資料

１

エチレンの使用状況について
エチレンは植物自身が作り出す植物ホルモンとして、その多様な生理活性作用が古くから知られていた。その作用を利用した植物生育調節剤としてエテホン液剤（商品名：エスレル 10 など）
が果樹、トマト、キク、カボチャなどの多くの作物を対象として利用されている。エテホン液剤の成分は 2-クロロエチルホスホン酸であり、水溶液として作物に散布される。植物体内において散布後 1～2 日以内にほとんどが分解してエチレン（ガス）を発生し、効果を発現する機作となっている。このため、この農薬の人畜などへの安全性はエチレンではなく、エテホン（2-クロロエ
チルホスホン酸 ）の安全性が検討され、農薬登録がされている。
コーデックス委員会は、エチレンをバナナとキウイフルーツを追熟させるために有機農産物生産への使用が可能な資材として認定している。それを受けて国内でも同様の措置がとられており（有機農産物の農林規格 資料６）
、バナナとキウイフルーツの追熟用に一般農業資材として利用されている。一方、エチレンがばれいしょの萌芽抑制に効果があることも広く知られており、既にカナダやイギリスでは農薬として登録、利用されている（資料７、８）。
エチレンによる貯蔵ばれいしょの萌芽抑制効果に関する諸外国の情報や研究報告をもとに、国内でもその実用化をめざして北海道馬鈴しょ協議会は、萌芽抑制効果などの確認のための試験を研究機関に委託し、また酪農学園大学を中心として平成 21 年から農林水産省の外部委託研究として「エチレンを用いた加工用馬鈴しょの萌芽抑制による高品質貯蔵技術の開発」が実施されてきた。さらに北海道内の農業協同組合やばれいしょ加工会社は、技術の早急な確立を目指して平成
21 年秋から貯蔵倉庫の一部にエチレンガスを利用した発芽抑制効果の実証試験を開始している。
実証試験に使用されているエチレンガス制御装置を図１に示したが、既存の貯蔵倉庫に付置するだけの簡単なものである。ばれいしょの貯蔵倉庫は低温・定温となるように、外気が高温時には冷房機が稼働し、外気が低温時には外気が導入されて、庫内の空気が常時攪拌され定温が保たれている。エチレンの分子量は 28 と空気の平均分子量と近似するため、庫内におけるガスの均一化は容易である。したがって庫内の一カ所からエチレンガスを噴霧し、他の１ないし２カ所で空気をサンプリングしてガス濃度を測定し、噴霧量を調節することにより庫内を一定のエチレン濃度に保つことができる。
実際、萌芽抑制の効果は明瞭で、貯蔵庫内の場所による偏りもなかった。このような実態からばれいしょの萌芽抑制手法の決め手として、今後は貯蔵庫におけるエチレンの利用が進むものと推察される。
これまでに得られた多くの知見から、エチレンは明確な萌芽抑制効果を有し、明らかに人畜および環境などへの有害な作用を及ぼすことがないと考えられる。

M

M

M

M

ばれいしょ
貯蔵庫

撹拌ファン

M

M

M

M

M

M

M

M

エチレン供給系統配管

ガス分析系統配管

外気導入管
戸外排気管
外気導入管

戸外排気管

分析制御盤

エチレン エチレン
ボンベ 調整器図１．エチレンガス制御装置の概要図（ＪＡ士幌で試用中）◆エチレンボンベ：100％液化エチレン 10kg
◆エチレン調整器：エチレンを空気で 1:200 に希釈し圧力を調整して供給する。
◆分析制御盤：各貯蔵庫内の空気を吸引してエチレンガス濃度を測定し、設定されたエチレ
ン濃度の下限を下回ると自動的にエチレンガスを供給、上限値で停止し、貯蔵庫内のエチ
レン濃度を自動制御する。全ての監視および操作は分析制御盤で行う。
◆各貯蔵庫内には鉄製コンテナーに収納されたばれいしょ７トンがおおむね 10 月頃から搬入され、エチレンを使用した発芽抑制貯蔵が開始される。
◆貯蔵庫内の温度は約８℃、湿度は９０％以上に制御され、また二酸化炭素濃度も測定、記録されている。
（参考）
１．ばれいしょ生産の現状
国内におけるばれいしょの年間需要量は約 3
6 0 万ｔであり、そのうち国内で生産・供給されるのは２７４万ｔと約８割の自給率である。
また北海道では約２１３万ｔが生産され、国産
ばれいしょの８ 割弱、年間需要量の約６ 割を供給する一大産地となっており、かつ畑作にお輸入
869千トン
(24%)

2008年
需要量
都府県
612千トン(17%)

3,612千トン(100%)

北海道
2,131千トン(59%)

資料 ： 農林水産省 食料需給表（２００８）」

図２．ばれいしょの供給状況

ける重要な基幹作物のひとつである（図２，数字はいずれも２００８年）。
ばれいしょは寒冷な気候に適した作物であることから、北海道では春に植え付けし秋に収穫されるが、都府県では秋冬に植え付けし、春～初夏に収穫される。国産ばれいしょは、生いもで流通する「青果（ 生食）用」のほか、ポテトチップス等に加工される「加工食品用」、でん粉に加工され片栗粉や清涼飲料用の異性化糖等に利用される「でん粉原料用」などに供給されている。
都府県産のバレイショは主として生食用および加工食品用として収穫後に速やかに消費されるが、年間需要の４分の１の期間に対応しているに過ぎない。一方、北海道産は生産量の約 50％はでん粉原料用として収穫後直ちに加工処理されるが、生食用および加工食品用は収穫後の秋から次年の夏まで貯蔵され、需要に応じて通年で利用されている。
２．ばれいしょ需要の動向
近年、食生活の多様化や外部化等が進む中で、総じて青果（ 生食）用としての需要量が減少し、フライドポテト等の加工食品用が増加する傾向にある。そのため、冷凍品等の形で輸入される加工食品用ばれいしょが増加し、国産のシェアが減少する傾向にある（図３，図４，図５）。
加工食品用

100%
80%

12%

12%

11%

28%

24%

22%

38%

20%
22%

32%

30%

32%

37%

平成9年

平成19年

100%

80%

青果用

60%

でん粉用

40%

56%
47%
37%

加工食品用

0%
昭和63年

青果用

100%

100%
その他

60%
40%

100%

資料 ： 農林水産省 「いも類の用途別消費実績調査」

図３．ばれいしょの用途別需要の推移
加工食品用ばれいしょ（ 約 1 3 5 万ｔ ）のうち、ポテトチップス用（ 約 2 9 万トン）はほぼ全量が国産で供給されており、大半が北海道産となっている。しかしながら後述するように、ばれいしょは低温で長期貯蔵した場合でん粉が糖類に変化して、ポテトチップス加工時に「焦げ」の原因となることから、通常、1 0℃ 前後で貯蔵される。しかし、この温度帯で貯蔵した場合には、春先までにいもが休眠から覚め、萌芽による品質低下や減耗が大きな問題となっている。このため、ポテトチッ
プス製造業者においては、新しい道産ばれいしょが収穫されるまでは、原料調達先を九州、関東、東北等の産地に切り換えているが、その品質と供給は必ずしも安定していない。

20%
0%
昭和63年

平成9年

平成19年

資料 ： 農林水産省 「いも類の用途別消費実績調査」

図４．ばれいしょの加工食品用・青果用の国産シェアの推移

図５．ばれいしょの用途別需要の推移

３．ばれいしょの貯蔵に関する問題
ばれいしょは水分含量が 75～80％であるため、穀物のように長期貯蔵には元来適していないものの、需要に応えるため低温（5～10℃程度）条件下で長期の保存をおこなっている。しかし品種によって早晩はあるものの、低温下でも数ヶ月を超えると萌芽（発芽）が始まる。萌芽はばれい
しょの外観上の商品価値を損なうのみならず、急激なでん粉含量の低下と還元糖の増加をもたらし、販売に適さない品質となる。とりわけ還元糖の増加は油で揚げた際に焦げ色を濃くし、商品価値を低下させると共に、発がん性が疑われているアクリルアミドの含量が高まるため、健康に悪影響をもたらす可能性のあることが懸念されている。
このため、低温条件に加えて萌芽を抑制する方策が従来から講じられてきた。一つは放射線照射（コバルト 60 によるガンマー線照射）による生理活性の失活である。しかし、この方法は設備の保守・維持管理が容易でないこと、さらには消費者から必ずしも理解が得られないことから広く普及するには至っていない。他方、従来から化学合成した植物生育調節剤による萌芽抑制処理が一般には用いられてきた。しかし萌芽抑制剤として使用されてきた「マレイン酸ヒドラジド」
は、不純物として含有するヒドラジンの発がん性などから２００２年に販売が中止された。
以上のことから、ばれいしょの長期貯蔵に伴う萌芽抑制に有効な手立ての開発と実用化が、ばれいしょの生産者および実需者にとって緊急かつ重要な問題となっている。

資料

２

化学物質等安全データシー ト

整理番 号

エ チ レン (可 燃性

)

作成
改訂
改訂
改訂
改訂

【
製品名】

ダイチ レン (液 化エチ レン)

化学物質等安全データシー ト

50

平成 5年 3月 31日
平成 8年 5月 31日
平成 16年 2月 23日
平成 16年 12月 1日
平成 20年 12月 1日

1.化 学物質等及 び会 社情報
)

エ
ユロ

所 Ｆ

当

住担

化学物質等 の名称 :エ チ レン (可 燃性:製 品 コー ド会 社 名:

連絡 先 : Tel:FAX:

E― mail・

整 理 番号
緊急連絡 先・ レン (可 燃性
: 'エラ

)

・

2.危 険有害性 の 要約

重 要危険有害性及び影響

空気 中で の爆発限界が低 く、又、 引火性 も極 めて高 いので爆発火災 に対す る危険性が大 き い。
高温、高圧下 で は分解爆発 を起 こす。
移送時 の流動や噴霧 、漏れな どの際 に静電気 を発生 し
やす く、わずかな放電火花で爆発す る危険性が ある。
高圧 ガス容器か らガスが噴 出 し、 日に入れ ば、 日の損傷、 ある いは失明 のおそれが ある。
高濃度 の このガスを吸入す る と、麻酔作用が あ り、また窒息 によ り死亡す る ことが ある。
超低温 のため、 直接 または超低温状態 の配管等 に接触
す る と凍傷 を起 こす ことが ある。
超低温容器 または貯槽が高温 にさ らされ ると、容器内の圧 力が異常上昇 して 破裂 のおそれが ある。

GHS分 類物 理 化 学 的危 険性

健康 に対す る有害性
環 境 に対す る有害性

可燃性 ・ 引火性ガス
高圧 ガス

区分 1
圧 縮 ガス または深冷液 化 ガス
特定標 的臓器/全 身毒性 (単 回暴露)区 分 3(麻 酔作用
水 生環 境有害性 (急 性
区分 3
水 生環境有害性 ‖曼性
区分 3
)

)

)

記載がな いものは分類対象外 または分類 できな い
GHSラ ベ ル要素

絵表示

注意 喚起語危 険有害性情報
高圧 ガス
深冷液化 ガス:危 険:極 めて可燃性/引 火性 の 高 いガス:熱 す る と爆発 のおそれ

:凍 傷 または負傷す るおそれ
:眠 気や めま いのお それ:水 生生物 に有害:長 期的影響 によ り水生物質 に有害

κυ

－１－

注意書 き [安 全対策 ]:屋 外 または換気 の良い場所 でのみ 使用す る こと。
:熱 /火 花/裸 火/高 温の もののよ うな着火源か ら遠 ざ ける こと。
:粉 じん/煙 /ガ ス/ミ ス ト/蒸 気 /ス プ レー を吸入 しな い こと。
:使 用前 に取 り扱 い説明書 を入手す る こと。
:す べ ての安全注意 を読み、理 解 す るまで取 り扱わな い こと。
:指 定 された個人用保護具 を使 用す る こと。
:こ の製品を使用す る ときは、飲食 または喫煙 を しな い こと。
:取 り扱 い後 はよ く手 を洗 う こと。
[応 急措置 ]:漏 洩 ガス火災 の場合 には、 漏洩 が 安 全 に停止 されな い限 り
消火 しない こと。 安全 に対処 で きるな らば着火源 を除去する こと。
:吸 入 した場合、空気 の新鮮な場所 に移動 し、呼吸 しや す い
姿勢 で休息 させ る こと。
:暴 露 した場合、医師 に連絡す る こと。
:気 分が悪 い時 は、医師の診 断/手 当て を受 ける こと。
管[保 ] :施 錠 して保管す る こと。
:日 光 か ら遮断 し、換気 の 良 い場所 で保管す る こと。
[廃 棄 ]:内 容物や容器 を都道府県 知事 の許可 を受 けた専門 の廃棄物処理業者 に業務委託す る こと。
3.組 成及 び成 分情報
単 一 製品 。混合物 の 区別 :単 一製品
化 学名又は一 般名 ヒ学式):エ チ レン (C2H0
成分及び含有量:化学物質
エ チ レンCASNo

分子量74‑85‑1 28.00

官報公示番号
化審法
安衛 法
成分濃度
適用外
適用外 99.9%以 上

4.応 急措 置
吸入 した場 合:新 鮮 な空気の場所 に移 し、安静 、保温 に努 め、医師 に連絡す る。
:呼 吸が弱 って い る場合、加湿 した純 酸素を吸入 させ る。
:呼 吸 が停止 して いる場合 には人工呼吸 を行 う。
皮膚 に付着 した場合 :直 ち に汚染 された衣服や靴 を脱 ぎ、 多量 の水で充分 に洗 う。
目に入 った場合:多 量 の流水で注意深 く洗眼 し、直 ち に医師 の診断 を受 ける。
飲 み込 んだ場合:口 を大量 の水ですす ぐこと。直 ち に医師 の診断 を受 ける。
応急措置 をす る者 の保護 :漏 出ガスが空気 または酸 素 と混合 し、燃焼 、爆発 を起 こす
い
危険 を防 くため、換気 を行 い拡散 させ る こと。
:こ のガスが 漏洩 または噴出 して い る場所 は、空気 中 の酸素濃度 が 低下 して い る可能性 が あるので、換気 を行 い、必 要に応 じ陽圧 自給式呼吸器 を着用す る。
5.火 災時 の措置
消火剤:自 己火災の場合には、速やかにガスの供給 を停止すること。

供給 を停止できな い場合は、噴霧散水 しなが ら、このガス－２－52

がな くな るまで燃焼 させ る とともに、火 災 の拡 大お よび類
焼 の 防止 に 努め る。
:周 辺火災 に合わ せた 消火斉」
を使 用す る。
゛
:容 器 の 昇温 を防 くため、水 で容 器 を冷却す る。
使 ってはな らな い消火剤 :棒 状注水
災 時 の特有 の有害危険性 :容 器 が火炎 にさ らされ ると内圧が上昇 し、安全装置 が作動
し、 このガスが 噴 出す る。
:火 災 によって刺激性 、または毒性 のガスが 発生す るおそれが ある。
:内 圧 の上 昇 が激 しいときは、容器 の破裂 に至 る こともある。
容器弁が壊れた ときな どは、容 器 は ロケ ッ トのよ うに飛ぶことが ある。
:容 器 を安全な場所 に搬 出す る こと。搬 出 できな い場合 には、で きるだけ風上か ら水 を噴霧 して容器 を冷却す る こと。
:火 が消えた後 も漏洩が続 く場合 には、そ のガスによ り爆発を起 こした り、中毒 によ り被害 を拡大 させ る恐れが ある。
:移 動可能な容器 は速やか に安 全な場所 に移す こと。
特有 の消火方法:火 災 を発見 した ら、まず部外者 を安全な場所 へ避難 させ る。
:漏 洩が安全 に停止 されない限 り、消火 しな い こと。
:安 全 に対 処 できるのな らば、着火源 を除去す る こと。
:危 険 でなければ火災区域か ら容器 を移動す る。
:ガ スの滞留 しな い場所で風 上 よ り消火 し、漏洩防止処置 を施す 。
:移 動不可能な場合、容器及 び周 囲 に散水 して 冷却す る。
:消 火後 も、大量の水 を用 いて 充分 に容器 を冷却す る。
:漏 洩部や安全装置 に直接水 をか けては い けな い。凍 る恐れが ある。
:消 火活動は、有効 に行 える充 分な距離 か ら行 う。
:周 辺設備等 の輻射熱 による温度上 昇 を防止す るため、水 ス
プ レー によ り周辺 を冷却す る。
:周 辺及び漏洩状況か ら判断 して消火す る と危険が増す と考 え られ るときは火災 の拡大延焼 を防止す るため周 辺 に噴霧散水 しなが ら容器 内 のガスが無 くな るまで燃焼 させ る。
の
を行
う者 保護
:適 切な空気呼吸器 、耐火手袋 、耐火服等 の保護具 を着用
消火し、火 炎 か らできるだけ離れた風 上か ら消火 にあた る。
6.漏 出時 の措 置

人体 に対す る注意事項 、 :窒 息 の危 険を防 ぐため、窓や扉 を開けて換気 を良 くす る こ
保護具及 び緊急時措置 と。換気設備があれ ば、速やか に起 動 し換気す る。
:大 量 の漏洩が続 く状況であれ ば、漏洩 区域 を ロー プ等で 囲
み部外者が立 ち入 らな いよ う周囲 を監 視す る。
:漏 洩 区域 に入 る者 は、 陽圧 自給 式呼吸器 を着用す る こと。
:空 気 中 の酸素濃度 を測定管理す る こと。
環 境 に対す る注意事項 :漏 れ た液 には土、砂 をか けるな ど、周辺 へ の流 出 を防 ぎ、換気 を充分 に して蒸 発 させ る。 または散水 し蒸 発 を促 しても良 い。 この際、液体 が 下水 、側溝、低所 に入 り込 まな
い よ うに注意す る こと。

－３－53

:漏 洩 した この ガスは換気 を良 くし、速やかに大気 中に回収、中和、封 じ込め及び浄化 の 方法・ 機羽 拡散、希釈 させ る。 この物 質 は蒸 発 させて もよ い。
二 次災害 の 防止策:漏 出源 を遮断 し、漏れ を lLめ る。
゛
人体 に対す る注意事項、 :着 火 を防 くため、全ての着火源 を速やか に取 り除 くこと。
:排 水満、下水溝、地下室 ある い は閉鎖 場所 へ の流入 を防保護具及 び緊急時措置
゛く。
:漏 洩物 または漏洩源 に直接水 をか けな い。
:風 下 の 人 を退避 させ、漏 出場所周辺 は立 入禁止 とす るとともに、火 災爆発 の危 険性 を警告す る。
:高 濃度では、窒息性 のガスで あるため、漏洩 したガスが滞留 しないよ うに注意す る こと。
:適 切な保護具 (送 気 マス ク また は空 気呼 吸器、 ゴー グル型保護 眼鏡 また は防災 面、耐薬品性手袋 な ど)を 着用 し、
風上か ら作業 を行 う。

取扱 い及 び 保管 上 の注意
取扱 い上 の注意
技術的対策

:低 温で使用す ると供給 ガス組成が 変化す る可能性が あ り、低温での使 用は注意す る こと。
:容 器 には、 転落、転倒等 を防止す る措 置 を講 じ、かつ粗暴な扱 いを しな い こと。 倒れた とき、容 器弁 の 損傷等 によ り、高圧 のガスが 噴 出す る と、容 器 が ロケ ッ トのよ うに飛ぶ ことがある。
:容 器 の使用前 に、容器 の刻印、塗装 (容 器 の表面積 の 1/2以 上
ねずみ色 )、 表示等 によ リガス名 を確 かめ、 内容物が 目的 の もの と異な るときには使用 せ ず に、販売元 に返 却す る こと。
:容 器弁 の 開閉に使用す るハ ン ドル は所定 の物 を使用 し、容器
弁 はゆっ くり開閉す る こと。
:開 閉 に際 し、ハ ンマ ー 等でたた いて はな らな い。手で 開閉がで きな い ときは、その 旨明示 して 、販売者 に返 却す る こと。
:容 器 か ら直接使用 しな いで、必ず圧 力調整器 を使用す る こと。
:圧 力調整器 の取 り付 けにあた っては、容 器弁 のネジ方 向を確
かめてネジにあった ものを使 用す る こと。
:圧 力調整器 を正 しい要領 にて 取 り付 けた後 、容器弁 を開 ける
前 に、圧 力調整器 の圧 力調整 ハ ン ドル を反 時 計方向 に 回 して
ゆるめ、そ の後、ゆ っ く りと容器弁 を開 く。 この作業 中は、
圧 力調整器 の側面 に立 ち、正面や背面 に立 たな い こと。
:継 手部、ホ ー ス、配管お よび機 器 に漏れがな いか調 べ る こと。
漏洩箇所 の検査 には、石 けん水等 の発泡液 による方法が簡単、
安 全で確実で ある。
:作 業 の 中断 ある いは終 了後 、作業場所 を離れ るときは、容 器
弁 を開 じる。そ の後 、圧 力調整器 内 のガス を出 し、圧 力調整
ハ ン ドル をゆるめてお くこと。
:容 器 を電 気 回路 の一 部 に使 用 しな い こと。特 に、アー ク溶接
時 のアー クス トライ クを発 生 させた りして 損傷 を与 えな い こと。
:容 器弁等 が 氷結 した ときは、4。 ℃ 以下 の温水で温め、 バー
ナ ー 等で直接加熱 しな い こ と。

－４－
54

局所排気

注意事項

安 全取扱 い注意事項

保管 上の注意
適 切な
保管条件:こ のガスを多量 に使用 す る場 合 には、使用量 によって 集 合装
置 等 の供給設備が特別 に設計、製作 され る ことが ある。使 用者 は、 これ らの設備・ 機器 の正 しい操作方法や使用方法 について、製造者 または販売者か ら指導 を受 け、取 り扱 い 説明書
お よび指示事 項 に従 う こと。
:こ のガス を使用す るにあた って は、麻酔作用 とともに空 気
中 の酸素濃度が全体換気低 くな る危 険性 がある。 また、強い 引火性がある ことか ら、密閉 された所や換気 の悪 い所 で取 り扱わな い こと。
:こ のガスを使 用す る設備 の安全弁 の放 出 日は、排 出されたガスが滞留 しな いよ うに、安全な場所 に放 出 口を設置す る こと。
:こ の ガスを使用す るタ ンク類 の 内部での作業 は、十 分な換気を行 い、労働安全衛生法 に従 い行 うこと。
:脱 着式 の保護キ ャップは、使用 前 に取 り外す こと:容 器 を使用 しない ときは、脱 着式 の保護キ ャップ を確 実 に取り付 ける こと。
:容 器 には、充てん許可 を受 けた者以外 はガスの充 てん を行 なってはな らな い。
:容 器 の修理、再塗装、容器弁お よび安全装置 の取 り外 しや交換等 は、容器検査所以外で は行わな い こと。
:容 器 の刻印、表示等 を改変 した り、消 した り、剥 した りしな
い こと。
:容 器 をロー ラー や型代わ り等 の容器本来 の 目的以外 に使用
しな い こと。
:容 器 の授受 に際 しては、あ らか じめ容器 を管理す る者 を定 め、容器 を管理す る こと。
:契 約 に示す 期間 を経過 した容 器 および使用済み の容器 は速やか に販 売者 に返 却す る こと。
:こ のガスを、圧 縮空気や空気 の代わ りに使用 しな い こと。
:高 圧 ガス保安法 の定 める ところによ り取 り扱 う こと。
:容 器弁 の 口金 内部 に付着 した塵 挨類 を除去す る目的で ガス を放 出す る場合 には、 日金 を人のいな い方向 に向 けて、
ガス出 口弁 を短時間微 開 して行 う こと。
:高 圧 のガスが直接人体 に吹 きつ け られ ると、損傷 を起 こす ことがあるので 。高圧 で 噴出す るガスに触れない こと。
:容 器 の圧力は0.lMPa以 上残 し、使用後 は確実 に容器弁 を 閉めた後、保護キ ャップ を付 けて、速やか に残ガス 容器置場 に返す こと。
:容 器 にこのガス以外 のガスが入 った可 能性 があるときは、 容器記号番号等 の詳細 を販売者 に連絡す る こと。
:可 燃性 ガスであるので、火 気 の 近 くで使用 しない こ と。
:こ のガスは、可燃 性で あ り、空気や酸素 と混合す る と燃焼 。
爆発 の危険性がある。

:熱、火花、裸火のよ うな着火源 か ら離 して保管す る こと。
一 禁煙。
:換 気 の良い場所で保管す る こと。
:酸 化剤、酸素、爆発物 、 ハ ロゲ ン、圧 縮空気 、酸 、塩 基 、－５－55

食謂1化 学品等 か ら離 して保管す る。
:容 器置場 の周 囲 2m以 内 には、必 要な障壁 を設 けた場合 を除き、火 気 また は引火性 もしくは発火性 の物 を置かな い こと。
:容 器置場 には、消火設備 を設 ける こと。
:火 炎や スパー クか ら遠 ざけ、火 の粉等が かか らな いよ うに
す る こと。
:電 気配線 や アー ス線 の近 くに保管 しな い こと。
:水 はけの良 い 、換気 の良好な乾燥 した場所 に置 くこと。
:腐 食性 の雰 囲気 や、連続 した振動 にさ らされな い よ うにする こと。
:直 射 日光 を受 けな い よ うに し、温 度 40℃ 以 下 に保つ こと。
:高 圧 ガス容器 として製作 された容器で ある こと。

安 全な容器包 装杖料
8.暴 露防止及び保護措置

設備対策
許容濃度

:防
:日

保 護具
呼 吸器 の保護具

爆仕様 の 局所排気 を設置す る。
本産業衛 生学会 (2008年 版):設 定 され ていな い。
:200pp血 4
ACGIH(2008年 版)TLV― TWA:必 要 によ り空気呼吸器、酸素呼吸器 、送気 マ

スク
の
手 保護具
:革 手袋
目の保護 具:保 護面、保護限鏡
の
び
身体
保護具
:誘 電性安全靴・ 作業衣 を着用す る こと。
皮膚及9.物 理的及び化学 的性質

外観
臭い

pH

融点・ 凝 固点
沸点 、初 留点
及 び 沸騰 範囲
引火点
自然発火温度
燃 焼 又は爆発 範囲の上 限/下 限蒸気圧
蒸気 密度
比重 体目対密度 )溶解 度
オ クタ ノー ル/水
分配 係数

分解温度

色で気体 または液体:無:特
殊 な甘 い臭 い:該
当 しな い:‑169.2℃ 偏虫点:‑103,7℃ 9卜 点)):‑136℃:543℃:2.7〜 36.Ovol%:8100kPa(15℃:0.98:0.00126(0℃:131mg/L(25℃ 水)))

アセ トン、 ベ ンゼ ンに可 溶:log Pow=1.13(測 定値):デ ータなし

10.安 定性及び反応性

安 定性・ 危険有害

:高 温の物体 との接触面、火花または裸火 によ り発

火する。比較的弱 い－６－56

エ ネル ギー の静電気花火で発火が起 こ りうる。
:600℃ 以 上の温 度下で重合 し、芳香族化合物 を生成
す る ことが ある。
:強 力な酸化剤 と反応 し、火災や爆発 の危険 をもた らす。
:高 温 の物体、火花、裸火、静電気火花。
:強 酸化剤。
:燃 焼 した とき、一酸化炭素、 二 酸化炭素 の有害ガ
スが発 生す る。

反応 可能性避 けるべ き条 件
混触 危険物質
危険有害な分 解 生成物

H。

有害性 情報
急性毒性 (吸 入)

慢性 毒性 ・
長期毒性 (吸 入):ヒ ト LCL。

(5分 )=950,000ppm(酸 素 との混合ガス
マ ウス LC5。
=950,000ppm(95%)
マ ウス麻酔作用 の現 れ る時間 800 mg/1(75"5分)

920 mg/1(80%) 3多 )1,050 mg/1(80%) 1′ ):ラ ッ トぽ‑3441濃 度 0、 300、 1,000、 3,000ppm各 群 120匹
6時 間/日 、5日 /週 、24ヶ 月被毒 の兆候等現れず。
:ラ ッ ト (ア ル ビノ)濃 度 0,300,1,000,31 000ppm各 群 120匹
6時 間/日 、5日 /週 、24ヶ 月被毒 の兆候等現れず。

が ん原 生変 異原性
そ の 他 (吸 入:ラ ッ ト)‑344)濃 度最高3,000ppm6時 間/日 、 5日 /週 、 24ヶ 月『
発がんは認 め られず。IARCモ ノグラフによれば、グル ー プ3〔 がん原 生の分類がで きな い〕 に分類す る。
:大 腸菌お よび 数種 の枯 草菌で、変異原性 はみ られな い。
:犬 ;血 中エ チ レン量は、 吸入ガス濃度 に関係 し、 66〜
77.5%← 760〜 89。 g/m3)の 濃度で、血 中 100mlに 8〜 10mlの エチ レンガスが 含 まれ る。血 中か らの排 泄 は 2分 以 内 に現れ 、回復 はかな り早 い。

12.環 境影響情報

生態 毒性
魚毒性
そ の他

:情 報な し:水 棲生物 、急性毒性TL皿 06時 間)100〜 1,000ppm:植 物 へ の影響 ;植 物 に対す る生理作用 は極めて広 く、気相

中濃度 0.01〜 0.lppmで 影響が現れ、通常 1〜 5ppmで 最大 の効
果 を示す場合が多 い。生理作用 としては伸長、生長 の促進または阻害、 開花 の促進 または阻害、花色 の退色、落葉の促進、果実 の成熟促進、たんぱ く質・ 核酸 の合成促進、その他報告 されて い る。
13.廃 棄 上 の 注意
:使 用済 み容器 はその まま容 器所有者 に返 却す る こと。
:容 器 に残 ったガスは、みだ りに放 出せず、圧 力を残 したまま容器弁 を閉 じ、製造者 また は販売 者 に返 却す る こと。
:容 器 の廃棄 は、容 器所有者が行 い、使用者が勝手 に行わない こと。
14.輸 送上 の 注意

危 険物輸送 に関す る国連分類及び国連番号:ク ラス 2.1(引 火性高圧ガス
国 連分 類)－７－57

:1962(圧 縮)10380夜 化
国連番号
国内規 制
:法 第 2条 (可 燃性 ガス、圧縮 ガス、液化 ガス
高圧 ガス保 安法
海 上 輸送船舶安全法:危 規則 第 3条 危 険物 告示別表 l高 圧 ガス (引 火性
航空輸送
航 空法
:施 行規則第 194条 告示別第 1高 圧 ガス (D一 旅禁
道路法:施 行 令第 19条 の 13車 両 の通行 の制限
追加 の規 制/そ の他:応 急措置指針番号 ;115(液 化 されて いる物:応 急措 置指針番号 ￨￨(圧 縮 されて いる物
特別 の 安全対策:高 圧 ガス保 安法 にお ける規定 に基 づ き安 全な輸送 を行 う。
:移 動時 の容器温度 は40℃ 以下 に保 つ 。特 に夏場 はシー ト
をか け温 度 上 昇 の 防止 に努 める。
:容 器 に衝撃が加 わ らな いよ うに、注意深 く取 り扱 う。
:移 動 中 の容器 の転倒、バル ブの損 傷等 を防 ぐための必要な措置 を施す こと。
:車 両等 によ り運搬す る場合 は、イ エ ロー カ ー ド、消火設備
お よび応急措置 に必 要な資材 、工具 を携行す る。
:酸 素ガス と混載す るときは、容 器弁 の方向 を反対 に向け る
か、 間隔 を十分 にとる こと。
)

)

)

)

)

:り

15.適 用法令

高圧 ガス保安法
労働安全衛 生法
航 空法
港則法
船 舶安全法道 路法):法 第 2条 (可 燃性 ガス、圧縮 ガス、液化 ガス:施 行令別 表第 1危 険物 (可 燃性 のガス:施 行規則第 194条 告示別表第 1高 圧 ガス ①一 旅禁:施 行規則第 12条 危 険物高圧 ガス:第 3条 危 険物告示別表第 1高 圧 ガス (引 火性:施 行令第 19条 の 13車 両 の通行 の制限別表 2‑2
)

)

)

)

16.そ の他 の情報

適 用範 囲:こ の化学物質等安全デー タシー トは、 エチ レン (可 燃性)に 限 り適用する ものである。

引用文献 :1)ILO:Occupational Exposure Limits for Airbone Toxic,Substanccs.
2nd.Ed.(1980),

2)後 藤棚他編 : 産業 中毒便覧

医歯薬出版 P510(1980,
3)N10SH:Registry of Toxic Effect of Chemical Substanccs Feb.2001,4)堀 口博著 :公 害 と毒 ・ 危 険物 有機編 三 共 出版 P448(1973),
5)T.E.hamm et al. : Fundamental and Applied Toxicology 4 473‑478,

Chemicals6)IARC Monographs on the Evaluation of Carcinogenic Risk of,
to Humans, 19163(1979),
7)IARC Monographs on the Evaluation of Carcinogenic Risks to,
Humans, Suppl. 7(1987),
8)Patty, IndustriaI Hygiene and Toxicology, Vol. 2B.4th. Ed(1994),

9)J.E.Filser rt al. : Mutation Rescrch 120 57‑60(1983),
10)太 田 保夫 著 :植 物 の一生 とエ チ レン 東海大学 出版会 (198η
そ の他 :記 載 内容 は現時点 で 入手できた資料や情報 に基づ いて作成 してお りますが、記載 のデ ー タや評価 につ いて は、情報 の完全 さ、正確 さを保証す るも－８－58

で はあ りません。 また、記載事項 は通常の取扱 い を対 象 とした ものです ので、特別 な取扱 い をす る場合 には新たに用途 ・ 用法 に適 した安全対策 を実施 の上、お 取扱 い願 います。

－９－
59

資料

３

エチレンによる馬鈴しょの萌芽抑制効果に関する試験（平成 19 年秋～20 年夏、酪農学園大学）

1. 目

的

ポテトチップス加工用馬鈴しょは低温貯蔵を行うと糖が増加し、油加工時の外観品質の低下を招くため、10℃前後の高温で貯蔵されている。そのため、貯蔵中に萌芽し、芽が著しく伸長し、加工時の芽の除去、除去した芽の処理、製品歩留の低下、品質の劣化など様々な問題がある。
本試験は、植物ホルモンであるエチレンを用いることにより馬鈴しょの萌芽および芽の伸長を抑制する長期貯蔵技術を確立し、国内産加工用馬鈴しょ原料を高品質で周年供給できる体制を構築する。
2. 試験方法
１）供試材料
平成19年、帯広市川西産「きたひめ」、「スノーデン」を用いた。
２）エチレンの供給と貯蔵方法(1)エチレンの供給装置
内寸560mm×483mm×986mmのアクリル製ガ
ス置換デシケータを貯蔵容器として用いた。
デシケータの下部からエチレン混合空気を供給し、上部から排出することによりエチ
レン供給および馬鈴しょの呼吸による二酸化炭素除去を行った。
エチレン混合空気は、コンプレッサーによる圧縮空気とボンベ入りエチレン１％含有
窒素ガスとをそれぞれロータメータにより流量調節後に混合してデシケータに供給した。

写真１：恒温室内に

写真２：デシケータ内のデシケータを設置「きたひめ」

写真３：デシケータ内の「スノーデン」

写真 4：エチレンと空気の流量計

写真 5：コンプレッサ－

写真 6：エチレンガスボンベ(2)貯蔵方法
各品種120個の試料（平均約150g）をデシケータ内にランダムに置いて貯蔵を行った。貯蔵
容器を8℃に設定した恒温室内に設置した。無処理区はダンボールに20個ずつ試料を入れて貯蔵庫に置いた。
３)測定項目
貯蔵環境の温湿度およびエチレン濃度については、貯蔵期間中継続して測定した。試料の品質については、貯蔵開始2ヵ月後から1ヶ月間隔で測定した。
(1)恒温室および貯蔵庫内の温湿度
恒温室および貯蔵庫内の温湿度は、データーロガーを用いて測定した。
(2)デシケータ容器内のエチレン濃度
ガスタイトシリンジによりデシケータ容器の上下2箇所から容器内ガスを採取し、ガスク
ロマトグラフを用いてエチレン濃度を測定した。
(3)試料質量、水分含量
電子天秤を用いて試料質量を測定し、質量減少率を求めた。水分含量は70℃24時間恒温
乾燥法により求めた。
(4)芽の長さ5mm以下、5mm以上の芽の塊茎当たりの個数、塊茎毎の最長芽の長さ、塊茎当たりの芽の-1-質量を測定した。
(5)糖含量HPLCを用いてショ糖、ブドウ糖、果糖含量を測定した。
(6)硬度
レオメータを用い、直径2mmの円筒状プランジャを50mm/sの速度で貫入させて荷重を測定した。
(7)ポテトチップカラー
試料を約1mmの厚さにスライスし、180℃のサラダオイルで約120秒間フライし、その色をアグトロンメーター（数値は、小さいほどポテトチップカラーは淡くなる、以下、同様）を用いて測定した。
3. 結果および考察
図１に、デシケータ容器内のエチレン濃度の推移を示す。エチレン濃度の計算上の設定値を5ppmとして貯蔵開始したが、貯蔵開始から約40日間は約2ppmで推移した。
その後エチレン濃度の設定を上げて4ppmとなるように調節を行った。これにより濃度は上昇し、多少の変動はあるものの4～6ppmで推移した。
このエチレン供給装置は、試料ガス採取、測定、濃度調節はいずれも手動によるため、精密な制御はできなかったが、ほぼ想定した濃度を得ることが可能であった。
貯蔵環境の温度・湿度は、エチレン処理区で平均 8.2℃、95％、無処理区で 7.4℃、84％であった。
10エチレン濃度(ppm)

8

KH-上
SD-上

KH-下
SD-下

6
4

2

0
10/28 11/27

12/27

1/26

2/25

3/26

4/25

5/25

6/24

日

図1 エチレン濃度の推移

図2に、最長芽の長さの平均値の推移を示す。
いずれの品種も12月28日までは萌芽が見られなかったが、その後萌芽が開始した。
7月4日のエチレン処理区では、「きたひめ」の最長芽は23mm、「スノーデン」では14mm、無処理区では、それぞれ約200mm、250mmであった。
エチレン処理区は無処理区より平均温度が約0.8℃高く推移したにもかかわらず、エチレンによる芽の生長抑制効果は明らかであった。

-2-

300

芽の長さ(mm)

250

KH-E

KH-N

SD-E

SD-N

200
150
100
50
0
10/28

12/27

2/25

4/25

6/24

8/23

日
図2 最長芽の長さの平均値

図3に、塊茎の損失率の推移を示す。
損失率は芽を含む塊茎の質量減少率に初期塊茎の質量に対する芽の質量百分率を加 えた値で示した。
温湿度環境が異なるため単純な比較はできないが、芽が大きく生長することによって損失も増大し、「スノーデン」の無処理区では35％にまで達し、萌芽抑制によって損失も低く抑
えられた。
40

損失率(%)

30

KH-E
SD-E

KH-N
SD-N

20

10

0
10/28

12/27

2/25

4/25

6/24

8/23

日
図3 塊茎の損失率

図4に、還元糖含量の推移を示す。
「きたひめ」は貯蔵開始後、無処理区で大きく増加し、その後徐々に低下して4月初旬以
降、エチレン区とほぼ同等になった。
その後はいずれも変化が小さく、0.1g/100gFW程度となった。「スノーデン」では貯蔵開始後エチレン処理区での増加が顕著であったが、その後低下し3月初旬には無処理区と同等になった。
4月初旬以降両区とも急激に増加したが、エチレン処理区は無処理区と同等あるいはやや少なく推移した。

-3-

還元糖含量(g/100gFW)

0.5
0.4

KH-E

KH-N

SD-E

SD-N

0.3
0.2
0.1
0.0
10/28

12/27

2/25

4/25

6/24

8/23

日
図4 還元糖含量の推移

図 5 に、ポテトチップカラーの推移を示す。
還元糖の増加が大きかった「きたひめ」の無処理区は、ポテトチップカラーの値が低く推移した。
無処理区でポテトチップカラーが低下したのは、貯蔵温度が低かったことが原因と考えられる。
「スノーデン」は、貯蔵初期においてエチレン処理区が無処理区と比較してやや低い値を示したが、2 月初旬以降無処理区と逆転した。
「スノーデン」の無処理区では、萌芽による塊茎の萎縮が顕著であり、貯蔵後期には塊茎周辺部分に黒変が見られ、ポテトチップカラーにも影響した。
70

チップカラー(-)

60

KH-E

KH-N

SD-E

SD-N

50
40
30
20
10/28

12/27

2/25

4/25

6/24

8/23

日
図5 チップカラーの推移

4. まとめ
定濃度エチレン環境下で貯蔵することにより、顕著に馬鈴しょの萌芽および芽の伸長を抑制することが可能であった。
還元糖含量は低レベルに抑制でき、ポテトチップカラーも無処理区と同等以上であった。

-4-

資料

４

エチレンによる馬鈴しょの萌芽抑制効果に関する試験（平成 20 年秋～21 年夏、酪農学園大学）

１．目 的
加工用馬鈴しょ原料の貯蔵中の萌芽および芽の伸長を抑制し、国産馬鈴しょの周年供給体制を確立することを目的とし、代表的な 3 品種を用いてエチレンによる芽の生長抑制効果を明らかにするとともに、加工適性の評価を行った。
２．試験方法１）供試材料
平成 20 年、帯広市川西産「きたひめ」、「スノーデン」、「トヨシロ」を用いた。
２）エチレンの供給方法および濃度
ガス置換デシケータを利用したエチレン供給貯蔵基礎実験装置を用いた（参考資料１を参照）。
エチレンの供給は 10 月 28 日から開始し、エチレン濃度は 4ppm とした。
昨年度は空気およびエチレン供給は連続としたが、今年度はタイマーを用いて間欠供給とした。
３）貯蔵方法エチレン処理区および無処理区は同様の貯蔵容器（デシケータ）を用いた（参考資料１を参照）。貯蔵容器内の温度は 8℃、湿度は約 85％であった。
４)測定項目
貯蔵環境の温度・湿度、エチレン濃度については、貯蔵期間中継続して測定した。
品質については、10月28日、12月26日、2月16日、3月20日、4月24日、5月29日、7月3日に測定した。
(1)恒温室内温湿度
恒温室内温湿度をデーターロガーを用いて測定した。
(2)貯蔵容器内（デシケータ）エチレン濃度、二酸化炭素濃度
ガスタイトシリンジにより貯蔵容器の上下２箇所から容器内ガスを採取し、ガスクロマ
トグラフを用いてエチレン濃度および二酸化炭素濃度を測定した。
(3)試料質量、水分含量
電子天秤を用いて試料質量を測定し、質量減少率を求めた。水分含量は70℃24時間恒温乾燥法により求めた。
(4)芽の長さ5mm以下、5mm以上の芽の塊茎当たりの個数、塊茎毎の最長芽の長さ、塊茎当たりの芽の質量を測定した。
(5)糖含量HPLCを用いてショ糖、ブドウ糖、果糖含量を測定した。
(6)硬度
レオメータを用い、直径2mmの円筒状プランジャを50mm/sの速度で貫入させて荷重を測定した。
(6)ポテトチップカラー
試料を約1mmの厚さにスライスし、180℃のサラダオイルで約120秒間フライし、その色をアグトロンメーターを用いて測定した。
３．結果
図 1～3 に、貯蔵中エチレン濃度の推移を示す。
「きたひめ」、「スノーデン」の貯蔵初期のエチレン処理区において、急激なエチレン濃度の上昇があったが、これはコンプレッサの不調により空気の供給が停止したためである。また、
このとき無処理区においてもエチレンが一時的に検出された。これ以外ではいずれもほぼ設定どおりにエチレンを制御することができた。
貯蔵開始当初は 1 時間換気、5 時間休止のサイクルで換気およびエチレンの供給を行っていたが、特に、エチレン処理区において CO 2 濃度の上昇が見られたため、「きたひめ」、「スノーデン」では 2 時間換気、4 時間換気に、「トヨシロ」においては、3 時間換気 3 時間休止に変更することにより CO 2 濃度は 0.1％以下に抑えることができ、以後このサイクルで行った。
10

10
KH-0

8
エチレン濃度(ppm)

4

2

6

4

2

0

0

11/8

11/28

12/18

1/7

1/27

2/16

3/8

日
図１ 貯蔵中エチレン濃度の推移（きたひめ）

10/19

11/8

11/28

12/18

1/7
1/27
日
図２ 貯蔵中エチレン濃度の推移（スノーデン）

2/16

3/8

10
TS-4
TS-0

8
エチレン濃度(ppm)

エチレン濃度(ppm)

SD-4

6

10/19

SD-0

8

KH-4

6

4

2

0
10/19

11/8

11/28

12/18

1/7
1/27
日
図３ 貯蔵中エチレン濃度の推移（トヨシロ）

-1-

2/16

3/8

図 4～6 に、塊茎毎の最長芽の長さの平均値の推移を示す。
いずれの品種においても 2 月 16 日の時点で萌芽が見られ、特に、無処理区において芽の伸長が大きかった。
貯蔵終了時点では、いずれの品種においてもエチレン処理区では芽の長さが 20mm 以下に抑
制された。
150

KH-0

芽の長さ(mm)

100

KH-4

50

0
10/28

12/27

2/25

4/26

6/25

8/24

日
図４ 最長芽の長さの推移（きたひめ）
150
SD-0
SD-4

芽の長さ(mm)

100

50

0
10/28

12/27

2/25

4/26
6/25
日
図5 最長芽の長さの推移（スノーデン）

8/24

150
TS-0

芽の長さ（mm)

TS-4
100

50

0
10/28

12/27

2/25

4/26

6/25

日

図6 最長芽の長さの推移（トヨシロ）
-2-

8/24

図 7～9 に、還元糖含量の推移を示す。
いずれの品種も貯蔵初期に還元糖が増加し、その後低下する傾向にあり、貯蔵末期に再び増加する傾向がみられた。
「トヨシロ」においては、エチレン処理区で還元糖の増加が大きかった。「トヨシロ」は無処理区においても還元糖の増加が大きいが、これは貯蔵温度を 8℃と通常より低温に設定したためと考えられる。
1.0
KH-0

還元糖含量(g/100gFW)

0.8

KH-4

0.6

0.4

0.2

0.0
10/19

12/18

2/16

4/17

6/16

8/15

6/16

8/15

日
図７ 還元糖含量の推移（きたひめ）
1.0
SD-0

還元糖含量(g/100gFW)

0.8
SD-4
0.6

0.4

0.2

0.0
10/19

12/18

2/16

4/17
日

図８ 還元糖含量の推移（スノーデン）

1.0
TS-0
TS-4

還元糖含量(g/100gFW)

