技術 ··························································································· 2792.1

除じん装置 ································································································································ 279

2.2

排ガス処理装置 ······················································································································· 290

2.3

廃液処理法 ································································································································ 292

vi 目次3

労働衛生保護具······························································································································· 294
3.1

呼吸用保護具 ···························································································································· 294

3.2

皮膚の保護具 ···························································································································· 310

3.3

眼と顔面の保護具 ··················································································································· 311

3.4

聴覚保護具（防音保護具）·································································································· 312

1.1

化学物質等による毒性総論 1

第 1 章 有害物質の体内動態（ばく露，吸収及び分布，代謝）と生体影響，有害性試験

1.1 化学物質等による毒性総論
1.1.1 化学物質等による毒性
1）化学物質の毒性とばく露期間
現代においては，様々な化学物質が産業職場において用いられているが，化学物質は生物及び環境に対して有害な影響を持つものが多い．この有害な影響が化学物質の毒性である．化学物質を毒性物質として理解するには，様々な視点からとらえることが有用である．
毒性は，人体を構成し又は機能を維持するのに必要な化学物質以外の（その意味では，ヒトの生命活動には不要な）化学物質が，ある量以上，人体の表面に接触しているか，人体内に存在するときに発現する．その人体にとって不要な化学物質と人体にとって必要な化学物質が何らかの化学反応を起こすことが，ほとんどの毒性の発現機序に関わっていると思われる．
毒性と化学物質の有害性は同じ意味の言葉として使われている．すべての化学物質は何らかの有害性を示す．天然物質にも，人体内で生成する化学物質にも，有害性はある．ば
く露する量（接触・吸入など）が少なければ，有害性が現実化しないということである．
例えば細胞レベルにおける生体反応に当該化学物質が作用することで一時的な有害影響（反応に関わる酵素が分解されて減少するなど）が生じても，ばく露が減少する，または無くなることにより正常な反応に復帰すれば，ヒトの健康に影響を与えるには至らない可能性が高い．
化学物質のヒトに対する危険有害性は，表 1.1 のように多種多様なものがある．2003 年に国連が勧告した GHS のハザード分類では，人の健康に対する有害性として表 1.2 に示した 10 クラス（種類）に分類している．さらに，急性毒性におけるばく露経路による違いなどのサブクラス（小分類）がある．
なお影響とは，化学物質によって引き起こされる生体の変化をいう．健康度の低下と考えられる影響は，「健康にとって不利な影響（Adverse effect）」といい，その他の影響は，「健康にとって不利でない影響（Non-adverse effect）」という．健康にとって不利でないか否かを判定するのは難しいことが多い．
化学物質の毒性影響を，そのばく露期間別に捉えることは一般的に行われる 2）．すなわ

2 第 1 章 有害物質の体内動態（ばく露，吸収及び分布，代謝）と生体影響，有害性試験

ち，急性（24 時間以内に現れる影響），亜急性（1 か月以内），亜慢性（1～3 か月），慢性（3 か月以上）影響と分けられる．内閣府食品安全委員会では，化学物質の 1 回の投与（ばく露）又は短期間（24 時間以内）の複数回投与によって短期間（一般的には 14 日以内）に生じる毒性のことを「急性毒性」と，比較的短期間（通常 1 か月〜3 か月程度）の反復投与によって生じる毒性のことを亜急性毒性（亜慢性毒性）と，長期間（通常 6 か月以上）の反復投与によって生じる毒性のことを慢性毒性としている．一方，数日未満のばく露で成立する中毒を急性中毒，数か月以上のばく露で成立する中毒を慢性中毒，中間を亜急性中毒という場合もある．
，つ急性影響に用いられる指標として，半数致死量（LD50, lethal dose 50％ of population）まり急性投与において半数のヒト（動物）が死亡する用量がある．また半数影響量（ED50effective dose），50％のヒト（動物）に効果が現れる用量を指標として用いる場合もある．
産業職場で急性の影響（急性中毒）が現れるときは，相対的に大きなばく露を受けるとき，例えば事故などから高いレベルのばく露があったときが多い．急性中毒が起きない程度であっても有害なレベルのばく露を継続して受けていると，亜急性中毒や，慢性中毒が起こる．慢性影響は，比較的低いレベルのばく露が繰り返して起きたときに現れ，産業職場で問題になることが多い．同じ化学物質でも，ばく露を受ける濃度及び期間により中毒（急性，亜急性，慢性）の症状は異なることが多いが，同じこともある．例えば，有機溶剤類のほとんどすべては麻酔作用を持つので，高い濃度の空気を吸入すると，短時間で麻酔作用（中枢神経機能の抑制）が現れ，低い濃度に長期間ばく露するとベンゼンは白血病を起こし，n－ヘキサンは末梢神経障害を起こす．