0.8

0.6

0.4

0.2

0.0
10/19

12/18

2/16

4/17
6/16
日
図９ 還元糖含量の推移（トヨシロ）

-3-

8/15

図 10～12 に、ポテトチップカラーの推移を示す。
還元糖含量の推移を反映し、貯蔵初期にポテトチップカラーが低下し、その後回復する傾向にあるが、「きたひめ」は低下の度合いが小さい。また、貯蔵末期に低下する傾向にあった。
「トヨシロ」はポテトチップカラーの低下は回復しておらず、原料として使用できるレベル
にない。

60

アグトロン値(-)

50

40
KH-0

30

KH-4

20
10/19

12/18

2/16

4/17

6/16

8/15

日
図10 チップカラーの推移（きたひめ）

60

アグトロン値(-)

50

40
SD-0

30
SD-4

20
10/19

12/18

2/16

4/17
日

6/16

図１１ チップカラーの推移（スノーデン）

-4-

8/15

60
TS-0
TS-4

アグトロン値(-)

50

40

30

20
10/19

12/18

2/16

4/17

6/16

8/15

日
図１２ チップカラーの推移(トヨシロ)

４．要約
いずれの品種においても芽の伸長は顕著に抑制することができた。
ポテトチップカラーは「きたひめ」、「スノーデン」については、エチレン処理による大きな低下は認められなかった。
「トヨシロ」については、エチレン処理の効果は明らかであったが、貯蔵温度が低いことによってポテトチップカラーの低下が著しく、特に、エチレン処理による貯蔵初期の低下が大き
かった。

-5-

資料

５

エチレンによる馬鈴しょの萌芽抑制効果に関する試験（平成 20 年秋～21 年夏、十勝農業試験場）
１．目 的
酪農学園大学におけるエチレンによる長期貯蔵中の加工用馬鈴しょの萌芽を抑制する試験成果を受けて、エチレン供給装置を試作し、JA 士幌町において、実用化のための萌芽抑制効
果および品質保持効果を検証する。
２．試験方法
１）試験の実施場所は JA 士幌町（北海道河東郡士幌町）、試験の担当は十勝農業試験場（北海道河西郡芽室町）である。
２）供試材料：平成 20 年、士幌町産の「トヨシロ」、「きたひめ」、「スノーデン｣で、各品
種 200 ㎏を供試した（各品種、約 20kg 入りミニコンテナ 10 個を使用）。
３）貯蔵庫
貯蔵庫は 3 室を使用した。床面積は約 2 坪である。
貯 蔵 庫 内 の 温度は 8℃、湿度は 85％に制御した。
(1)１ 号 室 ： エ チ レ ン 処 理 区（ 二 酸 化 炭 素 は 0.2%以 下 、酸 素 は 18％ 以 上 に 制 御 した。以上、以下になったら自動的にダンパーが開閉する）(2)2 号 室 ： 無 処 理 区 （ 二 酸 化 炭 素 、 酸 素 は 無 制 御 ）(3)3 号 室 ： エ チ レ ン 処 理 区 （ 二 酸 化 炭 素 、 酸 素 は 無 制 御 ）４）エチレン(1)エ チ レ ン の 供 給 開 始 は 12 月 3 日 で あ る 。
( 2 ) エ チ レ ン の 濃 度 は 、12 月 3 日～12 月 9 日は 2 p p m 、12 月 10 日～12 月 16 日は 4ppm と順次濃度を上げ、12 月 17 日からは 8ppm とした。
(3)エ チ レ ン の 供 給 装 置
フジプラント株式会社と三菱電機冷熱プラント株式会社の協同製作による特注品

写 真 1.実 験 棟 の 内 部 、

写 真 2.貯 蔵 庫 内 、左 側 に 貯 蔵 庫 1、 2、 3 室

ミニコンを 4 段

正面奥にコンロトール盤

写 真 3． 貯 蔵 庫 の 内 部

写 真 4.実 験 庫 内 部 、

写 真 5.庫 内 の セ ン サ ー

加湿噴霧の状態

写 真 6.エ チ レ ン 、 酸 素 、二酸化炭素、温度、湿度のコントロール盤

写 真 7.プ ラ ン ト フ ロ ー
エチレン、二酸化炭素、酸素、写 真 8.二 酸 化 炭 素 、 エ ア ー

写 真 9.エ チ レ ン

ポンプの表示ランプ

ガスボンベ

湿度、温度の表示盤

５）萌芽調査萌芽した芽の長さを 0mm（無）、1～５㎜、６～10 ㎜、10～20 ㎜、21 ㎜以上の５区分に分けて塊茎数を調査した。
６）品質の調査
貯蔵前、貯蔵中（3 月）、試験終了時(7 月)について、糖含量、ポテトチップカラーを調
査した。
３．結 果
エチレン処理区については、二酸化炭素と酸素の無制御（3 号室）の試験結果は、制御（1 号室）と同様であっ
たので、ここでは制御の貯蔵庫（１号室）から得られたデータについて述べる。
無処理区では、「トヨシロ」で１月下旬、「きたひめ」で１月上旬、「スノーデン」で 2 月
上旬より萌芽は始まった。
エチレン処理区では、「トヨシロ」は 3 月より、「きたひめ」は 1 月下旬より萌芽している塊茎がみられた。「スノーデン」は萌芽はしているものの、10 ㎜を超えたものは無かった。「トヨシロ」、「きたひめ」ともに徐々に芽は伸びているが、芽長は短く 20 ㎜を超えたものは少なく、伸びても 30 ㎜以下であった。
いずれの品種もエチレン処理による萌芽抑制効果は明らかに認められた。
エチレン処理をした塊茎の芽の形状には、品種間差異が見られた。
「トヨシロ」は芽は伸びないが、小さい芽が多数発生しカリフラワー状となった。「きたひめ」は団子状の芽となり、非常に脱落しやすかった。「スノーデン」は「トヨシロ」に似て芽-1-

の数は増加しているが、芽の伸びは一番少なく、10 ㎜を超えるものは無かった。

写真１：「トヨシロ」（無処理区）

写真２：「トヨシロ」（処理区）

写真３：「きたひめ」（無処理区）

写真４：「きたひめ」（処理区）

写真５：「スノーデン」（無処理区）

写真６：「スノーデン」（処理区）

図１．エチレン無処理区と処理区の芽の状況（平成 21 年 4 月 22 日）

-2-

-3-

30

20

10

0
4/22

4/7

3/24

3/10

2/20

2/5

1/26

1/9

▲

処理区

■

無処理区

図１．エチレン処理における萌芽率の推移

注）萌芽率は、芽の長さ 10 ㎜以上の割合を示す
7/14

6/24

6/11

7/14

40

7/14

50

6/24

60

6/24

70

6/11

80

6/11

90
5/25

100

5/25

ス ノ ー デ ン

5/25

50
40
30
20
10
0
5/7

100
90
80
70
60

5/7

4/22

4/7

3/24

3/10

2/20

2/5

1/26

1/9

萌芽率（％）

きたひめめ

5/7

4/22

4/7

3/24

3/10

2/20

2/5

1/26

1/9

萌芽率（％）

萌芽率（％）ト ヨ シ ロ

100
90

80

70

60

50

40

30

20

10

0

表１．７月 14 日時点の萌芽の状況（数値は個数割合％）

芽長（㎜）

0

～5

5～10

10～20

20～

トヨシロ

0

0

16

74

10

きたひめ

4

4

14

60

18

スノーデン

0

22

78

0

0

要約：20 ㎜を超えるものでも 30 ㎜に達している塊茎はない

写 真 1.「 ト ヨ シ ロ 」 の 芽 の 長 さ

写 真 2.「 ト ヨ シ ロ 」 の 処 理 区

左：処理区、右：無処理区芽の形状

写 真 3.「 き た ひ め 」 の 芽 の 長 さ

写 真 4.「 き た ひ め 」 の 処 理 区

左：処理区、右：無処理区

芽の形状

写 真 5.「 ス ノ ー デ ン 」 の 芽 の 長 さ

写 真 6.「 ス ノ ー デ ン 」 の 処 理 区

左：処理区、右：無処理区

芽の形状

図２．7 月 14 日時点の芽の伸びと形状-4-

図３．ポテトチップカラーの推移（▲：処理区、■：無処理区、アグトロン値は多いとカラーは淡くなる）
４．ポテトチップカラー「トヨシロ」は試験温度が８℃であったため、無処理であってもポテトチップカラーは低下したが、エチレン処理区での低下程度の方が大きかった。
「きたひめ」は、エチレン処理による影響は小さかった。
「スノーデン」では、処理 1 週間後にはポテトチップカラーが低下したが、徐々に回復し、3 月には無処理との差は小さくなった。その後、5 月までエチレン処理区と無処理区はほぼ同じ数値であったが、6 月にはエチレン処理区が低下した。
-5-

資料

６

有機農産物の日本農林規格
制
定
一部改正
全部改正
最終改正

平成12年 1月20日農林水産省告示第 59号
平成15年11月18日農林水産省告示第1884号
平成17年10月27日農林水産省告示第1605号
平成21年 8月27日農林水産省告示第1180号（目的）
第１条 この規格は、有機農産物の生産の方法についての基準等を定めることを目的とする。
（有機農産物の生産の原則）
第２条 有機農産物は、次のいずれかに従い生産することとする。
 農業の自然循環機能の維持増進を図るため、化学的に合成された肥料及び農薬の使用を避けることを基本として、土壌の性質に由来する農地の生産力（きのこ類の生産にあっては農林産物に由来する生産力を含む 。）を発揮させるとともに、農業生産に由来する環境への負荷をできる限り低減した栽培管理方法を採用したほ場において生産すること。
 採取場（自生している農産物を採取する場所をいう。以下同じ 。）において、採取場の生態系の維持に支障を生じない方法により採取すること。
（定義）
第３条 この規格において、次の表左欄の用語の定義は、それぞれ同表右欄のとおりとする。
用 語
定
義
有機農産物
次条の基準に従い生産された農産物（飲食料品に限る。）をいう。
使用禁止資材
肥料及び土壌改良資材（別表１に掲げるものを除く 。）、農薬（別表２に掲げるものを除く 。）及び土壌又は植物に施されるその他の資材（天然物
質又は化学的処理を行っていない天然物質に由来するものを除く 。）をいう。
組換えＤＮＡ技術 酵素等を用いた切断及び再結合の操作によって、ＤＮＡをつなぎ合わせた
組換えＤＮＡ分子を作製し、それを生細胞に移入し、かつ、増殖させる技術をいう。
（生産の方法についての基準）
第４条 有機農産物の生産の方法についての基準は、次のとおりとする。
事 項
基
準
ほ場又は採取場
１ ほ場については、周辺から使用禁止資材が飛来し、又は流入しないよ
うに必要な措置を講じているものであり、かつ、次のいずれかに該当するものであること。
 多年生の植物から収穫される農産物にあってはその最初の収穫前３年以上、それ以外の農産物にあってはは種又は植付け前２年以上（開拓されたほ場又は耕作の目的に供されていなかったほ場であって、２年以上使用禁止資材が使用されていないほ場において新たに農産物の生産を開始した場合にあってはは種又は植付け前１年以上）の間、この表ほ場に使用する種子、苗等又は種菌の項、ほ場における肥培管理の項、ほ場における有害動植物の防除の項及び一般管理の項の基準に従い農産物の生産を行っていること。
 転換期間中のほ場（に規定するほ場への転換を開始したほ場であって、  に規定する要件に適合していないものをいう。以下同じ 。）
については転換開始後最初の収穫前１年以上の間、この表ほ場に使用する種子、苗等又は種菌の項、ほ場における肥培管理の項、ほ場における有害動植物の防除の項及び一般管理の項の基準に従い農産物の生産を行っていること。

- 1 -

２

ほ場に使用する種
子、苗等又は種菌

ほ場における肥培管理

採取場については、周辺から使用禁止資材が飛来又は流入しない一定の区域であり、かつ、当該採取場において農産物採取前３年以上の間、使用禁止資材を使用していないものであること。
１ この表ほ場又は採取場の項、ほ場における肥培管理の項、ほ場における有害動植物の防除の項、一般管理の項、育苗管理の項及び収穫、輸送、選別、調製、洗浄、貯蔵、包装その他の収穫以後の工程に係る管理の項の基準に適合する種子、苗等（苗、苗木、穂木、台木その他植物体の全部又は一部（種子を除く 。）で繁殖の用に供されるものをいう。以下同じ。）又は種菌であること。
２ １の種子、苗等又は種菌の入手が困難な場合は、使用禁止資材を使用することなく生産されたものを、これらの種子、苗等又は種菌の入手が困難な場合は、種子繁殖する品種にあっては種子、栄養繁殖する品種にあっては入手可能な最も若齢な苗等又は天然物質若しくは化学的処理を行っていない天然物質に由来する培養資材を使用して生産された種菌を使用することができる（は種され、又は植え付けられた作期において食用新芽の生産を目的とする場合を除く。）。
３ １及び２に掲げる種子、苗等又は種菌は、組換えＤＮＡ技術を用いて生産されたものでないこと。
１ 当該ほ場において生産された農産物の残さに由来するたい肥の施用又は当該ほ場若しくはその周辺に生息し、若しくは生育する生物の機能を活用した方法のみによって土壌の性質に由来する農地の生産力の維持増進を図ること。ただし、当該ほ場又はその周辺に生息し、又は生育する生物の機能を活用した方法のみによっては土壌の性質に由来する農地の生産力の維持増進を図ることができない場合にあっては、別表１の肥料及び土壌改良資材（製造工程において化学的に合成された物質が添加されていないもの及びその原材料の生産段階において組換えＤＮＡ技術が用いられていないものに限る。以下同じ 。）に限り使用することができる。
２ 前項の規定にかかわらず、きのこ類の生産に用いる資材にあっては、次のからまでに掲げる基準に適合していること。ただし、たい肥栽
培きのこの生産においてこれらの資材の入手が困難な場合にあっては、
別表１の肥料及び土壌改良資材に限り使用することができる。
 樹木に由来する資材については、過去３年以上、周辺から使用禁止資材が飛来せず、又は流入せず、かつ、使用禁止資材が使用されていない一定の区域で伐採され、伐採後に化学物質により処理されていな
いものであること。
 樹木に由来する資材以外の資材については、以下に掲げるものに由来するものに限ること。
ア 農産物（この条に規定する生産の方法についての基準に従って栽培されたものに限る。）
イ 加工食品（有機加工食品の日本農林規格（平成１７年１０月２７日農林水産省告示第１６０６号）第４条に規定する生産の方法についての基準に従って生産されたものに限る。）
ウ 飼料（有機飼料の日本農林規格（平成１７年１０月２７日農林水産省告示第１６０７号）第４条に規定する生産の方法についての基準に従って生産されたものに限る。）
エ 有機畜産物の日本農林規格（平成１７年１０月２７日農林水産省
告示第１６０８号）第４条に規定する生産の方法についての基準に- 2 -従って飼養された家畜及び家きんの排せつ物に由来するもの アに掲げる基準に従ってきのこ類を生産する過程で産出される廃ほだ等については、これらを再利用することにより自然循環機能の維持増進が図られていること。
ほ場における有害 耕種的防除（作目及び品種の選定、作付け時期の調整、その他農作物の栽
動植物の防除培管理の一環として通常行われる作業を有害動植物の発生を抑制することを意図して計画的に実施することにより、有害動植物の防除を行うことをいう 。）、物理的防除（光、熱、音等を利用する方法又は人力若しくは機
械的な方法により有害動植物の防除を行うことをいう。）、生物的防除（病害の原因となる微生物の増殖を抑制する微生物、有害動植物を捕食する動物若しくは有害動植物が忌避する植物若しくは有害動植物の発生を抑制する効果を有する植物の導入又はその生育に適するような環境の整備により有害動植物の防除を行うことをいう 。）又はこれらを適切に組み合わせた方法のみにより有害動植物の防除を行うこと。ただし、農産物に重大な損害が生ずる危険が急迫している場合であって、耕種的防除、物理的防除、
生物的防除又はこれらを適切に組み合わせた方法のみによってはほ場における有害動植物を効果的に防除することができない場合にあっては、別表２の農薬（組換えＤＮＡ技術を用いて製造されたものを除く。以下同じ。）に限り使用することができる。
一般管理
土壌、植物又はきのこ類に使用禁止資材（古紙に由来する農業用資材（製造工程において化学的に合成された物質が添加されていないものに限る。）
及び種子が帯状に封入された農業用資材（コットンリンターに由来する再生繊維を原料とし、製造工程において化学的に合成された物質が添加されていないものに限る。）を除く。）を施さないこと。
育苗管理
育苗を行う場合（ほ場において育苗を行う場合を除く 。）にあっては、周辺から使用禁止資材が飛来し、又は流入しないように必要な措置を講じ、その用土として次の１から３までに掲げるものに限り使用するとともに、
この表ほ場における肥培管理の項、ほ場における有害動植物の防除の項及び一般管理の項の基準に従い管理を行うこと。
１ この表ほ場又は採取場の項の基準に適合したほ場又は採取場の土壌
２ 過去３年以上の間、周辺から使用禁止資材が飛来又は流入せず、かつ、使用されていない一定の区域で採取され、採取後においても使用禁止
資材が使用されていない土壌
３ 別表１の肥料及び土壌改良資材
収穫、輸送、選別、 １ この表ほ場又は採取場の項、ほ場に使用する種子、苗等又は種菌の項、調製、洗浄、貯蔵、
ほ場における肥培管理の項、ほ場における有害動植物の防除の項、一般
包装その他の収穫管理の項又は育苗管理の項の基準（以下「ほ場又は採取場の項等の基準」
以後の工程に係るという。）に適合しない農産物が混入しないように管理を行うこと。
管理
２ 有害動植物の防除又は品質の保持改善は、物理的又は生物の機能を利用した方法（組換えＤＮＡ技術を用いて生産された生物を利用した方法を除く。以下同じ 。）によること。ただし、物理的又は生物の機能を利用した方法のみによっては効果が不十分な場合には、以下の資材に限り使用することができる。
 有害動植物の防除目的 別表２の農薬及び有機加工食品の日本農林規格（平成１７年１０月２７日農林水産省告示第１６０６号）別表２の薬剤（ただし、農産物への混入を防止すること。）
 農産物の品質の保持改善目的 別表３の調製用等資材（製造工程において化学的に合成された物質が添加されていないものであって、組- 3 -換えＤＮＡ技術を用いて製造されていないものに限る。）
３ 放射線照射を行わないこと。
４ この表ほ場又は採取場の項等の基準及びこの項１から３までに掲げる基準に従い生産された農産物が農薬、洗浄剤、消毒剤その他の資材により汚染されないように管理を行うこと。
（有機農産物の名称の表示）
第５条 有機農産物の名称の表示は、次の例のいずれかによることとする。
 「有機農産物」
 「有機栽培農産物」
 「有機農産物○○」又は「○○（有機農産物）」
 「有機栽培農産物○○」又は「○○（有機栽培農産物）」
 「有機栽培○○」又は「○○（有機栽培）」
 「有機○○」又は「○○（有機）」 「オーガニック○○」又は「○○（オーガニック）」（注）「○○」には、当該農産物の一般的な名称を記載すること。
２ 前項の基準にかかわらず、転換期間中のほ場において生産されたものにあっては、前項の例のいずれかにより記載する名称の前又は後に「転換期間中」と記載すること。
３ 第１項の基準にかかわらず、採取場において採取された農産物にあっては、同項、、及び
の例のいずれかにより記載すること。
別表１
肥料及び土壌改良
基
準資材
植物及びその残さ由来の資材
発酵、乾燥又は焼成した排せつ物由来の資材
食品工場及び繊維工場からの農畜水産物由来の資材
と畜場又は水産加工場からの動物性産品由来の資材
発酵した食品廃棄物由来の資材バークたい肥グアノ
乾燥藻及びその粉末
草木灰
炭酸カルシウム
塩化加里
硫酸加里

家畜及び家きんの排せつ物に由来するものであること。

天然物質又は化学的処理（有機溶剤による油の抽出を除く 。）を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
食品廃棄物以外の物質が混入していないものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。

天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するもの（苦土炭酸カルシウムを含む。）であること。
天然鉱石を粉砕又は水洗精製したもの及び天然かん水から回収したものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであるこ
と。

- 4 -

硫酸加里苦土
天然りん鉱石
硫酸苦土
水酸化苦土
石こう（硫酸カル
シウム）
硫黄
生石灰（苦土生石
灰を含む。）
消石灰
微量要素（マンガン、ほう素、鉄、
銅、亜鉛、モリブ
デン及び塩素）岩石を粉砕したもの
木炭
泥炭

ベントナイト
パーライト
ゼオライト
バーミキュライト
けいそう土焼成粒
塩基性スラグ
鉱さいけい酸質肥料
よう成りん肥

塩化ナトリウム
リン酸アルミニウ
ムカルシウム塩化カルシウム
食酢
乳酸

天然鉱石を水洗精製したものであること。
カドミウムが五酸化リンに換算して１ｋｇ中９０ｍｇ以下であるものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然鉱石を粉砕したものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
上記生石灰に由来するものであること。
微量要素の不足により、作物の正常な生育が確保されない場合に使用するものであること。

天然物質又は化学的処理を行っていない天然物質に由来するものであって、含有する有害重金属その他の有害物質により土壌等を汚染するものでないこと。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。ただし、土壌改良資材としての使用は、育苗用土としての使用に限ること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであること。
天然物質又は化学的処理を行っていない天然物質に由来するものであって、カドミウムが五酸化リンに換算して１ｋｇ中９０ｍｇ以下であるもの
であること。
海水又は湖水から化学的方法によらず生産されたもの又は採掘されたものであること。
カドミウムが五酸化リンに換算して１ｋｇ中９０ｍｇ以下であるものであること。

植物を原料として発酵させたものであって、育苗用土等のｐＨ調整に使用する場合に限ること。

- 5 -製糖産業の副産物
肥料の造粒材及び固結防止材

その他の肥料及び土壌改良資材

天然物質又は化学的処理を行っていない天然物質に由来するものであること。ただし、当該資材によっては肥料の造粒材及び固結防止材を製造する
ことができない場合には、リグニンスルホン酸塩に限り使用することができる。
植物の栄養に供すること又は土壌改良を目的として土地に施される物（生物を含む 。）及び植物の栄養に供することを目的として植物に施される物（生物を含む 。）であって、天然物質又は化学的処理を行っていない天然物質に由来するもの（燃焼、焼成、溶融、乾留又はけん化することにより製造されたもの並びに化学的な方法によらずに製造されたものであって、組換えＤＮＡ技術を用いて製造されていないものに限る。）であり、かつ、
病害虫の防除効果を有することが明らかなものでないこと。ただし、この資材はこの表に掲げる他の資材によっては土壌の性質に由来する農地の生産力の維持増進を図ることができない場合に限り使用することができる。

別表２
農薬
除虫菊乳剤及びピレトリン乳剤
なたね油乳剤
マシン油エアゾル
マシン油乳剤
デンプン水和剤
脂肪酸グリセリド
乳剤
メタアルデヒド粒剤
硫黄くん煙剤
硫黄粉剤
硫黄・銅水和剤
水和硫黄剤
石灰硫黄合剤
シイタケ菌糸体抽
出物液剤
炭酸水素ナトリウ
ム水溶剤及び重曹
炭酸水素ナトリウ
ム・銅水和剤
銅水和剤
銅粉剤
硫酸銅
生石灰
天敵等生物農薬性フェロモン剤基
準除虫菊から抽出したものであって、共力剤としてピペロニルブトキサイドを含まないものに限ること。

捕虫器に使用する場合に限ること。

ボルドー剤調製用に使用する場合に限ること。
ボルドー剤調製用に使用する場合に限ること。
農作物を害する昆虫のフェロモン作用を有する物質を有効成分とするものに限ること。

クロレラ抽出物液剤
混合生薬抽出物液剤- 6 -ワックス水和剤
展着剤
二酸化炭素くん蒸剤
ケイソウ土粉剤
食酢
燐酸第二鉄粒剤
炭酸水素カリウム
水溶剤
別表３
調製用等資材
炭酸カルシウム
水酸化カルシウム
二酸化炭素
窒素
エタノール
カゼイン
ゼラチン
活性炭
タルク
ベントナイト
カオリン
ケイソウ土
パーライト
Ｌ－酒石酸
Ｌ－酒石酸水素カ
リウム
Ｌ－酒石酸ナトリ
ウム
クエン酸
微生物由来の調製
用等資材
酵素
卵白アルブミン
アイシングラス
植物油脂
樹皮成分の調製品
ヘーゼルナッツの殻
エチレン
硫酸アルミニウム
カリウム

カゼイン又はパラフィンを有効成分とするものに限ること。
保管施設で使用する場合に限ること。
保管施設で使用する場合に限ること。

基

準バナナ及びキウイフルーツの追熟に使用する場合に限ること。
バナナの房の切り口の黒変防止に使用する場合に限ること。

附 則（施行期日）
１ この告示は、公布の日から起算して３０日を経過した日から施行する。
（経過措置）
２ この告示の施行の日から起算して１年を経過した日までに行われる有機農産物の格付について- 7 -は、この告示による改正前の有機農産物の日本農林規格の規定の例によることができる。
３ この告示の公布の日から起算して３年を経過するまでの間は、この告示による改正後の有機農産
物の日本農林規格第４条の表育苗管理の項基準の欄２中「過去３年以上の間、周辺」とあるのは、「周辺」と読み替えて適用する。
４ 第４条の表ほ場には種する種子又は植え付ける苗等の項の基準に適合する種子又は苗等の入手が困難な場合は、当分の間、同項の規定にかかわらず、同項の基準に適合する種子又は苗等以外のもの（組換えＤＮＡ技術を用いて生産されたものを除く。）を使用することができる。
附 則（平成１８年１０月２７日農林水産省告示第１４６３号） 抄（施行期日）
１ この告示は、公布の日から起算して３０日を経過した日から施行する。
（経過措置）
２ この告示による改正後の有機農産物の日本農林規格（以下「新有機農産物規格」という。）別表１に掲げる肥料及び土壌改良資材のうち、植物及びその残さ由来の資材、発酵、乾燥又は焼成した
排せつ物由来の資材、食品工場及び繊維工場からの農畜水産物由来の資材並びに発酵した食品廃棄物由来の資材については、新有機農産物規格第４条の表ほ場における肥培管理の項基準の欄１に規定するその原材料の生産段階において組換えＤＮＡ技術が用いられていない資材に該当するものの入手が困難である場合には、当分の間、同項の規定にかかわらず、これらの資材に該当する資材以外のものを使用することができる。
３ 新有機農産物規格第４条の表一般管理の項の規定にかかわらず、他に適当な管理方法がない場合には、この告示の公布の日から起算して３年を経過するまでの間は、古紙に由来する農業用資材（製造工程において化学的に合成された物質が添加されていないものに限る 。）及び種子が帯状に封入された農業用資材を使用することができる。
４ この告示の公布の日から起算して３年を経過するまでの間は、別表３エチレンの項中「バナナ」とあるのは、「バナナ及びキウイフルーツ」と読み替えるものとする。
附 則（平成２１年８月２７日農林水産省告示第１１８０号） 抄
この告示による改正後の有機農産物の日本農林規格第４条の表育苗管理の項の規定にかかわらず、
平成２３年１２月３１日までの間は、たまねぎの育苗用土に粘度調整のためにやむを得ず使用する場
合に限り、ポリビニルアルコール、ポリアクリルアミド及び天然物質に由来するもので化学的処理を行ったものを使用することができる。
（最終改正の施行期日）
平成２１年８月２７日農林水産省告示第１１８０号については、平成２１年１０月２７日から施行
する。

- 8 -

資料

7
３－２

カナダにおけるエチレン登録の現状
PMRA (農薬管理規制局)による資料
2001 年１０月５日

申請規則決定書（案）PRDD2001-04

エチレン（商品名 Eco Sprout Guard）

Proposed Regulatory Decision Document

PRDD2001-04

Ethylene
Eco Sprout Guard
The active ingredient ethylene, as Eco Sprout Guard technical grade active ingredient (TGAI) andthe associated end-use product Eco Sprout Guard EP containing 2–100% ethylene in compressed gas
cylinders for the control of sprouting in stored “Russet Burbank” processing potatoes, are proposed
for registration under Section 13 of the Pest Control Products Regulations.
This proposed regulatory decision document (PRDD) provides a summary of data reviewed and therationale for the proposed full registration of these products. The Pest Management Regulatory
Agency (PMRA) will accept written comments on this proposal up to 45 days from the date of
publication of this document. Please forward all comments to the Publications Coordinator at theaddress listed below.

October 5, 2001

(publié aussi en français)This document is published by the Submission Coordination and Documentation Division,
Pest Management Regulatory Agency. For further information, please contact:
Publications Coordinator
Pest Management Regulatory Agency
Health Canada
2720 Riverside Drive
A.L. 6602A
Ottawa, Ontario
K1A 0K9Internet:

pmra_publications@hc-sc.gc.ca
www.hc-sc.gc.ca/pmra-arla/
Information Service:
1-800-267-6315 or (613) 736-3799
Facsimile: (613) 736-3798

ISBN: 0-662-31130-2
Catalogue number: H113-9/2001-4E-IN© Her Majesty the Queen in Right of Canada, represented by the Minister of Public Works and Government Services
Canada 2001
All rights reserved. No part of this information (publication or product) may be reproduced or transmitted in any form or by anymeans, electronic, mechanical photocopying, recording or otherwise, or stored in a retrieval system, without prior written
permission of the Minister of Public Works and Government Services Canada, Ottawa, Ontario K1A 0S5.

Foreword
The submissions for registration of Eco Sprout Guard TGAI (ethylene) and its end-use productEco Sprout Guard EP, supplied by Praxair Inc. and marketed by McCain Foods Limited, havebeen reviewed by the Pest Management Regulatory Agency (PMRA).
Eco Sprout Guard EP, containing 2–100% ethylene in compressed gas cylinders, wasinvestigated as an alternative product to conventional pesticides for the inhibition of sprouting instored processing potato tubers. Ethylene occurs ubiquitously in the natural environment and is anatural plant hormone. Ethylene is relatively nontoxic and has a long history of use as a clinicalanaesthetic at high concentrations (up to 80–90% in oxygen). At the recommended concentrationof 4 ppm, ethylene inhibits excessive sprout growth by reducing apical dominance. Levels of
ethylene and its major metabolites in treated potatoes are similar to those in untreated potatoes.
The PMRA has carried out an assessment of available information in accordance with Section 9of the Pest Control Products (PCP) Regulations and has found it sufficient, pursuant to Section
18.b, to allow a determination of the safety, merit and value of Eco Sprout Guard TGAI
(ethylene) and its end-use product Eco Sprout Guard EP. The Agency has concluded that the useof Eco Sprout Guard TGAI (ethylene) and its end-use product Eco Sprout Guard EP in
accordance with the label has merit and value consistent with section 18.c of the PCPRegulations and does not entail an unacceptable risk of harm pursuant to Section 18.d. Therefore,
based on the considerations outlined above, the use of Eco Sprout Guard TGAI (ethylene) and its
end-use product Eco Sprout Guard EP is proposed for full registration, pursuant to Section 13 of
the Pest Control Products Regulations.
The PMRA is proposing to grant full registration to this product. The PMRA will accept writtencomments on this proposal up to 45 days from the date of publication of this document to allow
interested parties an opportunity to provide input into the proposed registration decision for thisproduct.

Proposed Regulatory Decision Document - PRDD2001-04

Table of Contents
1.0

The active substance, its properties, and uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1
Identity of the active substance and preparation containing it . . . . . . . . . . . . . . . . 1
1.2
Physical and chemical properties of the active substance andend-use product . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3
Details of uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2.0

Methods of analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1
Methods for analysis of the active substance as manufactured . . . . . . . . . . . . . . . 3
2.2
Method for formulation analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

3.0

Impact on human and animal health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3.1
Integrated toxicological summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3.2
Determination of acceptable daily intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.3
Acute reference dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.4
Toxicology end-point selection—occupational and bystanderrisk assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.5
Impact on human and animal health arising from exposure to theactive substance or to its impurities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.5.1 Operator exposure assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.5.2 Bystanders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.5.3 Workers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4.0

Residues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

5.0

Fate and behaviour in the environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5.1
Physical and chemical properties relevant to the environment . . . . . . . . . . . . . . 10

6.0

Effects on non-target species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

7.0

Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7.1
Effectiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7.1.1 Intended use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7.1.2 Mode of action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7.1.3 Crops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7.1.4 Effectiveness against sprouting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7.2
Undesirable or unintended side effects on treated plant products . . . . . . . . . . . . 13
7.3
Observations on undesirable or unintended side effects . . . . . . . . . . . . . . . . . . . 14
7.4
Economics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
7.5
Sustainability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
7.5.1 Survey of alternatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
7.6
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
7.6.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Proposed Regulatory Decision Document - PRDD2001-04

8.0

Toxic Substances Management Policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

9.0

Proposed regulatory decision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

List of abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Proposed Regulatory Decision Document - PRDD2001-04

1.0

The active substance, its properties, and uses

1.1

Identity of the active substance and preparation containing it
Active substance

Ethylene

Function

Sprout inhibitor

Chemical name1.

International
Union of Pureand Applied
Chemistry

Ethene2.

Chemical
Abstract
Services (CAS)

EtheneCAS Number

74-85-1

Molecular formula

C2H4

Molecular weight

28.06

Structural formula

CH2=CH2

Nominal purity ofactivePure ethylene gas, 100%

Identity of relevant
impurities of
toxicological,
environmental, andother significanceThe product contains carbon monoxide at a maximum levelof <0.1%. Impurities of toxicological concern as identified
in Section 2.13.4 of DIR98-04 Chemistry Requirements for
the Registration of a Technical Grade of Active Ingredientor an Integrated System Product or Toxic Substances
Management Policy (TSMP) Track-1 materials as identified
in Appendix II of DIR99-03 The Pest Management
Regulatory Agency’s Strategy for Implementing the Toxic
Substances Management Policy are not expected to bepresent or formed in the product.

Proposed Regulatory Decision Document - PRDD2001-04

1.2

Physical and chemical properties of the active substance and end-use product
Technical product: Eco Sprout Guard TGAI

Property

ResultComment

Colour andphysical state

Colourless compressed gas

Odour

Sweet odour

Melting
point/range

N/A

Boiling point/range–103ECSpecific gravity

0.978 at 0EC (air = 1)

Vapour density(g/mL)

0.001 26 at 0EC

Ultraviolet (UV) /visible spectrum

Not expected to absorb UV at
wavelengths >300 nm

Solubility in waterat 20EC

Slightlyn-Octanol/waterpartitioncoefficient (Kow)log Kow = 1.16

Dissociation
constant

Does not dissociate

Stability(temperature,
metal)

The flash point is –136EC.

Photolysis will not be expected

Bioaccumulation is not expected

Avoid impact and hightemperature at cylinder pressure;incompatible with oxidizing
agents, halogens, acid, aluminum
chloride and halocarbons

End-use product: Eco Sprout Guard EP
Property

ResultColourColourless

Odour

Sweet
Proposed Regulatory Decision Document - PRDD2001-04
Page 2

Property

ResultPhysical state

Gas

Formulation type

Compressed gas

Guarantee

2–100%, nominal

Formulants

The product does not contain any EPA List 1 formulants orformulants known to be TSMP Track-1 substances.

Container material anddescription

Compressed gas cylinders

Oxidizing or reducing action

Incompatible with oxidizing agents, halogens, acids,
aluminum chloride and halocarbons

Storage stability

Expected to be stable when stored in the cylinders

Explodability

Spontaneously explosive in sunlight with chlorine. Forms
explosive mixture with air and oxidizing agents. Containers
may rupture due to heat or fire. Avoid impacts against
containers.

1.3

Details of uses
Ethylene is a growth regulator. In potato tubers, ethylene has been documented to shorten
the post-harvest rest period, often resulting in earlier sprouting but inhibiting theelongation of sprouts by reducing apical dominance.
Eco Sprout Guard EP, containing from 2 to 100% ethylene in pressurized cylinders, isrecommended for application to “Russet Burbank” processing potato tubers incommercial potato storages. Eco Sprout Guard EP is recommended for daily application
into the ventilation airstream of the storage facility to attain an ethylene concentration of
up to 4 ppm.

2.0

Methods of analysis

2.1

Methods for analysis of the active substance as manufactured
The active was determined using two gas chromatographic (GC) methods.

2.2

Method for formulation analysis
The active was determined using two GC methods.

Proposed Regulatory Decision Document - PRDD2001-04
Page 33.0

Impact on human and animal health

3.1

Integrated toxicological summary
Ethylene is a naturally occurring gaseous chemical produced by all plant tissues insignificant amounts and acts as an endogenous plant growth regulator. Ethylene is also anaturally occurring endogenous chemical in humans and laboratory animals and has been
identified in the air exhaled by unexposed rats and humans. Possible sources ofendogenous ethylene in humans and laboratory animals include lipid peroxidation of
unsaturated fats, oxidation of free methionine, oxidation of hemin in haemoglobin andmetabolism of intestinal bacteria. In humans, the concentration of ethylene in the blood
resulting from its endogenous production is approximately 0.097 nmol/L.
Under environmental conditions, ethylene is a gas; therefore, the most probable route ofhuman exposure to ethylene is by inhalation. Ethylene at high concentrations (up to
80–90% in oxygen) has a long history of use as a clinical anaesthetic, with little
concomitant toxicity. Anaesthesia is complete within 20–30 min with 90% in oxygen.
Ethylene is more advantageous than ether as an anaesthetic because of safer induction andmore rapid recovery. Ethylene has been classified as an asphyxiant in Canada because its
presence at high concentrations in air lowers the available oxygen concentration.
The uptake, exhalation and metabolism of ethylene can be described by first-orderkinetics. Uptake of ethylene into the body is low due to its low solubility in blood. For
rats it is estimated that approximately 15–17% of inhaled ethylene reaches the alveolar
blood. In humans, it is estimated that approximately 21% of inhaled ethylene reaches thealveolar blood using a physiological toxicokinetic model which is similar to values
obtained for rats. Inhalation of ethylene in human volunteers at atomosphericconcentrations of up to 50 ppm by gas uptake in a closed spirometer system indicates thatat an alveolar ventilation rate of 150 L/h, approximately 5.6% of inhaled ethylene reaches
the alveolar blood with the majority, 94.4%, being exhaled again without becoming
systemically available via the blood system. At steady state the estimated alveolar
retention in humans is approximately 2–3%. Due to its low blood/gas solubility, ethylene
is rapidly excreted and does not appear to accumulate in the body. Ethylene from bothendogenous and exogenous sources is metabolized to ethylene oxide in vivo in rats, miceand humans. Studies in healthy volunteers suggest that approximately 2–3% of ethylene
absorbed is metabolized to ethylene oxide, whereas up to 98% of ethylene is exhaledunchanged. The data also suggest that the metabolism of ethylene can be stimulated by an
inducer of the mixed-function oxidase system.
Ethylene has low acute toxicity via the inhalation route of exposure in mice. There issome acute hazard of dermal and ocular frost burns and of flammability posed by thecompressed gas. In a subchronic inhalation study with Sprague-Dawley rats, there were
no toxic effects at concentrations up to and including 10 000 ppm, the highest dose tested.
In a chronic toxicity/oncogenicity inhalation study with Fischer 344 rats, no significant
treatment-related findings or evidence of oncogenicity were observed at ethylene
Proposed Regulatory Decision Document - PRDD2001-04
Page 4

concentrations up to and including 3000 ppm, the highest dose tested. The weight ofevidence suggests that ethylene is not genotoxic. There is inadequate evidence in humans
and experimental animals for carcinogenicity of ethylene. Overall, ethylene is notclassifiable as to its carcinogenicity to humans (International Agency for Research on
Cancer (IARC) classification - Group 3). Ethylene is not listed as a carcinogen by the
National Toxicology Program (NTP) or Occupational Safety and Health Association(OSHA).
The toxicological concerns regarding ethylene are related primarily to its metabolites,
specifically the initial metabolite, ethylene oxide. Ethylene oxide is a direct alkylating
agent that is genotoxic in numerous in vitro and in vivo test systems and is carcinogenic
in mice and rats. Positive results have been obtained using the mouse lung tumour
bioassay ($70 ppm) and the standard 2-year bioassays in mice and rats at concentrations$100 ppm. Based on these findings, ethylene oxide is classified as carcinogenic tohumans by IARC (IARC classification - Group 1) and NTP (Report on Carcinogens, 9thedition “known carcinogen”). However, published literature indicates that exposures to1000 and 40 ppm ethylene in closed inhalation chambers are equivalent to ethylene oxide
exposures of 5.6 and 1 ppm, respectively, in rats. When exposure data was combined withpreviously obtained rat tumour induction data for ethylene oxide, extrapolation of thetumour data to the highest possible ethylene oxide equivalent, 5.6 ppm, indicated thathigh ethylene exposures would not result in tumour incidence more than 2% above thetumour background level. It was concluded that the body burden of ethylene oxide
resulting from such low ethylene oxide exposures (i.e., 5.6 ppm) is too small to lead to asignificant increase in tumours in ethylene exposed rats. Published literature also
indicates that above concentrations of approximately 1000 ppm ethylene, the Vmax for
ethylene is reached, thus, higher exposures would not yield greater conversion of ethylene
to ethylene oxide. Published literature suggest that it would be difficult to obtainstatistically significant positive tumour results for ethylene regardless of the dose. In
humans, using a physiological model, predicted blood levels resulting from one 8-h
exposure to 1 ppm ethylene oxide would be equivalent ethylene oxide levels expectedfollowing an 8-h exposure to 45 ppm ethylene assuming bioavailability of 100% for the
metabolically formed ethylene oxide (there is some evidence that at low ethylene
exposure concentrations the bioavailability of metabolically formed ethylene oxide may
be 100%). Based on measurements of haemoglobin adduct levels in humans exposed to
up to 5 ppm ethylene, it is estimated that an average of 2–3% of absorbed ethylene ismetabolized to ethylene oxide. The current threshold for ethylene oxide of 1 ppm[current OSHA standard for ethylene oxide, i.e., 8-h time-weighted average (TWA) per
40-h work week] is toxicologically equivalent to an ethylene concentration of 37 ppm.
Published literature indicates that long-term human occupational exposure to low
airborne concentration of ethylene oxide, at or below current occupational exposure limitsof 1 ppm (1.83 mg/m3) would not produce unacceptable increased genotoxic or
carcinogenic risk.

Proposed Regulatory Decision Document - PRDD2001-04
Page 5Based on these findings and on the proposed conditions of use for ethylene (the ethylene
concentration will be a maximum of 4 ppm until the end of the storage period), it isunlikely that ethylene oxide concentrations would reach levels that would produce
unacceptable genotoxic or carcinogenic risks.
There is sufficient information from published literature to make a risk assessment for the
proposed use of ethylene. Based on information from published literature, ethylene has
low toxicity concerns and has been used extensively as an anaesthetic with little
concomitant toxicity. Based on the proposed low levels of ethylene exposure, the low
absorption rate for ethylene and the low conversion rate of ethylene to ethylene oxide, it
is unlikely that ethylene oxide levels would reach unacceptable levels (i.e., >1.0 ppm). It
can be concluded that ethylene will be nontoxic to humans under the conditions of use asa plant growth regulator for suppression of sprout growth on stored potatoes, provided
that it is used as indicated on the product label; therefore, under the proposed conditionsof use as indicated on the product label, it is unlikely that ethylene will present a risk.
3.2

Determination of acceptable daily intake
As indicated by the Health Protection Branch of Health Canada in the “Health and Safety
Status Report” for ethylene (May 1994), an acceptable daily intake (ADI) is not required
for ethylene, since it is a naturally occurring chemical produced by fruits and vegetables,
including potatoes, during senescence. Ethylene is also a naturally occurring endogenous
chemical in humans and laboratory animals and has been identified in the air exhaled by
unexposed rats and humans. Potential ethylene metabolites have also been shown tooccur naturally. Analytical data for these metabolites in treated potatoes showed that
residue levels were either nondetectable or were at levels similar to any measurable
residues found in controls.

3.3

Acute reference doseAn acute reference dose (ARfD) was not established, since ethylene was considered
unlikely to present an acute hazard. The available literature suggests that there are no
significant treatment-related findings to indicate a concern in acute dietary risk
assessment. The potential risks to humans from exposure to ethylene are considerednegligible due to low toxicity concerns and the widespread use of ethylene as ananaesthetic with little concomitant toxicity.

3.4

Toxicology end-point selection—occupational and bystander risk assessment
The primary route of exposure is inhalation. Ethylene has low acute toxicity via theinhalation route. Ethylene is considered a simple asphyxiant. In a subchronic inhalation
study from the published literature, there were no toxic effects in Sprague-Dawley rats at
concentrations up to and including 10 000 ppm, the highest dose tested. In a publishedchronic toxicity/oncogenicity inhalation study with Fischer 344 rats, no significant
treatment-related findings or evidence of oncogenicity were observed at ethylene

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Page 6

concentrations up to and including 3000 ppm, the highest dose tested. Contact with
ethylene as a compressed gas can cause dermal and ocular frost burns and present a
hazard due to its flammability. Potential for this type of exposure can be mitigatedthrough labelling. This was considered to be the most appropriate regulatory approach forthis active ingredient and a qualitative assessment of exposure and risk for the proposed
use of ethylene was conducted.
3.5

Impact on human and animal health arising from exposure to the active substanceor to its impurities

3.5.1

Operator exposure assessment
Application to stored potatoes
Eco Sprout Guard consists of compressed ethylene gas contained in pressurized cylindersof varying concentrations (ranging from 2 to 100% ethylene), the balance being made up
with nitrogen. Eco Sprout Guard would be applied by releasing the gas in the ventilation
system of the potato storage facility at a specific rate up 4 ppm for the duration of thestorage period. The proposed label indicates that for best results application must begin at
1–7 days after the potatoes are harvested and continue until 1–7 days before processing.
Typically storage operators would have gas cylinders containing concentrations of
ethylene to be used. The concentration in the storage facility would be determined by thedelivery rate and the percent concentration of ethylene in Eco Sprout Guard. The
concentration of ethylene in the storage building would be monitored, continuously andremotely, to ensure that it remains near the target level throughout the storage period.
Typically, the ethylene gas delivery system uses programmable controls to operate valves
in response to ventilation conditions in the building. The system is self contained andrequires human intervention to review and adjust parameters, to connect or disconnect
cylinders to replace empty ones or in the event of a leak in the system.
Operator exposure
Potential occupational exposure to ethylene may occur when entering the storage building
or its ventilation duct work (e.g., for repair) during application of ethylene or when
standing near the ventilation exhaust. The primary route of exposure would be inhalation.
Ethylene is a naturally occurring gaseous chemical produced by both plants and animals.
It has had a long history of use as a clinical anaesthetic (anaesthesia is obtained with
exposure to concentrations of 80–90% in oxygen) with little concomitant toxicity. It is
generally recognized as safe (GRAS) in the U.S. No exposure limits have been
established for ethylene by the American Conference of Governmental Industrial
Hygienists (ACGIH). The ACGIH classifies ethylene as a “simple asphyxiant.”
Respiratory protection is not normally required for simple asphyxiants except inemergency or planned entry into unknown concentration or in areas of oxygen deficiency.
In a published subchronic inhalation study with Sprague-Dawley rats, there were no toxic
effects at concentrations up to and including 10 000 ppm, the highest dose tested. A
2-year chronic rat inhalation study from the published literature showed no effects in rats

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Page 7

exposed to 3000 ppm ethylene (6 h/day, 5 days/week). Based on this, it is concluded thatthe potential risk of workers from exposure to ethylene via inhalation, when used under
the proposed conditions, is considered negligible.
Potential exposure to high concentrations of ethylene may occur in the event of a leak in
an enclosed space. The proposed label includes precautionary statements regarding proper
handling of cylinders and gas release system to avoid leaks; as well, the registrant would
provide the user with access to information on proper equipment to use for releasing andmonitoring ethylene gas. Respiratory protection for entry into an area of unknown
ethylene concentration is recommended on the draft label. These precautionary statements
are considered adequate.
Handling cylinders of compressed gas or any equipment under pressure represents ahazard due to its flammability and a potential for acute dermal or ocular exposure to theliquefied gas (i.e., it may cause frost burns if in contact with skin or eyes). This risk canbe adequately mitigated with use of appropriate protective equipment; long sleeves, longpants, goggles or faceshield and appropriate gloves are considered adequate.
3.5.2

Bystanders
Based on the nature of the proposed use pattern of Eco Sprout Guard, there would be
negligible potential for exposure of bystanders.

3.5.3

Workers
Workers may enter a storage area (e.g., for potato inspection) during or after treatment
with ethylene before ventilation is complete (see section 3.5.1 for an assessment ofworker potential exposure).

4.0

Residues
No residue data were submitted with this petition. However, previously submitted dataand information in support of a former petition to register use of ethylene as a potato
sprout inhibitor were summarized by the Health Protection Branch of Health Canada in
May 1994 in the “Health and Safety Status Report” for ethylene. Information excerpted
from this report is presented in this chapter.
Data provided indicate that the metabolism of ethylene, while not specifically elucidated
in potatoes, is similar and probably identical to those metabolic pathways determined for
ethylene metabolism in many plants. Potato tubers, as senescent tissues, exhibit low basal
metabolic rates such that ethylene is metabolized very slowly, if at all. Endogenous
concentrations of ethylene range between 0.0007–0.15 ppm for nonsprouting tubers and
0.1–3 ppm for sprouted tubers. These low concentrations of ethylene, combined with the
low diffusion rates suggest that low concentrations of ethylene metabolites would be
expected in stored tubers.
Proposed Regulatory Decision Document - PRDD2001-04
Page 8Ethylene and its potential metabolites were not identified in treated potatoes at levels
exceeding those found in control potatoes, and therefore, animal metabolism andlivestock feeding studies were not considered necessary for evaluation.
Residue data was provided for potatoes treated with 4 ppm ethylene for up to 150 days ofstorage. Residues of chloroethanol, dichloroethane, bromoethanol, ethylene oxide, andethylene glycol (including its glucoside) residues were in total less than 0.1 ppm.
Residues for the metabolite of greatest toxicological concern, ethylene oxide, were
<2 ppm (the lower limit of quantitation (LLQ) of the analytical method employed). In
addition, the processing or cooking of tubers is expected to result in a reduction ofvolatile residues (ethylene oxide) by up to 90%. This dissipation of residues would occur
by diffusion out of potato tissues during processing of the tubers and by heat-assisted
volatilization during cooking.
The partition coefficient for ethylene into potato tuber tissue is very low (0.207),
indicating that there is little if any metabolism, compartmentalization of 14C-ethylene bypotato tubers or both. Typical soil atmospheres contain about 10 ppm endogenous
ethylene levels that can increase as the moisture status of the soil increases. This indicatesthat developing potato tubers, which are metabolically active, might be expected tometabolize and bioaccumulate ethylene residues. This level of background exposure is
2.5 times greater than that proposed for supplementation of ambient storage bin
atmospheres. No residues of ethylene metabolites (after correction for some measurable
residues of ethylene glycol and its glucoside) were determined above LLQs in mature
tubers for any treated potato tubers in the 1993 and 1994 research trial residue studies.
Evidence was presented that elucidated the impermeability of ethylene into potato tubers.
Potato tubers have a high resistance to diffusion because the periderm of the tuber
presents a barrier to gaseous diffusion and the bulk of the diffusion occurs through a verysmall area of the tuber, up to 2% of its volume. This condition effectively blocks
movement of exogenous ethylene into the tuber (even against a concentration gradient)
thereby maintaining internal concentrations of ethylene in the tuber at endogenous levels.
Processing studies were not performed for ethylene-treated potatoes. However, theprocessing of treated tubers into french fries, powdered potatoes, potato flour or cookingof raw potato tubers would reduce the residue of most concern, ethylene oxide, if it were
present at levels above background. Ethylene oxide is a gas at room temperature and aliquid below 12EC. It would be expected to volatilize out of potatoes during cooking.
Based on the data submitted, residues in potatoes treated according to the proposed label
directions will not result in residues of ethylene or its probable major metabolites above
levels found in untreated potatoes. Therefore, no dietary risk assessment is considerednecessary, and no MRLs are proposed.

Proposed Regulatory Decision Document - PRDD2001-04
Page 95.0

Fate and behaviour in the environment

5.1

Physical and chemical properties relevant to the environment
The physicochemical properties of ethylene, summarized in Table 5.1, are based on areview conducted by the Laboratory Services Subdivision and other information gatheredfrom various sources. Active ingredient purity was >98.5% in the reviewed studies.

Table 5.1

Physical and chemical properties relevant to the environment

Property

Value

Comments

Water solubility

22.6 mL/100 mL at 0EC;
12.2 mL/100 mL at 20EC

Sparingly soluble

Vapour pressure

4100 kPa at 0EC; 1063 kPa
at 50EC

Product is a gas

log Kow (25EC)

1.16

Bioaccumulation is not expected

Dissociation constant(pKa at 20EC)

Not applicable

No dissociable groups present in the active
ingredient (a.i.)

UV / visible spectrum

Not expected to absorb UV
at wavelength >300 nm

Photolysis is not expected to be route ofdissipation in the environment

Summary of environmental chemistry and fate studies
No data were submitted or requested on the environmental fate of ethylene because thisgas occurs naturally in the environment and the contribution from the proposed use will
not be significant.
Expected environmental concentrations
Ethylene use in storage will only impact the expected environmental concentrations(EEC) of ethylene in the atmosphere; however, the contribution of ethylene from the
proposed use site to atmospheric concentrations is considered to be negligible.
It is estimated that 89% of natural and anthropogenically produced ethylene gas is
destroyed in the troposphere by OH– radicals, and 8% is destroyed in reactions withozone. Approximately 3% is transported into the stratosphere. Estimated lifetime in theatmosphere is approximately 2–4 days.

Proposed Regulatory Decision Document - PRDD2001-04
Page 10

6.0

Effects on non-target species
No data were submitted or requested on effects to nontarget organisms because thecontributions from the proposed use will not be significant. Adverse effects on nontarget
organisms from the proposed use of ethylene, therefore, are not expected.

7.0

Efficacy

7.1

Effectiveness

7.1.1

Intended use
Eco Sprout Guard EP is intended for use on “Russet Burbank” potatoes in commercial
storage facilities to inhibit sprout growth.

7.1.2

Mode of action
Ethylene is a plant growth regulator. In potatoes, ethylene has been documented toshorten the post-harvest rest period, resulting in earlier sprouting but inhibiting theelongation of sprouts by reducing apical dominance. Ethylene also enhances theabscission of sprouts.

7.1.3

Crops
Eco Sprout Guard EP is intended for use on stored “Russet Burbank” potatoes forprocessing.

7.1.4

Effectiveness against sprouting
Laboratory and commercial scale trials were conducted in which the efficacy of Eco
Sprout Guard EP was assessed for the inhibition of sprouting in “Russet Burbank”
processing potato tubers. In laboratory trials conducted from 1991–1992 to 1995–1996,
Eco Sprout Guard EP was applied to tubers in barrels or steel cabinets to abruptly raise
the concentration to 4 ppm once tubers had been permitted to cure (suberize) and cool to
the final storage temperature of 9EC, about 8 weeks after the beginning of storage. A
commercial standard treatment of chlorpropham (CIPC) was applied to tubers (dipped in
1% emulsion) in each trial.
No sprouting was observed in the CIPC treatment. In the ethylene treatment, the weightof large sprouts (>5 mm) was minimal or absent and ranged from 0 to 0.01 and from 0 to
0.5 g·kg–1 tuber fresh weight at 20 and 25 weeks after the initiation of application,
respectively. In contrast, large sprout weight in the untreated control at 20 and 25 weeks
ranged from 2.2 to 17.4, and from 8.5 to 38.5 g·kg–1 tuber fresh weight, respectively.

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Page 11

Sprout length increased over time but was always less for ethylene-treated tubers thanuntreated control tubers. Sprout length averaged 9 mm after 25 weeks of ethylene
treatment whereas that in the untreated control averaged 204 mm.
Ethylene often increased number of small sprouts (2–5 mm) relative to the untreatedcontrol. At the biochemical and cellular level, continual ethylene exposure may haveterminated rest (dormancy) in tuber eyes, possibly leading to an increase in sprout
initiation while preventing excessive growth of these sprouts through the inhibition ofcell differentiation and elongation. The force required to remove sprouts on ethylene
treated potatoes was quantitatively assessed in the 1993–1994 trial and was determined tobe significantly less than on untreated tubers.
In a laboratory trial conducted in 1997–1998, ethylene applied in accordance with theproposed application method resulted in sprouts that were less than 5 mm long at
33 weeks after the beginning of treatment. No sprouting was observed in the CIPC
control treatment.
In commercial-scale trials conducted from 1992–1993 to 1994–1995, ethylene wasapplied to potato tubers to abruptly raise the ethylene concentration in the storage
building to 4 ppm once tubers had been permitted to cure and cool to the final storage
temperature of 9EC. In each trial, a commercial standard treatment of CIPC was applied
once to cured tubers in a neighbouring storage building as an aerosol (Stanchem Sprout
Nip 840). Ethylene reduced sprout number, sprout weight and sprout length. In
1992–1993, the longest sprout observed after 4 months of ethylene treatment was 2 mm,
and total sprout weight averaged less than 0.01 g per tuber. No sprouting was observed in
the CIPC treatment in this trial. In the trial conducted in 1993–1994, ethylene-treatedtubers had higher sprout weight and sprout number than CIPC-treated tubers up until
22 weeks of storage. After this time, CIPC-treated tubers had large increases in sprout
length and weight, such that by week 29, CIPC-treated tubers had about five times the
sprout weight that ethylene-treated tubers had. CIPC residues are known to gradually
decline over time, such that retreatment is often required to maintain sprout inhibition
following 4–6 months of storage. In 1994–1995, it was stated in the trial report that asimilar degree of sprout control was achieved with ethylene as in the previous 2 years andthat sprout control was less than that achieved with CIPC. In the latter two trials, somesprouting was observed in CIPC treatment along the wall of the storage building, where it
was likely CIPC did not reach the tubers. Ethylene is a lighter gas than CIPC applied as
an aerosol, and therefore, ethylene is distributed more evenly throughout the storage pilethan CIPC. The percentage of tubers with internal sprouts was lower for the ethylene
treatment (0.01–0.05%) than for the CIPC treatment (0.5–0.7%).
In an additional commercial-scale trial conducted in 1998–1999, the degree of sprout
inhibition was observed to be greater for the treatment of ethylene, applied in accordancewith the proposed method, than for the CIPC treatment after 6 months of storage probably
due to decreasing CIPC residues on tubers. At 6 months after the beginning of storage,
about 17 and 48% of tubers treated with ethylene and CIPC had at least one sprout,

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Page 12

respectively. By the final removal at 8 months, 37 and 56% of tubers treated with
ethylene and CIPC, respectively, had at least one sprout. After 6 months of ethylene
treatment, weight of small and large sprouts each averaged less than 1 g in tuber samples
of approximately 35 kg, whereas the weight of small and large sprouts in CIPC-treatedtubers averaged 3 and 7 g in similar-sized samples. After 8 months of ethylene treatment,
the mean weight of small and large sprouts was about 17 and 42 g per 35 kg sample,
respectively, whereas the mean weight of small and large sprouts of tubers treated with
CIPC averaged 16 and 167 g, respectively. The mean maximum sprout length observed in
ethylene-treated tubers was 6.5 and 27.5 mm at 6 and 8 months of storage, respectively,
much shorter than the 45 and 122 mm observed for the CIPC treatment at these two
evaluation times.
In each of the commercial trials, sprouts of ethylene-treated tubers were typically stunted,
often branched and very brittle, such that these club-shaped sprouts easily fell off when
the tubers were removed from storage.
7.2

Undesirable or unintended side effects on treated plant products
Potato tuber fry colour, as measured on an Agtron reflectance colorimeter (range of
0 = black to 100 = white), was assessed in the same laboratory trials in which efficacy
was evaluated. In trials conducted from 1991–1992 to 1995–1996, fry colour generally
improved (higher Agtron scale value) with storage time for all treatments. Tubers treateddaily with 4 ppm ethylene were usually darker upon frying than either the untreatedcontrol or the CIPC treatment, which was related to higher reducing sugar levels in
ethylene-treated tubers. At the 25-week evaluation date, relative fry colour among
treatments was variable over years. Fry colour of ethylene-treated tubers was darker thanuntreated control tubers in two trials and darker than CIPC-treated tubers in three trials,
was similar to that of CIPC-treated tubers in one trial and was lighter than CIPC-treatedtubers in one trial. When averaged over the 5 years, ethylene-treated tubers had a lower
Agtron value (by 7–10 points) than CIPC-treated tubers when assessed from 5 to
25 weeks. In the trial conducted in 1997–1998, ethylene was applied in accordance withthe proposed application method to attain a maximum ethylene concentration of 4 ppm inthe storage facility. The treatment evaluated in earlier trials was included for comparison
along with a CIPC control. Fry colour of tubers treated with ethylene according to the
proposed application method was 6–7 Agtron units darker than CIPC-treated potatoes
from 18 to 33 weeks after the beginning of storage. In contrast, potato tubers treated with
ethylene beginning at the end of the cooling period resulted in fry colour that was
19–25 Agtron units darker than that treated with CIPC. In an additional trial conducted in
1996–1997, ethylene applied in accordance with the proposed application method
resulted in fry colour that was 15–22 Agtron units higher (lighter) than where ethylene
had been applied at the end of the cooling period.
Fry colour was assessed in the same commercial-scale trials in which efficacy wasevaluated. Fry colour of potato tubers randomly selected from the storage pile wasassessed weekly in each of the trials conducted in 1992–1993, 1993–1994 andProposed Regulatory Decision Document - PRDD2001-04
Page 13

1994–1995. Fry colour was generally darker in ethylene-treated tubers than in CIPCtreated tubers in all 3 years, regardless of when data were collected. Unlike the laboratory
trials conducted from 1991–1992 until 1995–1996, fry colour did not improve overstorage time for either of these treatments. Over the 26 weeks following the initiation of
ethylene treatment, U.S. Department of Agriculture fry colour grade ratings (range of
1=light to 7=dark) for ethylene- and CIPC-treated tubers were 3.0 and 2.6 in 1992–1993,
3.4 and 2.8 in 1993–1994, and 2.5 and 1.7 in 1994–1995, respectively.
In the commercial-scale trial conducted in 1998–1999, potato tubers treated with ethylene
applied in accordance with the proposed application method resulted in darker fry colour
than CIPC after 3 and 6 months of storage. After 3 and 6 months of storage, the fry colourof tubers treated with ethylene were, respectively, 5 and 6 Agtron points lower on averagethan tubers treated with CIPC. Fry colour of ethylene-treated tubers and CIPC-treatedtubers were similar after 8 months of storage.
7.3

Observations on undesirable or unintended side effects
Eco Sprout Guard EP is proposed for post-harvest use only on stored “Russet Burbank”
potato tubers for processing in closed-system commercial storage facilities. It would not
be expected to impact other crops. It would not be used on or near seed potatoes.

7.4

Economics
In 1998–1999, 4 292 000 t of potatoes were produced in Canada on 156 000 ha. Since
1992–1993, potato production has increased by 2–3% per year. In 1998, 620 000 t ofpotatoes were exported, mainly to the U.S. In that year, 30% of fresh exports were seedpotatoes, and 70% were table stock potatoes and potatoes for processing. Approximately
50% of all potatoes grown in Canada are processed, much of which is exported as frozen
french fries. In 1998, 483 436 t of frozen french fries valued at $461 million were
exported, mainly to the U.S., but also to more than 90 countries worldwide. Between
1995 and 1998, the quantity and value of exported frozen french fries more than doubled.
The importance of processed potato products to the Canadian economy is expected tocontinue to increase.

7.5

Sustainability

7.5.1

Survey of alternatives

7.5.1.1 Nonchemical control practices
Storage at very low temperatures (3 or 4EC) may be used to delay sprouting of potato
tubers; however, these temperatures may induce high levels of reducing sugars, thereby
resulting in fry colour of the processed product that is too dark to command top gradesand prices.

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Page 14

7.5.1.2 Chemical control practices
Products containing maleic hydrazide or chlorpropham, listed in Table 7.5, are registeredfor control of sprouting in potatoes. There are two types of chlorpropham products: thosethat are applied as aerosols in the ventilation system of the potato storage building andthose that are applied as emulsions to potatoes in the packing line. Products of the latter
type are not typically used for processing potatoes and are not shown in Table 7.5.
Table 7.5

Alternative products for control of sprouting of stored processing potatoes

Active ingredientEnd-use products

Mode ofactionApplication timing

Application rate

Maleic hydrazide

Royal MH 60SG
(Reg. No. 18143)

Inhibits cell
division

Applied in the field
between 2–3 weeks
past full bloom and2 weeks before
expected date of
topkill or first frost,and when tubers areat least 4–5 cm indiameter

3.4 kg a.i./ha

Chlorpropham

Sprout Nip 840(Reg. No. 18833)

Sufficient product applied
to achieve deposit of
6–12 ppm on potatoes

Decco 273 Aerosol
Potato Sprout
Inhibitor(Reg. No. 24007)

For <4 months storage:
1 kg a.i./60 t potatoes;
For 4–6 months storage:
2 kg a.i./50 t potatoes

Clean Crop SpudNic Aerosol Grade(Reg. No. 24691)

For 3 months storage:
1.5–2 kg a.i./100 t
potatoes;
For 4–6 months storage:
3–3.75 kg a.i./100 t
potatoes

Inhibits cell
division
Ag-Services Potato
Sprout Inhibitor(Fogging Grade)(Reg. No. 11848)

After harvesting,potatoes are allowed
to cure (suberize) forat least 2 weeks
before application

Ag-Services 750A
Potato Sprout
Inhibitor(Fogging Grade)(Reg. No. 25834)

For 3 months storage:
1.5–2 kg a.i./100 t
potatoes;
For 4–6 months storage:
3–3.75 kg a.i./100 t
potatoes
For 3 months storage:
1.5–2 kg a.i./100 t
potatoes;
For 4–6 months storage:
3–3.75 kg a.i./100 t
potatoes

Proposed Regulatory Decision Document - PRDD2001-04
Page 15

7.6

Conclusions

7.6.1

Summary
Data generated in laboratory and commercial-scale trials demonstrated that Eco Sprout
Guard EP, when applied in accordance with the proposed method, can be expected toeffectively inhibit sprouting of stored “Russet Burbank” processing potatoes while having
minimal impact on processed product quality, such as fry colour. The accepted usessummarized in Table 7.6 are based on the value assessment.

Table 7.6

Summary of accepted use for Eco Sprout Guard EP

Crop

Potatoes (Solanum tuberosum)

Cultivar

Russet Burbank (for processing only)

Application timing

Throughout the storage period (up to 10 months)

Frequency of application

Daily during ventilation cycles

Application method

Applied from a pressurized gas cylinder into the ventilation airstream of thestorage building to attain an ethylene concentration of up to 4 ppm.

Pest controlled

Sprouting

8.0

Toxic Substances Management Policy
Ethylene occurs naturally in the environment. The contribution from this use will not besignificant. The technical grade ethylene does not contain any impurities or
microcontaminants known to be Toxic Substances Management Policy (TSMP) Track-1
substances. The end-use product, Eco Sprout Guard EP does not contain any U.S.
Environmental Protection Agency List 1 formulants or formulants known to be TSMP
Track-1 substances.

9.0

Proposed regulatory decision
The Pest Management Regulatory Agency (PMRA) has carried out an assessment ofavailable information in accordance with Section 9 of the Pest Control Products (PCP)
Regulations and has found it sufficient, pursuant to Section 18.b, to allow a determinationof the safety, merit, and value of Eco Sprout Guard TGAI and Eco Sprout Guard EP,
proposed for registration by McCain Foods Ltd. The PMRA has concluded that the use of
Eco Sprout Guard TGAI and Eco Sprout Guard EP in accordance with the label has meritand value consistent with Section 18.c of the PCP Regulations and does not entail an
unacceptable risk of harm pursuant to Section 18.d. Therefore, based on theconsiderations outlined above, the use of Eco Sprout Guard TGAI and Eco Sprout Guard
EP for the control of sprouting on stored “Russet Burbank” potatoes for processing is
proposed for full registration, pursuant to Section 13 of the PCP Regulations.
Proposed Regulatory Decision Document - PRDD2001-04
Page 16

The PMRA will accept written comments on this proposal up to 45 days from the date of
publication of this document to allow interested parties an opportunity to provide input
into the proposed registration decision for this product.

Proposed Regulatory Decision Document - PRDD2001-04
Page 17

List of abbreviations

List of abbreviations
ACGIH
a.i.
ADI
ARfD
bw
CIPC
d
DNA
EEC
EP
EPA
g
GC
GRAS
h
ha
IARC
Kow
kg
kPa
L
LLQ
m
mL
mm
nm
nmol
NTP
OSHA
PMRA
PRDD
ppm
t
TGAI
TS
TSMP
TWA
UV
FL

American Conference of Governmental Industrial Hygienists
active ingredientacceptable daily intake
acute reference dosebody weightchlorpropham
day(s)
deoxyribonucleic acidexpected environmental concentration
end-use productU.S. Environmental Protection Agency
gram(s)gas chromatography
generally recognized as safehour(s)hectare(s)International Agency for Research on Cancer
n-octanol/water partition coefficientkilogram(s)kilo-Pascal(s)litre(s)lower limit of quantitation
metre(s)millilitre(s)millimetre(s)nanometre(s)nanomoles(s)National Toxicology Program
Occupational Safety and Health Administration
Pest Management Regulatory Agency
proposed regulatory decision document
parts per million
tonnestechnical grade active ingredient
test substance
Toxic Substances Management Policy
time-weighted averageultraviolet
microlitre

Proposed Regulatory Decision Document - PRDD2001-04
Page 18

Regulatory Decision Document

RDD2001-07

Ethylene
Eco Sprout Guard
The active ingredient ethylene, as Eco Sprout Guard TGAI, and the associated end-use product Eco
Sprout Guard EP containing 2–100% ethylene in compressed gas cylinders for the control ofsprouting in stored “Russet Burbank” processing potatoes, are eligible for full registration under
Section 13 of the Pest Control Products Regulations.
This Decision Document outlines this stage of the Pest Management Regulatory Agency’s regulatory
decision-making process concerning the use of ethylene and the end-use product Eco Sprout Guard
EP for the control of sprouting in stored “Russet Burbank” processing potatoes.

December 28, 2001

(publié aussi en français)This document is published by the Submission Coordination and Documentation Division,
Pest Management Regulatory Agency. For further information, please contact:
Publications Coordinator
Pest Management Regulatory Agency
Health Canada
2720 Riverside Drive
A.L. 6605C
Ottawa, Ontario
K1A 0K9Internet:

pmra_publications@hc-sc.gc.ca
www.hc-sc.gc.ca/pmra-arla/
Information Service:
1-800-267-6315 or (613) 736-3799
Facsimile: (613) 736-3798

ISBN: 0-662-31524-3
Catalogue number: H113-6/2001-7E-IN© Her Majesty the Queen in Right of Canada, represented by the Minister of Public Works and Government Services
Canada 2001
All rights reserved. No part of this information (publication or product) may be reproduced or transmitted in any form or by anymeans, electronic, mechanical photocopying, recording or otherwise, or stored in a retrieval system, without prior written
permission of the Minister of Public Works and Government Services Canada, Ottawa, Ontario K1A 0S5.

1.0

Introduction
This Decision Document outlines the Pest Management Regulatory Agency’s (PMRA)
regulatory decision-making process concerning the use of Eco Sprout Guard EP
containing ethylene, for the control of sprouting in stored “Russet Burbank” processing
potatoes.

2.0

Background
The PMRA carried out an assessment of available information in accordance with Section
9 of the Pest Control Products (PCP) Regulations. The assessment found that there wassufficient information, pursuant to Section 18.b, to allow a determination of the safety,
merit, and value of ethylene and the end-use product Eco Sprout Guard EP marketed by
McCain Foods Ltd. The PMRA concluded that the use of Eco Sprout Guard EP in
accordance with the label accompanying the product has merit and value consistent with
Section 18.c of the PCP Regulations and does not entail an unacceptable risk of harm
under Section 18.d.
These products were proposed for registration in Proposed Regulatory Decision
Document PRDD2001-04. No comments were received by the PMRA concerning
PRDD2001-04.

3.0

Regulatory Decision
Based on the considerations outlined above, ethylene and the associated end-use productEco Sprout Guard EP, for the control of sprouting in stored “Russet Burbank” processing
potatoes, are eligible for full registration, pursuant to Section 13 of the PCP Regulations.

Regulatory Decision Document - RDD2001-07

（参考資料） カナダにおけるエチレン登録の現状
PMRA (農薬管理規制局)による資料
2001 年１０月５日

申請規則決定書（案）PRDD2001-04

エチレン（商品名 Eco Sprout Guard）
活性物質エチレン、Eco Sprout Guard TGAI および Eco Sprout Guard EP（2-100%圧縮ガスシリンダー）は、加工用貯蔵”Russet Burbank”ジャガイモの萌芽抑制に使用するために、PCP 規則の第 13 条のもとに登録が提案される。
登録申請書には、データの要約とこの製品の完全登録のための理論的根拠が示されている。
PMRA(農薬管理規制局)は、この書類の提出日付から４５日以内にこの提案について文書でコメントする予定である。下記に示した住所に Publications Coordinators に対して意見を期待している。

はじめにPMRA (農薬管理規制局)は、Eco Sprout Guard TGAI (エチレン)とその商品 Eco Sprout Guard EP（Praxian 会社によって製造、McCain Foods 会社によって販売）の登録出願書を審査する。
Eco Sprout Guard EP は、2-100%圧縮ガスシリンダー状容器、加工用貯蔵ジャガイモでの萌芽抑制のための代替農薬として実験された。エチレンは、自然環境ではどこにでも存在する自然植物ホルモンである。エチレンは毒性がなく、高濃度（大気中 80-90%）では臨床用の麻酔剤として使用された歴史がある。４ppm の濃度のエチレンは、頂芽優性を抑えることによりジャガイモ塊茎の萌芽を抑制する。エチレ
ンを処理したジャガイモのエチレンレベルとその主要代謝産物は、無処理のものと同じである。
PMRI は、PCP Regulations(害虫駆除製剤規則)の第９条の規定に従って提出案件の評価を行い、第18.b 条によって Eco Sprout Guard TGAI (エチレン)およびその最終商品 Eco Sprout Guard EP の安全性、利点、価値について決定を下した。当局は、表示に基づいた Eco Sprout Guard TGAI (エチレン)およびその最終商品 Eco Sprout Guard の使用が、PCP 規則の第 18.c 条に合致してメリットと価値があり、第 18d 条によって危害の認容できない危険性も引き起こさないと結論した。それ故に、上記に概略した事項に基づき、Eco Sprout Guard TGAI（エチレン）およびその最終産物 Eco Sprout Guard EP の使用について、PCP 規則の第 13 条によって完全登録を提案する。
PMRA は、この商品の完全登録を取得するための提案を行っている。この製品が提案された規則決定に関係機関が加わるための機会を与えるために、PMRA は、この提出日付から４５日以内に この申請書について文書によってコメントを受理する予定である。

目

次

１ 活性物質、特性および使用
１、活性物質の同定とそれを含む製剤
２、活性物質と最終用途製品の物理化学的性質
３、使用詳細２ 分析方法１、工場における活性物質の分析方法
２、製剤の分析方法
３ヒトと動物に対する影響
1、 総合的な毒性についての要約
2、1 日当たりの許容摂取量の決定
３、急性参照用量
４、毒性エンドポイント選抜：業務従事者および第三者危険評価
５、活性物質またはその不純物暴露によって生じるヒトと動物の健康に対する影響(1) オペレーターの暴露評価(2) 第三者(3) 作業者
４ 残留
５ 環境における運命と性質
１、環境に関係のある物理化学的性質
6 非標的種に対する影響
7 有効性
１、効果
２、処理した植物生産物における望ましくないまたは偶然の副作用
３、望ましくないまたは偶然の副作用の観察
４、経済性
５、持続性
６、結論
8 毒性物質管理方針
9 申請規則決定 (PRD)

１ 活性物質、特性および使用
1.1 活性物質の同定とそれを含む製剤

活性物質：エチレン
機能：萌芽抑制
化学名：
１、

国際純正応用化学連合、エチレン

２、

化学情報検索サービス機関 (CAS)、エチレン

CAS 番号：74-85-1
分子式：C2H4
分子量：28.06
構造式：CH2=CH2
純度：純粋エチレンガス、100%
毒性、環境、その他意味のある関連不純物の同定：製品は最大 0.1%以下の１酸化炭素を含む。毒性関蓮不純物は、下記に示す。（省略）

1.2 活性物質の物理化学的性質と最終用途製品
工業製品:Eco Sprout Guard TGAI
特性

結果

色と物理的状況

無色で圧縮ガス

匂い

甘い

融点／範囲

なし

沸点／範囲

マイナス 103 C

比重0.978 (0 C) (大気＝１)

蒸気密度 （g/mL）

0.00126 (0 C)

紫外線／可視スペクトル波長＞300nm, UV 吸収なし

溶解性（20C）

わずか

オクタノール/水分配係数(KOW)

logKOW=1.16

解離定数

解離しない

安定性（温度、金属）

引火点はマイナス 136 C
圧縮状態では衝撃と高温はさける；酸化物、ハロゲン、酸、塩化
アルミニウムおよびハロカーボンとは不親和性である

コメント

光分解は可能性がない

生物濃縮は可能性がない

最終用途製品：Eco Sprout Guard EP
特性

結果

色

無色

匂い

甘い

物理的状態

ガス

製剤のタイプ

圧縮ガス

保証2-100%, 公称

製剤

生産物はどのような EPA List 1 製剤や TSMP-1
物質として知られている製剤も含まない。

容器材料と表示圧縮ガスシリンダー容器

酸化および還元作用

酸化物、ハロゲン、酸、塩化アルミニウムおよびハロカーボンとは不親和性である

貯蔵安定性

シリンダー状容器で貯蔵する場合は安定である。

爆発性

自然では塩素を含む日光のもとでは爆発性である。大気と酸化剤と爆発性混合の型になっている。熱を火災によって容器が破裂することがある。
容器に対する衝撃を防ぐこと。

1.2 使用詳細
エチレンは成長調節剤である。ジャガイモ塊茎では、エチレンは収穫後の休眠期間を短縮させ、時に早期萌芽を生じるが、しかし頂芽優性を抑制することによって萌芽伸長を阻害する。

Eco Sprout Guard EP は、2-100%エチレンの圧縮円筒型容器に充填され、貯蔵中の加工用ジャガイモ”Russet Burbank”の使用に適用される。Eco Sprout Guard EP は、４ppm のエチレン濃度に調節できる貯蔵施設の循環換気システムに連続処理される。

2 分析方法2.1 工場における活性物質の分析方法
活性は、２種のガスグロマトグラフィー法によって測定された。

2.2 製剤の分析方法
活性は２種のガスグロマトグラフィー法によって測定された。

３ ヒトと動物に対する影響
3.1 総合的な毒性についての要約
エチレンは、すべての植物組織から生産されるガス状の化学物質として自然に存在し、植物成長調節作用として機能する。エチレンはまたヒトおよび家畜の内生の化学物質として自然に存在し、未暴露のラットやヒトによって吐き出された大気中からも検出される。ヒトや家畜のもつ内生エチレンの発生源は、不飽和脂肪の過酸化、フリーのメチオニンの酸化、ヘモグロビンのヘミンの酸化および腸内細菌の代謝などが考えられる。ヒトでは、内生生産から生じる血液中のエチレン濃度は、約 0.097 nmol/L である。

環境条件のもとでは、エチレンはガス状である。そのためエチレンによるヒトへの汚染のルートは吸入による。高濃度のエチレン（酸素中 80-90%まで）は、臨床的な麻酔剤として使用された歴史的な経緯があるが、ほとんど合併毒性はないとされている。酸素中に 90%エチレンが含まれると、20-30 分以内に完
全に麻酔がかかる。麻酔剤としてのエチレンは、吸入に安全性が高く、回復性が早いことから、エーテ
ルより利点が多いとされている。エチレンはカナダでは、大気中に高濃度で存在すると酸素濃度を低下させるため窒息剤として分類されている。

エチレンの摂取、発散および代謝は、一時速度式によって表現することができる。体内へのエチレンの摂取は、血液中では低溶解性のために低い。ラットでは、摂取されたエチレンの 15-17%が肺胞血液に達すると算出されている。ヒトでは、21%のエチレンが肺胞血液に達する（生理的毒性カイネテックシス
テムを用いて）。密閉条件では、50 ppm の濃度のエチレンをヒトの体内に取り込ませると、150L/H の割
合で約 5.6%のエチレンが肺胞血液中に達し、94.4%が血液システムを通じて全身に利用されずに排出される。定常状態では、ヒトで算出された肺胞保持割合は、約 2-3%である。血液中ではガス溶解性が低い
ため、エチレンは敏速に排泄され、体内には蓄積されない。内部また外部から供給されたエチレンは、
ラット、マウス、ヒトにおいても生体内で酸化エチレンに代謝される。健全なヒトでの実験から、吸収された約 2-3%のエチレンは酸化エチレンに代謝されるが、それに対して 98%のエチレンは変化せず放出される。またエチレンの代謝は混合機能オキシダーゼ系の誘導因子によって活性化されるというデータもある。

マウスを用いた暴露実験から、エチレンは低急性毒性であるとされている。圧縮ガスに接触すると、皮膚、目の霜、やけどなどいくつかの急性的な危険がある。Sprague-Dawley ラットを用いた摂取実験では、
10000 ppm 摂取（試験中最高濃度）でも毒性の影響は認められなかった。Fischer 344 ラットを用いた慢
性毒性／発がん性吸入実験では、エチレン濃度 3000 ppm（試験中の最高濃度）でも、処理区における有意な違いや発がん性の証拠は観察されなかった。重要な証拠はエチレンが遺伝毒性でないことである。ヒトと動物実験からエチレンは発がん性がないとされている。総括すると、エチレンは、ヒトに対する発がん性としては分類されていない（ IARC 国際癌研究機関の分類、グループ３）。エチレンは、
NTP(国家毒性プログラム)および OSHA (職業安全衛生管理局)でも発がん物質としてリストされていな
い。

エチレンの毒性について重要なことは、基本的にはその代謝産物、特に初期代謝産物である酸化エチレンとの関係である。酸化エチレンは直接アルキル化剤である。それは多くの生体内、生体外実験例
から遺伝毒性があり、マウスやラットに発がん性があるとされている。マウス肺がん生物検定（70ppm）と標準２年間マウスとラット生物検定（100ppm 濃度）から陽性の結果を得ている。これらの実験に基づき、IARC(IRAC 分類、グループ１)と NTP(発ガン物質報告，９版、“既知の発がん物質“)は、酸化エチレンがヒトに対して発がん性であると分類している。 しかしながら、文献上では、ラットを用いた密閉容器内吸入実験、1000 および 40ppm エチレンの暴露は、それぞれ 5.6 および１ppm の酸化エチレンに匹敵する。
この暴露結果をすでに得られた酸化エチレンに対するラットガン誘因結果と加味して考えると、酸化エチレンが発がん性を示す推定値、5.6 ppm は、発ガン発生率２％を超えるレベルに至っていない。そのような低い酸化エチレン暴露（5.6ppm）から生じる酸化エチレンの身体負荷量(体内蓄積物)は、エチレンを暴露したラットにおいて発ガン性を誘因するにはあまりにも低すぎると結論された。また、文献上では、約 1000ppm のエチレン濃度は、すでにエチレンの Vmax に達している。すなわち、より高い濃度のエチレン暴露は、必ずしも高濃度の酸化エチレンへの変換を伴っていないことを意味している。文献によると、エチレンの濃度に関わらず、統計的に有意な発がん性を示す数値を得るのは困難である。生理的モデルを用いたヒト実験では、1 ppm 酸化エチレンを８時間暴露で生じる予測血液レベルは、45 ppm
エチレンを８時間暴露後に生じる予測レベルと同等であることが示された。5 ppm エチレンを暴露したヒト
におけるヘモグロビン付加物レベルの測定から、吸収されたエチレンの平均 2-3%は、酸化エチレンに代謝されると算出されている。最新の基準（酸化エチレンの最新 OSHA 基準、週 40 時間就業、８時間加重平均）によると、1 ppm の酸化エチレンは毒性的には 37 ppm のエチレン濃度と同等である。文献上、
酸化エチレンの低大気濃度での長時間職業上の暴露は、その限界濃度は 1ppm (1.83 mg/m3)かそれ
以下では、遺伝毒性や発がん性の危険はないとされている。

これらの事実およびエチレンの使用条件（エチレン濃度が貯蔵期間の最終まで最大 4 ppm であること）から、酸化エチレン濃度が許容できない遺伝毒性および発がん性の危険を起こすレベルに達することはあり得ないと考えられる。

文献上、エチレンの使用についてリスクアセスメントのための十分な情報がある。その情報に基づくと、エチレンは低毒性であり、低毒性麻酔剤として広く用いられていた。低レベルのエチレン暴露、エチレンの低吸収率およびエチレンの酸化エチレンへの低変換に基づいて、酸化エチレン濃度が認容できないレベル（＞1.0 ppm）に達するとは考えられない。エチレンは、貯蔵ジャガイモの萌芽抑制のための植物
成長調節剤としての使用条件のもとでヒトに対して無害であると結論できる。製品ラベルの表示に基づいて提案された使用条件を厳守すれば、エチレンの危険性はないと考えられる。

3.2 一日摂取許容量の決定
HPBHC（カナダ健康省、健康保護支局）発刊の”健康・安全状況報告”（1994 年５月）には、エチレンの ADI (一日摂取許容量)は要求されていない。それは、エチレンが果物やジャガイモを含む野菜類の老化とともにに自然に生じるからである。エチレンはまたヒトや室内家畜において自然に生じる内生化学

物質であり、暴露していないラットやヒトの呼吸によっても放出されるため大気中からも検出される。潜在的なエチレン代謝は自然にも存在している。処理ジャガイモにおける代謝産物の分析データには、残留レベルが検出限界レベル以下または対照区とほぼ同じレベルであると示されている。

3.3 急性参照用量
エチレンが急性危険性でないことから、急性参照用量(ARfD)は算定されていない。文献では、急性食事危険評価の事項に関して有意な処理証拠はないとされている。低毒性であることそして麻酔剤として広く使用されていたことから、エチレン暴露によるヒトの潜在的危険性は無視してもよいと考えられている。

3.4 毒性エンドポイント選抜：業務従事者および第三者危険評価
暴露の一次的ルートは吸入である。エチレンは吸入ルートを通しても低急性毒性である。エチレンは
単純な麻酔剤と考えられている。文献上から、Sprague-Dawley ラットを用いた亜慢性吸入実験では10000 ppm（試験中最高量）でも毒性効果はみられなかった。Fischer 344 ラットを用いた毒性／発ガン性吸入実験では、処理区に有意な結果は見られず、また 3000 rpm の濃度（試験中最高濃度）でも発がん性の証拠はみられなかった。圧縮ガスとしてエチレンに接触すると皮膚と目にやけどを起こすことがあり、可燃性による危険性がある。このタイプの暴露の可能性は表示（注意事項）を厳守することよって軽減することができる。このような表示はこの活性成分の最も適切な規制アプローチと考えられ、エチレン
使用上の暴露と危険性の質的評価が実施されている。

3.5 活性物質またはその不純物暴露によるヒトと動物の健康に対する影響
3.5.1 オペレーターの暴露評価
貯蔵ジャガイモへの適用
Eco Sprout Guard は、種々の濃度（２から 100％）の圧縮エチレンガスからなり、シリンダー容器に充填されている。窒素ガスを補充することでバランスをとっている。Eco Sprout Guard は、ジャガイモ貯蔵施設の空調システムで貯蔵期間中 4 ppm の濃度でエチレンガスを放出することによって効果が得られる。最もよい結果を得るためには、ジャガイモを収穫後１−７日で処理を開始し、加工前１−７日まで処理を継続することである。貯蔵業務従事者は、規定のガス濃度を示す濃縮エチレンガス容器を管理しなければならない。貯蔵施設内のガス濃度は注入速度とエチレン濃度（％）によって決定される。貯蔵建物内のエチレン濃度はモニターされ、継続的に遠方からでも貯蔵期間を通して目標レベルに近い値であることを確認しなければならない。一般的には、エチレンガス注入システムは、建物内で空調条件に応じてバルブを操作するためのプログラム制御法を用いている。システム自身は自動的に組み込まれているが、パラメーターの設定、容器の連結と取り外し、使用済み容器やシステムの欠陥箇所の取り替えの場合には人の介入が必要である。

オペレーターへの暴露
作業従事者へのエチレンの暴露は、エチレン処理中に貯蔵建物に入室時、循環ダクト工事中（例えば修理のため）あるいはベンチレーションの排出口の近くにいる時におこる可能性がある。暴露の基本的ルートは吸入である。

エチレンは、植物と動物によって作られる自然発生ガス状化学物質である。ほとんど付随毒性なしに麻酔剤（麻酔剤は酸素中 80-90%のエチレンを暴露することで使用される）として使用された長い歴史がある。一般に米国では安全性であることの確認（GRAS）がなされている。ACGIH(米国産業衛生専門家会議)では、エチレンの暴露限界は示されていない。ACGIH はエチレンを“単純な窒息剤”として分類している。単純な窒息剤使用の場合、緊急時または未知の濃度の施設に意図的に入室する場合または酸素欠乏の場所を除いて、呼吸保護は必要とされていない。文献上、亜急性吸入毒性実験では、Sprague-Dawley ラットで 10000 ppm（試験中最高量）まで、毒性効果はみられなかった。ラットを用いた２年間の長期吸入実験でも 3000 ppm (1 日６時間、週５日間)の暴露で影響がないことが示された。このことから、指定された条件で用いる場合、吸入によってエチレンに暴露された従事者の危険性の可能性は無視できると結論される。

高濃度のエチレンの暴露は、密閉施設でリークしたときに生じる可能性がある。予防説明書には、ガス容器の適切な取り扱いとリークを防ぐためのガス放出システムについて示されている。同じように登録者
は使用者に対して、エチレンガスの放出と監視を代用する設備についての情報を提供している。未知の濃度のエチレンガス使用施設に入室する場合、呼吸保護は図面表示に従うことが大切である。これらの予備説明は適切であると考えている。

圧縮ガス容器の取り扱いや圧力のかかった設備では、その可燃性による危険性、液体ガスによる急性
皮膚または目への暴露の可能性（皮膚や目に接触した場合にやけどを起こす）が示されている。この危険性は適切な保護設備の使用によって適切に軽減することができる。長めのスリーブ、長めのズボン、ゴーグルまたはフェイス・シールド、適切なグローブの着用を勧める。

3.5.2 第三者
Eco Sprout Guard の適切な使用形態に特性から第三者への暴露の可能性は無視できる。

3.5.3 作業者
作業者は、ベンチレーションが終了する前にエチレン処理中または処理後に貯蔵場所（例えば点検のため）に入ることができる （3.5.1 を参照）

４ 残 留
本請願では、残留についてのデータは提出されていない。しかし、ジャガイモ萌芽抑制剤としてエチレンを登録するためにすでにデータが提出されている。その情報は 1994 年５月にエチレンのための“健康・安全状況報告”の中のカナダ健康省健康保護支局によって要約されている。この報告から抜粋した情報をこの章に記載する。

エチレンの代謝作用は、ジャガイモでは特別に調べられていないが、多くの植物で調べられているエチレン代謝および代謝経路と類似しているかほとんど同じである。老化組織としてのジャガイモ塊茎では、エチレンはもしあったとしても非常にゆっくり代謝されるため、基本的には低いエチレン代謝速度である。内生濃度は、未萌芽塊茎で 0.0007-0.15 ppm、萌芽塊茎で 0.1-3ppm の範囲である。エチレンが低浸透性であることを加味すると貯蔵塊茎中のエチレン代謝は低濃度であると予想される。

エチレンとその可能な代謝産物について、処理ジャガイモと対照の無処理のジャガイモとの間には検出レベルに有意な差はみられない。それ故に評価として動物代謝と家畜の飼料の研究は必要がないと考えられる。

4 ppm のエチレンを 150 日間処理したジャガイモについてエチレン残留のデータがある。クロロエタノール、ジクロロエタン、ブロモエタノール、酸化エチレンおよびエチレングリコール（そのグルコサイドを含む）の残留は全体で 0.1 ppm 以下であった。最も毒性の高い代謝産物、酸化エチレンの残留は 2 ppm
以下であった。さらに、揮発性の残留物（酸化エチレン）は塊茎の加工や調理の過程で 90%まで低下すると予想される。この残留の散逸は、加工中のジャガイモ組織の拡散と調理中の加熱による揮発によって生じる。

ジャガイモ塊茎組織内のエチレンの分配係数は非常に低い（0.207）、このことは、もし代謝しているとしてもジャガイモ塊茎における 14C-エチレンの 区別がほとんどできないことを示している。一般に土壌中には約 10 ppm レベルの内生エチレンを含む、そのレベルは土壌の湿度が高くなるにつれて増加する。代謝的に活性のある発達中のジャガイモ塊茎では、エチレン残留を代謝して生物濃縮すると予想される。1993 年と 1994 年の実験で処理したジャガイモ塊茎の成熟塊茎について調べられたエチレン代謝産物の残留は LLQ 以上には至らなかった。

ジャガイモ塊茎内ではエチレンの不浸透性が証明されている。ジャガイモ塊茎は拡散に対して高い抵抗性をもつ。それは塊茎の表皮がガス状物質の拡散のバリアーになることと塊茎全体の約２％を占める
非常に小さな組織を通して拡散されるためである。この状態が塊茎内における外生エチレンの移行を効率的にブロックしている（濃度こう配に対しても）。それによって塊茎内のエチレンの内部濃度は内生レベルで維持されている。

エチレンを処理したジャガイモについて加工実験は行われていない。しかしながら、処理した塊茎をフレンチフライ、パウダーポテト、ポテトフラワーまたは生のジャガイモ料理に加工すると、最も注目される
酸化エチレンの残留がもしバックグラウンド以上のレベルにあったとしても非常に減少する。酸化エチレンは室温ではガスであり、12C 以下では液体である。調理中にジャガイモから蒸発されると考えられる。

提出データによると、常法によって処理されたジャガイモでは、エチレンまたその主要な代謝物は無処理レベル以上には残留しない。それ故に、食物としての危険評価の必要性がなく、MRL は提案されていない。

５ 環境における運命と性質
5.1 環境に関係のある物理化学的性質
エチレンの物理化学的性質は表 5.1(省略)に要約する。LSS とその他の種々のソースから集めた情報によって行われたレビューに基づいている。活性成分は 98.5%以上である。

環境化学と運命実験の要約
エチレンの環境運命についてのデータは、このガスは自然に存在するため、要求されていない。

予想される環境濃度
貯蔵でのエチレンの使用は大気中におけるエチレンの EEC(予想される環境濃度)に影響をあたえる。
しかし、使用場所から大気濃度へのエチレンの貢献は無視してもよいと考えられる。

自然および人為的に発生されるエチレンガスの 89%は、対流圏では OH-ラディカルによって分解され、8%はオゾンと反応して破壊される。約３％は成層圏に運ばれる。大気中に放出されたエチレンの寿命は約２−４日である。

６ 非標的種に対する影響
（省略）

７ 有効性
（省略）

８ 毒性物質管理方針（省略）

９ 提案された規則決定 (PRD)
（省略）

資料

英国（EU 連合）におけるエチレン登録の現状
食料環境保護法令 1985
農薬規則条例 1986（SI 1986 No.1510）: 承認
2006 年５月 19 日発刊

農薬の承認

エチレン（99.9%）３－３
8Schedule:Conllnodity Substance:99。 9%v/v Ethylene

http://wヽ Vヽ V.peSticides.80Ⅵ uk/approvals.asp?id=271

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You are in:Home》 Pesucide Approvals》 Commodity Substance:Ethylene

Schedule:Commodity Substance1 99.9%
vノ

v Ethylene
Food and Environment Protection Act 1985
Control of Pesticides Regulations 1986(S11986 No.1510):Approva:
Date ofissue:19 May 2006
Date of expiry:31 December 2013(unleSS earlier decisions are rnade or further
prescribed extensions are granted)

Notice is hereby given thatin exercise ofthe powers conferred by Regulation 5 oftheCο rfro′ ofPesfilcides RegJrafiOns f986 rS′ f986/f5プ の ●s a177er7deり and Of all otherpowers enabling them in that behalf,the Secretary of State,and the Scottish Ministers(aS
regards Scouand)and the Nalonal Assembly for Wales and the Secretary of State(actingales)have g市 en full approvalfor use ofthe following cOmmodly
iOinJy as regards Ⅵ′
substance:Cornrnodity substance:being 99.90/。 vA′ Ethylene.