表 1.1

ヒトに対する危険有害性（1）可燃性・爆発性（2）刺激性（皮膚，目，呼吸器）（3）腐食性（4）急性毒性（酸素欠乏を含む）（5）慢性毒性（6）変異原性（7）発がん性（8）感作性（皮膚感作性，呼吸器感作性）（9）免疫毒性（感作性以外の免疫異常）（10）神経毒性（中枢神経，知覚神経，運動神経，自律神経）（11）生殖毒性（卵巣，子宮，精巣，前立腺，高次の内分泌系，その他）（12）遺伝毒性（13）発生毒性（14）胎児毒性（15）内分泌かく乱作用（受容体毒性）

1.1

化学物質等による毒性総論 3（16）内分泌臓器障害性（脳下垂体，甲状腺，副甲状腺，副腎，卵巣，精巣，膵臓）（17）呼吸器毒性（気管，気管支，肺胞，間質）（18）その他の諸臓器，組織に対する毒性（眼，内耳，心臓，血管系，肝臓，胆道，膵臓，消化管，腎臓，脾臓，造血器，血液，皮膚，毛髪，筋肉，骨，関節，結合組織，細網内皮系組織）

表 1.2

GHS 分類による人に対する有害性の分類

1

急性毒性

物質の経口または経皮からの単回投与，あるいは 24 時間以内に与えられる複数回投与ないしは 4 時間の吸入ばく露によっておこる有害な影響．
小分類：
「経口」
，「経皮」，「気体」，「蒸気」，「粉塵・ミスト」

2

皮膚腐食性/刺激性それぞれ，皮膚に対する不可逆的な/可逆的な損傷を生じさせること．

3眼に対する重篤な損傷性/眼刺激性

眼の表面に試験物質を付着させることによる，眼の組織損傷の生成，あるいは重篤な視力低下．

4

呼吸器感作性または皮膚感作性それぞれ，物質の吸入の後で気道過敏症を引き起こすこと，物質との皮膚接触の後でアレルギー反応を引き起こすこと．気道刺激性は特定標的臓器毒性（単回ばく露）に分類する．

5

生殖細胞変異原性

主として，ヒトにおいて次世代に受継がれる可能性のある突然変異を誘発すると思われるもの．

6

発がん性

がんを誘発するか，またはその発生率を増加させるもの．

7

生殖毒性

雌雄の成体の生殖機能および受精能力に対する悪影響に加えて，子の発生毒性も含まれる．

8

特定標的臓器毒性（単回ばく露）

単回ばく露によって，特定の標的となる臓器に対する毒性があるか，およびそれにばく露したヒトに対して健康に有害な影響を及ぼす可能性があるかを示す．ここに，気道刺激性を分類する．

9

特定標的臓器毒性（反復ばく露）

反復ばく露によって，特定の標的となる臓器に対する毒性があるか，およびそれにばく露したヒトに対して健康に有害な影響を及ぼす可能性があるかどうかを示す．

10 吸引性呼吸器有害性

誤嚥後に化学肺炎，種々の程度の肺損傷を引き起こす，あるいは死亡のような重篤な急性の作用．

2）化学物質の毒性と物理的性質（性状）等化学物質の毒性を考える際に，その空気中の物理的性質（性状）から捉える考え方も有用である．我々は労働しているとき，そうでないときにかかわらず，常に呼吸をしながら生命を維持しているために，必然的に空気を取り込まなければならず，人体の周囲の空気中の化学物質の性状は重要である．一般に通常の生活条件では人は 1 日 2 万回以上の呼吸で 15 m3 程度の空気を吸引しているが，作業負担が大きくなれば 1 日 30 m3 程度の空気を吸入する．化学物質は，その利用形態により，物理的形状に変化を来し，空気中においてはガス（gas），蒸気（vapor）の気体か，粉じん（dust），フューム（fume），ミスト（mist）等の粒子状物質（aerosol）して存在する 26）．この物理的性状により，人体への侵入が変わってくる．有害な気体状の化学物質と粒子状の化学物質が，職場の環境の空気中に存在し，潜在的な人への危険性・有害性を示す化学的ハザードとなっている．