This Approvalis SuliecttO the Fo‖ owing Conditions
Fieid of use
Only as a plant growth regulatorin food storage practice.

Situations
Post haⅣ est crops.

Target atrrlospheric ethy:ene concentrations● 150 ppm(172.5 mg/m3)in frul百 pening:● 100 ppm(115 mg/m3)in OniOn storage:●50 ppm (57.5 rng/rn3)in pOtatO storage.

Operator protection
l. Engineering control of operator exposure rnust be used、 ″here reasonably practicablein addition to the fb‖ owing personal protective equipmenti(Э perators must wear
suitable self‐ contained breathing apparatus in atrnospheres with an ethylene
concentra誦 on exceeding 1000 ppm(0.1%V/v;1150 mg/m3).

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Schedule:Commodity Substance:99.9%v/V Ethylene

http://1〜ヽヽ
V.peSticides.go、 Luk/approvals.asp?id=271〜

2. However,engineering controls rnay replace personal protective equipmentif a Controlof Substances Hazardous、 to Health(COSHH)asseSSment shows they provide anequal or higher standard of protection.

Other Specific Restrictions
l. Handling and release of ethylene rnust only be undertaken by operators suitablytrained and competentto carry outthe、″ork.
2. Operators rnust vacate treated areas irnrnediately after ethylene introduction.
3. Unprotected persons rnust be excluded from the treated areas until atrnospheres
have been thoroughiy venllated ffor 15 minutes minimum before re― entry).
4. Arnbient atrnospheric ethylene concentration FnuSt not exceed 1000 ppm (0.10/o Vrv;
1150 rngノ rn3).suitable self‐ contained breathing apparatus rnust be worn inatrnospheres containing ethyiene in excess of 1 000 ppm.
5. A rninirnurn 3 day post treatrnent period is required before removal oftreated crop
frorn storage.
6. Ethylene treatrnent must only be undertaken in fu‖ y enclosed storage areas that are
air tight vvith appropriate air circulation and venting facilities.

Advisory Notes
See also HSE Local Authoritv Circular 31/2 July 2000(Revised November 2004).
Further lnformation

Aooroval of Commoditv Substances
The Aoolicant Guide:Details of application procedures ibr approval of commodity
substances.
Code of Practice for Usinq Plant Protection Products(replaCes"C)reen Code")

Guidance Concerning the Approval of Ethvlene and Ethanol Based Products as Pesticides―
Reoulatorv Update

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Guidance Concerning the Approval of
Ethylene and Ethanol Based Products as
Pesticides
The purpose of this update is to remind manufacturers and users of the approvalrequirements that apply to the use of ethylene as a pesticide. This includes the use of
products containing ethanol to produce ethylene. For the purpose of this update the term'marketing' means the sale, supply, storage and advertisement of pesticide products.

BackgroundOn 2 August 2005 the Pesticides Safety Directorate published a new commodity
chemical approval for the use of the commodity chemical 99.9% v/v ethylene in fruit
ripening, onion storage and in potato storage. This type of approval relates only to theuse of ethylene; it does not permit the marketing of pesticide products containing
ethylene or ethanol labeled for use as a growth regulating pesticide. The placing on themarket of any such products is an offence.
Any company wishing to market ethylene or an ethanol based product for generating
ethylene as a pesticide, must apply to PSD in the usual way for a product approval tomarket the product under an approved label.
PSD has received a number of queries in the past about the approval of ethylene
generators in their own right. Our regulations apply only to pesticides; they do not coverequipment employed in the manufacture, use or application of pesticides.
Both ethanol and ethylene are being supported for inclusion in Annex I of European
Community (EC) Directive 91/414 as part of the fourth stage of the EC review
programme. If it is agreed that these compounds are to be included in Annex I, theexisting commodity chemical approval will be revoked. This is because only approvals
for products marketed as pesticides are recognised by the EU. At the risk of pre-empting
whether ethylene may be included, any company wishing to supply ethylene products tothe market for use as a pesticide after inclusion on Annex 1 (which could be in 2007,
but may not be until 2008), should be thinking now about seeking a product approval.
Guidance on how to submit a package to support Annex I inclusion is included in the
Applicant Guide on the PSD website. Information on registering a product is alsoavailable on our website.
You should note that this principle also applies to all other commodity approvals. If apesticide product is approved ahead of the commodity chemical's inclusion in Annex I,
both the commodity chemical approval and that for any product approval will exist side
by side until the commodity chemical use is revoked. We will issue further guidance on
this in due course.

Contact Information
If you would like any further information or have any questions on the above, pleasecontact either Matthew Wells on 01904 455749, email: matthew.wells@hse.gsi.gov.uk,
or Mark Wilson on 01904 455705, email: mark.wilson@hse.gsi.gov.uk.

Regulatory Update
Regulatory Update: 22/2005
Issued: 20 October 2005

（参考資料）英国（EU 連合）におけるエチレン登録の現状
農薬の承認、商品物質：エチレン

スケジュール：汎用物質：エチレン（99.9%）
食料環境保護法令 1985
農薬規則条例 1986（SI 1986 No.1510）: 承認
2006 年５月 19 日発刊
2013 年 12 月 31 日効力消失

本通知文は、CPR 農薬規制法 1986 (SI 1986/1510)(改正案として)の規則５条によって協議されたものであり、次の汎用物質使用のための完全な承認を与えることである：汎用物質とは 99.9%エチレンであること。

本承認は次のような条件に従うことである
使用分野：
食品貯蔵のための植物成長調節剤としてのみ使用。
状況：
収穫後の作物
目標の大気エチレンの濃度：
果物の熟成、150 ppm (172.5 mg/m3)
タマネギの貯蔵、100 ppm (115 mg/m3)
ジャガイモの貯蔵、50 ppm (57.5 mg/m3)

オペレーターの保護：
1, オペレター汚染への技術的制御は、次のような身体防御装置に加えて合理的に実施できる場所で使用しなければならない：オペレーターはエチレン濃度 1000 ppm を超えない適切な自給式呼吸器を装備しなければならない。
2, しかしながら、もし COSHH 評価委員が同等または高水準の保護を用意していると判断される場合は、
技術的制御は身体保護装置に置き換えることができる。

その他の特別規制：
１、

エチレンの取り扱いと放出は、その仕事を行える適度に訓練された有能なオペレーターによって実施されること。

２、オペレーターはエチレン注入後、直ちに処理場所から退去すること。

３、保護装備をしていない人は、大気が完全にベンチレートされるまで処理場所から離れなければならない（再注入前最短１５分間）

４、

大気中のエチレン濃度は 1000 ppm を超えないこと。1000 ppm を超えるところでは、適切な自給式
呼吸器を装備すること。

５、貯蔵庫から処理作物を除去する前には、最短３日間の後処理期間を必要とする。

６、エチレン処理は、適切な空調設備を備えた気密性のある完全に密閉された貯蔵庫で実施すること。

農薬としてのエチレン製品の承認に関する指針
本更新(改正)の目的は、エチレンを農薬として使用申請するための生産者と使用者に対する承認要件を通知することである。これには、エチレンを生じるエタノールを含む製品の使用も含まれる。この最新情報の意図する“マーケティング”いう定義は、農薬の販売、供給、貯蔵および広告を意味する。

背 景：2005 年８月２日に PSD（農薬安全総局）は、）を果物の成熟、タマネギの貯蔵、ジャガイモの貯蔵における汎用化学物質エチレン（99.9%）の使用に対する新たな汎用化学物質に認可を公開した。この認可は、エチレンの使用のみに限定している：つまり成長抑制農薬として使用表示のあるエチレンやエタノールを含む製品のマーケティングは許可していない。そのような製品の上市は違法である。エチレ
ンを農薬として市場に出したい会社は、正規な手続きを経て、PSD に申請しなければならない。

資料

OECD: Screening Information Data Set(SIDS)（ 経 済 開発協力機構：審査情報データセット： エチレン
1998 年 10 月

ETHYLENE
CAS N°: 74-85-1（後半に和訳を添付）

９３－４

OECD SIDSETHYLENE

FOREWORDINTRODUCTIONETHYLENE
CAS N°: 74-85-1

UNEP PUBLICATIONSOECD SIDSETHYLENE

SIDS DOSSIER ON ETHYLENE

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Summary of Responses to the OECD Request for
Available Data on HPV Chemicals
SIDS PROFILE

1.01 A

CAS NO.

74-85-1

1.01 CCHEMICAL NAME

Ethylene

1.01 GSTRUCTURAL FORMULA

H

H
C

H

C
H

OTHER CHEMICALIDENTITY INFORMATION
1.5

QUANTITY

1.7

USE PATTERN

1.9

SOURCES OF EXPOSURE

ISSUES FORDISCUSSION(IDENTITY, IF ANY)

No further testing required

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Millions metric tonnes per year:(capacity for 1996)
Norway: 0.4
World: 83.0
Chemical industry; as raw material forsynthesis of chemicals, petrochemicals
and resins.
Minor quantities used for fruit ripening
and as anaesthetic gas.
Fuel, coal and gas combustion.
Leakage from chemical industry.
Rural areas: < 1 - 5 µg/m3(0.9 - 4.3 ppb)
Heavy traffic areas:
up to 1.0 mg/m3 (0.9 ppm)
Petrochemical plants:
up to 5 mg/m3 (4.3 ppm)

OECD SIDSETHYLENE

1. GENERAL INFORMATIONA.

CAS number:

74-85-1B.

Name (IUPAC):

EthyleneC.

Name (OECD):

EthyleneF.

Molecular formula:

CH2CH2G.

Structural formula:

H

H
C

H

C
H

H.

Substance group: Industrial chemical; as raw material for synthesis of chemicals,
petrochemicals and resins.

J.

Molecular Weight: 28.05

1.02

OECD INFORMATIONA.

Sponsor Country: Norway

B.

Lead Organisation:
Norwegian Pollution Control Authority (SFT),
P.O. Box 8100 Dep.,
N-0032 OsloNORWAY
Contact person:
Marit KopangenTel.: +47 22 573400
Fax.: +47 22 676706

C.

Name of responder:
Noretyl ANS,Petrochemical division,
Norsk Hydro ANS,
N-0240 OsloNORWAY

1.1

GENERAL SUBSTANCE INFORMATION

A.

Type of Substance:

B.

Physical state ( at 20 oC and 1.013 hPa): GaseousC.

Purity:Organic, hydrocarbon

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1)
2)
1.2

High purity :Commercial purity :> 99.9 %about 99.9 %SYNONYMS
Ethene, acetene, bicarburetted hydrogen, olefiant gas, elayl.

1.3

IMPURITIESWestern Europe product, (ppm range):
Methane + ethane (50-200), propylene and heavier (7-200), CO2 (2.2-50), H2(0.1-10), O2 (0.610), acetylene (1.4-10), total sulphur (1-10), water (0.6-20) and CO (0.15-10) [3].

1.4

ADDITIVES
None known.

1.5

QUANTITY
More than 1,000,000 tonnes per annum.
Capacity for 1996 [2]:Norway:405,000 tonnes
World:
83,000,000 tonnes

1.6

LABELLING AND CLASSIFICATION
EEC:
S2
S9
S 16
S 33

Fx, R12 (Extremely flammable).
(Keep out of reach of children.
(Keep container in well-ventilated place)(Keep away from sources of ignition - No smoking)(Take precautionary measures against static discharges)

Norway: F, R13 (Extremely flammable liquid gas)
S 9-16-33
According to IARC Monograph Volume 60, (1994):
Ethylene: The agent is not classifiable as to its carcinogenicity to humans [3].
1.7

USE PATTERN
Ethylene is the petrochemical product produced in largest quantities world-wide. More than 95%
of the annual commercial production of ethylene is currently based on steam cracking of
petroleum hydrocarbons [4].
About 80 % of the ethylene consumed in US, Western Europe and Japan is used for productionof ethylene oxide, ethylene dichloride and low density, linear low density and high density
polyethylene. Significant amounts are also used to make ethylbenzene, alcohols, olefins,acetaldehyde and vinylacetate. Most of these products are further prosessed into products such asfilm, blow and injection moulding, extrusion coating, cable insulation and PVC. Minor quantities
have been used as anaesthetic gas, for fruit ripening and for welding and cutting metals.

A.

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Type of use:

Category:a)Mainindustrialuse

Use in closed systems
Chemical Industry: used in synthesis
Raw material

b)

Main
industrialuse

Non dispersive use
Agricultural Industry
As fruit ripener

B.

Uses in Consumer Products
Not known

1.8

OCCUPATIONAL EXPOSURE LIMIT VALUE
No exposure limits have been recommended in most countries, but Switzerland established atime-weighted average occupational exposure limit of 11 500 mg/m3 [3].

1.9

SOURCES OF EXPOSURE
Ethylene is ubiquitous in the environment, arising from both natural and man made sources.
Major sources are as a natural product from vegetation of all types [5].
The main anthropogenic sources are from combustion of gas, fuel, coal and biomass. Maximal
exposure of ethylene to humans is considered to be through fossil combustion by vehicles. The
total ethylene emission from the global surface has been estimated to be 18-45 .106 t/y, of whichapproximately 74% is released from natural sources and 26 % from anthropogenic sources.
Emission from oil combustion is estimated to 1.54 .106 t/y [5]. Ethylene produced and consumed
in chemical industry is kept in closed systems and the production facility is normally next door to
the factory using ethylene as a raw material. Exposure to ethylene from industrial sources arethus mainly due to uncontrolled leakage or blow outs. Such events occur at a rate of once every
2.0 .106 t/y of produced ethylene and may result in an immediate release of about 1 ton.

1.10

ADDITIONAL REMARKS

A.

Option for disposal
Incineration.

B.

Other remarks
No data.

2.

PHYSICAL-CHEMICAL DATA

2.1

MELTING POINT-169.15 °C [4]2.2

BOILING POINT-103.71 °C [4]2.3

DENSITY
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d = 0.57 g/cm3 at boiling point [4].
Gas density at STP 1.2603 g/l [4].
Density relative to air 0.9686 [4].
2.4

VAPOUR PRESSURE
4.27 MPa at 0 °C [4].

2.5PARTITION COEFFICIENT log10Pow
Log10 Pow =1.13 (calculated) [6].

2.6WATER SOLUBILITY

A.

Solubility
According to Merck Index, "One volume of ethylene gas dissolves in 4 vol of water at 0°C" [7].
One volume of ethylene gas dissolves in 9 volumes of water at 25 °C [8].
Solubility: 131 mg/l at 20°C [9].
At 15 °C the solubility in water is 200 mg/l [10].

B.

pH Value, pKa ValueNo data available. There is no chemical evidence to suggest a reaction between dissolved
ethylene and water and pH remains unchanged.

2.7

FLASH POINT- 136.11 °C [11].

2.8

AUTO FLAMMABILITY
Autoignition temp:
Ignition temp:

2.9

543°C [7].
425-527°C [4].

FLAMMABILITY
Extremely flammable - liquefied gas.

2.10

EXPLOSIVE PROPERTIES
Explosive limits in air (0.1 MPa and 20oC) [4] :Lower explosive limit (LEL): 2.75 vol %Upper explosive limit (UEL): 28.6 vol %2.11

OXIDIZING PROPERTIES
No information

2.12

OXIDATION:REDUCTION POTENTIAL
No information.

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2.13

ADDITIONAL DATA

A.

Partition co-efficient between soil/sediment and water (Kd).
No information

B.

Other data
Conversion factor for ethylene in air:
1 ppm in air = 1.15 mg/m3 = 912 nl/l [1,4]Odour threshold:
Odour low: 299 mg/m3
Odour high: 4600 mg/m3 [12]3.

ENVIRONMENTAL FATE AND PATHWAYS

3.1

STABILITY

3.1.1

STABILITY IN AIR
The fate of atmospheric ethylene emitted from natural and anthropogenic sources has been
estimated by Sawada and Totsuka, 1986 [5]. They concluded that 89 % was destroyed in the
troposphere by reaction with OH radical, and 8 % in the reaction with O3. The remaining 3 %was transported into the stratosphere. The atmospheric lifetime of ethylene was estimated to be
between 2 and 4 days.
Indirect calculation of photodegradation with O3 as a sensibilizer gave a lifetime of 9.4 days
[13]. Using OH as the sensibilizer a lifetime of 2.7 days was calculated [14].
The following lifetimes are according to Howard, P.H. et al (1991) [15]: Handbook ofenvironmental degradation rates:
Lifetimes:
Air:
High:
3.36 days
Low:
0.37 days
This is based upon combined, measured photoxidation rate constants for .OH and O3.
If the calculation procedures for organic compounds in atmosphere of Atkinson, R. (1996) [75]are used the following depletion rates are found:Air

Due to .OH reaction
Due to O3 reaction
Due to stratospheric removal

Lifetimes
1.7
days
10
days
1900 days

Stratospheric removal can be calculated according to IPPC (1995) [76], assuming a similar
removal of ethylene as CO.
3.1.2

STABILITY IN WATERNo data available

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3.1.3

ETHYLENE

STABILITY IN SOIL
No data available

3.2

MONITORING DATA (ENVIRONMENT)
Rudolph and Johnen, [16] did more than 200 in situ measurements of ethylene and other selected
Light Atmospheric Hydrocarbons during, a cruise from Puerto Madryn (Argentina) to
Bremerhaven (Germany) in 1987. The measuring locations were remote with low biologicalactivity in the surrounding ocean areas. The ethylene level, expressed as mixing ratio was in therange 10-30 ppt (12-35 ng/m3) in the southern hemisphere and in the northern hemisphere afactor of 2 higher. The observed ethylene levels were primarily a result of oceanic emissions andthe differences were indicated to be caused by changes in oceanic phytoplankton concentration.
The oceanic distribution of ethylene and other low molecular weight (LMW) hydrocarbons has
been studied by Swinnerton and Lamontagne, 1974 [17]. They analyzed 452 water samples fromthe open ocean and near shore for LMW hydrocarbons and found a baseline (average) ethyleneof: 4.8 nanoliters/litre (6.0 µg/l) . Upper values were: Mississippi R. Delta ; 35.0 nl/l (44 µg/l)
and Miami dockside; 30.0 nl/l (38 µg/l).
Fuel, coal and gas combustion. Leakage from chemical industry. Rural areas: < 1 - 5 µg/m3,
heavy traffic areas: up to 1.0 mg/m3 [1, 3].
During burning of wood (white pine) an ethylene concentration of about 50 ml/m3 (63 mg/m3
was measured in the smoke [18].

3.3

TRANSPORTAND
DISTRIBUTION
BETWEEN
COMPARTMENTS
INCLUDINGESTIMATEDCONCENTRATIONS AND DISTRIBUTION PATHWAYSENVIRONMENTAL
ENVIRONMENTAL

In their study of the dynamics of atmospheric ethylene, Sawada and Totsuka, [5] estimated thefollowing emissons of ethylene (in 106 t/y):Natural:Terrestrial
Aquatic
Sum

23.3
2.9
26.2

(65.8 %)
( 8.2 %)
(74.0 %)

Sum

1.5
0.42
0.03
0.10
7.10
9.19

(4.28 %)
(1.20 %)
(0.09 %)
(0.29 %)
(20.1 %)
(26.0 %)

Anthropogenic:
Fuel oil combustion
Coal cumbustion
Leakage from Industri
Søppel forbrenning
Biomass burning.

Total Natural + Anthropogenic = 35.4 106 t/yAtmospheric depletion of ethylene:
Ethylene reacts with OH radical to form an adduct which in the presence of O2 and NOx forms
formaldehyde. The products of reaction of ethylene with O3 are mostly CO, CO2, H2O andCH2O. Some ethylene is also transported into the stratosphere [76]. Using the most recent
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estimates [75] of the depletion rates (lifetime) of ethylene in the atmosphere due to these
prosesses give::
Reaction with .OH radical
Reaction with O3
into the stratospheretotal lifetime in atmospherelifetime (days)
1.7
10
1900
1.45

Ethylene sinks (removal capacity, 106 tons/y):
Reaction with .OH radical
44.4
Reaction with O3
7.5
Into stratosphere
0.036
Sum 52.0(85.4%)( 14.5 %)( 0.07 %)The ethylene transported into the stratosphere will eventually react with O3 with the productionof a krü
ger molecule, which again may react with NO regenerating O3. ethylene is therefore notsuspected of being a potential ozone depletor.
3.3.1

TRANSPORT
Physical properties of ethylene indicate that it will rapidly move into the atmosphere from any
type of release.

3.3.2

THEORETICAL DISTRIBUTION (FUGACITY CALCULATION)
A fugacity level I calculation, using a six compartment model (air, water, soil solids, sedimented
solids, suspended sediments and fish) was conducted using the global reference model of OECD[19]. Default values for the environmental parameters were not changed. Entered genericparameters were: melting point - 169.15 oC, vapour pressure 4.27 MPa, water solubility 200
g/m3, log10POW 1.13, half-life in air 56 hours, half-life in water, soil and sediment 672 hours.
This gave the following distribution:in airin waterin soil solids
in sedimented solids
in suspended sediments
in fish99.99915 %,8.27.10-4 %,9.88.10-6 %2.20. 10-7 %.
6.87. 10-9 %5.58.10-10 %This means that for all practical purposes, emitted ethylene is distributed to air only.
3.4

IDENTIFICATION OF MAIN MODE OF DEGRADABILITY IN ACTUAL USE
See 3.3

3.5

BIODEGRADATION
Also a number of research orientated studies were designed to examine theoxidation/hydroxylation and epoxidation of various hydrocarbons by microorganisms isolated
from soil, fresh water systems or other natural systems and pure cultures. Generally, results ofthese studies show that ethylene is subject to biodegradation by various microorganisms and that
ethylene oxide and ethylene glycol are most likely initial degradation products [21].
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Aqueous biodegradation rates have been estimated both for aerobic and anaerobic conditions[15]:
Aerobic half-life:
High: 672 hours
Low:
24 hours
Anaerobic half life:

3.6

High:
Low:

2688 hours
96 hours

BOD5, COD OR RATIO BOD5/COD
No data available

3.7

BIOACCUMULATION
Ethylene is not expected to bioaccumulate because of Log10 Pow = 1.13.
BCF (Bioconcentration factor) is calculated (QSAR) to be 4 on the basis of the toxic action of
nonpolar molecules in the freshwater fish Fathead minnow (pimephales promelas), exposure
duration 2.00 - 304 days [22].

3.8

ADDITIONAL REMARKSNo data.

4.

ECOTOXICOLOGICAL DATA

4.1

ACUTE TOXICITY TO FISH
Little is known about the acute toxicity of ethylene to fish, but the "Water Quality Criteria,
California State Water Resources Control Board, 1963" [23] refers to two reports of toxicity of
ethylene to Orange-spotted sunfish from 1917 [24] and 1921 [25]. The findings were thefollowing:
Lethal conc after 1 hour :Lethal conc after > 1 hour :22 - 25 mg/l [24]22 - 65 mg/l [25]Calculated (QSAR) values reported in the database Ecotoxicity Profile database [26]:Fathead minnow (Pimephales promelas)
4 days LC50 116 mg/l
Bluegill, (Lepomis macrochirus)
4 days LC50 85 mg/l
Channel catfish, (Ictalurus punctatus)
4 days LC50 50 mg/l
Rainbow trout, Donaldson trout,(Onchorhynchus mykiss)4 days LC50 55 mg/l
Calculated (QSAR) values reported by Leeuwen et. al. [27]:Fathead minnow (Pimephales promelas)
4 days LC50 120 mg/l

4.2

ACUTE TOXICITY TO AQUATIC INVERTEBRATESA.

Daphnia
Calculated (QSAR) value reported in the database Ecotoxicity Profile [26]:
Water flea, (Daphnia magna) 48 hours
LC50 53 mg/l

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Calculated (QSAR) value according to Leeuwen et. al. [27]:Daphnid
48 hours
LC50 153 mg/l
B.

Other aquatic organisms
No data available.

4.3

TOXICITY TO ALGAE
A growth inhibition test with Selenastrum capricornutum was performed according to OECD
201 and conducted according to GLP guidelines in 1996 [74]. The 5 nominal test concentrationsin the growth medium ranged from 8.2 to 131 mg/l. During the 72 hr exposure period there was aloss of ethylene, however the mean measured ethylene concentrations (mean of zero time and 72
h measurement) were used for calculation of growth inhibition. Actual test concentrations (mean)
were therfore: 3.3, 7.8, 13.9, 32 and 58mg/l. Loss of ethylene during the 72 hr incubation period
ranged from 64 to 91 %. EC50 for the growth inhibition based on reduction in biomass compared
to control, was calculated to be 40 mg/l (95 % conf. lim.36-46 mg/l). Based on the specificgrowth rate (µ), the 0 - 72 hr EC 50 was calculated to be 72 mg/l (95 % conf. lim. could not becalculated due to that the EC50 value was outside the range of the test). The highest NOEC was
13.9 mg/l. The results agree fairly well with QSAR calculation for Selenastrum capricornutum
which gave an EC50 after 48 hour value of 122.5 mg/l [27].

4.4

TOXICITY TO BACTERIA
E.coli bacteria were treated with ethylene by passing the gas through a bacterial suspension atconstant rate for 10 minutes. After 24 hours exposure, the suspensions were plated on agar
medium and incubated for 24 hours at 37 °C. Survival of colonies from gas treated cells was 79 ±1.3 % of controls. The survival of the E. coli Sd-4 strain after the same treatment was 84.2 ±1.6
% compared to controls. It was concluded that treatment seemed to have little if any effect on thesurvival of both bacteria strains [28].

4.5

CHRONIC TOXICITY TO AQUATIC ORGANISMS

4.5.1

CHRONIC TOXICITY TO FISH
Calculated (QSAR) value reported in the database Ecotoxicity Profile [26]:Fathead minnow, (Pimephales promelas)
32 days
MATC 15.3 mg/l
Calculated (QSAR) value according to Leeuwen et. al. [27]:Fathead minnow, (Pimephales promelas) 28 days

4.5.2

NOEC 13 mg/l

CHRONIC TOXICITY TO AQUATIC INVERTEBRATES
Calculated (QSAR) value according to Leeuwen et. al. [27]:Daphnia
16 days

4.6

TOXICITY TO TERRESTRIAL ORGANISMS

4.6.1

TOXICITY TO SOIL DWELLING ORGANISMSNOEC 37.4 mg/l

No data available

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4.6.2

ETHYLENE

TOXICITY TO TERRESTRIAL PLANTS
A large and diverse literature exists on the effects of ethylene on vascular plants, including
several hundred observations of ethylene exposure and effects. This is mainly due to the fact that
ethylene acts as a plant hormone, regulating a whole range of different reactions. Most of thesereactions can be categorised as growth regulation and include such effects as defloration,
ripening, inhibition of elongation, leaf loss and senescence [9,11, 29, 30, 31, 32]. While most ofthese effects are non reversible, they do not all constitute effects that reduce a plants fitness nor
growth and reproduction. One may categorise the effects into 3 groups based on assumed longterm effects, where long term effects are associated with reduced fitness, growth or reproduction.
In the table below exotic and tropical plants have been excluded in order to present data that givea more realistic view of risks associated with exposure in industrial areas.
Summary table of effects of ethylene exposure to vascular plants. Exotic and tropical plants
are not included. Epinasty=leaf curling, Abcission=loss
Effects

exposuretime1) None or small long term effects:
Epinasty, Lemon
Epinasty, tomato
Epinasty, Chenopodium
Epinasty, Potato

concentrationµg . m-3

Ref

16 h

25-50
46
60
60

[77]
[9]
[9]
[9]

2d
2d
2h
1h

12
58
115
575

[77]
[77]
[77]
[33]

100d
28 d
28 d

8
27
50
116
115
700

[77]
[77]
[77]
[9]
[77]
[9]

3-4 h

2) Effects that may cause long term effects
Inhib growth, sweet pea, (NOEC)
Abscission flower, Carnation
Inhibition of photosynth. Pea (NOEL)
Abscission flower, Snapdragon
3) Long term effects:
Decreased amount flowers, Oats
Growth inhibition, Potato
Yield reduction, Tomato
Growth retardation, Pea
Yield reduction, Garden cress (30 %)Yield reduction, Cotton

14 d
30 d

Among the more sensitive agricultural or horticultural crops are peas, potatoes, tomatoes andoats where retardation effects were observed at concentrations in the range 8-50 µg/m3 (7-40
ppb) . The most susceptible non-woody plant reported, African marigold reacts with leaf
epinasty (downward curling of leaves at 1.16 µg/m3 (1.0 ppb) ethylene [9], the Cattleya orchid,reacts with sepal tissue collapse (loss of flower) at 2.3 gµ/m 3 (2.0 ppb) after ethylene exposure for24 hours [33].
4.6.3

TOXICITY TO OTHER(INCLUDING AVIAN)
No dataNON

MAMMALIAN

TERRESTRIAL

SPECIES

4.7

BIOLOGICAL EFFECTS MONITORING (INCLUDING BIOMAGNIFICATION)
No data

4.8

BIOTRANSFORMATION AND KINETICS IN ENVIRONMENTAL SPECIES

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No data
4.9

ADDITIONAL REMARKSNo data5.

TOXICITY

5.1.

ACUTE TOXICITY

5.1.1

ACUTE ORAL TOXICITY:
Not relevant. Ethylene is a gas with a low boiling point (-103.71 °C).

5.1.2

ACUTE INHALATION TOXICITY
The acute toxicity of ethylene is low, but very high concentrations may cause asphyxia due tooxygen displacement. The lethal ethylene concentration in air to mice is thus estimated to be
950,000 ppm. [34].
When male rats were exposed to 10, 25 or 57.103 ppm for 4 hours, all groups showed increased
serum pyruvate and liver weight [35]. Non of the studies were GLP.

5.1.3

ACUTE DERMAL TOXICITY
Not relevant. Very little ethylene is likely to be absorbed through the skin because of ethylene's
low solubility in fat and low boiling point.

5.1.4

ACUTE TOXICITY, OTHER ROUTES OF ADMINISTRATION
No information

5.2

CORROSIVENESS/IRRITATION

5.2.1

SKIN IRRITATION/CORROSION
There is no evidence to suggest that the liquid ethylene gas is irritant, but it might cause frost
injuries.

5.2.2

EYE IRRITATION
There is no evidence to suggest that the liquid ethylene gas is irritant, but it might cause frost
injuries.

5.3

SKIN SENSITISATION
No data.

5.4

REPEATED DOSE TOXICITY
The toxicity of ethylene has been tested in a 90 days inhalation study on 4 exposed and one
control groups of 30 rats (15 males, 15 females) [36]. The animals were exposed 6 hours/day 5
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days/week for 13 weeks. The exposure groups were T-I: 300 ppm, T-II: 1,000 ppm, T-III: 3,000
ppm and T-IV: 10,000 ppm. The study was not conducted according GLP, but the study heldhigh scientific standard and a quality assurance statement was issued. There were no differences
between controls and treated rats with respect to total weights, weight change, food consumption,haematology, clinical chemistry, gross pathology or histopathology. Male rats in the control, T-I
and T-IV groups showed red deposits or red discharge around the nose, whereas the male T-II
had red deposits around the eyes. Amongst the female rats, a red deposit was observed aroundleft eye of one T-I rat and alopecia around both ears of one T-II rat. Compared with the controls,
the liver weights in several groups of exposed rats were significantly lower. There was, however,no dose response relationship for this weight reduction and the cause was unknown. Ethylene
was not toxic to rats when administered under a stratified regimen of exposure up to 10,000
ppm.
In an explorative non-GLP study, where a group of six male Sprague-Dawley albino rats (50-60g) were exposed to a continuous flow of 60% ethylene in oxygen as inhalation for 6 days, effects
could be seen on several haematology parameters [37]. There were significant reductions inthrombocyte count (-19.3%) and leukocyte count (-48.2%). A reduction was also seen in thebone marrow cellularity (-30%).
During chronic tests on rats (newborn) exposed to a concentration of 2.62 ppm (continuous asinhalation) for 90 days, a delay in coat appearance, dentition, eye opening and circulation
hypotension, cholinesterase activity inhibition, subordination disruption were reported [38].
There were no information on the quality of the study.
In rats treated by inhalation with a concentration of 100 ppm for 70 days, a change in the reflex
nerve impulses, a decrease of cholinesterase activity and a reduction of the blood pressure wereobserved [39]. There were no information on the quality of the study.
5.5

GENETIC TOXICITY IN VITRO

A.

Bacterial test
Ethylene at atmospheric concentrations up to 20 % gave no indication of mutagenic potential in
Salmonella typhimurium in the presence or absence of a metabolic activation system (Ames test)[40]. The study was not conducted according to GLP, and only one (TA 100) of the fourbacterial test strains recommended in the guidelines was tested. Previous testing with the fullrange of Salmonella strains in the presence and absence of a metabolic activation system havealso given negative results [41, 42]. Ethylene showed no gentoxic activity in Escherichia coli.
[28].

B.

Non-bacterial in vitro test
The effect of ethylene on chromosomes was tested in an in vitro cytogenetics assay using
duplicate cultures of CHO cells [71]. The methodology in this study complies with GLP and theOECD Test Guideline 473, "Genetic Toxicology: In vitro Mammalian Cytogenetic Test".
Treatments covering a broad range of doses, separated by narrow intervals, were performed bothin the absence and presence of metabolic activation (S9) from Aroclor 1254 induced rats. The
highest dose level used, approximately 280.5 mg/ml, was equivalent to a concentration of 10mM, corresponding to about 25 % of ethylene.
Due to the explosive properties of the test article when mixed with air, it was not possible toachieve the maximum concentration required by the Regulatory Guidelines using air as carriergas. Nitrogen was therefore used as carrier gas, which allowed higher doses to be achieved.
There are, however, technical problems associated with continuous treatment in a nitrogen
atmosphere, and short (3 hour) pulse treatments were the only practical option.

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A preliminary range-finding study was performed to investigate the toxic effects of ethylene on
CHO cells. In this trial, treatment in the absence and presence of S9 lasted for 3 hours only
followed by a 17 hours recovery period prior to harvest (3+17). The dose levels for the main
study were selected by evaluating the effect of ethylene on mitotic index.
The treatment regimes used in the range-finder were repeated in the main study. Chromosomal
aberrations were analyzed at three consecutive dose levels. No mitotic inhibition (reduction in
mitotic index) was observed at the highest concentration chosen for analysis (280.5 µg/ml) ineither the absence or presence of S9.
Appropriate negative (carrier gas) controls were included in the test system in both experiments
under each treatment condition. Untreated controls were also included in the main study. The
proportion of cells with structural aberrations in the negative and untreated cultures fell within
historical solvent control ranges. 4-Nitroquinoline 1-oxide and cyclophosphamide were employed
as positive controls in the absence and presence of liver S9 respectively. Cells receiving thesewere sampled in the main study, 20 hours after the start of treatment; both compounds induced
statistically significant increases in the proportion of cells with structural aberrations.
Treatment of cultures with ethylene in the absence and presence of S9 resulted in frequencies ofcells with structural aberrations that were similar to, and not significantly different from, thoseseen in concurrent negative controls. Frequencies seen in treated cultures fell within the normal
range.
It is concluded that ethylene did not induce chromosome aberrations in cultured Chinese hamster
ovary cells exposed to a concentration of 10 mM (25 %) in the absence and presence of S9.
5.6

GENETIC TOXICITY IN VIVO
The effects on micronucleus formation in bone marrow cells of rats and mice have been studied
following ethylene inhalation [43]. Each group consisted of 10 animals of each of the two species
and they were dosed with concentrations of 0; 40; 1,000 and 3,000 ppm for 6 hours/ day, 5 daysa week for 4 weeks. An ethylene oxide control group with both species was exposed using thesame conditions at a concentration of 200 ppm. Bone marrow was collected approximately 24hours after the final exposure. Ethylene did not produce, statistically significant, exposure related
increases in the frequencies of micronucleated polychromatic erythrocytes in the bone marrow ofeither rats or mice, while ethylene oxide exposure resulted in signifcant increases in thefrequencies in both species. It is not stated if the study was conducted according to GLP.
Absorption, distribution, elimination of ethylene and formation of haemoglobin and DNA
adducts were studied in rats after inhalation of 300 ppm ethylene for 12 hours/day for 3
consecutive days [44]. DNA adduct formation was measured in liver and lymphocytes andhaemoglobin adducts determined in erythrocytes. The adduct formation with ethylene wascompared to other alkenes and adduct formation decreased with increasing number of carbon
atoms in the molecule. This was an explorative study not conducted according to GLP.
Alkylation of 7-guanine was measured in DNA from liver spleen and testis of mice 14 hours
after exposure by inhalation of 14C-ethylene at an initial concentration of 11 ppm for 8 hours[45]. The degree of alkylation was much higher in the liver than in the other tissues. This study
was an explorative non-GLP study.

5.7

CARCINOGENICITY

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The potential carcinogenicity of ethylene has been tested in a two years study with rats (Fischer 344 inbred) [46]. The study was conducted prior to OECD Guideline 451 for carcinogenicity
testing (1981), but still the study comply with this guideline except for some minor points. In the
study, 960 rats were randomly divided into 4 groups of 120 animals of each sex and exposed 6
hr/day, 5 days/week to 0(control); 300; 1,000 and 3,000 ppm for up to 24 months.
During the course of the study there were observations of hair loss, deposits on and around thenose and eyes and gross eye abnormalities, but there were no obvious differences among thedifferent treatment groups.
There was an overall increase in the number of animals exhibiting gross tissue masses for the test
groups as compared with the control group, although this trend was not statistically significant.
The spontaneous mortality (15.7 %) was roughly equal in all treated groups. The final bodyweights and total weight changes for treated males were higher than those in the control groups,
but no dose-related pattern was seen.
There were no statistically significant differences among any of the treatment groups on any of
the haematology, blood chemistry or other parameters investigated.
No gross or histopathologic tissue changes attributable to the effects of the test material wereobserved in any of the treated rats. The summary reports only few findings which could indicate
any carcinogenic effect of the treatment, but lacks a conclusion at this point.
In a publication from the carcinogenicity study [41], it was concluded that the results provided"no evidence that ethylene at these concentrations causes chronic toxicity or is oncogenic in
Fischer - 344 rats". However, this publication and the summary have later been criticised [47]since they do not discuss the mononuclear cell leukaemia described in the full report. It wasclaimed that the number of animals affected (out of 90) rose from 12 and 8 in the male andfemale control groups to 21 and 11, respectively in the groups receiving 3,000 ppm. On the other
hand, it has been stated that mononuclear cell leukemia may occur in F344 rats at a backgroundincidence > 75 %, and that a further increase in exposed animals is difficult to interpret withrespect to human cancer development.
When the carcinogenic risk of ethylene was evaluated by the International Agency for Research
on Cancer (IARC) in 1979 [1], no data were available to the working group on the
carcinogenicity or mutagenicity of the substance in animals and humans. In supplement 7
published in 1987 [48] it is still summarised that no adequate data were available and ethylene isstated to be not classifiable as to its carcinogenicity to humans. The latest evaluation of ethylene
by the IARC working group (1994) concludes that there is inadequate evidence in humans and inexperimental animals for the carcinogenicity of ethylene [3]. Overall, ethylene was evaluated as
not being classifiable as to its carcinogenicity to humans.
In the Ecotoxicity Profile database it is stated to be no information in the QSAR system which
would suggest that this chemical is a potential carcinogen or mutagen [26].
In another recent evaluation of ethylene as a cancer risk factor it was concluded that it was a risk
factor of concern [49]. This conclusion was based on the observed metabolism of ethylene toethylene oxide, a compound which has been shown to be both mutagenic and carcinogenic. The
linearity hypothesis for dose response relationship can not be applied in this case, since there is asaturation of the metabolism of ethylene. The findings from administration of high doses toanimals can thus not be extrapolated to the human exposure level.
The carcinogenic potential of ethylene has also been reviewed in the BIBRA Bulletin [50]. This
review concludes also on the basis of metabolic production of ethylene oxide that it is timely with
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a detailed reconsideration of the possible carcinogenic risks of inhaling ethylene. The evaluation
also calls for re-evaluation of the need for a specific industrial limit of ethylene.
5.8

TOXICITY TO REPRODUCTION
The potential effects of ethylene inhalation on male and female rat reproduction and on growthand development of the offspring has been studied [70]. The experimental study was carried out
according to GLP (OECD Guideline 421; Reproduction/Development Toxicity Screening Test).
Four groups of rats (10 females and 10 males per group) were dosed by head only inhalation for
6 hours daily; air only (control); 200; 1,000 or 5,000 ppm of ethylene (corresponding to 0; 230;
1,150 or 5,750 mg/m3). This dosing regime was calculated to give about 80; 400 and 2,000
mg/kg/day of ethylene for the three dosed groups respectively. Since the uptake from the lungs
most likely is in the range of 5-10 % , the absorbed dose probably was substantially less than the
figures given above.
The test material was administered to parent animals for two weeks prior to mating, during themating period and until the day prior to necropsy for the males (minimum 28 days) and until day
20 of gestation for the females. The females were allowed to litter and rear their offspring to day
4 post-partum, when they and their offspring were killed.
Morbidity, mortality, clinical condition, weight and food intake were observed throughout the
study, and mating was carefully observed. For each female, litter data and also observations foreach offspring were recorded. At termination of the study, all animals were subject tomacroscopic examination for structural or pathological changes. Ovaries, testes andepididymides of the control and high dose animals were subject to a histopathologicalexamination.
There were no deaths attributable to the test article, and body weight gain was not adversely
affected during the pre-pairing, gestation or lactation periods. The treatment had no effect on
fertility or fecundity and all females became pregnant. Litter size, sex ratio, mean pup weight andpup growth and clinical condition were not adversely affected by treatment.
Necropsy revealed no macroscopic finding suggestive of toxicity due to test article
administration. There was no evidence of any toxic effect on the testis due to test substanceadministration and there were no other microscopic findings suggestive of toxicity due to test
article administration.
In conclusion, head-only administration of ethylene at nominal concentrations of 200; 1,000 or
5,000 ppm was without evidence of toxicity or adverse effects on male and female reproductive
performance, fertility, pregnancy, maternal and suckling behaviour and growth and developmentof the offspring from conception to Day 4 post-partum.

5.9

DEVELOPMENTAL TOXICITY/TERATOGENICITY
It is referred to the experimental study [70] carried out according to the OECD Guideline 421;
Reproduction/Development Toxicity Screening Test. The study is summarised under point 5.8
above.

5.10

OTHER RELEVANT INFORMATIONA.

Specific toxicities (neurotoxicity, immunotoxicity etc.)
No data
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ETHYLENE

Toxicodynamics, toxico-kinetics
Cowles, A.L. et al [51], studied the uptake and distribution of four inhalation anaesthetics indogs. In a series of 21 experiments, 13 large mongrel dogs were ventilated with a constantconcentration of ethylene (1.4 % = 12 g/m3) and three other inhalation anaesthetics.
Concentrations of the anaesthetic were measured by gas chromatography in alveolar gas, arterial
blood, brain, muscle and central venous blood. The average times necessary for the partialpressure of ethylene to reach 50 % of the inspired partial pressure (1.4 %) were: alveolar gas,<2.0 min; arterial blood, <2.0 min; brain, 3.7 min; muscle, 8.2 min and central venous, 5.2 min.
Biotransformation of ethylene to ethylene oxide
Ehrenberg et. al, 1977 [52] showed that 14C-labelled ethylene was metabolized to ethylene oxide
when administered to male CBA mice by inhalation. This metabolism is of significant concern
since ethylene oxide is a potent alkylating agent, a carcinogen and a gentoxicant, and hence more
toxic than ethylene. The amount of epoxide formed was quantitatively determined from thedegree of alkylation of cysteine and histidine residues in haemoglobin.
In a later study from the same laboratory [45], it was shown that ethylene oxide alkylated
nucleophilic sites of mouse DNA. Since the ratio between the degree of alkylation of DNA andthat of haemoglobin was the same when exposed to ethylene and ethylene oxide, it was concluded
that the latter was the reactive intermediate formed from ethylene in vivo. A comparison of thedegrees of alkylation obtained per unit exposure of ethylene oxide and ethylene, showed that at
low levels of ethylene, about 8% of the inhaled amount was metabolized to ethylene oxide. The
rate of ethylene oxidation followed saturation kinetics with increasing ethylene concentration. At
218 ppm ethylene, the oxidation rate was half of the maximal rate (Km value). It was estimatedthat the maximal rate of metabolism (Vmax) of ethylene corresponds to exposure to an air level of
4 ppm of ethylene oxide.
After exposing rats to automotive engine exhaust, Törnqvist et. al., 1988 [53] identified alkylatedamino acids in haemoglobin. These resulted from conversion of about 5-10 % of inhaled ethylene
and propylene to their respective epoxides which again alkylated the nucleophilic sites inhaemoglobin. This quantification of the fraction of ethylene to be oxidised form agreed very wellwith the conversion factor of around 8 % found for the mouse in the above mentioned study [45].
Results from Törnqvist and Ehrenberg in 1990, estimate that in humans, some 6 % of inhaled
ethylene in mainstream smoke is converted to ethylene oxide in smokers [54] and some 3 % in
non-smokers [55].
Metabolic conversion of ethylene to ethylene oxide results in the formation of adducts to DNA
and proteins, and this offers a means for identifying ethylene exposure in vivo. Determination of
haemoglobin adducts using the N-alkyl Edman method has proven valuable [53]. This method
has been used for monitoring adduct formation after ethylene exposure from different sources[49].
Toxicity of ethylene oxide
Ethylene oxide causes dose-related increases in the incidence of gliomas, peritoneal
mesotheliomas and mononuclear cell leukemias in F 344 rats and lymphomas andadenomas/adenocarcinomas of the lung, uterus, harderian gland and mammary gland in B6C3F1
mice (for a review see Walker et. al., 1990 [56]).
Epidemiologic data on ethylene oxide support the anticipation that ethylene oxide is a
carcinogenic agent. When mortality and incidence of cancer in totally 733 workers exposed to

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ethylene oxide were assessed, 8 cases of leukaemia and 6 cases of stomach cancer occurred,
while the expected numbers were 0.8 and 0.65 respectively [57].
In vivo as well as in vitro, ethylene oxide is seen to react both with amino acid residues inproteins and with the purine bases in DNA. When mouse, human or rat erythrocytes were
exposed to ethylene oxide, the main reaction products with haemoglobin were 2hydroxyethylations of cysteines, N-terminal valine, imidazole nitrogens of histidines andcarboxylic groups [58]. The main reaction product after reaction with calf thymus DNA was N7-(2-hydroxyethyl) guanine, whereas O-6-(2-hydroxyethyl)guanine was only about 0.5 % of this.
Species differences were also observed, as rat and mouse erythrocytes were more susceptible toalkylation than the human erythrocytes.
The alkylation of DNA-bases with ethylene oxide has been studied further after exposure of rats
to ethylene oxide by inhalation [59, 56, 60]. The main alkylation site both in vivo and in vitro is
the N-7 position in guanine, resulting in 7-(2-hydroxyethyl) guanine, and this modification isprobably the reason for its carcinogenic and mutagenic effects.
The IARC working group evaluated ethylene oxide in 1994 and came to the overall conclusionthat it was carcinogenic to humans [61]. This was mainly based on the evidence for
carcinogenicity from experimental studies in animals.
Effects of PCB-pre-treatment on ethylene toxicity and biotransformation
It has been demonstrated that ethylene, as well as halogenated ethylenes are acute hepatotoxic inrats pretreated with polychlorinated biphenyl (PCB) [62]. The hepatotoxicity was evident asincreased serum alanine-α-ketoglutarate transaminase (SAKT) and sorbitol dehydrogenase(SDH) in rats pretreated with PCB and exposed to 20,000 ppm ethylene for 4 hours. Without
pretreatment with PCB, ethylene and halogenated ethylenes are not acute toxic. From thesefindings it was suggested that the acute toxicity was mediated through epoxide intermediates
formed by hepatic mixed function oxidases induced by the PCB pre-treatment.
When rats were exposed to ethylene in a closed desiccator jar chamber, the rate of metabolic
elimination of the compound is influenced by pretreatment with PCB (single dose of Aroclor
1254, 500 mg/kg in oil 6 days prior to the experiment) [63]. Biotransformation of ethylene leadto ethylene oxide which was exhaled.
The effects of PCB pre-treatment and high exposure levels of ethylene, due to induction of
mono-oxygenases and increased formation of ethylene oxide, demonstrates that the toxicity of
ethylene is of concern for organisms also exposed to mono-oxygenase inducers. However, it
should be kept in mind that the concentrations used are far above actual exposure levels.
5.11

EXPERIENCE WITH HUMAN EXPOSURE
Ethylene was in general use as an anaesthetic for many years. It has been replaced by more
modern anaesthetics, mostly due to the high explosion risk. Chronic injury in humans resulting
from prolonged and repeated exposure to low concentrations of ethylene (less than 2.5 %) was
not reported in "Patty's Industrial Hygiene and Toxicology (1981)" [11].
Inhalation pharmacokinetics
The inhalation of ethylene was investigated in human volunteers at atmospheric concentrations of
up to 50 ppm. The uptake, exhalation and metabolism could be described by first-order kinetics[64]. The clearance due to uptake was low, only 5.6 %, while the rest was exhaled without
entering the blood stream. Clearance due to metabolism was 36 % of systemic available ethylene.
The biological half-life of ethylene was 0.65 hours. The alveolar retention of ethylene at steady
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state was calculated to be 2 %. The low uptake rate of ethylene was considered due to its low
solubility in blood.
Reproduction effects
In a preliminary study, the miscarriage rate (six out of 15 pregnancies) amongst Swedish women
who had worked in the local petrochemical industry was higher than that seen in 1549 women
outside the industry. Ethylene was the main product in four of the five local petrochemical plants.
No data were provided on occupational levels but measurements made in areas surrounding theplants indicated that ethylene was present in concentrations up to tenfold higher than the otherpollutants (propylene, ethane, propane and phenol) [65].
A brief abstract notes that there was a higher than expected rate of miscarriage andgynaecological disease among female operatives of a polyethylene plant who were exposed toethylene concentrations in the range of about 40-60 ppm and high levels of noise [66].
Carcinogenicity
A preliminary study found no increase in lung cancer incidence in 31 workers exposed toethylene (at unspecified levels) at a US petrochemical factory [67].
A study of workers at an US petrochemical plant found that an increased risk of developing brain
cancer was associated with exposure to (unspecified levels of) a number of chemicals including
ethylene. However, the investigators were unconvinced that the association reflected a casual
relationship [68].
Work Place Exposure
Personal and stationary monitoring of ethylene in a company where this gas was used forcontrolling the ripening of bananas showed air concentrations to be in the range of 0.02-3.35
ppm (0.02 - 3.85 mg/m3), with an estimated average concentration of 0.3 ppm (0.35 mg/m3). In a
study on exposure of fire-fighters, samples taken during the "knockdown" phase of a fire showeda concentration of 46 ppm (53 mg/m3) ethylene, while none was detected during the "overhaul"
phase [3]A study was carried out among workers at a Swedish petrochemical plant using measurements of
haemoglobin adducts formed from ethylene oxide for monitoring of ethylene exposure [69]. The
study was carried out in two parts, part one in 1989 and part two in 1993. Eight workers
exposed to high levels of ethylene ( 4 mg/m3) and 3 workers exposed to low levels (0.1 -0.3
mg/m3) were compared to nine controls exposed to 0.01 mg/m3. All exposed workers showedelevated levels of haemoglobin adducts and adduct formation was dose-related. The results
indicated that about 1 % of the inhaled ethylene was metabolized to ethylene oxide.
The second part of the study, which included four workers, was designed to more accurately
determine the exposure levels, which turned out to have a mean of 4.5 mg/m3. The results
confirmed part one, showing that about 1 % of inhaled ethylene was metabolized to ethyleneoxide and the maximum fraction to be converted was estimated to be 4 %.
The peak level of ethylene reported for human exposure is about 50 ppm ( 57.5 mg/m3 ), while
3.5 ppm ( 4.0 mg/m3 ) has been characterized as a high average level for longer term exposure.
The conversion will then correspond to maximum 2 ppm (3.6 mg/m3) of ethylene oxide for the
peak level and to maximum 0.14 ppm (0.25 mg/m3) for the high averaged level. Givenoccupational exposure limit levels for ethylene oxide (time-weighted averages) are 1.8 mg/m3(Denmark, Japan, USA, Norway) and 2.0 mg/m3 (France, Canada, Sweden) [3].

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6REFERENCES

1.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some monomers,
plastics and synthetic elastomers, and acrolein. 1979, Vol. 19:157-86.

2.

CMAI, World Light Olefin Analysis, 1996.

3.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Industrial
Chemicals. 1994, Vol. 60:45-71.

4.

Granton RL, Roger DJ. Ullmann`s encyclopedia of industrial chemistry.1987;10:45-93.

5.

Sawada S, Totsuka T. Natural and anthropogenic sources and fate of atmospheric ethylene.
Atmospheric Environment. 1986;20:821-32

6.

Hanch C, Leo A. Substituent Constants for Correlation Analysis in Chemistry and Biology, John
Wiley & Sons, New York, 1979.

7.

The Merck Index, 10th edn, 1983, Merck & Co.

8.

HSDB Database, 1991.

9.

Verschueren K. Handbook of Environment Data on Organic Chemicals. Second edition. 1983.

10.

Seidell A. Solubilities of organic compounds. 1941;2:96.

11.

Clayton GD, Clayton FE. Patty`s industrial hygiene and toxicology. 1981. Vol 2b. Toxicology
3rd edn. John Wiley & sons.

12.

Ruth JH. Odour thresholds and irritation levels of several chemical substances: a review. Am Ind
Hyg Assoc J. 1986;47:A142-51.

13.

Atkinson R, Carter WPL. Chem Rev. 1984;84:437-70.

14.

Atkinson R. Journal of Phys and Chem Reference Data. 1989, Monograph no. 1.

15.

Howard PH. et. al. Handbook of environmental degradation rates. 1991, Lewis Publ. Inc.

16.

Rudolph J, Johnen FJ. Measurements of light atmospheric hydrocarbons over the Atlantic inregions of low biological activity. 1990;

17.

Swinnerton JW, Lamontagne RA. Oceanic distribution of low-molecular-weight hydrocarbons.
Baseline measurements. Environ Sci & Technol. 1974;8:657-63.

18.

O'Mara MM. J Fire Flammability. 1974;5:34-53.

19.

Mackay D, Paterson S, Shin WY. Generic Models for Evaluation of the Regional Fate ofChemicals. Chemisphere 1992; 24: 695-717.

20.

BIODEG database, Jan. 1993, version 3.03.U.S EPA, OTC, Washington DC.

21.

EUCLID Dataset, Ethylene, BASF AG, May 1994.
35
UNEP Publications

OECD SIDSETHYLENE

22.

Veith GD, Kosian P. Estimating bioconcentration potential from octanol/water partition
coefficients. in Mackay D et al. (eds.) Physical behaviour of PCBs in the Great Lakes. Ann
Arbor Science Publishers, Ann Arbor, Mi. 1983:269-82.

23.

Mcku JE, Wolf HW (eds). Water quality criteria. US Department of Commerce, NTIS.
1963;186.

24.

Sheford VE. An experimental study of the effects of gas waste upon fishes with special reference
to stream pollution. Bulletin of the Illinois State Laboratory of Natural History. 1917;11:379.

25.

Gutsell JS. Danger to fisheries from oil and tar pollution of waters. Bureau of Fisheries.
Document 910, 1921.

26.

Ecotoxicity Profile Data Base (EPA), Environ. Res. Lab. Duluth, Cont.;SCI. Out. Prog 18/720.

27.

Van Leeuwen et al. Predictions of aquatic toxicity of High-Production-Volume-Chemicals. Part
B. Publikatiereeks Stoffen, Veiligheid, Straling br 1993/9B. Ministerie van Volkshuisvesting,Ruimtelijke Ordening en Milieubeheer. 1993.

28.

Landry MM, Fuerst R. Gas ecology of bacteria. Dev Ind Microbiol. 1968;9:370-81

29.

Bilthoven SW, Bont PFH, Janus JA, Rab E. Exploratory report ethylene. Report no. 710401010,
National Institute of Public Health and Environmental Protection, The Netherlands. 1991.

30.

Sloof W, Bont PFH, Janus JA, Rab E. Exploratory report ethylene. Report no 710401010,
National Institute of Public Health and Environmental Protection, The Netherlands. 1991.

31.

Smith WH. Air pollution and forests - interaction between air contaminants and forest
ecosystems. Springer Verlag 1981;26.

32.

Rademaker BC, Guinée EP, Van de Plassche EJ. The derivation of preliminary maximum
permissable concentrations of volatile compounds in air. RIVM report no.: 679101009. 1993.
National Institute of Public Health and Environmental Protection, Postbus 1, 3720 BA
Bilthoven, The Netherlands.

33.

Davidson OW. Effects of Ethylene on Orchid Flowers. Proc Amer Soc Hort Sci 1949;53:440.

34.

Flury. Arch Exp Pathol Pharmacol. 1928;138:65.

35.

Gaeb S, Cochrane WP, Parlar H, Korte F. Zeitschridt für Naturforschung. 1975;2.

36.

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA. CIIT
summary report, a ninety day inhalation toxicology study in albino rats exposed to atmospheric
ethylene gas. 1977.

37.

Fink B.R. Toxicity of anesthetics. Williams & Wilkins Co. Baltimore, 1968.

38.

Krasovitskaya ML, Mabyarova LK. Gig Sanit 1968;33:5-7.

39.

Krasovitskaya ML, Mabyarova LK. Beol Deistive I Gig 1966.

36
UNEP Publications

OECD SIDSETHYLENE

40.

Victorin K, Stålberg M. A method for studying the mutagenicity of some gaseous compounds in
Salmonella typhimurium. Environ mol Mutag. 1988;11:65 & 79.

41.

Hamm TE jr, Guest D, Dent JG. Chronic toxicity and oncogenicity bioassay of inhaled ethylene
in Fisher-344 rats. Fundamental and Appl Toxicol. 1984;4:473-8.

42.

Huges TJ. et al. Chemical Abstracts. 1984;101:85417t.

43.

Vergenes JS, Pritts IM. Effects of ethylene on micronucleus formation in the bone marrow of rats
and mice following four weeks of inhalation exposure. Mutat Res. 1994; 324: 87-91.

44.

Eide I. et al. Uptake, distribution and formation of haemoglobin and DNA adducts after
inhalation of C2-C8 1-alkene (olefins) in the rat. Carcinogenesis. 1995;16: 1603-9.

45.

Segerbäck D. Alkylation of DNA and haemoglobin in the mouse following exposure to ethene andethene oxide. Chem Biol Interactions. 1983;45:139-51.

46.

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA. CIIT
report, two year chronic inhalation toxicology study with ethylene in F 344 rats, 1979.

47.

Rostron C. Ethylene metabolism and carcinogenicity. FD Chem. Toxic 19xx;24:70.

48.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall evaluations ofcarcinogenicity: an updating of IARC monographs volumes 1 to 42. IARC, Suppl 7, 1987.

49.

Törnqvist M. Is ambient ethene a cancer risk factor ? Environ Health Perspectives. 1994;102(Suppl 4):157-160.

50.

Hopkins J. The carcinogenic potential of ethylene. BIBRA Bulletin. 1993;32 (Oct.): 245-7.

51.

Cowles AL, Borgstedt HH, Gillies AJ. The uptake and distribution of four inhalation anesthetics
in dogs. Anaesthesiology. 1972;36:558-70.

52.

Ehrenberg L, Osterman-Galkar S, Segerbäck D, Svensson K, Calleman CJ. Evaluation of genetic
risks of alkylating agents. iii. Alkylation of haemoglobin after metabolic conversion of ethene toethene oxide in vivo. Mutation Res. 1977;45:175-84.

53.

Törnqvist M, Kautiainen A, Gatz RN, Ehrenberg L. Haemoglobin adducts in animals exposed togasoline and diesel exhausts 1. Alkene. J Appl Toxicol. 1988;8:159-70.

54.

Törnqvist M, Ehrenberg L. Approaches to risk assessment of automotive engine exhausts. In:
Vaino H, Sorsa M, McMichael AJ (eds.) Complex Mixtures and Cancer Risk. Lyon IARC,
1990:277-87.

55.

Törnqvist M et. al. Ethylene oxide doses in ethene-exposed fruit store workers. Scand J Work
Environ Health. 1989;15:436-8.

56.

Walker VE, Fennell TR, Boucheron JA, Fedtke N, Ciroussel F, Swenberg JA. Macromolecularadducts of ethylene oxide: a literature review and a time-course study on the formation of 7-(2hydroxyethyl) guanine following exposures of rats by inhalation. Mutation Res. 1990;233:15164.

37
UNEP Publications

OECD SIDSETHYLENE

57.

Hogstedt C, Aringer L, Gustavsson A. Epidemiologic support for ethylene oxide as a cancercausing agent. JAMA 1986;255:1575-8.

58.

Segerbäck D. Reaction products in haemoglobin and DNA after in vitro treatment with ethyleneoxide and n-(2-hydroxyethyl)-n-nitrosurea. Carcinogenesis. 1990;11:307-12.

59.

Young LT, Habraken Y, Ludlum DB, Santella RM. Development of monoclonal antibodies
recognizing 7-(2-hydroxyethyl) guanine and imidazole ring-opened 7-(2-hydroxyethyl)guanine.
Carcinogenesis 1990;11:1685-9.

60.

Fürst U, Marczynski B, Kasemann RP. Determination of 1-(2-hydroxyethyl) guanine with gas
chromatography/mass spectrometry as a parameter for genotoxicity of ethylene oxide. Arch
Toxicol. 1989;Suppl.13:250-3.

61.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Industrial
Chemicals. 1994, Vol. 60:73-159.

62.

Conolly RB, Jaeger RJ. Acute hepatotoxicity of ethylene and halogenated ethylenes after PCB
pretreatment. Environmental Health Perspectives. 1977;21:131-5.

63.

Filser JG, Bolt HM. Exhalation of ethylene oxide by rats on exposure to ethylene. Mutation Res.
1983;120:57-60.

64.

Filser JG, Denk B, Törnqvist M, Kessler W, Ehrenberg L. Pharmacokinetics of ethylene in man;body burden with ethylene oxide and hydroxyethylation of haemoglobin due to endogenous andenvironmental ethylene. Arch Toxicol. 1992;66: 157-63.

65.

Axelsson G, Molin I. Int J Epidem. 1988;17:363.

66.

Yakubova ZN. Chemical Abstracts. 1976;87:28224w.

67.

Bond GG, et al. Am J Epidemiol. 1986;124;53.

68.

Leffingwell SS, et al. Neuroepidemiology. 1983;2:179.

69.

Törnqvist M, Granath F. Studier av doser av etylenoxid i etenexponerad personal vid
Borealis/Neste. Slutrapport. [Studies of doses of ethylene oxide in personnel exposed to ethylene
at Borealis/Neste. Final Report.]. May 17, 1994.

70.

Aveyard L. Ethylene: Inhalation (Head-only) Reproduction/Development Toxicity Study in the
Rat. Corning Hazleton Report No. 1458/2-1050, April 1996.

71.

Riley S. Ethylene: Induction of Chromosome Aberrations in Cultured Chinese Hamster Ovary(CHO) cells. Corning Hazleton Report No. 1458/1-1052, April 1996.

72.

Victorin K. Uppdaterad hälsoriskbedömning av etenoxid, eten och propen. Institutet för miljömedicin- Karolinska institutet, IMM-Rapport 8/92, Stockholm, 1992. [Updated medical risk assessmentof ethylene oxide, ethylene and propene. Institute of environmental medicine].

73.

BIBRA Tox Profile on Ethylene, 199374.

Mattock SD. Ethylene: Inhibition of growth to the Alga Selenastrum capricornutum. Corning
Hazleton Report No. 1458/3-1018, May 1996.

38
UNEP Publications

OECD SIDSETHYLENE

75.

Atkinson, R.Kintics and mechanisms of gas-phase reactions of the hydroxyl radical with organic
compounds under atmospheric conditions. Chem. Rev. 85:69-201. 1986.

76.

IPCC, Climate change 1994. 1995.

77.

Van der Eerden, L.J. Luchtkwaliteitsevaluatie met behulp van indicatorplanten en agrarishe
gewassen in de omgeving van industrieterrein Moerdijk.IPO report 279. 1981.

39
UNEP Publications

SIDS エチレン評価文書
OECD からの HPV 化学物質に関する利用可能なデータの要求に対する回答の要約
SIDS プロファイル
1.01A

CAS NO.

1.01C

化学名

1.01G

分子式
その他の化学的性質
情報

1.5

量

数百万トン／年（1996 年生産量）
ノルウェー：0.4
世界：83.0

1.7

利用パターン

化学工業;化学薬品、石油化学製品および樹脂の合成用原料として。
尐量は果実の成熟、および麻酔薬ガスとして使用される。

1.9

曝露源

燃料、石炭およびガス燃焼。
化学工業からの漏出。
田園地帯:<1 - 5mg/m3(0.9 -4.3ppb)
渋滞エリア:1.0mg/m3(0.9ppm)以内
石油化学プラント:5mg/m3(4.3ppm)
以内

議論のため

さらなる試験を要しない。

の出版物(も
しあれば同
一性)

-1-

1. 一般情報
A. CAS number: 74-85-1
B. Name (IUPAC): エチレン
C. Name (OECD): エチレン
F. 分子式: CH2CH2
G. 構造式:

H

H
C

C

H

H

H. 物質グループ: 産業化学薬品;化学薬品、石油化学製品および樹脂の合成用原料として。
J. 分子量: 28.05
1.02 OECD 情報
A. スポンサー国: ノルウェー
B. 指導組織:
ノルウェー汚染管理局 (SFT),
P.O. Box 8100 Dep.,
N-0032 OsloNORWAY
Contact person:
Marit KopangenTel.: +47 22 573400
Fax.: +47 22 676706
C. Name of responder:
Noretyl ANS,Petrochemical division,
Norsk Hydro ANS,
N-0240 OsloNORWAY
1.1 一般的な物質情報
A. 物質のタイプ: 有機物, 炭化水素
B. 物理的形状 ( 20℃、1.013hPaにおいて): 気体-2-

C. 純度:1) 高純度: > 99.9 %2) 商業的純度 : 約 99.9 %1.2 同意語
Ethene, acetene, bicarburetted hydrogen, olefiant gas, elayl.
1.3不純物
西ヨーロッパ製, (ppm range):
Methane + ethane (50-200), propylene and heavier (7-200), CO2 (2.2-50),
H2(0.1-10), O2 (0.6-10), acetylene (1.4-10), total sulphur (1-10), water (0.6-20)
and CO (0.15-10) [3].
1.4 添加剤
知られていない
1.5 生産量
年間1,000,000 トン以上
1996年の生産 [2]:ノルウェー: 405,000 トン
世界: 83,000,000 トン
1.6 表示と分類
EEC: Fx, R12 (非常に可燃性).
S 2 (子どもの手の届かない場所).
S 9 (よく換気された場所に容器で保存)
S 16 (発火源から離しておく－禁煙)
S 33 (静電気放電に対して予防策をとる)
Norway: F, R13 (非常に可燃性の液体ガス)
S 9-16-33
IARC モノグラフ Volume 60, (1994)による:Ethylene:人間に対する発癌性物質には分類されていない。[3].

1.7 用途エチレンは、世界中の大多数で石油製品として生産されている。現在、エチレンの-3-

毎年の商業生産の95%以上は石油の炭化水素のスチームクラッキング(無触媒水蒸気改質）によっている[4]。
米国、西欧、および日本で消費されたエチレンの約80%は酸化エチレン、二塩化エ
チレン、低密度、直鎖状低密度、および高密度ポリエチレンの生産に使用されている。 また、かなりの量は、エチルベンゼン、アルコール、オレフィン、アセトア
ルデヒド、およびビニルアセテートを作るのに使用されている。これらの製品の大部分はさらにフィルムや、吹き出し、射出成形や、押出コーティングや、ケーブル
絶縁やPVCなどの製品に加工される。 尐量が麻酔薬のガス、果実の熟成と金属の溶接と切断に使用されている。
A.

一般
a)

b)

B.

利用形態：

カテゴリー：

主閉鎖系における利用

産業

化学工業： 合成に利用

利用

原材料

主

非分散的利用

産業

農産業

利用

果実熟成剤として消費者向け製品
知られていない

1.8 職業上の曝露限界
被曝限界はほとんどの国で勧告されていないが、スイスでは時間加重平均による職業的被曝限界を11 500mg/m3と制定した。
1.9 曝露源
エチレンは自然および人工を発生源として環境中のどこにでもある。主たる発生源は全てのタイプの植物からの自然の産物である[5]。
主な人為的発生源はガス、石油、石炭、およびバイオマスの燃焼による。人に対するエチレンの最大の曝露は自動車による化石燃料の燃焼を通してと考えられている。地球上の総エチレン排出量は18-45.106 t/yであり、うち約74%は自然源、26%は人為的発生源から放出されていると見積もられている。石油の燃焼からの排出量は1.54 .106 t/y [5]と推定される。化学産業で生産されて消費されるエチレンは、-4-

閉鎖システム内に保たれており、通常、生産施設はエチレンを原材料として使用している工場に隣接している。その結果、産業からのエチレンの曝露は主に制御できない漏出か破裂によるものである。そのような出来事は年間２百万トンのエチレン製造につき一度の割合で起き、約１トンの直接放出の結果となるかも知れない。
1.10 追加の特記事項
A.

処分に対するオプション
焼却B.

その他の注意
データ無し

2.

物理化学データ

2.1 融点-169.15 C [4]2.2 沸点-103.71 C [4]2.3 密度d = 0.57 g/cm3
ガス密度

沸騰点下 [4].

STP 1.2603 g/l [4].

空気比密度 0.9686 [4].
2.4 蒸気圧4.27 MPaat

0 C [4].

2.5 分配係数log10Pow
Log10 Pow = 1.13 (calculated) [6].
2.6 水溶性A.

溶解度
メルクインデックスによると, "０℃においてエチレンガスは４倍量の水に溶ける"[7]。25℃では９倍量の水に溶ける。[8].
溶解度： 131 mg/l
200 mg/l

20C [9]15 C [10].

-5-B. 水素イオン指数 pH 価,

酸解離定数 pKa 価

有効なデータ無し。溶解したエチレンと水との間の反応およびpHが残って変化しないことを示唆する化学的証拠はない。
2.7 引火点- 136.11 C [11].
2.8 自然発火性
自然発火温度： 543C [7].
点火温度： 425-527C [4].
2.9 引火性
強燃性－液化ガス.
2.10 爆発性
空気中における爆発限界： (0.1 MPa and 20oC) [4] :下限爆発限界 (LEL): 2.75 vol %上限爆発限界 (UEL): 28.6 vol %2.11 酸化特性
情報無し
2.12 酸化：還元電位
情報無し
2.13 追加データ
A.

土壌／沈殿物と水との間の分配係数

(Kd).

情報無し
B.

その他のデータ
空気中のエチレンに対する換算要素：
1 ppm in air = 1.15 mg/m3 = 912 nl/l [1,4]臭い閾値:
臭いの下限： 299 mg/m3-6-

臭いの上限： 4600 mg/m3 [12]3.

環境中運命および経路

3.1 安定性
3.1.1 空気中安定性
自然および人為起源の大気中エチレンの運命は沢田と戸塚によって1986年に推定された[5]。89％は対流圏においてOHラジカルと反応して、８％はオゾンとの反応によって破壊されたと彼等は結論した。残りの３％は成層圏に運ばれた。エチレ
ンの大気中の寿命は２～４日間と推定された。
増感剤としてオゾンを用いた光分解性による間接的な計算では、9.4日間の寿命であった。OHラジカルを用いた場合は2.7日と算出された。以下の寿命はHoward, P.H.
らの (1991) [15] 環境的分解率ハンドブックによるものである。
寿命
空気：

高

3.36日

低

0.37日

これはOHとオゾンに対して測定された光分解率に基づいている。
もしAtkinson, R. (1996) [75]による大気中の有機化合物に対する計算手順が使用されるなら、以下の減尐率が認められる。
寿命
空気：

OHに帰する反応

1.7日

オゾンに帰する反応

10日

成層圏への移動1900日

成層圏へのエチレンへの移動がCOと同じと仮定すれば、IPPC (1995) [76]の方法によって計算できる。
3.1.2 水中における安定性
有効なデータはない。
3.1.3 土壌中における安定性
有効なデータはない。
3.2 監視データ（環境中）
Rudolph and Johnen, [16] は、1987年にプエルト・マドリン(アルゼンチン)からブレ-7-

ーマーハーベン (ドイツ)までの航海中に、200以上の場所でエチレンとその他の選択された大気中炭化水素成分を測定した。測定場所は周辺に生物活動が尐ない遠い海域であった。混合率で表されたエチレンのレベルは南半球では10-30 ppt(12-35 ng/m3)の範囲であり、北半球では２倍であった。観測されたエチレン値は主として海洋放出の結果であり、示された差は海洋性植物プランクトンの集まり方の変化によって引き起こされていた。
エチレンとその他の低分子炭化水素（ＬＭＷ）の海洋における分布はSwinnertonand Lamontagne, 1974 [17] によって調べられた。彼等は遠洋および沿海から452の海水サンプルから低分子炭化水素を分析し、エチレンの平均的な基準値は4.8
nanoliters/litre (6.0 g/l)であることを発見した。高い方の値は、ミシシッピのR.．
Deltaの35.0 nl/l (44 g/l)およびマイアミのドック側の地域の30.0 nl/l (38 g/l)であった。
燃料、石炭、ガスの燃焼、化学産業からの漏出。農村：< 1 - 5 g/m3、交通量の多い地域：1.0 mg/m3 まで[1, 3]
森林（モミ）火災の時に煙の中から約50 ml/m3 (63 mg/m3）の濃度のエチレンが計測された。
3.3 推定環境濃度を含む環境区画間の移動と分布および分布経路
沢田と戸塚[5]による大気中のエチレンの動態に関する研究では、以下のようなエチレン（in 106 t/y）の排出が推定された。
自然：
陸上

23.3

（65.8％）

水中

2.9（8.2％）

26.2（74.0％）

石油燃焼

1.5（4.28％）

石炭燃焼

0.42

（1.20％）

工場からの漏出 0.03

（0.09％）

焼却

0.10（0.29％）

山火事

7.10（20.1％）

9.19（26.0％）

計
人為：

計

-8-

分布経路合計

自然＋人為＝35.4*106 t/y

エチレンの大気中の減尐エチレンはOHラジカルと反応して、酸素と窒素酸化物があればフォルムアルデヒ
ドを形成する付加体を作る。エチレンとオゾンの反応による産物はほとんど一酸
化炭素、二酸化炭素、水およびフォルムアルデヒドである[76]。いくらかの量のエ
チレンは成層圏へも移動している。最新の推定による大気中のエチレンの減尐率（寿命）は以下のプロセスのようである。
寿命（日）OHラジカルとの反応

1.7

オゾンとの反応

10

成層圏へ

1900

大気中における合計寿命1.45

エチレン（移動容量、106 tons/y)
OHラジカルとの反応44.4（85.4％）

オゾンとの反応7.5（14.5％）

成層圏へ

0.036（0.07）
計

52.0

成層圏へ移動するエチレンは結局はオゾンと反応してkrüger分子を産生し、それはふたたび一酸化窒素と反応してオゾンを再生するかもしれないので、エチレンは潜在的なオゾンの破壊者としては疑われない。
3.3.1 移動エチレンの物理的性質は、それがどんなタイプの解放においても大気中に急速に移動するであろうことを示唆している。
3.3.2 理論的分配 (逃散能計算)
６区画モデル(空気、水、固体土壌、沈殿土壌、浮遊土砂および魚)を使用した逃散
能レベルⅠの計算が、OECDの世界的な参考モデルを用いて行われた[19]。環境変数としてのデフォルト値は変えられなかった。 入力された一般的な変数は以下の通りである： 融点－169.15℃、蒸気圧は4.27メガパスカル、水への溶解性は200g/m3、分配係数のlog10POWは1.13、空気中の半減期56時間、水、固体土壌、沈殿土壌での半減期は672時間であった。このことは以下の分配を与えた：

-9-

空気中

99.99915 %,水中

8.27.10-4 %,固体土壌中9.88.10-6 %

沈殿土壌中

2.20. 10-7 %.

浮遊物中

6.87. 10-9 %

魚類中

5.58.10-10 %このことは、すべての実用的な目的において、放出されたエチレンは空気中だけに分配されることを意味している。
3.4 実際の使用での分解性の主なモードの識別3.3を参照3.5 生分解
数多くの関連した調査研究は、土壌や淡水系またはその他の自然系や純粋培養から分離された微生物による、様々な炭化水素の酸化／ヒドロキシル化反応とエポキシ化を調べるように設計されていた。一般的に、これらの研究の結果は、エチ
レンは様々な微生物で生物分解を受けることがあるのを示しており、酸化エチレ
ンとエチレン・グリコールはたぶん初期の分解産物である[21]。
水の微生物分解速度は、有酸素と嫌気性の両方の状態で見積もられている[15]：3.6有酸素半減期： 高：

672 時間低：24 時間

無酸素半減期： 高：2688 時間

低：96 時間

BOD5, COD または BOD5/COD比
役立つデータはない。

3.7

生物蓄積性
エチレンはLog10 Pow = 1.13であるために生物蓄積性は期待されていない。
BCF（生物濃縮係数）は淡水魚ファットヘッド・ミノウ (pimephales promelas)において無極性分子の毒性作用に基づき4になるように計算された(QSAR：定量的構造活性相関)、露出持続時間2.00－304日間であった[22]。

- 10 -

3.8

追加の特記事項無し

4.

生態毒性データ

4.1 魚類への急性毒性魚類に対するエチレンの急性毒性についてはあまり知られていない。しかし、1963
年の“カリフォルニア州水資源管理部の水質基準[23]”は、オレンジスポッティド・
サンフィッシュに対するエチレンの毒性についての1917年[24]と1921年[25]の二つの報告を参照している。研究結果は次のようである：

１時間後の致死濃度：

22 - 25 mg/l [24]１時間以上の致死濃度： 22 - 65 mg/l [25]Ecotoxicity Profile database [26]で計算値（QSAR：定量的構造活性相関）が報告された。
Fathead minnow (Pimephales promelas) 4 days LC50 116 mg/l
Bluegill, (Lepomis macrochirus) 4 days LC50 85 mg/l
Channel catfish, (Ictalurus punctatus) 4 days LC50 50 mg/l
Rainbow trout, Donaldson trout,(Onchorhynchus mykiss) 4 days LC50 55 mg/l
Leeuwen [27]らによって計算値（QSAR：定量的構造活性相関）が報告された
Fathead minnow (Pimephales promelas) 4 days LC50 120 mg/l
4.2

水棲無脊椎動物に対する急性毒性

A.

ミジンコ
Ecotoxicity Profile [26]のデータベースで計算値(QSAR)が報告された。
Water flea, (Daphnia magna) 48 hours LC50 53 mg/l
Leeuwen ら[27]による計算値は：Daphnid 48 hours LC50 153 mg/l

B. その他の水生生物
有効なデータは無い。
4.3 藻類に対する毒性
Selenastrum capricornutum に対する生長阻害試験が1996年にOECD201による
GLP(優良試験所基準)のガイドラインに従って実施された[74]。8.2 から131 mg/l.

- 11 -

の間の５つの設定濃度が培養基においてテストされた。72時間の期間中にエチレンの喪失はあったものの、測定された平均エチレン濃度（０と72時間の測定値の平均）が、生長阻害の計算に用いられた。そのため実際の試験濃度は3.3, 7.8, 13.9,
32 and 58mg/l.であった。培養期間の72時間の間のエチレンの損失は64～91％の範囲であった。対照と比較した生体量の減尐に基づく生長阻害に対する半数影響度（EC50）は40 mg/l (95 % conf. lim.36-46 mg/l)であろうと算出された。種特有の成長率に基づいて、0-72時間のEC50は72 mg/lと計算された（95 % conf. lim.はEC50が試験した範囲外であったために計算できなかった）。最も高いNOEC（無影響濃度）は13.9 mg/lであった。その結果は、QSARによるSelenastrum capricornutumに対して得られた48時間後のEC50：122.5 mg/l [27]とかなり良く一致した。
4.4 細菌に対する毒性
バクテリア懸濁液の中を10分間一定の速度でガスを通過させるやり方で、E.coli
細菌を処理した。24時間の曝露後に、懸濁液は寒天培地に塗布されて24時間37℃で培養された。ガス処理された細胞からのコロニーの生存数は対照の79 ±1.3 %であった。同様の処理を受けたE. coliのSd-4株の生存数は対照と比較して84.2 ± 1.6%であった。その処理は両方の細菌株の生存に何らかの影響があったとしても軽微であるように思われると結論された[28]。
4.5 水生生物に対する慢性毒性
4.5.1 魚類に対する慢性毒性
Ecotoxicity Profile [26]のデータベースに算定値（QSAR）が報告されている。
ファットヘッド・ミノウ（Pimephales promelas）における32日間の最大許容毒性濃度（MATC）は15.3 mg/lである。
Leeuwen et. al. [27]による算定値（QSAR）は
ファットヘッド・ミノウ（Pimephales promelas）における28日間の無影響度（NOEC）は13 mg/l。
4.5.2 水生無脊椎動物に対する慢性毒性
Leeuwen et. al. [27]による算定値(QSAR) ：ミジンコにおける16日間の無影響度（NOEC）は 37.4 mg/l
4.6 陸生生物に対する慢性毒性
4.6.1 土壌生物に対する慢性毒性
データ無し- 12 -

4.6.2 陸生植物に対する慢性毒性
エチレンの曝露と影響について数百の観察結果を含む、維管束植物へのエチレンの影響について多数の種々の文献がある。これは主としてエチレンが、異なる反応の範囲の全体を調節する植物ホルモンとして作用しているという事実による。
これらの反応の大部分は、摘花、成熟、伸張の抑制、葉の損失と老齢化のような効果を含む成長調節として分類することができる[9,11, 29, 30, 31, 32]。これらの効
果のほとんどは非可逆的である一方、植物の生長と繁殖の適合性を減ずるような影響を全くもたらさない。その影響は適合性、生長または繁殖の減尐に関連している長期間の影響と想定されることに基づく３グループに分類されるかもしれな
い。産業地帯における曝露に関連した危険性についてのより現実的な観点を与えている現在のデータに従って、以下の表では熱帯植物は除かれている。
維管束植物へのエチレン露出の効果の概要表。熱帯植物は含まれていない。
上偏生長（Epinasty）=縮葉、器官脱離（Abcission）=喪失
影響

曝露時間

濃度μg. m-3

参照

25-50

[77]

46

[9]

60

[9]

60

[9]

1) 長期間の影響が無しまたは尐
上偏生長,レモン
上偏生長,トマト

3-4 h

上偏生長, アカザ属
上偏生長, じゃがいも

16 h2) 長期間の影響によるかもしれない効果
生長抑制, スイートピー, (NOEC)

2d

12

[77]

花の部分欠如, カーネーション

2d

58

[77]

光合成の阻害. エンドウ (NOEL)

2h

115

[77]

花の部分欠如, キンギョソウ

1h

575

[33]

花の量の減尐, エンバク

100d

8

[77]

生長阻害, ジャガイモ

28 d

27

[77]

収量減尐, トマト

28 d

50

[77]

116

[9]

3) 長期間の影響:

成長遅延, エンドウ
収量減尐, コショウソウ (30 %)

14 d

115

[77]

収量減尐, ワタ

30 d

700

[9]

農業または園芸作物の中ではエンドウ、ジャガイモ、トマトおよびエンバクがよ- 13 -

り感受性であり、8-50 g/m3 (7-40ppb)の範囲の濃度において遅延効果が観察された。最も影響されやすい非木本植物がアフリカン・マリーゴールドの葉の上偏生長反応（1.16 g/m3 (1.0 ppb)のエチレンで下向きの縮葉[9]、カトレヤに対して24
時間のエチレン曝露後に2.3 μg/m3 (2.0 ppb)においてガク片の組織崩壊（花の損失）の反応が報告された。
4.6.3 哺乳動物以外のその他の陸生種に対する毒性（鳥類を含む）
データ無し
4.7 生物学的影響のモニタリング(生物濃縮を含む)
データ無し
4.8 環境種における体内変化と動力学
データ無し
4.9 追加の特記事項
データ無し
5.

毒性

5.1. 急性毒性
5.1.1 急性経口毒性：
関係がない。エチレンは沸点の低いガスである（-103.71 ）
5.1.2 急性吸入毒性
エチレンの急性毒性は低いが、非常に高い濃度は酸素置換による窒息を引き起こ
すかもしれない。 ネズミに対する空気中の致命的なエチレン濃度は95万ppmであると推定されている[34]。
雄のラットを４時間10, 25 or 57.103 ppmに曝露した時、全てのグループが血清中のピルビン酸イオンと肝臓の重量増加を示した。GLP（優良試験所基準）に準拠した研究はなかった。
5.1.3 急性経皮毒性
関係がない。エチレンの脂肪に対する低い溶解性と低い沸点のために、エチレン
は皮膚を通して吸収されることはほとんど無いと思われる。

- 14 -

5.1.4 管理の他のルートにおける急性毒性
情報がない
5.2

腐食性／刺激性

5.2.1 皮膚刺激／腐食
液体エチレンが刺激性であることを示唆する証拠はないが、霜害を引き起こすかもしれない。
5.2.2 眼刺激性
液体エチレンが刺激性であることを示唆する証拠はないが、霜害を引き起こすかもしれない。
5.3

皮膚感作性
データ無し

5.4

反復投与毒性
エチレンの毒性が４区の曝露処理と無処理に区分したそれぞれ30頭（雄15、雌15）のラット群について90日間の吸入試験でテストされた[36]。ネズミたちは一日６時
間、週に５日間で13週の間曝露された。曝露グループはT-I: 300 ppm, T-II: 1,000
ppm, T-III: 3,000ppm および T-IV: 10,000 ppm.であった。研究はＧＬＰに準拠してはいなかったが、高い科学的規格を保持し、品質を保証する声明書が発行された。
無処理と処理されたネズミの間には、総重量、体重変化、食糧消費量、血液学、
臨床化学、総計の病理学または組織病理学に関して違いが全くなかった。無処理、T-I および T-IV処理グループの雄ネズミは鼻の周りに赤い付着物または排出物を見せた。一方、T-II グループの雄ネズミは眼の周りに赤い付着物があった。雌の中で一頭のT-I の左目の周囲に赤い付着物が、一頭のT-I の両耳の周囲に脱毛が認められた。対照と比較して曝露処理の幾つかのグループにおいて肝臓重量が有意に低かった。しかしながら、この重量減尐は無投与との関係が無く、その原因は不明であった。エチレンは段階的に管理された曝露では10,000ppmまではネズミに毒性はなかった。
試行的な非GLP研究では、6匹の雄のSprague‐Dawley系アルビノ・ラット(50-60g)
が６日間、吸入剤として酸素中に60％のエチレンの連続フローに曝露されたグループにおいて、いくつかの血液学パラメタで影響を見ることができ [37]、栓球の数(-19.3%)と白血球数(-48.2%)の有意な減尐があった。骨髄細胞においても同じ減尐(-30%)が見られた。

- 15 -

新生ラットについて90日間2.62ppmの濃度での曝露(連続吸入)した慢性試験中に、発毛の遅延、歯列状態、開眼と低血圧、コリンエステラーゼ活性阻害、従属分裂が報告された[38]。この研究の質に関する情報はない。
濃度100ppmで70日間の吸入処理されたネズミでは、反射神経刺激における変化、
コリンエステラーゼ活性の減尐、および血圧の減尐が観察された[39]。この研究の質に関する情報はない。
5.5
A.

IN VITRO 遺伝毒性
細菌試験
20％までの空気中濃度のエチレンが、ネズミチフス菌（Salmonella typhimurium）
に対して、代謝活性化の添加および無添加のシステム(エームス試験)において突然変異性の兆候を示さなかった[40]。研究はＧＬＰに従って行われておらず、ガイダ

ンスで推奨されている四分の一の細菌供試株(TA 100)しかテストされていない。
サルモネラ菌の全範囲について代謝活性化システムを添加および無添加の以前のテストでもネガティブの結果が得られている[41, 42]。エチレンはエシュリキア属
大腸菌に遺伝的毒性の活性を全く示さなかった[28]。
B.

l in vitro での非細菌試験
染色体へのエチレンの影響が、CHO細胞の複製培養を用いてインビトロの細胞遺伝学的分析で試験された。この研究における方法論はＧＬＰとＯＥＣＤの試験ガ
イドライン473“遺伝毒性：インビトロの哺乳類遺伝学的試験”に従っている。広範囲な投与量をカバーする狭い間隔で分けられた処理が、ラットに導入された
Aroclor1254による代謝活性化(S9)の添加および無添加の両方において実施された。
使用した中で最も高いレベルの投与量(約280.5mg/ml)は、10mMの濃度に同等であり、エチレンの約25%に一致している。
空気に混ぜた時の試験品の爆発性のために、搬送ガスとして空気を使用する規定
ガイドラインによって、必要な最高濃度を達成することは出来なかった。したがって、高投与量の達成を許容する窒素が搬送ガスとして使用された。しかしながら、窒素大気には連続処理に関連している技術的問題があり、短い周期(3時間)の処理が唯一の実用的な選択肢であった。
CHO細胞へのエチレンの毒性効果を調べるための範囲を見つける予備試験が行われた。この試行において、結果を収める前に17時間の回復期が伴ってのみ、S9の添加および無添加処理が３時間続けられた。主たる研究における投与量レベルは、- 16 -

分裂指数によるエチレンの影響評価によって、選択された。
距離計（range-finder）を使用した処理工程が主たる研究において繰り返された。
染色体の異常は3つの連続した投与量レベルで分析されました。解析で選ばれた最も高い濃度(280.5 g/ml)において、S9を添加してもしなくても、細胞分裂の阻害（分裂指数の減尐）は観察されなかった。また、無処理の対照群は主な研究に含まれていました。
適切なネガティブ(搬送ガス)コントロールがそれぞれの処理状態で両方の実験におけるテスト・システムに含まれていた。ネガティブと無処理の培地における構造的な異常を伴う細胞の割合は、歴史的な溶媒によるコントロールの範囲の中にあった。4-Nitroquinoline 1-oxideとシクロフォスファミドがそれぞれ肝臓S9が添加
および無添加の陽性対照物質として使われた。これらを受ける細胞が、主な研究で処理開始の20時間後に抽出され、両方の化合物とも構造に異常のある細胞の割合が統計的に有意な増加を引き起こした。
S9の添加および無添加でのエチレンを伴う培養処理は、構造に異常のある細胞の頻度は同じようであったが、陰性対照に伴って見られたそれとは有意な違いはなかった。処理培地で見られた頻度は正常の範囲内にあった。
Ｓ９の添加および無添加のいずれでも10 mM (25 %)の濃度に曝露されたチャイニーズ・ハムスターの卵巣細胞の培養において、エチレンは染色体異常を引き起こ
さないと結論された。
5.6

IN VIVO 遺伝毒性
ラットとマウスの骨髄細胞における小核形成への影響が、次のエチレン吸入で研究された[43]。の2種それぞれ10匹の動物から成る各グループは、一日６時間、週に５日で４週間の期間に0; 40; 1,000 and 3,000 ppmの濃度が投与された。両種の酸化エチレン対照群が、同じ条件で200ppmの濃度で曝露された。骨髄は最後の曝露の約24時間後に集められた。エチレンはどちらのネズミの骨髄において曝露に関係した小核を有する多染性赤血球の頻度の統計的に有意な増加を産み出さなかった。一方、酸化エチレンの曝露は両種ともに有意な増加であった。その研究がＧＬＰに従って運営されたかどうかは記述されていない。
エチレンの吸収、分配、除去と、ヘモグロビンおよびDNAの付加体の形態が、一日12時間の３日連続した300ppmのエチレンの吸入の後のラットで研究された[44]。
DNA付加体の形成は肝臓とリンパ球で測られ、ヘモグロビン付加体は赤血球の中- 17 -

で測定された。エチレンによる付加体形成は他のアルケン類((二重結合を一つ持つ
不飽和脂肪族炭化水素))と比較され、付加体形成の減尐は分子中の炭素原子の数が増加することでわかる。この研究はＧＬＰの指針によらない試行的な研究であった。
7－グアニンのアルキル化は、８時間の初期濃度が11ppmであるときの14C-エチレ
ンに14時間吸入曝露させたマウスの肝臓、脾臓と睾丸からのDNAで測定された。
アルキル化の度合いは他の組織よりはるかに肝臓で高かった。 この研究は試行的な非GLP研究であった。

5.7

発がん性
エチレンの潜在的な発癌性はラット（Fischer -344系）を用いた2年間の研究でテストされた。研究は発癌試験のためのOECD ガイドライン451(1981)に先だって行われたが、それでも、研究はいくつかの小さな点を除いてこのガイドラインに従っている。研究では、960匹のラットから無作為に分けられた雌雄それぞれ120匹の４グループが、0(対照); 300; 1,000 ,3,000 ppm に１日６時間、週５日間、24ヶ月間
以上にわたって曝露された。
研究期間中、抜け毛と鼻と目の周りのでき物、総体的な眼の異常が観察されたが、異なる処理グループの間に明確な差はなかった。
対照グループと比べてテストグループに組織肥大を示しているネズミの数の総合的な増加があったけれど、この傾向は統計的に有意ではなかった。自然死亡率(15.7%)はすべての処理グループでほぼ等しかった。処理された雄の最終的な体重と総重量の変化は対照グループよりも大きかったが、投与量に関連したパターン
は見られなかった。
血液学的、血液化学的および他の調査したパラメタのいずれにおいても処理グループ間に統計的な有意差はなかった。テスト材料の効果に起因する大まかな、または組織病理的な組織の変化も供試されたラットのいずれにも見られなかった。
要約は処理による発がん性効果を示すことができる所見がほんのわずかであると報告し、この点についての結論はない。
発がん性の研究からの発表[41]では、結果が「これらの濃度におけるエチレンが慢性の毒性を引き起こす、またはFischer - 344 ラットに対して発がん因子であると- 18 -

いう証拠はない」との結果を出して結論づけた。しかしながら、、彼らが単完全なレポートの中で説明されている核細胞白血病について議論していないので、後でこの公表と概要は批評された[47]。影響を受けたネズミの数が（90匹のうち）対
照グループでは雄が12匹、雌が８匹なのに比べて3,000 ppmを受けたグループでそれぞれ21と11匹に上がっていると主張されていた。他方では、背景としてF344ラ
ットでは単核細胞白血病が75％以上の発生率があるかもしれず、曝露されたネズ
ミにおける更なる増加は人間のがん発生に関して解釈するのが難しいと述べられている。
エチレンの発がん性リスクが1979年に国際がん研究機関(IARC)によって評価された時[1]、動物と人間における物質の発がん性または変異誘発性のワーキンググル
ープには役立つデータが全くなかった。1987年に公表された補足7 [48]では役立つ
十分なデータはないと要約されており、エチレンが人間にとって発がん性であると分類できないと述べられていた。IARCワーキンググループ(1994)によるエチレンの最新の評価は、エチレンの発がん性について人間と実験動物では十分な証拠がないと結論した[3]。総合的に見て、エチレンは人間にとって発がん性と分類できないと評価された。生態毒性プロファイルデータベースではQSARシステムにおいて、この化学物質が潜在的な発がん性または突然変異誘発要因であることを示
唆する情報はないと述べられている。
がんの危険因子としてエチレンの別の最近の評価では、それが重要な危険因子であると結論づけられた[49]。この結論は突然変異性と発がん性の双方が示されている酸化エチレンへのエチレンの代謝の観察に基づいていた。エチレンの代謝の飽和があるので、用量反応関係による直線的な仮説をこの場合には適用できない。
その結果、動物へ多量に投与した実験における知見からは、人間の曝露レベルに対して推定できない。
エチレンの潜在的発がん性は、BIBRA（British Industrial Biological Research
Association） の会報でも総括された。このレビューも、酸化エチレンの代謝産物に基づいて、エチレン吸入の潜在的発がん性リスクの詳細な再考に時宜を得ていると結論している。また、評価はエチレンの明確な産業的制限の必要性の再評価を求めている。
5.8

繁殖への毒性雄と雌のラットにおける繁殖および子の生長と発育へのエチレン吸入の潜在的影響が研究された[70]。その実験的研究はGLP(OECD Guideline421; 繁殖/発育への毒- 19 -

性審査テスト)に従って行われた。４グループのラット(1グループあたり匹の雌と10匹の雄)が毎日６時間の頭部だけでの吸入で200; 1,000 or 5,000 ppmのエチレンと、空気だけの投与（0; 230; 1,150 or 5,750 mg/m3に相当）が行われた。この投与
制は、投与の３グループに対してそれぞれ80; 400 and 2,000mg/kg/dayを与えるために計算された。肺からの摂取がたぶん5-10%の範囲にあったため、吸収量はたぶん
上記の数字より実質的に尐なかったであろう。
交配に先立つ２週間、交配期間中、および雄では検死の前日まで(最小28日間)、雌では妊娠の20日目まで、供試物が親ネズミたちに施された。雌は出産と、親子が殺されるまでの分娩後４日間は世話をすることを許された。
病的状態、死亡率、臨床の状態、体重および食物摂取量が研究期間中観察され、また交配が注意深く調べられ。それぞれの雌について、産子数および各子ネズミの測定が記録された。研究の終了時、すべての動物が形態的または病理学的な変化を肉眼で検査された。対照および高投与量動物の卵巣、睾丸、および副睾丸が組織病理学検査を受けた。
テスト品に起因する死亡はなく、交配前、妊娠および授乳期間における体重増加
は悪影響を受けなかった。繁殖力や多産性に対して処理の影響はなく、すべての雌が妊娠した。産子数、性比、子ネズミの平均体重、成長および臨床状態は処理による悪影響を受けなかった。
検死は、肉眼による検査がテスト品の投与による毒性を示唆する肉眼的発見がないことを示した。試験物の投与による睾丸への毒性影響に関する証拠はなく、さらに毒性を示唆する顕微鏡的所見もなかった。
結論として、名目上の濃度が200; 1,000 or 5,000 ppmのエチレンの頭部だけの投与
は、毒性の証拠または、雄と雌における繁殖行動、繁殖力、妊娠、母と子の行動、および受胎から産後４日目の子の生長と発育への悪影響はなかった。
5.9

発生毒性／催奇形性
それはOECD Guideline421にそって行われた繁殖／発育毒性の選択試験が実験的研究に参照されている。その研究は上記の5.8に要約されている。

5.10
A.

他の関連情報
特異的毒性（神経毒性、免疫毒性など）- 20 -

データなしB.

毒力学、毒物動態学
コールズ，A.Lら[51]は犬での４種類の4吸入麻酔薬の摂取と分布を研究した。21の一連の実験では、13頭の大型雑種犬に一定濃度のエチレン(1.4%＝12g/m3)と他に３種類の吸入麻酔薬を吸入させた。肺胞気、動脈血、脳、筋肉、および中央の静脈血の中の麻酔薬の濃度がガスクロマトグラフィーによって測定された。エチレ
ンの分圧が吸気分圧(1.4%)の50%に達するのに必要な平均時間は以下の通りである： 肺胞気、２分以下、 動脈血 ２分以下、 脳、3.7分、筋肉 8.２分、中央の静脈、5.2分
エチレンの酸化エチレンへの生体内変換
エーレンバーグらは1977 [52]、雄のCBAマウスに吸入させた14Cでラベルしたエチレンが酸化エチレンに代謝されたことを示した。酸化エチレンは発癌物質であり遺伝子毒である強力なアルキル化剤(DNAを不可逆修飾する抗悪性腫瘍薬の一群)としてエチレンより毒性が強いので、この代謝はとても重要である。形成されたエポキシドの量はヘモグロビン中に残っているシステインとヒスチジンのアルキ
ル化の度合いから量的に決定された。
同じ実験室における後の研究では[45]、酸化エチレンがマウスのDNAの求核部をアルキル化したことが示された。エチレンと酸化エチレンに曝露された時に、DNAとヘモグロビンのアルキル化の度合いの比率が同じであったので、後者が生体内でエチレンから形成された反応中間物であると結論づけられた。酸化エチレンとエチレンの単位あたりの曝露で得られたアルキル化の度合いの比較は、低レベルのエチレンでは、吸入された量の約8%が酸化エチレンに代謝されたことを示した。
エチレン濃度の増加に伴うエチレン酸化の割合は飽和濃度まで続いた。218ppmのエチレンでは、酸化率は最高割合の半分(Km 値)であった。エチレンの最大限度の代謝速度(Vmax)が空気中濃度4ppmの酸化エチレンへの曝露に対応すると推定された。
Törnqvist ら., 1988 [53]は、自動車エンジンの排気に曝露した後のラットで、ヘモ
グロビンちゅうにアルキル化されたアミノ酸を確認した。これらは吸入されたエチレンとプロピレンの約5-10%がそれぞれのエポキシドに転換し、さらにヘモグロビンの求核サイトをアルキル化した結果である。約8%の換算率にとてもよく一致していたエチレンの酸化される部分の定量化は、上記の研究の中でのマウスで発見された。Törnqvist とエーレンバーグ1990による結果では、人間では、喫煙家において吸入された主流煙中のエチレンの約6%[54]、非喫煙者で約3%[55]が酸化エ- 21 -

チレンに変換されると推定された。
エチレンの酸化エチレンへの代謝的変換はDNAとタンパク質付加体の形成をもた
らし、これは生体内でエチレン曝露を特定するための手段を提供する。N-アルキ
ル・エドマン法を使用したヘモグロビン付加体の測定は役立つと証明した[53]。この方法は異なるソースからのエチレン曝露後の付加体形成を調べるために用いられた[49]。
酸化エチレンの毒性
酸化エチレンは投与量の増加と関連して、F344ラットでグリオーマ、腹膜悪性中
皮腫、単核細胞白血病を、B6C3F1マウスでリンパ腫および肺、子宮、ハーダー腺、乳腺の腺腫/悪性腺腫引き起こす（ウォーカーら、1990によるレビュー1990 [56]）。
酸化エチレンに関する疫学データは酸化エチレンが発がん性作用物であるという予想を支持している。酸化エチレンに曝露された733人の労働者の死亡率と発がん率が調べられた時、それぞれの期待数は0.8と0.65であったが[57]、８例の白血病と６例の胃がんが見つけられた。
生体内と同じく生体外で、酸化エチレンはタンパク質のアミノ酸残基とDNAのプ
リン塩基の双方に反応しているのが見られる。マウス、人間またはラットの赤血球が酸化エチレンにさらされたとき、主な反応の生成物はヘモグロビンでシステ
インの2ヒドロキシエチレイション、N-末端バリン、ヒスチジンとカルボキシルグ
ループのイミダゾール窒素であった[58]。仔ウシ胸腺のDNAとの反応の後の主な反応生成物はN7(2-hydroxyethyl)グアニンであったが、O-6(2-hydroxyethyl)のグアニ
ンはこの約0.5%にすぎなかった。
また、ラットとマウスの赤血球がヒトの赤血球よりアルキル化に感受性であった
ように、種間差が見られた。
酸化エチレンによるDNA 塩基のアルキル化が、吸入によって酸化エチレンに曝露させたラットでさらに研究された[59, 56, 60]。
生体内および生体外ともにおける主なアルキル化部位は7(2-hydroxyethyl)グアニンに由来するグアニンのN-7位置であり、この変更がたぶん発がん性と突然変異的な効果の理由である。
IARC（国際がん研究機関）のワーキンググループは、1994年に酸化エチレンを評価し、人間対して発がん性があるという総体的結論に至った。これは主として動- 22 -

物に対する発がん性に関する実験的研究からの証拠に基づいていた。
エチレン毒性と体内変化におけるPCBの前処理の効果
ハロゲン化エチレンと同様にエチレンがポリ塩化ビフェニル(PCB)で前処理されたラットに対して急性の肝細胞毒であることが示された[62]。PCBの前処理と2万ppmのエチレンに４時間曝露されたラットにおいて、血清のアラニン・α・ケト
グルタル酸塩トランスアミナーゼ(SAKT)とソルビトール脱水素酵素(SDH)の増加
で肝毒性は明白であった。PCBの前処理がなければ、エチレンとハロゲン化エチ
レンは急性毒ではない。これらの発見から、急性毒性がPCBの前処理で引き起こされた肝臓の混合機能酸化酵素によって形成されたエポキシドの仲介を通して成立していることが示唆された。
ラットが閉じている乾燥機瓶の部屋でエチレンに曝露されたとき、化合物を除去する代謝速度はPCB前処理(実験の6日前にアロクロール125を500mg/kg油に入れて単回投与)によって影響を受ける[63]。エチレンの体内変化は酸化エチレンとなって放出された。
PCBプレ処理と高い被ばくレベルのエチレンの影響は、モノオキシゲナーゼの誘導と酸化エチレン形成の増加のために、モノオキシゲナーゼ誘導酸素に曝露された生物にとって、エチレンの毒性が重要であることを示している。しかしながら、使用された濃度が、実際の被ばくレベルをはるかに超えていることを心に留めておくべきである。
5.11 人のばく露経験
一般的にエチレンは麻酔薬として長年にわたって使用された。たいていはその高
い爆発の危険性のために、より近代的な麻酔薬に取り替えられた。低濃度のエチレン（2.5 %以下）の長期で反復した曝露の結果としての人における慢性的な障害は「Pattyの産業衛生と毒物学(1981)」の中では報告されなかった[11]。
吸入薬物動態学
エチレンの吸入が人間のボランティアで最大50ppmの大気中濃度で調査された。
摂取、発散および代謝は一次反応速度論によって説明できた[64]。摂取による除去はわずか5.6％と低く、残りは血流に入ることなく吐き出された。代謝による除去
はシステムで使われたエチレンの36%であった。エチレンの生物学的半減期は0.65
時間だった。肺胞に定常的に留まったエチレンは２％と算出された。エチレンの低い摂取率は血液への低い溶解度のためと考えられた。

- 23 -

繁殖への影響
予備的な研究では、地方の石油化学産業で働いていたスウェーデン人女性における流産率(15回の妊娠のうちの6回)は、産業の外部にいた1549人の女性に見られたそれより高かった。エチレンは5ヶ所の地方石油化学工場のうちの4ヶ所における主な生産物であった。職業レベルで提供されたデータは全くないが、領域を囲っている植物での測定では、エチレンがその他の汚染物質(プロピレン、エタン、プ
ロパンおよびフェノール)よりも10倍高い濃度で存在しているのを示した[65]。
簡潔な要約は、約40-60ppmの範囲のエチレン濃度と高いレベルの雑音に曝露されたポリエチレンプラントの女子工員における流産と婦人科病は期待値よりも高い割合であったことが簡潔な要約で言及された[66]。
発がん性予備的な研究では、米国の石油化学工場でエチレン(不特定のレベルにおける)に曝
露された31人の労働者において肺がん発生の増加を全く見つけなかった[67]。
アメリカの石油化学プラント労働者についての研究で、脳腫瘍を発症する危険性の増加がエチレンを含む多くの化学物質の曝露(不特定のレベル)と関連していることが分かった。しかしながら、研究者はその関連性が偶発的な関係を反映していたと確信してはいなかった[68]。
職場の曝露
バナナの成熟を制御するのに使用されている会社における、個人的で定常的なエチレンの観測は、大気中濃度が0.02-3.35ppm(0.02--3.85mg/m3)の範囲にあり、平均濃度は0.3ppm(0.35mg/m3)であったことを示した。
消防士の曝露に関する研究では、炎の「圧倒的な（knockdown）」様相の間に取られたサンプルは、46ppm(53mg/m3)の濃度のエチレンを示した一方、精密検査（overhaul）の間には検出されなかった[3]。
スウェーデンの石油化学プラントの労働者を対象に、エチレン曝露のモニターのために酸化エチレンから形成されたヘモグロビン付加体の測定をする研究が実施された[69]。研究は1989年のパート1および1993年のパート2の2つのパートで実施された。高いレベルのエチレンに曝露された8人の労働者(4mg/m3)と、低レベルに曝露された3人の労働者(0.1 -0.3mg/m3)が、対照とした0.01mg/m3に曝露された9人と比較された。全ての被ばく労働者がヘモグロビン付加体のレベルを上げ、付加- 24 -

体形成は投与量に関連していた。結果は、吸入されたエチレンの約1%が酸化エチレンに代謝されたことを示した。
4人の労働者を含んでいた研究の第二部は、より正確に被ばくレベル、平均
4.5mg/m3となるに設計された。結果はパート1を追認し、吸入されたエチレンの約1%が酸化エチレンに代謝されて、変換されるべき最大区分が4%であると推定された。
ヒトの曝露関して報告されたエチレンのピーク水準は約50ppm(57.5mg/m3)であり、一方3.5ppm(4.0mg/m3)は、より長い期間の曝露の高位平均値とみなされた。そして、ピーク水準に対しては最大の2ppm(3.6mg/m3)、高位平均値に対しては最大
0.14ppm (0.25mg/m3)の酸化エチレンへの変換に対応するであろう。酸化エチレン(時間加重平均)について定められた職業被曝限界水準は、1.8mg/m3(デンマーク、
日本、米国、ノルウェー)と2.0mg/m3(フランス、カナダ、スウェーデン)である[3]。

6

参考文献

1.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some monomers,
plastics and synthetic elastomers, and acrolein. 1979, Vol. 19:157-86.
（人間への発がん性リスクの評価に関するIARC研究論文。 いくつかの単量体、プラスチック、合成エラストマー、およびアクロレイン）

2.

CMAI, World Light Olefin Analysis, 1996.
（世界の軽質オレフィン分析）

3.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Industrial
Chemicals. 1994, Vol. 60:45-71.
（人間への発がん性リスクの評価に関するIARC研究論文。いくつかの工業用化学
薬品）

4.

Granton RL, Roger DJ. Ullmann`s encyclopedia of industrial chemistry.1987;10:45-93.
（Ullmann`s5.

工業化学の百科事典）

Sawada S, Totsuka T. Natural and anthropogenic sources and fate of atmospheric
ethylene.

Atmospheric Environment. 1986;20:821-32（大気中のエチレンの自然および人為の発生源と運命）
6.

Hanch C, Leo A. Substituent Constants for Correlation Analysis in Chemistry and Biology,- 25 -

John Wiley & Sons, New York, 1979.
（化学と生物学における相関分析のための置換分定数）
7.

The Merck Index, 10th edn, 1983, Merck & Co.

8.

HSDB Database, 1991.

9.

Verschueren K. Handbook of Environment Data on Organic Chemicals. Second edition.
1983.
（有機化学における環境データ・ハンドブック）

10.

Seidell A. Solubilities of organic compounds. 1941;2:96.
（有機化合物の溶解性）

11.

Clayton GD, Clayton FE. Patty`s industrial hygiene and toxicology. 1981. Vol 2b.
Toxicology 3rd edn. John Wiley & sons.
（Patty`s 産業衛生と毒物学）

12.

Ruth JH. Odour thresholds and irritation levels of several chemical substances: a review.
Am IndHyg Assoc J. 1986;47:A142-51.

（いくつかの化学物質の匂いの閾値と刺激水準）
13.

Atkinson R, Carter WPL. Chem Rev. 1984;84:437-70.

14.

Atkinson R. Journal of Phys and Chem Reference Data. 1989, Monograph no. 1.

15.

Howard PH. et. al. Handbook of environmental degradation rates. 1991, Lewis Publ. Inc.
（環境による分解速度ハンドブック）

16.

Rudolph J, Johnen FJ. Measurements of light atmospheric hydrocarbons over the
Atlantic in regions of low biological activity. 1990;（大西洋の生物活動低レベル地帯の軽い大気中の炭化水素の測定）

17.

Swinnerton JW, Lamontagne RA. Oceanic distribution of low-molecular-weighthydrocarbons. Baseline measurements. Environ Sci & Technol. 1974;8:657-63.
（低分子量炭化水素の海洋分配。 基線測定値）

18.

O'Mara MM. J Fire Flammability. 1974;5:34-53.
（引火性）

19.

Mackay D, Paterson S, Shin WY. Generic Models for Evaluation of the Regional Fate ofChemicals. Chemisphere 1992; 24: 695-717.
（化学物質の局部的運命の一般評価モデル）

20.

BIODEG database, Jan. 1993, version 3.03.U.S EPA, OTC, Washington DC.

21.

EUCLID Dataset, Ethylene, BASF AG, May 1994.

22.

Veith GD, Kosian P. Estimating bioconcentration potential from octanol/water partition
coefficients. in Mackay D et al. (eds.) Physical behaviour of PCBs in the Great Lakes.
Ann Arbor Science Publishers, Ann Arbor, Mi. 1983:269-82.
（オクタノール/水分配係数による生物濃縮潜在能力の推定：大きな湖における- 26 -

ＰＣＢの物理的挙動より）
23.

Mcku JE, Wolf HW (eds). Water quality criteria. US Department of Commerce, NTIS.
1963;186.
（アメリカ商務省の水質基準）

24.

Sheford VE. An experimental study of the effects of gas waste upon fishes with specialreference to stream pollution. Bulletin of the Illinois State Laboratory of Natural
History. 1917;11:379.
（河川の汚染に注目した魚類へのガスの影響に関する実験的研究）

25.

Gutsell JS. Danger to fisheries from oil and tar pollution of waters. Bureau of Fisheries.
Document 910, 1921.
（油とタールの水汚染による漁業への脅威）

26.

Ecotoxicity Profile Data Base (EPA), Environ. Res. Lab. Duluth, Cont.;SCI. Out. Prog
18/720.
（生態毒性プロファイルに関するデータベース）

27.

Van Leeuwen et al. Predictions of aquatic toxicity of High Production Volume
Chemicals. Part B. Publikatiereeks Stoffen, Veiligheid, Straling br 1993/9B. Ministerie
van Volkshuisvesting, Ruimtelijke Ordening en Milieubeheer. 1993.
（大量生産化学物質の水生毒性の予測）

28.

Landry MM, Fuerst R. Gas ecology of bacteria. Dev Ind Microbiol. 1968;9:370-81

29.

Bilthoven SW, Bont PFH, Janus JA, Rab E. Exploratory report ethylene. Report no.
710401010,National Institute of Public Health and Environmental Protection, The
Netherlands. 1991.
（調査報告 エチレン）30.

Sloof W, Bont PFH, Janus JA, Rab E. Exploratory report ethylene. Report no 710401010,
National Institute of Public Health and Environmental Protection, The Netherlands.
1991.

31.

Smith WH. Air pollution and forests - interaction between air contaminants and forest
ecosystems. Springer Verlag 1981;26.
（大気汚染と森林-- 大気汚染物質と森林生態系との相互作用）

32.

Rademaker BC, Guinée EP, Van de Plassche EJ. The derivation of preliminary
maximum permissable concentrations of volatile compounds in air. RIVM report no.:679101009. 1993. National Institute of Public Health and Environmental Protection,
Postbus 1, 3720 BA Bilthoven, The Netherlands.
（空気中の揮発性化合物の予備的な最大許容濃度の誘導）

33.

Davidson OW. Effects of Ethylene on Orchid Flowers. Proc Amer Soc Hort Sci
1949;53:440.

- 27 -

（蘭の花に対するエチレンの影響）
34.

Flury. Arch Exp Pathol Pharmacol. 1928;138:65.

35.

Gaeb S, Cochrane WP, Parlar H, Korte F. Zeitschridt für Naturforschung. 1975;2.

36.

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA.
CIIT summary report, a ninety day inhalation toxicology study in albino rats exposed toatmospheric ethylene gas. 1977.
（CIIT概略報告、空気中のエチレンガスに曝露されたシロネズミの90日間の吸入毒
性研究）

37.

Fink B.R. Toxicity of anesthetics. Williams & Wilkins Co. Baltimore, 1968.
（麻酔剤の毒性）38.

Krasovitskaya ML, Mabyarova LK. Gig Sanit 1968;33:5-7.

39.

Krasovitskaya ML, Mabyarova LK. Beol Deistive I Gig 1966.

40.

Victorin K, Stålberg M. A method for studying the mutagenicity of some gaseouscompounds in Salmonella typhimurium. Environ mol Mutag. 1988;11:65 & 79.
（Salmonella typhimuriumにおける数種のガス状化合物の変異誘発性に関する研究法）

41. Hamm TE jr, Guest D, Dent JG. Chronic toxicity and oncogenicity bioassay of inhaled
ethylene in Fisher-344 rats. Fundamental and Appl Toxicol. 1984;4:473-8.
（Fisher-344ラットにおける吸入エチレンの慢性毒性と腫瘍原性の生物検定）
42.

Huges TJ. et al. Chemical Abstracts. 1984;101:85417t.

43.

Vergenes JS, Pritts IM. Effects of ethylene on micronucleus formation in the bonemarrow of rats and mice following four weeks of inhalation exposure. Mutat Res. 1994;
324: 87-91.
（ラットとマウスの骨髄における小核形成に対するエチレンの4週間の連続吸入曝
露の影響）

44.

Eide I. et al. Uptake, distribution and formation of haemoglobin and DNA adducts after
inhalation of C2-C8 1-alkene (olefins) in the rat. Carcinogenesis. 1995;16: 1603-9.
（ラットでのC2-C8 1-アルケン(オレフィン)吸入後の摂取と分配およびヘモグロ
ビンとDNA付加体の形成）

45.

Segerbäck D. Alkylation of DNA and haemoglobin in the mouse following exposure toethene and ethene oxide. Chem Biol Interactions. 1983;45:139-51.
（マウスに対するエテンと酸化エテンの連続曝露におけるDNAとヘモグロビンのアルキル化）

46.

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina,
USA., two year chronic inhalation toxicology study with ethylene in F 344 rats, 1979.
（CIIT報告：F344ラットに対する2年間の慢性吸入毒性の研究）- 28 -

47.

Rostron C. Ethylene metabolism and carcinogenicity. FD Chem. Toxic 19xx;24:70.
（エチレンの代謝と発がん性）

48.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall
evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to 42.
IARC, Suppl 7, 1987.
（人間への発がん性リスクの評価に関するIARC研究論文：発がん性の総体評価）

49.

Törnqvist M. Is ambient ethene a cancer risk factor ? Environ Health Perspectives.
1994;102 (Suppl 4):157-160.
（周りにあるエテンはがんの危険因子か?）50.

Hopkins J. The carcinogenic potential of ethylene. BIBRA Bulletin. 1993;32 (Oct.):
245-7.
（エチレンの潜在発がん能力）51.

Cowles AL, Borgstedt HH, Gillies AJ. The uptake and distribution of four inhalation
anesthetics in dogs. Anaesthesiology. 1972;36:558-70.
（犬における４種の吸入麻酔薬の摂取と分配）

52.

Ehrenberg L, Osterman-Galkar S, Segerbäck D, Svensson K, Calleman CJ. Evaluation ofgenetic risks of alkylating agents. iii. Alkylation of haemoglobin after metabolic
conversion of ethene to ethene oxide in vivo. Mutation Res. 1977;45:175-84.
（アルキル化剤の遺伝子的リスクの評価 iii 生体内でのエテンから酸化エテンへの代謝的変換後のヘモグロビンのアルキル化）

53.

Törnqvist M, Kautiainen A, Gatz RN, Ehrenberg L. Haemoglobin adducts in animals
exposed to gasoline and diesel exhausts 1. Alkene. J Appl Toxicol. 1988;8:159-70.
（ガソリンとディーゼル排気に曝露された動物におけるヘモグロビン付加体）

54.

Törnqvist M, Ehrenberg L. Approaches to risk assessment of automotive engine exhausts.
In: Vaino H, Sorsa M, McMichael AJ (eds.) Complex Mixtures and Cancer Risk. Lyon
IARC, 1990:277-87.
（自動車エンジン排気のリスク評価へのアプローチ）

55.

Törnqvist M et. al. Ethylene oxide doses in ethene-exposed fruit store workers. Scand J
Work Environ Health. 1989;15:436-8.
（エテンに曝露されている果物屋の労働者における酸化エチレンの服用）

56.

Walker VE, Fennell TR, Boucheron JA, Fedtke N, Ciroussel F, Swenberg JA.
Macromolecular adducts of ethylene oxide: a literature review and a time-course study
on the formation of 7-(2- hydroxyethyl) guanine following exposures of rats byinhalation. Mutation Res. 1990;233:151- 64.
（酸化エチレンの高分子付加体：吸入による連続した曝露のラットにおける7(2hydroxyethyl)グアニンの形成に関する文献レビューと時間的経過の研究）- 29 -

57.

Hogstedt C, Aringer L, Gustavsson A. Epidemiologic support for ethylene oxide as acancercausing agent. JAMA 1986;255:1575-8.
（発がん誘因剤としての酸化エチレンの疫学的支持）58.

Segerbäck D. Reaction products in haemoglobin and DNA after in vitro treatment with
ethylene oxide and n-(2-hydroxyethyl)-n-nitrosurea. Carcinogenesis. 1990;11:307-12.
（酸化エチレンとn(2-hydroxyethyl)-n-nitrosureaの生体外処理後のヘモグロビンとDNAにおける反応生成物）

59.

Young LT, Habraken Y, Ludlum DB, Santella RM. Development of monoclonal
antibodies recognizing 7-(2-hydroxyethyl) guanine and imidazole ring-opened
7-(2-hydroxyethyl)guanine. Carcinogenesis 1990;11:1685-9.
（7-(2-hydroxyethyl)のグアニンとイミダゾール開環7-(2-hydroxyethyl)グアニンを認識するモノクロナール抗体の開発）

60.

Fürst U, Marczynski B, Kasemann RP. Determination of 1-(2-hydroxyethyl) guaninewith gas chromatography/mass spectrometry as a parameter for genotoxicity of ethyleneoxide. Arch Toxicol. 1989;Suppl.13:250-3.
（ガスクロマトグラフィー/大規模な分光法による酸化エチレンの遺伝毒性のパラメタとしての1-(2-hydroxyethyl)グアニンの測定法）

61.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Industrial
Chemicals. 1994, Vol. 60:73-159.
（人間への発がん性リスクの評価に関するIARC研究論文：工業用化学薬品）

62.

Conolly RB, Jaeger RJ. Acute hepatotoxicity of ethylene and halogenated ethylenes after
PCB pretreatment. Environmental Health Perspectives. 1977;21:131-5.
（PCB前処理の後のエチレンとハロゲン化エチレンの急性肝毒性。 環境衛生見解）

63.

Filser JG, Bolt HM. Exhalation of ethylene oxide by rats on exposure to ethylene.
Mutation Res. 1983;120:57-60.
（エチレンへ曝露におけるラットによる酸化エチレンの発散）

64.

Filser JG, Denk B, Törnqvist M, Kessler W, Ehrenberg L. Pharmacokinetics of ethylene
in man; body burden with ethylene oxide and hydroxyethylation of haemoglobin due toendogenous and environmental ethylene. Arch Toxicol. 1992;66: 157-63.
（人におけるエチレンの薬物動力学。酸化エチレンの身体的負荷と、内生的および環境的エチレンによるヘモグロビンのヒドロキシエチル化）

65.

Axelsson G, Molin I. Int J Epidem. 1988;17:363.

66.

Yakubova ZN. Chemical Abstracts. 1976;87:28224w.

67.

Bond GG, et al. Am J Epidemiol. 1986;124;53.

68.

Leffingwell SS, et al. Neuroepidemiology. 1983;2:179.

- 30 -

69.

Törnqvist M, Granath F. Studier av doser av etylenoxid i etenexponerad personal vid
Borealis/Neste. Slutrapport. [Studies of doses of ethylene oxide in personnel exposed toEthylene at Borealis/Neste. Final Report.]. May 17, 1994.
（Borealis/Nesteでの人のエチレン曝露における酸化エチレン服用量の研究）

70.

Aveyard L. Ethylene: Inhalation (Head-only) Reproduction/Development Toxicity StudyIn the Rat. Corning Hazleton Report No. 1458/2-1050, April 1996.
（ラットにおける繁殖／発育の毒性研究）

71.

Riley S. Ethylene: Induction of Chromosome Aberrations in Cultured Chinese Hamster
Ovary (CHO) cells. Corning Hazleton Report No. 1458/1-1052, April 1996.
（チャイニーズ・ハムスターの卵巣細胞の培養における染色体異常の誘導）

72.

Victorin K. Uppdaterad hälsoriskbedömning av etenoxid, eten och propen. Institutet för
miljömedicin - Karolinska institutet, IMM-Rapport 8/92, Stockholm, 1992. [Updated
medical risk assessment of ethylene oxide, ethylene and propene. Institute ofenvironmental medicine].

73.

BIBRA Tox Profile on Ethylene, 199374.

Mattock SD. Ethylene: Inhibition of growth to the Alga Selenastrum capricornutum.
Corning Hazleton Report No. 1458/3-1018, May 1996.

75.

Atkinson, R.Kinetics and mechanisms of gas-phase reactions of the hydroxyl radical withorganic compounds under atmospheric conditions. Chem. Rev. 85:69-201. 1986.
（大気条件の下の有機化合物とのヒドロキシル・ラジカルの気相反応の動力学とメ
カニズム）

76.

IPCC, Climate change 1994. 1995.

77.

Van der Eerden, L.J. Luchtkwaliteitsevaluatie met behulp van indicatorplanten enagrarishe gewassen in de omgeving van industrieterrein Moerdijk.IPO report 279. 1981.

IRPTC（International Register of Potentially Toxic Chemicals 国際有害化学物質登録制度）の法的なファイルからの抽出- 31 -

資料

３－５
１０

欧 州 経 済共同体理事会指令 91/414：評価報告書に対する最終補遺
エ タ ノ ールについての補遺－第３巻、 付属書Ｂ．７
反 応 お よび分解生成物の毒性（エチレンおよび酸化エチレン ）（抜粋、p.80-139 の部分は省略）
2008 年 10 月

Final addendum to theDraft Assessment Report (DAR)- public version -ETHANOL

Final addendum to theDraft Assessment Report (DAR)- public version -Initial risk assessment provided by the rapporteur Member StateThe United Kingdom for the Existing active substance

ETHANOLof the fourth stage of the review programme referred to in Article
8(2) of Council Directive 91/414/EEC

November 20081

Table of contents
Addendum to Volume 4

July 2008 ................................................................3
Confidential (Cover page)

Addendum 1 to Volume 3

October 2008...........................................................5
B.6 Toxicology and metabolism

Addendum 2 to Volume 3

October 2008.........................................................94
B.7 Residue Data

Addendum 3 to Volume 3

October 2008.......................................................100
B.8 Environmental fate and behaviour

Addendum 4 to Volume 3

October 2008.......................................................122
B.9 Ecotoxicology

2Council Directive 91/414/EEC

Ethanol
Volume 4

Annex Cto the Report and Proposed Decision of the United Kingdom
made to the European Commission under Article 8(1) of
91/414/EEC

Confidential Information
Draft: August 20083

confidential information available at RMS

4

Council Directive 91/414/EEC

Ethanol
Addendum 2 to the Report and Proposed Decision of theUnited Kingdom made to the European Commission under
Article 8(1) of 91/414/EEC
Assessment of available information on the toxicology of thereaction and degradation products (ethylene and ethyleneoxide)

Note: The sole supported use of ethanol is as a precursor for
ethylene. Ethanol is converted to ethylene using a catalytic
generator.

October 20085

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

B.6

TOXICOLOGY AND METABOLISM
Introduction
Ethylene (or ethene) is the simplest alkene (i.e. an unsaturated hydrocarbon or olefin);
it is a very flammable gas and forms explosive mixtures with air. It is an endogenous
growth regulator in plants which is used to ripen bananas. The biosynthesis of
ethylene in plants is well documented in the literature (Wang et al, 2002).

Figure B.6.1 Structure of ethylene

H

H
C

C

H

H

Chemical name: ethylene.
Other names: ethene, acetone, bicarburetted hydrogen and olefiant gas.
CAS Number: 74-85-1.
Molecular weight: 28.05 g/mol.
Molecular shape: planar.
Molecular formula: C2H4
Octanol/water partition coefficient: Log Kow = 1.13.
Solubility in water: 131 mg/l at 20ºC.
Vapour pressure: 4.2 x 106 Pa.
Physical state: Colourless gas with a slight, sweet and musty odour.
Conversion factors (NTP): i) 1 ppm = 1.15 mg/m3; ii) 0.86 ppm = 1.0 mg/m3.
Ethylene is a gas at normal temperature and pressure. It is an asphyxiant and induces
hypoxia by reducing the oxygen content of air by dilution.
Ethylene is an important industrial chemical; its uses include the manufacture ofpolyethylene, ethylene oxide (a fumigant and sterilizing agent), ethylene dichloride,
ethylene glycol, linear alcohols, olefins, ethylbenzene, acetaldehyde and vinylacetate.
In addition, it is used as a fuel in metal cutting and welding and as an anaesthetic.
Ethylene is ubiquitous in the environment being released into the atmosphere fromnatural and man made sources. Approximately 75% of the atmospheric ethylene
originates from organic sources (e.g. an endogenous growth regulator in plants that isemitted by vegetation and it is produced by micro-organisms as part of their normal
metabolism) and 25% from anthropogenic sources (e.g. combustion of gas, fuel, coaland biomass). Atmospheric ethylene can be degraded by ozone (half-life 6.5
days/estimated to destroy 8%), nitrate radicals (half-life 190 days) or byphotochemically-produced hydroxyl radicals (half-life 1.9 days/estimated to destroy89%). The atmospheric lifetime of ethylene has been estimated to be 2-4 days.
Environmental human exposure mainly occurs from the combustion of fossil fuels(e.g. motor vehicle emissions) and the burning of organic matter (e.g. smoking).
Ethylene concentrations in ambient air at rural and remote sites are generally in the4Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

range of <0.001-0.005 mg/l and up to 0.05 mg/l in urban and indoor areas (values of
up to 1 mg/l have been recorded in heavy traffic). Ethylene is produced endogenously
by humans and other mammals and several mechanisms have been proposed for its
endogenous production: lipid peroxidation, enzymatic reactions or oxidative
destruction of methionione and haemoglobin and by intestinal bacteria.
No metabolism or toxicity studies have been submitted or evaluated for ethylene or its
metabolite ethylene oxide (a potent alkylating agent and genotoxic carcinogen). The
information and toxicological data cited in this document is entirely dependant on thedata cited in the published literature (mainly summarised in the publications listed
below). It should be noted that details of the protocols, the dosing patterns and the
GLP status of cited studies were minimal and the source, age and quality of thedata/information were often unclear and difficult to assess. In addition, no reliable
quantitative toxicity data have been submitted for ethylene exposure to experimental
animals via the oral route (normally required for determining NOAELs and the settingof reference doses for the consumer risk assessment).
The main publications/sources of information cited in the following ethylene
evaluation are as follows:i) OECD Screening Information Data Set (SIDS): Ethylene. Date not specified.
Organisation for Economic Co-operation and Development (OECD: SIDS).
ii) IUCLID Dataset, Ethylene, European Chemicals Bureau, 2000 CD-ROM Edition.
iii) Hazardous Substances Data Bank, No 168, 2003 (HSDB 2003,
toxnet.nlm.nih.gov).
iv) IARC Monograph on the Evaluation of Carcinogenic Risks to Humans (1994).
Some Industrial chemicals, Vol 60 (Ethylene pages 45-70) (IARC 1994).
v) Proposed Regulatory Decision Document. Ethylene Eco Sprout Guard. Health
Canada October 2001 (HC 2001).
Inevitably, the publications listed above are mainly summarising and citing the samestudies and data. Since there are minor differences in the reporting of the details by
the different sources, individual studies may be cited more than once especially where
additional information has been reported. To assist in identifying the studies cited bythese publications, the original references (where available) have been cited together
with the relevant publication in this evaluation (these references have not been
individually evaluated by the RMS). The quality of the studies cited and the extent
and depth of the investigations carried out are impossible to ascertain without an
extensive evaluation of the individual published studies.

5Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

B.6.1

Absorption, distribution, metabolism and excretion (toxicokinetics) (IIA 5.1)

B.6.1.1

Absorption, distribution and excretion

Male Fischer 344 rats (170-220g) were exposed to 14C-ethylene (free of 14C-acetylene
or greater than or equal to 97% pure) for 5 hours in a closed chamber (35 litres) to
10000 ppm (11.5 mg/l). In each experiment, up to four rats were exposed together in asingle chamber. Within one minute after the end of exposure, animals weretransferred to individual all glass metabolism cages and the elimination ofradioactivity monitored for up to 36 hours. Most of the eliminated 14C was exhaled as
ethylene [(18 µmol (504 µg) per rat exposed to acetylene-containing ethylene; thisstatement is not consistent with the material tested/no explanation)]; smaller amounts
were excreted in urine (2.7 µmol ethylene equivalents/rat) and faeces (0.4 µmol) andexhaled as carbon dioxide. Radioactivity was found in blood (0.022 µmol ethylene
equivalents/ml), liver (0.047 µmol ethylene equivalents/liver), gut (0.034 µmol
ethylene equivalents/gut) and kidney (0.006 µmol ethylene equivalent/kidney). Pretreatment of animals with a mixture of polychlorinated biphenyls (Aroclor 1254: 500
mg/kg bw; single intraperitoneal injection 5 days before exposure) had no measurable
influence on ethylene exhalation but resulted in a significant (p< 0.05) increase inexhaled 14CO2 (2.04 µmol ethylene equivalents/rat) and of 14C in urine (11.1 µmol
ethylene equivalents/ml). The organ burden of 14C was one to two orders ofmagnitude greater in Aroclor 1254-treated than in untreated animals. Radioactivity
was also detectable in lungs, brain, fat, spleen, heart and skeletal muscle. The data
were interpreted as indicating that an inducer of the mixed-function oxidase system
can stimulate the metabolism of ethylene.
(Guest et al, 1981/IARC 1994)b)

Male Fischer 344 rats (with and without pre-treatment with Aroclor 1254) were
exposed to 14C-ethylene (12.56 mg/l= 10000 ppm) for 5 hours. Samples werecollected for 36 hr following exposure. Aroclor pre-treatment did not affect theamount of ethylene expired but did cause a 4-fold increase in expired 14CO2 and a 2fold urinary excretion of radioactivity. Aroclor pre-treatment increased theconcentrations in blood, gut, kidney, liver and lung by factors of 1.5-, 6-, 8-, 16-, 17fold; detectable concentrations of radioactivity were also found in brain, heart, fat andmuscle. The rats pre-treated with Aroclor showed centrilobular hepatic necrosis (lightmicroscope) which was not seen in the rats exposed to ethylene alone. The author
suggested that ethylene metabolism is stimulated by Aroclor treatment.
(Guest et al, 1981, IUCLID 2000)c)

Several studies have investigated the pharmacokinetics of inhaled ethylene in maleSprague Dawley rats using closed exposure chambers in which the atmosphericconcentration-time course was measured after injection of a single dose into thechamber atmosphere (Bolt et al, 1984; Bolt & Filser, 1987; Shen et al, 1989; Filser,
1992). Uptake of ethylene into the body was low. Clearance due to uptake (asdescribed above) was 20ml/min for one rat of 250 g which represents only 17% of thealveolar ventilation (117 ml mins; Arms & Travis, 1980). Most (83%) inhaled
ethylene that reaches the lungs is exhaled again without becoming systemicallyavailable via the blood stream. Maximum accumulation of ethylene in the organism,
determined as the thermodynamic partition coefficient, whole body:air (Keq =6

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Concanimal/Concair), was 0.7. The concentration ratio at steady-state whole body:air
was somewhat lower owing to metabolic elimination ad it decreased from 0.7 to 0.54
at exposure concentrations below 92 mg/m3 (80 ppm). However, at very low
atmospheric concentrations, the concentration ratio at steady-state whole body:air
increased, owing to endogenous production of ethylene. For instance, it was almost
twice the value of the thermodynamic partition coefficient whole body:air at an
exposure concentration of 0.06 mg/m3 (0.05 ppm); calculated using pharmacokinetic
parameters and equation 18 of Filser,1992. At concentrations between 92 and 0.12
mg/m3 (80and 0.1 ppm), clearance was seen, due to metabolism related to theconcentration in the atmosphere of about 4.7 ml/min for the 250g rat. In thatconcentration range at steady state, therefore, about 24% of systemically available
ethylene is eliminated by metabolism and 76% by exhalation of the unchanged
substance (taking into account values of clearance of uptake and clearance of
metabolism). The alveolar retention of ethylene at steady state value was 3.5% andthe biological half-life was 4.7 minutes (Filser et al, 1992). At atmosphericconcentrations greater than 92 mg/m3 (80 ppm), metabolism of ethylene became
increasingly saturated, reaching a maximum rate of metabolism (Vmax) of 0.035µmol/(min x 250 g bw) [0.24 mg/(h x kg bw)] at about 1150 mg/m3 (1000 ppm). The
apparent Michaelis constant (km) related to the average concentration of ethylene gas
within the organism was 130 nl/ml tissue, which corresponds to an atmosphericconcentration of 239 mg/m3 (208 ppm) at Vmax/2, calculated by means of the kinetic
parameters given by Filser (1992).
(IARC 1994)d)B.6.1.2

In a series of 21 experiments, 13 large mongrel dogs were ventilated with a constantconcentration of ethylene (1.4% = 12g/m3). Concentrations were measured by gas
chromatography in alveolar gas, arterial blood, brain, muscle and central venous
blood. The average times necessary for the partial pressure of ethylene to reach 50%of the inspired partial pressure (1.4%) were: alveolar gas, <2.0 minutes; arterial blood,<2.0 minutes; brain, 3.7 minutes; muscle, 8.2 minutes and central venous blood, 5.2
minutes.
(Cowles, 1972/OECD: SIDS)
Metabolism
A metabolic pathway for the biotransformation of ethylene in mammals was notproposed.

a)Four male CBA mice (average body weight, 31 g) were exposed together for one hour
in a closed glass chamber (5.6 litre) to 14C-ethylene (22 mCi/mmol) in air at 17 ppm(0.0223 mg/l) which is equivalent to about 1 mg/kg bw. Blood and organs from two
mice were pooled 4 hours after the end of exposure. Radioactivity was about the samein kidney (0.16 μCi/ g) and liver (0.14 μCi/ g) but lower in testis (0.035 µCi/ g), brain(0.02 µCi/ g) and haemoglobin (0.0094 µCi/G Hb). Urine was collected from the twoother mice during the 48 hour period and blood was collected after 21 days. A urinary
metabolite, 5-(2-hydroxyethyl)cysteine was identified by thin-layer chromatography(3% of 14C in urine). The radioactivity in haemoglobin was 0.011 µCi/g Hb. Thisdata, together with those on specific hydroxyethyl derivatives at amino acid residuesof haemoglobin indicates that ethylene was metabolised to ethylene oxide.
(Ehrenberg et al, 1977/IARC 1994)7

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

In liver microsomes prepared for male Sprague-Dawley rats, ethylene atconcentrations of up to 115 g/m3 (10%) in the gas phase was metabolized to ethyleneoxide in the presence of an NADPH regenerating system (1 hour, pH 7.5, 37ºC). The
rate of formation of ethylene oxide was saturable (Vmax 0.67 nmol/h per mg protein)and could be reduced by the addition of diethyldithiocarbonate or β-naphthoflavone tothe microsomal suspension. Treatment of rats with phenobarbital (single
intraperitoneal injection of 80 mg/kg bw followed by three days of 0.1% in drinking
water) before preparation of liver microsomes did not change the Vmax.
(Schmiedel et al, 1983/IARC 1994)b)

In mice, it was shown that ethylene oxide alkylated nucleophilic sites of DNA in liver,spleen and testes. Since the ratio between the degree of alkylation of DNA and that of
haemoglobin was the same when exposed to ethylene and ethylene oxide, it was
concluded that ethylene oxide was an in vivo reactive intermediate formed fromethylene. A comparison of the degrees of alkylation obtained per unit exposure ofethylene oxide and ethylene showed that at low levels of ethylene, about 8% of theinhaled amount was metabolised to ethylene oxide. The rate of ethylene oxidation
followed saturation kinetics with increasing concentration. At 218 ppm ethylene, theoxidation rate was half of the maximal rate (km value). It was estimated that the
maximal rate of metabolism (Vmax) of ethylene corresponds to exposure to an air levelof 4 ppm of ethylene oxide.
(Segerback, 1983/OECD:SIDS)

c)

Involvement of cytochrome P450-dependent monooxygenases in the metabolism of
ethylene in male Sprague-Dawley rats was suggested by the complete inhibition of
metabolic elimination after intraperitoneal treatment with 200 mg/kg
diethyldithiocarbonate 15 min before exposure and by an increase in the rate of its
metabolism with a Vmax of about 14 µmol/(h x kg bw) [0.33 mg/(h x kg bw)] after
treatment with a single dose of Aroclor 1254 (500 mg/kg bw) six days before theexperiment.
(Bolt et al, 1984/IARC 1994)d)Male Sprague-Dawley rats exposed to ethylene exhaled ethylene oxide. In theseexperiments, two animals were kept together up to 21 hours in a closed chamber (6.4
litres). The concentration of ethylene in the atmosphere of the chamber wasmaintained at greater than 1115 mg/m3 (1000 ppm) by repeated additions, in order tomaintain Vmax. conditions for ethylene. One hour after the beginning of exposure, theatmospheric concentration of exhaled ethylene oxide reached a peak value of 0.69
mg/m3 (0.6 ppm). After about 2.5 hours, the concentration had decreased to about of
0.345 mg/m3 (0.3 ppm) and then remained constant. On the basis of theconcentration- courses of atmospheric ethylene, it was speculated that this decease wasdue to rapid induction of ethylene oxide metabolizing enzymes, whereas the rate ofethylene metabolism remained unaffected (Filser and Bolt, 1984). In male SpragueDawley rats exposed to ethylene at concentrations greater than 1115 mg/m3 (1000ppm), the amount of ethylene taken up per unit time from the atmosphere of a closed
chamber remained constant over exposure times of up to 30 hours (Bolt et al, 1984).
Pharmacokinetic data for ethylene and ethylene oxide indicate that in steady state
conditions only 29% of metabolised ethylene is available systemically as ethylene
8Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

oxide. Therefore, assuming that the liver is the principle organ in which ethylene ismetabolised, an intrahepatic first-pass effect for the intermediate ethylene oxide wassuggested (Filser and Bolt, 1984). In view of the saturability of ethylene metabolism,
the maximal possible average body concentration of its metabolite, ethylene oxide,
was calculated to be 0.34 nmol/ml tissue [15 µg/kg bw] in an open exposure system(infinitely large atmospheric volume). The same value was computed to result fromexposure to ethylene oxide at an atmospheric concentration of 10.2 mg/m3 (5.6 ppm)
at steady state (Bolt and Filser, 1987).
(IARC 1994)e)Metabolic conversion of ethylene oxide results in the formation of DNA andhaemoglobin adducts that can be used to identify ethylene exposure. Alkylated aminoacids in haemoglobin have been shown in rats exposed to automotive engine exhaust.
These adducts resulted from the conversion of 5-10% of inhaled ethylene.
(Tornqvist et al, 1988/OECD:SIDS)f)

Ethylene oxide was found in the blood of male Fisher 344 rats during exposure to an
atmospheric ethylene concentration of 690 mg/m3 (600 ppm). A maximal value ofabout 3µg/g blood of ethylene oxide was seen 8 minutes after the start of exposure to
ethylene; this value was followed 4 minutes later by an immediate decrease to about
0.6 µg/g blood and this level remained constant for the following 46 minutes. Duringexposure, “the cytochrome P450 content in the liver was reduced to 94% after 20
minutes and 68% after 360 minutes” (no further details). It was speculated that an
ethylene-specific cytochrome P450 isozyme was rapidly deactivated during exposure
to ethylene, resulting in reduced formation of ethylene oxide (Maples & Dahl, 1993).
This speculation is based on results obtained by an unspecific method for thedetermination of cytochrome P450 isozyme which is not suitable for the determinationof cytochrome P450 isozymes.
(IARC 1994)g)

In male Sprague Dawley rats treated with phenobarbital (intraperitoneal injection of 80
mg/kg bw/day for 4 days and exposure to ethylene on day 5) and then exposed for 3
hours to a mixture of commercial ethylene (contaminated with about 10 ppm
acetylene) and air (1:1 v/v), a green pigment was formed in the liver 4 hours after
exposure. The same pigment was formed in vitro during incubation of acetylene-freeethylene with 9000 x g supernatant of a rat liver homogenate (from phenobarbital-pretreated animals) in the presence of NADPH. No controls were used (Ortz deMontellano & Mico, 1980). The pigment was identified as a N-(2hydroxyethyl)protoporphyrin IX, an alkylation product of the prosthetic haem ofcytochrome P450-dependent monooxygenases. It was conclude that thephenobarbital-inducible form of cytochrome P450 was destroyed during oxidative
metabolism of ethylene (Ortz de Montellano et al, 1980 & 1981).
(IARC 1994)h)

Ethylene oxide is exhaled by untreated rats (Shen et al, 1989). The endogenous
production rate in a Sprague-Dawley rat (250g bw) was determined to be 2.8 nmol/h[0.31 µg/(h x kg bw)] resulting in a body burden of ethylene gas of 0.32 nl/ml tissue[0.036 µg/kg bw] (Filser, 1992). The corresponding exhalation rate may be calculated
from the pharmacokinetic parameters of Filser (1992) as 0.24µg/(h x kg bw). Four9

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

possible sources of endogenous ethylene have been suggested in the literature: lipid
peroxidation (Kautiainen et al, 1991), enzyme- copper- or iron-mediated catalysedoxidation destruction of methionine (Fu et al, 1979; Lieberman et al, 1965; Kessler &Remmer, 1990; respectively), oxidation of haemoglobin (Clemens et al, 1983) and themetabolism of intestinal bacteria (Tornqvist et al, 1989b).
(IARC 1994)
It has been demonstrated that ethylene and halogenated ethylenes are acute liver toxins
in rats pre-treated with polychlorinated biphenyl (PCB). Without pre-treatment with
PCB and exposed to 20000 ppm ethylene for 4 hours, ethylene and halogenatedethylenes did not induce liver toxicity. The rate of metabolic elimination of ethylene is
influenced by pre-treatment with PCB and leads to an increase in exhaled ethyleneoxide.
(Conelly and Jaeger, 1977; Filser and Bolt, 1983/OECD: SIDS)
B.6.1.3

Summary of toxicokinetics studies

No ADME studies have been submitted (no oral ADME studies have been cited). The
majority of the available data has been generated using inhalation exposure. A
metabolic pathway has not been proposed for ethylene in mammals. Apart fromethylene oxide and its metabolites and the urinary metabolite hydroxyethyl cysteine inmice, there appears to be little or no information or investigations into other potential
metabolites of ethylene (see B.6.8.1).
Following inhalation of radiolabelled ethylene, absorption appeared to be rapid (withinminutes) but the systemic uptake from the lungs was low (low solubility in blood).
The uptake, exhalation and metabolism can be described by first-order kinetics. It has
been estimated that approximately 83% of the ethylene that reaches the lungs isexhaled unchanged while 17% is absorbed. Distribution is widespread throughout the
body (i.e. nervous system, lungs, liver, kidneys, spleen, heart, blood, fat, skeletal
muscle and testes). In rats, about 24-29% of systemically available ethylene iseliminated by metabolism and the remainder by exhalation of the unchanged
substance. Elimination appears to be rapid. Most of the inhaled ethylene was exhaledunchanged with smaller amounts excreted in urine and faeces and as exhaled carbon
dioxide. Pre-treatment with cytochrome P450 inducers increased the amount of
14CO2 exhaled and the levels of 14C in urine and tissues.
Ethylene oxide has been identified as a metabolite of ethylene in rodents based on its
ability to form DNA and protein adducts (e.g. haemoglobin). The degree of alkylation
obtained per unit exposure of ethylene oxide and ethylene shows that at low levels of
ethylene, about 5-10% of the inhaled ethylene was metabolised to ethylene oxide inexperimental animals. The rate of ethylene oxidation followed saturation kinetics withincreasing concentration. In vitro studies using rodent liver also demonstrate that
ethylene can be metabolised to ethylene oxide. Inducers (PCBs) of the mixed-functionoxidase system can stimulate the metabolism of ethylene and increase the levels of
exhaled ethylene oxide. A urinary metabolite 5-(2-hydroxyethyl)cysteine, possibly
formed from ethylene oxide, was identified in mice.

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B.6.2

Acute toxicity, irritancy and skin sensitisation studies (IIA 5.2)

B.6.2.1

Acute oral toxicity (IIA 5.2.1)

No studies submitted (or data cited from the published literature).
B.6.2.2

Acute dermal toxicity (IIA 5.2.2)

No studies submitted (or data cited from the published literature).
B.6.2.3

Acute inhalation toxicity (IIA 5.2.3)

B.6.2.4

Male rats exposed to ethylene at concentrations of 11.5, 28.8 or 65.6 mg/l of air for 4
hours showed increased serum pyruvate and liver weight at all dose levels (no deaths
reported). The LC50 in male F344 rats was greater than 12.518 mg/l for a five hour
exposure. The lethal concentration of ethylene in air to mice was stated to be 950000
ppm (estimated to be approximately 1093 mg/l of air). No respiratory irritation has
been reported in patients. Therefore, ethylene would not be classifiable via theinhalational route according to EC criteria.
(Flury, 1928; Gaeb et al, 1975/OECD: SIDS)
Skin irritancy (IIA 5.2.4)

B.6.2.5

No studies submitted (or data cited from the published literature) but according to thereference there is no evidence that ethylene gas is a skin irritant.
(OECD: SIDS)
Eye irritancy (IIA 5.2.5)

B.6.2.6

No studies submitted (or data cited from the published literature) but according to thereference there is no evidence that ethylene gas is an eye irritant.
(OECD: SIDS)
Skin sensitisation (IIA 5.2.6)
No studies submitted (or data cited from the published literature).

B.6.2.7

Summary of acute toxicity, irritancy and sensitisation studies

Based on the cited data, ethylene is not classifiable via the acute inhalation routeaccording to EC criteria. There is insufficient data to classify ethylene via the acuteoral and dermal routes, for skin and eye irritancy or for skin sensitisation using thenormal EC criteria. However, based on industrial use and practice and its use as ananaesthetic, ethylene gas dose not appear to be classifiable as a skin or eye irritant or askin sensitiser. It should be noted that liquefied or pressurized ethylene gas can cause
frostbite damage (this may trigger part of Directive 2003/82/EC).

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B.6.3

Short-term toxicity studies (IIA 5.3)

B.6.3.1

Oral administration to rats
No studies submitted (or data cited from the published literature).

B.6.3.2

Oral administration to mice
No studies submitted (or data cited from the published literature).

B.6.3.3

Oral administration to dogs
No studies submitted (or data cited from the published literature).

B.6.3.4

Administration by other routes

B.6.3.4.1 Inhalation exposurea)

6-day exploratory study
A group of six male Sprague-Dawley albino rats were exposed to a continuous flow of
60% ethylene in oxygen for 6 days, i.e. 600,000 ppm equivalent to 690 mg/l (1968
publication). Effects were reported on several haematology parameters. There was asignificant reduction in thrombocyte count (-19.3%) and leukocyte count (-48.2%) anda reduction was also seen in the bone marrow cellularity (-30%).
(Fink, 1968/OECD: SIDS)b)

Liver damage occurred in mice repeatedly exposed (up to 20 times over 58 days) toatmospheric concentrations of 90% ethylene for periods of 60-90 minutes. There wasno cellular injury in the kidney, adrenal, heart or lungs.
(Reynolds, 1926/BIBRA Toxicity Profile 1993)c)70-day study
Rats were exposed to ethylene at a concentration of 100 ppm (0.15 mg/l) for 70 days
(non-GLP study reported in 1966 of unknown quality and no further exposure details).
Changes in the reflex nerve impulses, a decrease in cholinesterase activity and reduced
blood pressure were reported (no actual data or indications of the magnitude of thesechanges were reported).
(Krasovitskaya et al, 1966/ OECD: SIDS)d)90-day study
Groups of rats (15/sex/concentration) were exposed to ethylene at concentrations of 0,300, 1000, 3000 or 10000 ppm (0, 345, 1150, 3450, or 11500 mg/m3. respectively) for
6 hours/day, 5 days/week for 13 weeks (a non-GLP study).

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There were no differences between controls and treated rats with respect to total bodyweights, weight change, food consumption, haematology, clinical chemistry, grosspathology or histopathology. Male rats in the 0 (control), 300 and 10000 ppm groups
showed red deposits or red discharge around the nose whereas the males in the 1000
ppm group had red deposits around the eyes. Amongst the female rats, a red deposit
was discovered around the left eye of one 300 ppm female and alopecia around bothears of one 1000 ppm female. Compared with the controls, the liver weights in several
groups of exposed rats were significantly lower (no indication of magnitude in the
publication). There was no dose response relationship for this weight reduction andthe cause was unknown. Ethylene appeared to have a low toxicity in rats whenadministered up to 10000 ppm (11.5 mg/l of air). This was considered to be the
NOAEL for the 90-day study by the authors.
(Chemical Industry Institute of Toxicology, 1977/OECD: SIDS)
B.6.3.4.2 Dermal exposure
No studies submitted (or data cited from the published literature).
B.6.3.5

Summary of short term toxicity
No data were submitted for the oral or dermal routes of exposure (or cited from thepublished literature). A summary of the short-term inhalation data is presented inTable B.6.1.
The 6-day exploratory inhalation study in rats showed that at high exposure levels
there were marked effects on the thrombocyte and leukocyte counts and on bonemarrow cellularity. There are some limited citations that indicated the liver may be atarget for ethylene induced toxicity. In the 70-day rat study, changes in the reflex
nerve impulses, a decrease in cholinesterase activity and reduced blood pressure werereported. The 90-day inhalation study concluded that the NOAEL was greater than
11.5 mg/l of air for inhalation exposure, the highest dose tested. It should be noted that
this study may have been conducted by Industrial Bio-Test Laboratories Inc undercontract to the CIIT (see B.6.5). The background to IBT can be found at section 3.1.8
of http://www.oecd.org/dataoecd/13/15/36045203.pdf ]13

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Table B.6.1 Summary of the short-term inhalation toxicity of ethylene
Type of study
6 day exploratory
study in rats

NOAELs
Not set70-day study in rats

Not set90-day study in rats

11.5 mg/l

LOEL/effects
600000 ppm (690 mg/l, the only
dose tested): Marked effects on
haematological parameters andbone marrow.
100 ppm (0.15 mg/l): Changes in
the reflex nerve impulses, adecrease in cholinesterase activity
and reduced blood pressure.
No effects reported at highest
dose tested.

Reference
Fink,
1968/SIDS
Krasovitskaya
et al,
1966/SIDS
CIIT,
1977/SIDS

B.6.4

Genotoxicity studies (IIA 5.4)

B.6.4.1

In vitro testing (AII 5.4.1)

a)Bacterial mutationsb)

Ethylene has been tested in an Ames test at atmospheric concentrations up to 20% in
one strain (TA 100) of Salmonella typhimurium in the presence and absence of
metabolic activation (non-GLP study/Victorin and Stalberg, 1988). It was also
reported that previous testing in four strains of Salmonella typhimurium (non-GLP
studies/Hamm et al, 1984; Hughes et al, 1984) and in Escherichia coli (non-GLP
study/Landry and Fuerst, 1968) were also negative.
(OECD: SIDS)
Mutations in mammalian cells
No studies submitted (or data cited from the published literature).

c)

Chromosome aberrations in mammalian cells

B.6.4.2

Duplicate cultures of Chinese hamster ovarian (CHO) cells were tested in the absence
and presence metabolic activation (S9-mix) from Aroclor 1254-induced rats (GLP
compliant study conducted to OECD guideline 473). The cells were tested atconcentrations up to 280.5 mg/l (approximately 25% ethylene). Due to the explosive
properties of ethylene when mixed with air, nitrogen was used as a carrier gas. The
cells were exposed to a short 3 hour pulse treatment followed by a 17 hour expression
period prior to harvest. Negative (carrier gas, untreated and positive control groups
were tested. The positive control groups produced appropriate results. It was
concluded that there was no effects on the mitotic index and no increase in thefrequency of cells with structural chromosome aberrations.
(Riley, 1996/ OECD: SIDS)
In vivo genotoxicity in somatic cells (AII 5.4.2)

a)Micronucleus tests
Rats (10/dose) and mice (10/dose) were exposed to concentrations of 0, 40, 1000 or
3000 ppm for 6 hour/day, 5 days a week for 4 weeks (reported in 1994 but not statedwhether or not GLP status). Bone marrow samples were collected approximately 24hours after the final exposure. No significant differences in the PCE to NCE ratios
14Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

were observed in any exposure group. It was concluded that ethylene did not induce
statistically significant concentration-related increases in the frequencies of
micronucleated polychromatic erythrocytes in the bone marrow of rats or mice.
(Vergenes and Pritts, 1994/ OECD: SIDS)b)

Formation of DNA and haemoglobin adductsc)Absorption, distribution, elimination of ethylene and formation of haemoglobin and
DNA adducts were studied in rats after inhalation of 300 ppm ethylene for 12 hours
per day for 3 consecutive days (a non-GLP study reported in 1995). DNA adductformation was measured in liver and lymphocytes and haemoglobin adducts
determined in erythrocytes. The adduct formation with ethylene was compared toother alkenes and adduct formation decreased with increasing number of carbon atoms
in the molecule. No actual results or conclusions were provided in the publication (thestudy was stated to be an explorative study).
(Eide et al, 1995/OECD: SIDS)
Alkylation of DNA
Alkylation of 7-guanine was measured in DNA from liver spleen and testis of mice 14
hours after exposure by inhalation of 14C-ethylene at an initial concentration of 11
ppm for 8 hours (a non-GLP study reported in 1983). The degree of alkylation wasmuch higher in the liver than in the other tissues. No actual results or conclusions
were provided in the publication (the study was stated to be an explorative study).
(Segerback, 1983/OECD: SIDS)

B.6.4.3

In vivo studies in germ cells (AII 5.4.3)

No study submitted (or data cited from the published literature) but there are no
indications in the available data/information that such a study is necessary.
B.6.4.4

Summary of genotoxicity studies

A summary of the submitted genotoxicity data is provided in Table B.6.2.
The bacterial mutation and chromosome aberration assays conducted with ethylene gas
were stated to be negative for genotoxic activity (these conclusions may be equivocal
taking into consideration the low solubility of ethylene in aqueous media). However,following in vivo inhalation exposure to rats and mice, the bone marrow micronucleus
investigations were also reported to be negative (no significant differences in the PCE
to NCE ratios). There was insufficient information provided for the DNA andhaemoglobin adduct assays to draw any clear conclusions about the potential
genotoxicity of ethylene.
The overall genotoxicity database on ethylene is limited, but on the data available there
is no evidence for significant genotoxic potential.

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Table B.6.2 Summary of the genotoxicity data
Study
Ames test
Chromosome aberrationsin CHO cells
Bone marrow
micronucleus tests in rats
and mice.
Formation of DNA andhaemoglobin adducts
Alkylation of DNA

B.6.5

Concentrations
ResultIn vitro assays
Atmospheric concentrations
Negativeup to 20%280.5 mg/l
Negative(approximately 25% ethylene)
In vivo assays (inhalation exposure)3000 ppm
Negative(approximately 3.45 mg/l)
300 ppm(approximately 0.345 mg/l)
11 ppm(approximately 0.0126 mg/l)

Adduct formation
reported but noquantitative results
reported
Alkylation reported
but no quantitative
results reported

Reference
OECD: SIDS
Riley, 1996/
OECD: SIDS
Vergenes &Pritts, 1994
OECD: SIDS
Eide et al,
1995
OECD: SIDS
Segerback,1983
OECD: SIDS

Chronic toxicity and carcinogenicity studies (IIA 5.5)

A single long-term inhalation study has been summarised by the OECD: SIDS
publication (CIIT, 1979/SIDS & by Hamm et al, 1984). However, this study was
conducted 1977-1979 at the Industrial Bio-Test Laboratories Inc (IBT) under contract
to the Chemical Industry Institute of Toxicology (CIIT). It should be noted that IBT
was responsible for falsifying data which lead to the implementation of GLP principles
and practice in the USA. The background to IBT can be found at section 3.1.8 of
http://www.oecd.org/dataoecd/13/15/36045203.pdf ]B.6.5.1

Chronic dietary studies in rats

No studies submitted (or data cited from the published literature).
B.6.5.2

Chronic dietary study in mice

No studies submitted (or data cited from the published literature).
B.6.5.3

Carcinogenicity studies in ratsa)Fischer-344 inbred rats (120/sex/group) were exposed to ethylene at concentrations of
0, 300, 1000 and 3000 ppm for 6 hours per day, 5 day/week for up to 24months (nonGLP study).
The spontaneous mortality (15.7%) was stated to be roughly equal in all treatedgroups. Hair loss, deposits on and around the nose and eyes and gross eye
abnormalities were noted but there were no obvious differences among the treatmentgroups. There was an overall increase in the number of animals exhibiting gross tissue
masses for the test groups as compared with the control group but this trend was notstatistically significant.

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The final body weights and total weight changes for treated males were higher thanthose in the control groups but no dose related pattern was seen. There were no
significant differences among any of the treatment groups on any of the haematology,
blood chemistry or other parameters tested. No gross or histopathological tissuechanges attributable to the effects of the test material were observed in any of thetreated rats. The summary states that only a few findings were reported that could
indicate any carcinogenic effect of the treatment.
In a publication from the above 1979 carcinogenicity study (Hamm et al, 1984), it was
concluded that the results provided "no evidence that ethylene at these concentrations
causes chronic toxicity or is oncogenic in Fischer 344 rats". However, this publicationand the summary have been criticised since they do not discuss the mononuclear cellleukaemia described in the full report. It was stated that the number of animals
affected (out of 90) rose from 12 and 8 in the male and female control groups to 21 and
11, respectively, in the groups receiving 3000 ppm. On the other hand, it has beenstated that mononuclear cell leukaemia may occur in F344 rats at a backgroundincidence > 75% and that a further increase in exposed animals is difficult to interpretwith respect to human cancer development.
(Chemical Industry Institute of Toxicology/conducted by IBT, 1979/OECD: SIDS)b)

A summary of a 2-year rat inhalation study was submitted which was down loaded
from the Hazardous Substances Data Bank (HSDB) on 5th May (toxnet.nlm.nih.gov).
This summary appears to be another summary of the above 1979 inhalation study but
provides some further limited information on the methodology. The maximum
tolerated dose was not used as concentrations above 3000 ppm were consideredhazardous because of the risks associated with the explosive properties of the test
mixture. The calculated time weighted average concentrations for the 24 months of
exposure were 0, 301, 1003 and 3003 ppm, respectively. Randomly selected animals
were necropsied and examined after 6, 12 and 18 months and selected organs andtissues from all animals in the control and 3000 ppm groups were examined
microscopically at termination. Histologically, a variety of proliferative, degenerativeand inflammatory lesions were observed in both control and 3000 ppm groups. It wasstated that these lesions were typical of those seen in this strain of animal and wereunrelated to ethylene exposure.
(Hamm et al, 1984/HSDB)c)

Criticism of the above 2 year rat inhalation study and the Hamm summary has been
published by BIBRA scientists.
“CIIT scientists concluded that there was ‘no evidence that ethylene at theseconcentrations causes chronic toxicity or is oncogenic in Fischer 344 rats. According
to the ‘executive summary’ of the full report (published separately), unusual malignant
lung tumours were found in two rats exposed to 1000 ppm and one exposed to 3000
ppm, but the low incidence and lack of other related changes in bronchial epithelium
suggested they may have occurred spontaneously. The incidence of mononuclear cellleukaemia is not discussed in the summary, but the full report (available only on
microfiche) indicates that it was somewhat increased in both sexes at the top doselevel. The number of animals affected (out of 90) rose from 12 and 8 in male andfemale controls to 21 and 11, respectively, at 3000 ppm. The total number of organs or17

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

tissues affected rose to 106 in males and 83 in females from only 62 and 26,
respectively, in controls. Whether it increased at lower doses too is uncertain, since
only limited histological examination of the lower dose groups was conducted. In theview of EO to induce this form of cancer (NIOSH Current Intelligence Bulletin 1981,
No5, 22 May) it is strange that the incidence of leukaemias is not discussed in thereport’s executive or by Hamm et al, 1984”.
“Although one of the CIIT scientists was unable to detect any conversion of ethylene
to EO in an in vitro preparation of rat-liver microsomes (Hamm et al. loc. cit.), twoother metabolic studies indicate that rats and mice can indeed metabolize ethylene to
EO and that both chemicals can lead to the alkylation of proteins and DNA.”(Rostron, 1986, Fd Chem Toxic, Vol 24 No 1)
d)

Based on the pharmacokinetics of ethylene and its oxide in the rat, Bolt and Filser,
1987 estimated that exposure at an atmospheric concentration of 1000 ppm ethylene
would correspond to a theoretical atmospheric concentration of 5.6 ppm ethyleneoxide. Because of saturation kinetics, exposure concentrations of ethylene above 1000
ppm would not result in further increases in systemic ethylene oxide concentration.
Thus, the above ethylene bioassay could not expose rats to more than 5.6 ppm ethyleneoxide. By extrapolating the tumour/exposure data in the ethylene oxide studies to 5.6
ppm, the investigators concluded that the high ethylene exposures would not result in atumour incidence of more than 2% above the background incidence. This lead to theconclusion that should ethylene pose a carcinogenic threat to the rat by virtue of its
conversion to the oxide, the group sizes normally used in cancer study would beinsufficient to produce statistically significant increases tumour yield at attainableethylene concentrations.
(Hopkins, 1993, Fd Chem Toxic, Vol 32 No 2)e)Groups of male and female Sprague-Dawley rats, there to five days of age, were
exposed by inhalation to 0 (5 males and 9 females) or 11500 mg/m3 or 10000 ppm (2males and 10 females) ethylene (purity unspecified) for 8 hours per day on five days
per week for three weeks. One week later, the rats received oral administration of 10
mg/bw Clophen A50 (a mixture of PCBs not otherwise specified) by gavage twice aweek for up to eight additional weeks (promotion) at which time the experiment was
terminated and the livers examined for ATPase-deficient foci. The number of ATPasedeficient foci in the rats exposed to ethylene did not exceed the control values. In thesame experiment, ethylene oxide, administered as a positive control, produced asignificant increase in the incidence of ATPase- deficient foci in females.

B.6.5.4

Summary of chronic toxicity/carcinogenicity(Denk et al, 1988/IARC 1994)
No long-term studies were submitted for the oral route of exposure (or data cited fromthe published literature).
There are several summaries in the published literature of a single long-term inhalation
study in the rat. Generally, the authors of these summaries have concluded that there
no evidence of chronic toxicity in this study and no evidence of compound-induced
carcinogenicity. However, some authors have expressed doubts over the interpretationof the findings in this study (i.e. the mononuclear cell leukaemia). Although IARC
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(1994) concluded that the evidence of carcinogenicity in experimental animals andhumans was inadequate, Tornqvist (1994) and Hopkins (1993/OECD: SIDS) statedthat the possible carcinogenic risk from inhaling ethylene should be reconsidered/reevaluated based on the potential exposure to ethylene (very high tonnage), the limited
database and the metabolism of ethylene to ethylene oxide.
B.6.6

Reproductive and developmental toxicity studies (IIA 5.6)

A multigeneration study has not been submitted instead a summary of a single
generation screening test has been submitted to support the application. The
limitations of such a protocol for the detection of compound-induced post-natal effects
and the small number of animals tested should be noted.
B.6.6.1

Fertility and post-natal developmental toxicitya)Reproduction/Development Toxicity Screening Test (IIA 5.6.1)

Rats (10/sex/concentration) were exposed to ethylene (head only) at concentrations of
0, 200 (230 mg/m3), 1000 (1150 mg/m3) or 5000 ppm (5750 mg/m3) for 6 hours daily(the number of days/week was no stated). The calculated body burden wasapproximately 0, 80, 400 and 2000 mg/kg bw/day for the dosing regime. Since theuptake from the lungs is likely to be in the range of 5-10%, the actual absorbed dosewould be substantially less than the values given above. This study was GLP
compliant and carried out in accordance with OECD Guideline 421(Reproduction/Development Toxicity Screening Test).
The test material was administered to parent animals for two weeks prior to mating,during the mating period and until the day prior to necropsy for the males (minimum
28 days) and until day 20 of gestation for the females. The females were allowed tolitter and rear their offspring to day 4, post-partum, when they and their offspring were
killed.
Morbidity, mortality, clinical condition, weights and food intake were observed
throughout the study, and mating was carefully observed. For each female, litter data
and also observations for each offspring were recorded. At termination of the study,
all animals were subject to macroscopic examination for structural or pathologicalchanges. Ovaries, testes and epididymides of the control and high dose animals were
subject to a histopathological examination.
There were no deaths attributable to the test article, and body weight gain was notadversely affected during the pre-pairing, gestation or lactation periods. The treatment
had no effect on fertility or fecundity and all females became pregnant. Litter size, sex
ratio, mean pup weight and pup growth and clinical condition were not adversely
affected by treatment.
Necropsy revealed no macroscopic finding suggestive of toxicity due to test article
administration. There was no evidence of any toxic effect on the testis due to test
substance administration and there were no other microscopic findings suggestive of
toxicity due to test article administration.

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The summary concluded that at nominal concentrations of 200, 1000 or 5000 ppm
there was no evidence of toxicity or adverse effects on male and female reproductive
performance, fertility, pregnancy, maternal and suckling behaviour and growth anddevelopment of the offspring from conception to Day 4, post-partum. The NOEL wasestablished to be 5000 ppm (equivalent to 5.75 mg/l) with respect to parental toxicity
and foetal and reproductive performance.
(Aveyard, 1996/OECD: SIDS)
Post natal-development
In a published study, newborn rats exposed to a concentration of 2.62 ppm(approximately 0.003mg/l) for 90-days (continuous inhalation) exhibited a delay incoat appearance, dentition and eye opening; circulation hypotension, cholinesterase
inhibition and subordination disruption were also reported. It was stated that there was
no information on the quality of this study.
(Krasovitskaya and Mabyarova LK, 1968/OECD: SIDS)

B.6.6.2

Developmental toxicity studies (IIA 5.6.2)

a)Developmental study in rats
No studies submitted (or data cited from the published literature).

b)

Developmental study in rabbits
No studies submitted (or data cited from the published literature).

B.6.6.3

Summary of reproductive toxicity

The reproductive screen test concluded there was no compound induced parental or
foetal toxicity or developmental toxicity over a single generation (i.e. up to 4 days post
partum) at concentrations up to 5.75 mg/l (equivalent to a systemic exposure of 0.575mg/l). However, some published data (of unknown quality) appears to indicate that
post-natal development could be adversely affected at low dose levels.

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B.6.7

Neurotoxicity studies (IIA 5.7)

B.6.7.1

Delayed neurotoxicity studies

Ethylene is not of similar or related structure to those compounds such as theorganophosphates that are capable of inducing delayed neurotoxicity. Therefore,delayed neurotoxicity studies have not been carried out.
B.6.7.2

Acute and repeat dose neurotoxicity studies

No studies submitted (or data cited from the published literature).
B.6.7.3

Summary of the neurotoxicity studies

No specific neurotoxicity studies have been submitted for evaluation but there aresome indications of treatment-related effects on the nervous system. Two papers by
the same authors have reported changes in the reflex nerve impulses, a decrease incholinesterase activity and reduced blood pressure. Although there is no informationon the quality of the investigations or the magnitude of the changes in these two
papers, it should be noted that nerve impulses, cholinesterase activity and bloodpressure have not been routinely investigated in the standard toxicity studies.
B.6.8

Further toxicological studies (IIA 5.8)

B.6.8.1

Relevant metabolites (ethylene oxide)

Since ethylene is metabolised to ethylene oxide in experimental animals and humans, asummary of the submitted published data/information for ethylene oxide has been
included in this evaluation. It should be noted that the majority of data for ethyleneoxide has been primarily generated using the inhalation exposure route.
Ethylene oxide is officially classified by the ECB as a Cat: 2 for carcinogenicity (R45)
and Cat: 2 for mutagenicity (R46). In addition, the literature indicates that ethyleneoxide induces reproductive effects in experimental animals (foetal toxicity in thepresence and absence of maternal toxicity, teratogenicity in mice, sperm effects) andthere is some limited evidence of spontaneous abortions in humans.
Ethylene oxide is also officially classified by the ECB as Toxic by inhalation (R23)
and as an irritant (R36/37/38). The literature also indicates that it can also induce
sensitisation responses.
An updated MSDS (2005) obtained from the internet suggests that ethylene oxide may
be classifiable for acute oral and dermal toxicity (R24 & 25); an acute oral LD50 valueof 72 mg/kg bw is cited by this MSDS.
The current UK cut-off for ethylene oxide in pesticide formulations is the limited ofdetection (LOD) and the occupational maximum exposure level is 5 ppm; 8-hour TWA(EH64 Summary Criteria for Occupational Exposure Levels, as amended by update
supplements up to 2002).
Figure B.6.2 Structure of ethylene of ethylene oxide21Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

O
CH2

CH2

ethylene oxide
Chemical name: ethylene oxide.
CAS Number: 75-21-8.
Other names: dihydrooxirene, dimethylene oxide, EO, ETO, 1,2-epoxyethane,epoxyethane, ethene oxide, oxacyclopropane, oxane, oxidoethane and oxirane.
Molecular weight: 44.05 g/mol.
Octanol/water partition coefficient: Log Kow = -0.30.
Solubility in water: infinitely soluble.
Vapour pressure: 146 kPa @ 20 ºC
Physical state: Colourless gas at normal temperature and pressure.
Smell: described as having a characteristic ethereal odour.
Odour threshold: 470 mg/m3 for perception and 900-1260 mg/m3 for recognition.
Conversion factors (NTP): i) 1 ppm = 1.8 mg/m3; at 25ºC, ii) 0.55 ppm = 1.0 mg/m3.
Methods of production: i) catalytic oxidation of ethylene with air or oxygen, ii) the
chlorohydrin process.
Ethylene oxide is an important industrial chemical. It is used as an intermediate in the
production of various chemicals (e.g. ethylene glycol & surfactants), as a sterilant, afumigant and as a component of pest control products. Gas and liquid forms of
ethylene oxide may be released into the environment during industrial processes andsterilisation operations (e.g. medical equipment in hospitals). It is also released on
combustion of fossil fuels and is present in tobacco smoke.
Ethylene (a natural plant growth regulator) is degraded to ethylene oxide in certain
plants and by certain micro-organisms. Ethylene oxide is also produced by somenatural sources such as manure and sludge.
Ethylene oxide is used as a sterilant (micro-organisms) and fumigant (insects) on food
stuffs at concentrations that range from 250-1500 mg/litre (ECHC 2001).
The data/information in this section has mainly been taken from the following
publications:i) International Programme on Chemical Safety (IPCS). World Health Organisation(WHO). 1985 Environmental Health Criteria 55. Ethylene Oxide (WHO 1985).
ii) Environment Canada & Health Canada. Priority Substances List Assessment
Report (September 2001): Ethylene oxide (ECHC 2001).
iii) IARC Monograph on the Evaluation of Carcinogenic Risks to Humans (1994).
Some Industrial chemicals, Vol 60 (Ethylene oxide, pages 73-159) (IARC 1994).
iv) IPCS. WHO. Concise International Chemical Assessment Document 54 (2003)(CICADS 2003).

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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Inevitably, the publications listed above are mainly summarising and citing the samedata and studies. Since there are minor differences in the reporting of the details by
the different sources, individual studies may be cited more than once especially where
additional information has been reported.
B.6.8.1.1 Absorption, distribution, excretion and metabolism

Absorption, distribution and excretiona)Inhalation studies in mice show that ethylene oxide is very soluble in blood and thepulmonary uptake is expected to be rapid and to depend only on the alveolar
ventilation rate and the concentration of ethylene oxide in the inspired air. The rate of
uptake of ethylene oxide was 1.1µg/kg bw per min at an exposure level of 1 mg/m3.
This corresponds to nearly 100% absorption of ethylene oxide from 1.1 litre of air per
min and per kg bw which is the reported rate of alveolar ventilation in resting mice.
Approximately 74% of labelled ethylene oxide inhaled by mice was excreted in theurine within 24 hours in the form of unidentified metabolites.
(Ehrenberg et al, 1974/WHO, 1985)b)

Ethylene oxide is rapidly distributed throughout the body. In mice, whole body
autoradiograms 2 min after intravenous injection showed that concentrations of
ethylene oxide in the liver, kidneys, and pancreas were 3-4 times those in the blood.
Between 20 minutes and 4 hours after exposure, radioactivity was distributed
throughout the body. Directly after inhalation by mice, the highest concentrations oflabelled ethylene oxide were found in the liver, kidney, and lung. The radioactivity inthe liver and kidney dropped exponentially and approached the levels in the lung,testes, spleen, and brain within 4 hours, indicating rapid metabolism and excretion(Appelgren et al, 1977). On the basis of tissue alkylation data (Ehrenberg et al, 1976)
or haemoglobin alkylation data (Osterman-Golkar et al, 1976), a half-life of
approximately 10 min was estimated for the first-order clearance of ethylene oxidefrom mouse or rat tissues. A similar value for man was estimated on the basis of
haemoglobin alkylation data (Calleman et al, 1978).
(WHO, 1985)c)

When the degree of protein and DNA alkylation was investigated in mice and rats,
only small variations were observed between the different tissues in the species.
Apparently, most organs receive a more or less equal dose of ethylene oxide after
distribution throughout the body. The extent of protein alkylation was approximately
equal in the lung, liver, kidney, and spleen of mice, 120 min after inhalation of 2 mg
ethylene oxide/m3 air, for 75 min, but in the testes, it was about 50% lower. When thevapour concentration was increased (up to 59 mg/m3), the degree of protein alkylationin the liver increased relative to that in the other tissues. In all the tissues investigated,
protein alkylation increased linearly with the dose up to an exposure level of 59 mg/m3
and was relatively constant for at least 3.5 hours following exposure.
(Ehrenberg et al, 1974/WHO, 1985)23

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008d)

When 0.4 mg ethylene oxide/kg body weight was administered intraperitoneally to
mice, DNA alkylation in the testes and spleen was, respectively, 50 and 40% of that in
the liver, 5 hours after exposure. The approximate half-lives of the alkylation products
were 24 hours in the spleen, 10 hours in the testes, and 12 hours in the liver. For the
spleen, this half-life was found to be shorter in vivo than in vitro, indicating active
removal.
(Segerback, 1983/WHO, 1985)
Metabolism
The available animal data indicate two possible pathways for the metabolism of
ethylene oxide, i.e., hydrolysis to 1,2-ethanediol and conjugation with glutathione(Fig. B.6.2).

a)In dogs, peak levels of 13 and 33 mg 1,2-ethanediol/litre blood-plasma were measured
between 1 and 3 hr after intravenous administration of 25 or 75 mg ethylene oxide inwater/kg body weight, respectively. As the half-life for hydrolysis is about 60 h at 40°C in neutral fresh water, the involvement of an epoxide hydrolase has been suggested,
but this has not yet been confirmed. The peak concentration of 1,2-ethanediol at 25
mg ethylene oxide/kg body weight represented approximately 25% of the dose ofethylene oxide. Within 24 hr, 7-24% of the dose was excreted in the urine as 1,2ethanediol.
(Martis et al, 1982/WHO, 1985)b)

In the serum of workers exposed to ethylene oxide (0.54-27 m3 air; mean 7.56 m3 air,),
for an average of 5.3 years, the blood concentration of 1,2-ethanediol was elevatedcompared with that of unexposed controls.
(Wolfs et al, 1983/WHO, 1985)c)

The results of studies in rats, rabbits and monkeys have shown that some 1,2ethanediol is metabolised but most of it is excreted unchanged in urine.
(Gessner et al, 1961; McChessney et al, 1971/WHO, 1985)d)

When a single dose of 2 mg labelled ethylene oxide in propanediol was administeredintravenously to rats 43% was excreted in urine within 50 hours (41% within 24
hours); 9% as S-(2-hydroxyethyl)cysteine and 33% as N-acetyl- S-(2hydroxyethyl)cysteine. Ethylene oxide (1%) and labelled carbon dioxide (1.5%) werealso excreted via the lungs.
(Jones and Wells, 1981/WHO, 1985)e)

As ethylene oxide can react with chloride ions, and this reaction is acid catalysed, 2chloroethanol might be expected to be a metabolite, especially after oral
administration. However, neither 2-chloroethanol (also called ethylene or glycol
chlorohydrin), nor its metabolites have been found in the plasma, tissues, or urine of
species exposed to ethylene oxide.
(Grunow & Altman, 1982/WHO, 1985)24

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

B.6.8.1.2 Dermal penetrationa)

In vitro

The permeation rate of a solution of 1% ethylene oxide in water (w/v) through excised
human skin at 30ºC was determined to be 0.125 mg/cm2/hour.
(Baumbach et al, 1987/IARC 1994)b)

In vivo

The range of skin penetration of ethylene oxide was reported to be 1-14% from avariety of formulated products.
(Kreuzer, 1992/ECHC 2001)
B.6.8.1.3 Summary of ADME studies
No ADME studies using oral administration of ethylene oxide have been submitted (orcited from the literature).
Inhalation and intravenous administration of labelled ethylene indicate that theexcretion occurs mainly via urine. Minor amounts of unchanged parent and labelledcarbon dioxide are excreted via the lungs. Distribution is widespread based on theprotein and DNA alkylation in various organs and tissues (e.g. lung, liver, kidney,spleen and testes).
Two metabolic pathways have been identified in experimental animals and humans,
the hydrolysis of ethylene oxide to 1,2-ethanediol and conjugation with glutathione to
produce S-(2-hydroxyethyl)cysteine and N-acetyl- S-(2-hydroxyethyl)cysteine.

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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Figure B.6.3 Proposed pathway for the metabolism of ethylene oxide in mammals
O
CH2

CH2

ethylene oxideglutathione(GHS)

glutathionetransferasewater(epoxide hydrolase?)

HOCH2CH2OH*
1,2-ethanediol

CH2CH2OH
S-2-(hydroxyethyl glutathione)

HOCH2CHOURINE

HOOCCHNH2CH2SCH2CH2OH*
S-2-(hydroxyethyl) cysteinehydroxyacetaldehyde

HOCH2COOH*
hydroxyacetic acid(glyoxylic acid)

HOOCCHNHRCH2SCH2CH2OH*
N-acetyl-S-(2-hydroxyethyl) cysteine[S-(2-hydroxyethyl) mercapturic acid]
HCOCOOH
oxoacetic acid(glyoxylic acid)

HCOOH +
CO2
formic acidcarbon dioxide

COOHCOOH*
ethanedioic acid(oxalic acid)

KEY: a) * metabolites identified by Gessnar et al, 1961; McChessney et al, 1971; Jones and Wells, 1981.
b) GSH = glutamylcysteinylglycine. c) R = COCH
3. d) Taken from WHO, IPCS, Environmental HealthCriteria 55, Ethylene Oxide.

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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

B.6.8.1.2 Acute toxicity, irritancy and sensitisation
B.6.8.1.2.1 Acute oral toxicitya)

The acute LD50 values cited for ethylene oxide administered orally (in water) torodents were 330 mg/kg bw for male rats and 365 and 280 mg/kg bw for male andfemale mice, respectively.
(Smyth et al, 1941; Woodward & Woodward 1971/WHO 1985)b)

A MSDS (updated 2005) reports an acute LD50 value of 72 mg/kg bw for ethyleneoxide in the rat.
(http://www.physchem.ox.ac.uk/MSDS/ET/ethylene_oxide.html)c)After oral administration to rats, the difference between 0.1% mortality (325 mg/kg)
and 99.9% mortality (975 mg/kg) was approximately 650 mg/kg body weight.
(Smyth et al, 1941/WHO, 1985)

B.6.8.1.2.2 Acute dermal toxicity

A MSDS (updated 2005) states that ethylene oxide is classified as ‘Toxic in contact
with skin’.
(http://www.physchem.ox.ac.uk/MSDS/ET/ethylene_oxide.html)
B.6.8.1.2.3 Acute inhalation toxicitya)Ethylene oxide was stated to be toxic by inhalation with 4 hour LC50 values of 1460, 835
and 960 ppm (2672, 1528 and 1757 mg/m3) for rats, mice and dogs, respectively. No
deaths occurred in dogs at 1280 mg/m3. No guinea pigs died after inhalation of ethyleneoxide at a level of 450 mg /m3 air for 8 hours, the majority died at 2400 mg/m3. Guinea
pigs exposed to ethylene oxide at a concentration of 13000 mg/m3 for 2.5 hours were
found lying on their sides and unable to stand.
In the above studies, the respiratory system and nervous system were the main targets inrodents and dogs. The clinical effects included nasal irritation, scratching the nose, nasal
discharge, lachrymation, salivation, respiratory effects (gasping and laboured breathing)vomiting and convulsions. The gross findings in animals that died included congestionand oedema in the lungs, petecchial haemorrhage of the trachea and hyperaemia of theliver and kidneys and parenchymatous changes in the kidneys.
(Jacobson et al, 1956; Waite et al, 1930/WHO, 1985)b)

A MSDS (updated 2005) states the LC50 for ethylene oxide in the rat for a 4 hour
exposure was 800 ppm (920 mg/m3).
(http://www.physchem.ox.ac.uk/MSDS/ET/ethylene_oxide.html)

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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Male and female mice were exposed to concentrations of up to 1600 ppm (2928 mg/m3)
for 4 hours. At 800 ppm (1464 mg/m3), all the males and 4 of the 5 females died withinsix days post exposure.
(Jacobson et al, 1956/WHO, 1985)
B.6.8.1.2.4 Skin irritancyc)a)

Cotton pads moistened with solutions of 100 or 500 g ethylene oxide/litre water wereapplied to shaved rabbit skin under a plastic cover. After an exposure period of six
minutes, skin irritation (with hyperaemia), oedema and scar formation were observed. The
intensity of the response was reported to be roughly proportional to the length of exposure
time (1 - 60 min) and the concentration.
(Hollingsworth et al, 1956/WHO, 1985)
B.6.8.1.2.5 Eye irritancya)

A maximal non-damaging concentration of 0.1% ethylene oxide in physiological salt
solution was established after instillation of 0.05 ml solution, every 10 minutes for 6 hours,
into the conjunctival sac of rabbits. The concentration above 1% caused reversible
changes in conjunctiva such as hyperanemia and swelling and irreversible opacity both in
the cornea and in the lens. In–vitro studies with isolated rabbit cornea were in agreementwith these results.
(McDonald et al, 1973; Edelhauser et al, 1983/WHO, 1985)
B.6.8.1.2.6 Skin sensitisationa)

No study submitted (or data cited from the published literature).

b)

Ethylene oxide is considered a strong sensitising agent owing to its strong reactivity
with various chemical groups (anaphylaxis and contact dermatitis are reported inhumans).
(Bommer and Ritz, 1987/ECHC 2001)

B.6.8.1.2.7 Summary of acute toxicity, irritancy and sensitisation

A summary of the cited acute toxicity data is presented in Table B.6.3.
A steep dose response curve was evident for ethylene oxide from the reported
mortalities in the acute studies. These studies indicate that the respiratory system, thenervous system and the liver and kidneys are target organs. It should also be notedthat liquefied or pressurized ethylene oxide gas can cause frostbite damage (Hine &Rowe, 1981/).
The official ECB classification of ethylene oxide: Cat 2: carcinogenicity, Cat: 2
mutagenicity, Toxic by inhalation (R23) and R/36/37/38 for irritancy.

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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Table B.6.3 Summary of the acute toxicity, irritancy and skin sensitisation of ethylene oxide
Study
Acute oral
Acute oral
Acute oral

Species
Rat
Rat
Mouse

Classification
Toxic (R25)
Harmful (R22)
Harmful (R22)

Referencephyschem.ox.ac.uk
WHO, 1985

NS

Results/comments
72 mg/kg bw.
Males: 330 mg/kg bw♂ & ♀: 365 & 280
mg/kg bw, respectively.
No details given

Acute dermal

Toxic (R24)physchem.ox.ac.uk

Acute inhalation

Rat

2.672 mg/l

WHO, 1985

Acute inhalation

Rat

0.92 mg/l

Acute inhalation

Mouse

1.528 mg/l

Acute inhalation

Dog

1.757 mg/l

Skin irritation

RabbitAqueous solutions

Harmful(R20 & R37)
Toxic
(R20 & R37)
Toxic
(R23 & R37)
Toxic
(R23 & R37)
Irritating toskin (R38)

Skin sensitisationNAphyschem.ox.ac.uk
WHO, 1985
WHO, 1985
WHO. 1985

Considered to be asensitiser based on
chemical reactivity.
Key: a) NS = not stated in MSDS/citation. b) NA = not applicable.

B.6.8.1.3 Short-term toxicity

The cited data for short-term repeat dose toxicity is primarily limited to inhalation
studies.
B.6.8.1.3.1 Oral administration to rats

In a reported subacute study, rats orally exposed to ethylene oxide at 100 mg/kg
bw/day in olive oil for 5 days/week for 3 weeks (15 doses in 21 days). The findings
included loss of body weight, gastric irritation and slight liver damage.
(Hollingsworth et al, 1956/WHO 1985)
B.6.8.1.3.2 Oral administration to mice

No studies submitted (or data cited from the published literature).
B.6.8.1.3.3 Oral administration to dogs

No studies submitted (or data cited from the published literature).
B.6.8.1.3.4 Inhalation exposure data/information for experimental animalsa)Groups of Wistar rats (10-20/sex), guinea pigs (8/sex), rabbits (1-2/sex) and Rhesus
monkeys (1-2 females) were each exposed to concentrations of ethylene oxide at levelsof 0, 90, 200, 370, 640, or 1510 mg/m3, for 7 hours per day/5 day per week. The
female monkeys were not tested at 90 mg/m3 and an additional 3 male monkeys were
tested at 640 mg/m3. The test period varied with the species tested and the severity of
exposure, i.e. approximately 26 weeks at 90 mg/m3; 25-32 weeks at 200 and 370
mg/m3; 7-25 weeks at 640 mg/m3 and 10 days at 1510 mg/m3.
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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Guinea pigs, rabbits, and monkeys tolerated 90 and 200 mg/m3 and rats tolerated
exposure to 90 mg/m3 without adverse effects on general appearance, behaviour,
mortality rate, growth, body and organ weight and gross and microscopic examination.
Rats showed elevated mortality rates from 370 mg/m3, rabbits from 640 mg/m3 and all
exposed animals died at 1510 mg/m3. Secondary respiratory infection was put forward
as a cause of death in an appreciable number of rats and mice in these studies.
Surviving rats showed increased relative lung weights after 26-27 weeks at 200 and
370 mg/m3. At 370 mg/m3, haemorrhages, hyperaemia, emphysema, and local
alveolar collapse were observed in these lungs. Lungs of male rabbits also showed
hyperaemia and slight oedema at 370 mg/m3. Even more severe lung injury was seen
in rats at 640 mg/m3 and the higher exposure. Gross respiratory tract irritation wasapparent in all species at 1510 mg/m3.
Delayed reversible effects were observed on the peripheral nervous system. Monkeys
and rabbits exhibited paralysis of the hind legs at 370 mg/m3 and rats at 640 mg/m3.
This was accompanied by atrophy of the muscles of the hind legs (except in rabbits at
370 mg/m3). The effects on the peripheral nervous system were investigated further inmonkeys and loss of both sensory and motor function was noted at levels of 370 and
640 mg/m3.
Significant increases in body weight were also observed in rats, at levels of 200 mg/m3
or more. Rats showed slight but significant increases in the relative weights of kidney
and liver at 370 mg/m3.
(Hollingworth et al, 1956/WHO, 1985)b)Groups of 20 male rats and 30 female mice were exposed to concentrations of ethyleneoxide at levels of 0, 180, or 730 mg/m3 for 6 hours/day/5 days per week. The
exposures lasted 26 weeks at 180 mg/m3 and 6 weeks at 730 mg/m3. Additional groupsof 15 rats and mice at the higher and 60 rats and mice at the lower exposure level wereused for interim gross pathology.
No clear toxic effects were reported at 180 mg/m3. No pathological changes wereobserved except for marked haemosiderosis in the spleen of a few rats at 730 mg/m3.
The highest exposure (730 mg/m3) resulted in death for both species without clinicalsigns in mice. Effects on the respiratory and nervous system were shown by rats aslaboured breathing, reddish nasal discharge, diarrhoea, tendency towards a side
position, and dragging of the hind-quarters. Rats also lost weight, which was regainedby survivors.
(Jacobson et al, 1956/WHO, 1985)c)Groups of 30 B6C3F1 mice of each sex were exposed to concentrations of ethyleneoxide at 0, 18, 86, 187, or 425 mg/m3, for 6 hr/day, and 5 days per week. The
exposures lasted for 10 weeks for males and 11 weeks for females. No effects wereobserved in relation to survival, body weight, clinical signs, white blood cell count,serum clinical chemistry, urinalysis and histopathology. At the highest exposure level,changes at terminal sacrifice included an increased relative liver weight in female
mice, and a decreased testicular weight in males. A decreased relative spleen weight
was observed at 187 and 425 mg/m3 in both sexes. In addition, the red blood cell30

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

count, the packed cell volume, and the haemoglobin concentrations were decreased at
425 mg/m3. Screening of neuromuscular function at week 6 (5 female mice) andweeks 10 or 11 (5 mice/sex) revealed altered reflex responses at 425 mg/m3 and adose-related trend in alterations of locomotor function from 86 mg/m3 upwards.
(Snellings et al, 1984a/WHO, 1985)d)Groups of 3 male beagle dogs each were exposed to concentrations of ethylene oxideof 180 and 530 mg/m3, for 1-3 days. No effects were observed on mortality rate, bodyweight, electrocardiogram, blood-calcium and -urea, icteric index and rectal
temperature. Anaemia was noted at both exposure levels. Effects on the respiratory
and nervous systems were shown at 530 mg/m3, such as hyperaemia and local alveolar
collapse in lungs, vomiting, and occasional slight tremors and transient weakness inthe hind legs. Muscular atrophy was also observed.
(Jacobson et al, 1956/WHO, 1985)e)

New Zealand rabbits (3 males/dose) were exposed to 0, 18, 90, or 450 mg/m3.for 12
weeks. No haematological changes were noted.
(Yager & Benz, 1982/WHO, 1985)

Fischer rats (groups of 3 or 4 animals) were exposed to 90, 270, or 810 mg/m3 for 6hours per day for 3 days. The white blood cell count was depressed but there was apoor correlation with exposure level.
(Kligermann et al, 1983/WHO, 1985)
B.6.8.1.3.5 Dermal exposuref)

No studies submitted (see section B.6.8.1.2).
B.6.8.1.3.6 Summary of short term toxicity

A summary of published short-term toxicity data are presented in Table B.6.4.
Following oral exposure in a subacute study, loss of body weight, gastric irritation andslight liver damage were evident (no further details).
Following inhalation exposure, mortalities and effects on respiratory system, thehaematological system (including bone marrow), the nervous system, ocular lens, liverand kidneys, thymus and spleen and the testes were reported. A dose-related in creasein pulmonary adenoma was also seen in mice after 6 mounts of exposure.

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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Table B.6.4 Subchronic effects of exposure to ethylene oxide, presented in tabulated form (takenfrom IARC 1994)
Species
Wistar rats(♂)

Wistar rats(♂ & ♀)

B6C3F1mice(♂ & ♀)a

B6C3F1mice(♂ & ♀)C57BL/6J
mice (♂)
ddY mice(♂)

ExposureEffects
General toxicity
0 & 500 ppm (915 mg/m3),
500 ppmi) Decrease in glutathione reductase in the
6 hours/day, 5 days/week for 13
brain, liver, ocular lens and erythrocytes (andweeks.
glutathione).
ii) Increase in lipid peroxidation in the liver(malondialdehyde liver).
iii) Anaemia (normocytic and normochromic)
decrease in the haemoglobin concentration.
iv) Disturbance of porphyrin-haem metabolism.
v) Decrease in hepatic cytochrome P450.
0 & 250 ppm (458 mg/m3),
250 ppmi) Decrease in hepatic cytochrome P450 in
6 hours/day, 5 days/week for 17
males.
weeks.
ii) Decrease in hepatic glutathione reductase
and an increase in glutathione-S-transferase(both sexes).
iii) Increase in hepatic NADPH-cytochrome creductase and liver weight in females.
iv) Increase in hepatic glutathione peroxidase.
0-250 ppm (0-458 mg/m3),
250 ppmi) Decrease in spleen weight and an increase in
6 hours/day, 5 days/week for 10
liver weight in females.
weeks (♂) or 11 weeks (♀).
ii) Decrease in absolute testicular weight.
iii) Slight decrease in haemoglobin
concentration and erythrocyte count.
100 ppm (183 mg/m3)i) Decrease in spleen weight in females.
0-600 ppm (0-1098 mg/m3),
600 ppm (1098 mg/m3)i) Renal tubular necrosis.
6 hours/day, 5 days/week for 14ii) Lymphocytic necrosis of the thymus andweeks.
spleen in males.
200-600 ppm (366-1098 mg/m3)i) Rhinitis of the nasal cavity.
100-400 ppm (366-1098 mg/m3)i) Renal tubular degeneration.

0 & 255 ppm (467 mg/m3),
6 hours/day, 5 days/week for 16
days; 6 hours/day, 5 days/week
for 4-10 weeks.
0 & 400 ppm (732 mg/m3),
6 hours/day, 3 days/week for 13
weeks.

Key: a) US National Toxicology Program (1987).

32

Also dose-related epithelial damage in the nasal
portion of the respiratory tract.
255 ppm
General depression of cellularity in blood andbone marrow (with large fluctuations) andtransient increase in granulocytes.
400 ppmi) Macrocytic anaemiaii) Two-fold increase in hepatic cytochrome
P450iii) Increase in ferricyanide reductase.
iv) Decrease in hepatic glutathione reductase
and glutathione peroxidase.
v) Increase in hepatic glutathione-S-transferase.

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Table B.6.4 Subchronic effects presented in tabulated form (taken from IARC)
Species
Wistar rats(♂)
Wistar rats(♂ & ♀)

Wistar rats(♂)

B6C3F1mice(♂ & ♀)

Neurotoxicity
ExposureEffects
0 & 250 ppm (458 mg/m3),
250 ppmi) Preferential distal axonal degeneration of
6 hours/day, 5 days/week for 9
myelinated fibres in sural nerves and gracilemonths.
fascicles.
0 & 250 ppm (458 mg/m3),
250 ppmi) Paresis of hindlegs
6 hours/day, 5 days/week for 17ii) Degeneration of myelinated fibres in the
weeks.
peroneal nerve, the nerve of the soleus muscle
and gracile fascicles.
iii) No sex differences.
0 & 500 ppm (915 mg/m3),
500 ppmi) Ataxic gait after 6 weeks
6 hours/day, 3 days/week for 13ii) Preferential distal axonal degeneration of
weeks.
myelinated fibres in hindleg nerves and gracile
fascicles.
iii) Decrease in creatine kinase activity inserum, brain and spinal cord after four weeks.
0-250 ppm (0-458 mg/m3),0-250 ppmi) Dose-related trend in reduction in locomotor
6 hours/day, 5 days/week for 10
activity and abnormal reflexes.
weeks (♂) or 11 weeks (♀).
ii) No microscopic findings.

B.6.8.1.4 Genotoxicity

Ethylene oxide is an alkylating agent and is considered to be a mutagen inexperimental animals and humans. It has consistently displayed genotoxic activity inalmost all in-vitro and in vivo studies reviewed by the cited publications (see B.6.8.9
for human data/information).
(IARC 1994)
B.6.8.1.4.1 In vitro testing
Ethylene oxide is an alkylating agent. It has induced gene mutations in plant, bacteria,
fungi, insect, mammalian and human cells (in vitro investigations with and without
metabolic activation). Numerous studies in mammalian cells are reported in theliterature showing gene mutations, micronucleus formation, chromosome aberrations,cell transformation, unscheduled DNA synthesis, DNA strand breaks and sister
chromatid exchanges.
(WHO 1985 & IARC 1994)
B.6.8.1.4.2 In vivo genotoxicity in somatic cells
The available in vivo studies have reported positive results following administration byingestion, inhalation or intraperitoneal injection of ethylene oxide. Genotoxic activity
has been reported in rats, mice, rabbits and monkeys and includes the endpoints list
below.
i) Formation of DNA adducts (haemoglobin used as a surrogate for DNA adducts) inbrain, kidney, lung and spleen (rats and mice).

33

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008ii) Gene mutations in rat and mouse splenic T-lymphocytes (HPRT locus) and in thelung (lacI locus) of transgenic mice.
iii) Sister chromatid exchanges in lymphocytes (rabbits, rats and monkeys) and bonemarrow cells (rats and mice).
iv) The induction of sister chromatid exchanges appears to be a more sensitive
endpoint than chromosome aberrations and the formation of micronuclei.
v) Micronucleus formation in bone marrow cells (rats and mice).
vi) Chromosome aberrations in lymphocytes (monkey) and bone marrow cells (ratsand mice).
(WHO 1985 & IARC 1994)
B.6.8.1.4.3 In vivo studies in germ cellsa)Ethylene oxide also induces heritable mutations or effects in germ cells. Dose-related
damage to germ cells was established in the mid and late spermatid stages in a mousedominant lethal assay after one oral dose of 150 mg/kg body. After short-term
repeated exposures, dominant lethal effects were induced in mice at intraperitoneal
doses from 40 mg/kg body weight (5 times per week for 3 months) and at inhalation
exposures from 460 mg/m3, (6 hours/day, 5 days per week for 11 weeks). Heritabletranslocations were induced in the germ cells of mice after repeated intraperitoneal
exposure at doses of 30 mg/kg body weight (administered on 5 days/week over a 5week period).
(Generoso et al, 1980 & 1983/WHO, 1985)b)

An abstract stated that DNA repair was induced in the germ cells of mice exposed to
540 mg/m3 for 8 hr. The repair seemed inhibited at higher exposures.
(Cumming & Michaud, 1979/WHO, 1985)c)

Ethylene oxide has induced DNA single strand breaks in mouse sperm and spermatids,
dominant lethal effects in mice and rats, chromosome aberrations in mouse
spermatocytes.
(IARC 1994)d)

In two studies, male mice were exposed to ethylene oxide by inhalation under similar
exposure conditions but using different mating regimens and examining different
genetic events. In one study, there were no significant increases in the frequency ofspecific locus mutations in the offspring (Russell et al, 1984) while dominant visible
and electrophoretically detected mutations were observed in another (Lewis et al,1986).
(IARC 1994)
B.6.8.1.4.4 Summary of genotoxicity studies
Ethylene oxide is a potent mutagen in different cell lines and experimental animals. It
forms DNA adducts and induces gene mutations, chromosome aberrations, celltransformation, unscheduled DNA synthesis, DNA strand breaks, sister chromatid
exchanges, dominant lethal mutations and heritable translocations.
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B.6.8.1.5 Long-term toxicity and carcinogenicity

Ethylene oxide has been tested in rats (1 oral and 2 inhalation studies) and in mice (2inhalation studies, 1 topical application study and 1 subcutaneous injection study).
However, since most of the studies focussed on carcinogenicity, ethylene-induced nonneoplastic effects have not been investigated extensively.
B.6.8.1.5.1 Dietary studies in ratsa)Groups of 50 female Sprague Dawley rats were orally (gavage) administered 7.5 or 30
mg/kg bw/day ethylene oxide in salad oil. The rats were dosed twice a week for 110
weeks. In addition, there were 50 vehicle controls, 50 untreated controls and 50
positive controls. No statistical analysis was reported.

The mean survival period was over 100 weeks for all groups. The mortality rateincreased at 30.0 mg/kg body weight from week 100 onward. Elevated incidences oftumours were only observed in the forestomach, the first tumour appearing in week 79.
The incidences of squamous cell carcinomas were 0/50, 8/50, and 29/50 at 0, 7.5, and30 mg/kg bw/day, respectively. At 30 mg/kg bw/day, invasive growth and metastases
were observed in 10 rats and 2 fibrosarcomas were also noted. At 7.5 and 30 mg/kg
bw/day, the incidences of hyperplasia, hyperkeratosis, papillomas and/or carcinomas
were increased in the forestomach.
(Dunkelberg, 1982/WHO, 1985)
B.6.8.1.5.2 Inhalation studies in ratsa)

In a combined toxicity-carcinogenicity study, groups of 120 male and 120 female
Fischer 344 rats were exposed to ethylene oxide at concentrations of 18 mg/m3 (10ppm), 58 mg/m3 (32 ppm), and 173 mg/m3 (96 ppm) for 6 hours per day, 5 day per
week, over 25 months. In addition, two control groups each comprising 120 male and
120 female rats were used. There was an exposure-free period of 2 weeks in month15, because of infection with sialoacryoadenitis virus. Interim sacrifices occurred at 6,
12, and 18 months.
The mortality rates of male and female rats increased significantly from the 22nd or
23rd month, at the highest exposure, with a trend towards an increase at a level of 58
mg/m3. Male and female body weights were depressed at 173 mg/m3 from the end of
the first week until the end of the study. At 58 mg/m3, the body weights of female rats
were decreased between week 10 and 80.
The ophthalmologic examinations did not reveal any abnormalities.
Haematological changes were found in rats at all doses but mainly at the end of thestudy in animals exposed to 173 mg/m3. These changes included an elevatedleukocyte count in both sexes, a depressed red blood cell count and depressedhaemoglobin values in females (some of these rats had leukaemia).
In females, the relative liver weights were increased in the 18th month at 173 mg/m3.
This effect on the liver could not be related to increases in the activities of serum
alkaline phosphatase, aspartate aminotransferase, or alanine aminotransferase found35Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

mainly at the 2 highest exposures during interim sacrifices. Relative spleen weights
were increased in rats that developed leukaemia.
Non-neoplastic histopathological changes observed included an elevated frequency of
focal fatty metamorphosis of the adrenal cortices in both sexes and bone marrow
hyperplasia in females at 173 mg/m3. Although no effect was observed on the hindquarter lift reflex (examined monthly), mild skeletal muscular atrophy was observed
after 2 years of exposure to 173 mg/m3.
Neoplastic findings included increased incidences of leukaemia, peritoneal
mesotheliomas, brain tumours and fibroma and the earlier appearance of pituitary
tumours. A dose-related increased incidence of mononuclear cell leukaemia wasfound in both sexes, significant at the 2 highest exposures in females from the 18th or
19th month onwards. Trend test revealed a treatment-related response in both sexes. In
males, an increased incidence of peritoneal mesotheliomas originating from thetesticular mesothelium occurred at 58 and 173 mg/m3 from the 23rd month onwards.
An increased incidence of subcutaneous fibroma was seen in male rats exposed to 173
mg/m3 that had survived for 24 months. Trend analysis showed that there was atreatment-related increase in peritoneal mesothelioma. There was no increased
incidence of pituitary tumours but they appeared earlier in the 173 mg/m3 group.
Following an increased incidence of brain tumours in Fischer 344 rats exposed toethylene oxide (Lynch et al, 1984a), the brain tissue from this study was re-examinedboth macro- and microscopically. A dose-related incidence of primary brain tumours
was observed at 58 and 173 mg/m3 that appeared to be treatment related in the trend
test but was not statistically significant. The tumours were mainly diagnosed as
gliomas and malignant reticular tumours. The percentage of rats with multiple
neoplasms was greater than in controls at all exposure levels in females and at 173
mg/m3 in males. At 58 and 173 mg/m3, the percentage of female rats with at least one
malignancy was increased. It was considered that a contribution of the viral outbreakto the toxicity of ethylene oxide was unlikely.
(Snellings et al, 1981 & 1984b/WHO, 1985)b)

In a combined toxicity-carcinogenicity study, groups of 80 male Fischer 344 rats were
exposed to ethylene oxide at concentrations of 92 mg/m3 (51 ppm) and 182 mg/m3 (101ppm), for 7 hours/day on 5 days per week for 2 years. The control group also
comprised 80 rats. There was an exposure-free period of 2 weeks in month 16 becauseof a pulmonary infection, which contributed to the mortality rate.
The mortality rate increased at both exposure levels, the increase being significant at
182 mg/m3. At 182 mg/m3, only 19% of the rats survived 2 years of exposurecompared with 49% in the unexposed group. Body weights were reduced from the 3rd
or 4th month onwards.
Serum aspartate aminotransferase activity was increased in rats exposed to 92 and 182
mg/m3. No other changes were found in the haematological or clinical chemistryparameters.

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Relative weights of the adrenal and brain were increased at both exposure levels andthe relative weights of lung and kidney were increased at 92 mg/m3.
Non-neoplastic histopathological changes included an elevated incidence of
vacuolisation and hyperplasia or hypertrophy in the adrenals at both exposure levels
and of atrophy and degeneration of skeletal muscle fibres at 182 mg/m3. There werealso increased incidences of inflammatory lesions of the lungs, nasal cavities, trachea
and internal ear at both exposure levels. Eye cataracts developed in 2/77 (2.6%), 3/79
(3.8%) and (11.5%) at 0, 92 and 182 mg/m3, respectively.
Neoplastic findings included increased incidences of leukaemia, peritoneal
mesotheliomas and brain tumours. An increased incidence of mononuclear cellleukaemia was found which was significant at the lower exposure level. The absenceof a dose-relationship was attributed to the increased mortality rate at 182 mg/m3.
Dose-related increased incidences of peritoneal mesotheliomas (originating from thetesticular mesothelium) and of mixed-cell gliomas in the brain were found. The
increases in both tumours were significant at 182 mg/m3.
(Lynch et al, 1984a/WHO, 1985)
B.6.8.1.5.3 Inhalation studies in micea)

B6C3F1 mice (50/sex) were exposed to ethylene oxide at concentrations of 0, 50 (92mg/m3) or 100 ppm (183 mg/m3) for 6 hours/day, five days/week for 102 weeks.
No treatment-related clinical signs were reported. However, there were significant
dose-related increases in the incidences of tumours. There was a dose-related increasein the incidence of alveolar/bronchiolar carcinoma [6/50, 10/50, and 16/50 in males(0/49, 1/48 and 7/49 in females) at 0, 50 and 100 ppm, respectively]. The incidencesof cystadenoma in the Harderian gland were increased 1/43, 9/44, and 8/42 in males(1/46, 6/46 and 8/47 in females) at 0, 50 and 100 ppm, respectively]. In females, there
were dose-related increases in the incidence of malignant lymphomas of thehaematopoietic system (9/49, 6/48 and 22/49 at 0, 50 and 100 ppm, respectively) anduterine adenocarcinoma (0/49, 1/47 and 5/49 at 0, 50 and 100 ppm, respectively). The
incidence of mammary adenocarcinoma and adenosquamous carcinoma combined was(1/49, 8/48 and 6/49 at 0, 50 and 100 ppm, respectively.
(US National Toxicology Program, 1987/IARC 1994 & ECHC 2001)b)

Female A/J mice (considered to be highly susceptible to lung tumours) were exposedto ethylene oxide at concentrations of 128 and 366 mg/m3 for 6 hours/day, 5days/week, for 6 months. A dose-related increase in pulmonary adenomas wasobserved (only lungs examined).
(Adkins et al, 1986/ECHC 2001)37

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B.6.8.1.5.4 Other studies in micea)

Subcutaneous exposureb)Groups of 100 female NMRI mice were injected once a week with a tricaprylin
solution containing 0.1, 0.3, or 1.0 mg ethylene oxide per animal, for 106 weeks. There
were 200 vehicle controls and 200 untreated controls. From week 35 to week 85, themortality rate increased by a maximum of 10% at a dose of 1.0 mg per mouse. The
mean length of survival in this group was 75 weeks. An elevated incidence of tumours
was only observed at the injection site, the first tumour appearing in week 79. There
was a dose-related increased incidence of sarcomas, mainly fibro sarcomas, which wassignificant at 0.3 and 1.0 mg per mouse. The tumour incidence was 11% at the highest
dose compared with 2% in vehicle controls.
(Dunkelberg, 1981/WHO, 1985)
Dermal exposure
Each of a group of 30 female Swiss Millerton mice received, for their lifetime,
approximately 100 mg of a 10% solution of ethylene oxide (purity 99.7%) in acetone,brushed on the clipped dorsal uncovered skin, 3 times a week. A group of 60 mice did
not receive any treatment and a group of 60 mice received the vehicle only. Skintumours were not found, nor were there any sign of skin irritation. The median lengthof survival was 493 days for treated mice and 445 days for controls. It is assumed that
ethylene oxide, applied in this manner, evaporated rapidly from the skin.
(Van Duuren et al, 1965/WHO, 1985)

B.6.8.1.5.5 Summary of chronic toxicity/carcinogenicity

Chronic toxicity
The main emphasis of the available chronic investigations was focussed on the
carcinogenic activity of ethylene oxide. There are limited information/data on the nonneoplastic effects of ethylene oxide.
In rats, the mortality rate and the incidences of hyperplasia and hyperkeratosis in theforestomach was increased following oral exposure. Following inhalation exposure,the mortality rate was increased, body weights decreased, inflammatory lesions of thelungs, nasal cavities, trachea and internal ear were increased and the development ofeye cataracts. The haematological changes included elevated leukocyte counts in both
sexes. In addition, bone marrow hyperplasia, depressed red blood cell counts andhaemoglobin values were seen in females. Serum aspartate aminotransferase activity
was increased. The relative weight of several organs was increased (brain, liver, lung,kidneys and adrenals). The microscope changes in the adrenals included an increased
frequency of focal fatty metamorphosis, vacuolisation and hyperplasia or hypertrophyin the adrenals and atrophy and degeneration of skeletal muscle.
Chronic non-neoplastic investigations in mice are not reported.

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Carcinogenicity
Following oral exposure, a dose-related increase in the incidence squamous cell
carcinomas in the forestomach was reported in rats at 7.5 & 30 mg/kg bw/day(invasive growth and metastases were also reported at the high dose).
Following inhalation exposure, there were significant dose-related increases in several
tumour types of tumours in rats (leukaemia, peritoneal mesotheliomas, brain tumours
and subcutaneous fibroma) and mice (alveolar/bronchiolar carcinoma, malignant
lymphomas of the haematopoietic system, uterine adenocarcinoma and mammary
adenocarcinoma and adenosquamous carcinoma). It is also noteworthy that pituitary
tumours appeared earlier in rats and that an increase in lung tumours was reported inmice after only 6 months of exposure.
Following subcutaneous injections to mice, there was a dose-related increased
incidence of sarcomas, mainly fibro sarcomas, at the injection sites. No skin tumours(or skin irritation) were found in mice after long-term dermal exposure but it was
assumed that ethylene oxide evaporated rapidly from the skin.
Overall conclusions
The extensive evidence of genotoxicity (in vitro and in vivo effects) andcarcinogenicity (a variety of tumours in rats and mice and the evidence of the early
appearance of certain tumours in rats and mice) indicates that ethylene oxide is apotent genotoxic carcinogen in experimental animals. A NOAEL for ethylene oxideinduced tumours cannot be established for oral or inhalation exposure. The nonneoplastic effects of ethylene have not been fully investigated but appear to occur atdose levels above tumour induction.
B6.8.1.6 Reproductive toxicity

No reproductive studies using oral administration were submitted (or cited from thepublished literature). The following studies used inhalation exposure.
B.6.8.1.6.1 Multigeneration studies in rats (IIA 5.6.1)

a)Fischer 344 rats (30/sex) were exposed to ethylene oxide at concentrations of 18, 58 or
173 mg/m3, for 6 hours/day, 5days per week, over 12 weeks. Two control groups of
30 rats per sex each exposed to air only. After mating, females were further exposedfor 7 days/week for up to three weeks after delivery with the exception of the first 5days of lactation. The percentages of pregnant females and fertile males were notaffected by ethylene oxide exposure. The number of pups per litter, the number of
implantation sites per female and the number of foetuses born per implantation sitewere decreased at 173 mg/m3. In addition, the number of females with a gestation
period longer than 22 days was also increased at this concentration but no effects werenoted on the average length of the gestation period. Neither parents nor pups showedsigns of toxicity from ethylene oxide.
(Snellings et al, 1982a/WHO, 1985)

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B.6.8.1.6.2 Developmental toxicity studies (IIA 5.6.2)

Developmental studies in ratsa)Groups of Sprague Dawley rats (32-45 females) were exposed to ethylene oxide atconcentrations of 0 or 270 mg/m3 for 7 hours/day. They were exposed on days 7-16 of
gestation (Group 1) or on days 1- 16 of gestation (Group 2) or during 3 weeks before
mating (5 per week) and on days 1 - 16 of gestation (Group 3).
No dams died during the study but body weights were decreased in Group 3. In all
exposed groups, the relative and absolute weights of kidney and spleen were increased.
The results of histopathological examination did not show any abnormalities. There
was a significant increase in resorptions per litter and per implantation site in Group 3
but no significant effects on the number of implants, live foetuses or pregnancies. In
all exposed groups, the weights and the lengths of the foetuses were decreased.
Reduced ossification of sternebrae and skull was observed.
(Hackett et al, 1982/WHO, 1985)b)Groups of Fischer 344 rats (22 females) were exposed to ethylene oxide atconcentrations of 18, 58, or 173 mg/m3, for 6 hours/day on days 6-15 of gestation. Twocontrol groups comprising 22 rats each were exposed to air only. The numbers ofpregnant dams ranged from 17 to 22. Maternal behaviour was normal, and there were
no deaths. The only effect on the foetuses was a 5-8% decrease in weight at 180
mg/m3.
(Snellings et al, 1982b/WHO, 1985)
Developmental studies in micea)Groups of CD-1 mice (24-37 females) each received intravenous injections of ethyleneoxide at doses of 0, 75 or 150 mg/kg bw in an aqueous dextrose solution on days 4-6,
6-8, 8-10 or 10-12 of pregnancy.
Dams exposed on days 6-8 of pregnancy did not show toxic signs but there was a 20%
decrease in foetal weight. In all the other groups at the top dose, clinical signs of
toxicity were observed and included increased mortality (19-48%), weakness, laboured
respiration and tremor. Foetal malformations were shown in 19.3% of foetuses in
exposed litters compared with 2% in control groups. These malformations weremainly fused cervical arches. In addition, fused thoracic arches, scrambled and fused
sternebrae and fused, branched, or missing thoracic ribs were observed.
(Laborde & Kimmel, 1980/WHO, 1985)b)

Exposure of F1 female mice (C3H x C57B1 or SEC x C57B1) mated with F1 males(C3H x C57B1) to ethylene oxide at a concentration of 2196 mg/m3 for 1.5 hours
could produce different results depending on the timing of exposure. Females were
exposed at 1, 6, 9 or 25 hours after timed 30 minute matings. These time intervals
correspond to time of sperm penetration, early pronuclear stage (before DNA
synthesis), pronuclear DNA synthesis and early two-cell stage, respectively. It wasnoted that maternal toxicity was not reported despite the high concentrations used.

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Exposure at 1 or 6 hours increased the number of mid-gestational and late foetal deaths
but few effects were seen after 9 hours and none were seen after 25 hours. A large
proportion of the foetuses that survived after exposure at 6 hours had a range ofcongenital malformations including omphalocoele, hydropia, open thorax, and limb
and tail defects (37% versus 2% in controls). Malformations were also seen in
foetuses exposed at 1 hour but not those exposed at 9 or 25 hours. In a later study,
with identical exposure protocols but more detailed foetal examination, an increased
incidence of malformations was found after exposure at 1, 6, 9 and 25 hours. Other
females exposed to ethylene oxide for up to 14 days before mating had mainly an
increase in early embryonic death around the time of implantation, probably as a resultof dominant lethal mutations.
(Generoso et al, 1987; Rutledge and Generoso, 1989/IARC 1994)
Developmental studies in rabbits
New Zealand rabbits were exposed to ethylene oxide at a concentration of 270 mg/m3
from days 1-19 or from days 7-19 of gestation. There was no evidence of toxicity inthe mothers, embryos, or foetuses, or of any developmental defects.
(Hackett et al, 1982/WHO, 1985)
B.6.8.1.6.3 Effects on sperm and reproductive tissues/organsa)

Wistar rats (12 or 6 males/dose) were exposed to ethylene oxide at concentrations of 0,91.5, 183, or 457.5 mg/m3 for 6 hours/day on fine days/week for 13 weeks. At 457.5
mg/m3, epididymal but not testicular weight was reduced, there was slightdegeneration in some seminiferous tubules, a reduced sperm count in the body and tailbut not the head of the epididymus and an increase in sperm head abnormalities due
mainly to the presence of immature sperm. An increase in malformed sperm heads
unrelated to dose was observed in all treated groups over that in control (15% versus
2%).
(Mori et al, 1991/IARC 1994)b)

Male Cynomolgus monkeys were exposed to ethylene oxide at concentrations of 0, 90
or 180 mg/m3 for 7 hours/day on 5 days/week for 2 years. A decline in sperm countand mobility was observed at both dose levels but the incidence of abnormal sperm
heads did not change.
(Lynch et al, 1984c/WHO)
B.6.8.1.6.4 Summary of reproductive toxicity
No data/information has been submitted (or cited from the literature) on the
reproductive toxicity of ethylene oxide via the oral exposure route. However, there aresufficient data/information generated by studies using inhalation exposure to establishthat ethylene oxide is a reproductive toxin that affects fertility and development inexperimental animals (some effects are evident in the absence of maternal toxicity). In
mice, there is clear evidence of teratogenic activity after intravenous injections andevidence that mutagens can induce foetal malformations and death when administeredaround the time of fertilisation. Sperm abnormalities have been reported in rats andmonkeys following inhalations exposure to ethylene oxide.

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B.6.8.1.7 Neurotoxicity studies

No specific neurotoxicity studies have been submitted (or cited from the literature).
All the reported effects of ethylene oxide on the nervous system in experimental
animals have been observed and reported in standard repeat-dose inhalation studies.
B.6.8.1.7.1 Repeat dose neurotoxicity studiesa)

In a limited, poorly reported study in rabbits and monkeys, paralysis of the hind limbs
was observed in both species accompanied by atrophy of the leg muscles, following
exposure to ≥ 370 mg/m3 for periods ranging from 7 to 32 weeks (exact exposure
periods were not clearly specified).
(Hollingsworth et al, 1956/ECHC, 2001)b)

In sub chronic or chronic studies, in rats exposed to ethylene oxide a concentrations
between 458-915 mg/m3 there was a range of neurological effects including awkward
or ataxic gait, paralysis and atrophy of the muscles of the hind limbs, accompanied insome cases by pathological evidence of axonal degeneration of myelinated fibers innerves of the hind legs.
(Hollingsworth et al, 1956 & Other workers/ECHC, 2001)c)

Poor coordination of the hind quarters was observed in rats and mice following
exposure to ethylene oxide at 810 mg/m3 for 7-8 weeks.
(Snellings et al 1982/ECHC, 2001)d)Abnormal posture during gait and reduced locomotor activity were also observed inmice after exposure to ethylene oxide at concentrations ranging from 86 to 425 mg/m3,
for 6 hours/day on 5 days/week for 10 or 11 weeks. Effects on various reflexes(righting, tail pinch, toe pinch) were also noted at the highest concentration examined.
(Snellings et al 1984a/ECHC, 2001)e)

In two studies of male cynomolgus monkeys exposed to ethylene oxide atconcentrations of 92 or 183 mg/m3 for 2 years, histological alterations in the axons
within the nucleus gracilis of the medulla oblongata and demyleination of the
fasciculus gracilis within the medulla were observed.
(Sprinz et al, 1982/Lynch et al, 1984b/ECHC, 2001)

B.6.8.1.7.2 Summary of the neurotoxicity studies

There is no data/information on the neurotoxicity of ethylene oxide via the oral
exposure route. There is sufficient data/information generated by studies using
inhalation exposure to establish that ethylene oxide is a neurotoxin in experimental
animals.

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B.6.8.1.8 Other toxicological data/information
B.6.8.1.8.1 Mode of action

Ethylene oxide is an electrophilic agent that alkylates nucleophilic groups in biologicalmacromolecules, i.e. including DNA and protein (e.g. haemoglobin & albumin). It isconsidered likely that the toxicological effects of ethylene oxide arise primarily fromthe direct alkylation of macromolecules.
Since ethylene oxide is formed during the metabolism of ethylene (a natural body
constituent) both endogenous and exogenous sources of ethylene and ethylene oxide
will contribute to the background alkylation of macromolecules.
(CICADS 54, 2003 & IARC 1994)
B.6.8.1.8.2 Ethylene oxide detected in food stuffs and cosmetics and on medical devicesa)Ethylene oxide was detected in 96 of 204 (47%) samples of food products taken fromretail stores in Denmark in 1995 (Jensen, 1988). The reported concentrations reflect
the total amount of ethylene chlorohydrin and ethylene oxide present at the time ofanalysis. These concentrations ranged from <0.05 to 1800 mg/kg in the individual
samples without correction for recoveries. Ethylene oxide was detected frequently
among 24 samples of spices at a mean concentration of 84 µg/g and a maximum
concentration of 580 µg/g.
(Jensen, 1988/ECHC 2001)b)

Ethylene oxide was detected, but not quantified, in 1 of 2372 samples of eggs and in 1
sample of 3262 samples of fish collected in the United States in 19975 as part of theFood and Drug Administration Monitoring Program (1970-1976).
(Duggan et al, 1983/ECHC 2001)c)

Ethylene oxide may be present as a contaminant of skin care products. Current
commercial preparations of polyglycol ethers may contain residues of ethylene
monomer up to approximately 1 µg/g.
(Filser et al, 1994/ECHC 2001)d)Ethylene oxide monomer in skin care products have been reported at 1.9 to 34
nmol/cm3 (0.08 to 1.5 mg/l) and a range of maximum skin penetration of ethyleneoxide of 1-14% in various product formulations.
(Kreuzer, 1992/ECHC 2001)e)

Ethylene oxide may be absorbed by medical equipment during sterilization and may
remain there as unchanged compound or as one of its reaction products (WHO, 1985).
Studies show that residual concentrations of ethylene oxide in medical equipment
immediately following their sterilization have ranged up to 1 or 2%. These
concentrations generally declined rapidly after a few days aeration, although levels
exceeding 100 ppm (183 mg/m3) were sometimes measured following aeration.
(Gillespie et al, 1979 & 1980/ECHC 2001)43

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B.6.8.1.9 Human data/information
B.6.8.1.9.1 Absorption, distribution, metabolism and excretiona)Ethylene oxide is very soluble in blood and readily taken up by the lungs;
approximately 20-25% of inhaled ethylene oxide reaching the alveolar space is exhaled
as unchanged compound and 75-80% is taken up by the body and metabolised. The
half-life in the body has been estimated to be less than 1 hour.
(Brugnone et al, 1986; 1988; Filser et al, 1992/IARC 1994)b)

Pharmacokinetic data obtained form experimental animals to calculate the internal
dose of ethylene oxide in man obtained from daily exposure. For a man exposed for 8hours to ethylene oxide at 1 ppm (1.8 µg/litre), the area under the concentration-time
curve in blood plasma was estimated to be 18.8 µg/hour/ml on the basis of data for rats
and 14.3 µg/hour/ml on the basis of dog data.
(Beliles and Parker, 1987/IARC 1994)c)

The blood concentrations of ethylene glycol were in sterilisation personnel exposed toethylene oxide. The mean concentrations of ethylene glycol in blood in exposed
worker (90 mg/litre) were twice that in unexposed workers (45 mg/ml).
(Wolfs et al, 1983; Brown et al, 1996 & Other workers/IARC 1994)d)

The concentration of thioesters excreted in urine collected from sterilisation workers at
the end of sterilisation processes was twice that in non-smoking personnel.
(Burgaz et al, 1992/IARC 1994)e)

In vitro investigations suggest that the human population can be divided into
conjugators (75%) and non-conjugators (25%) based on enzymic conjugation of
ethylene oxide with glutathione in erythrocytes.
(Hallier et al, 1993/IARC 1994)44

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008f)Ethylene oxide is an electrophilic agent that alkylates nucleophilic groups in biologicalmacromolecules, e.g. DNA and haemoglobin. There are numerous published studies
that have investigated the formation nitrogen adducts (hydroxethyl adducts of valine,
cysteine and histidine) in the haemoglobin of workers occupationally exposed toethylene oxide. Ethylene oxide binding to DNA primarily results in the formation 7(2-hydroxethyl) guanine adducts but other adducts have been identified at lower levels.
DNA extracted from lymphocytes of unexposed individuals had mean backgroundlevels of 7-(2-hydroxethyl) guanine that ranged between 2-8.5 pmol/mg DNA. It has
been reported that human tissue contains 10- to 15-fold higher levels of endogenous 7(2-hydroxethyl) guanine adducts than rodents.
(Bolt, 1996; Bolt et al, 1997; Wu et al, 1999a/CICADS 2003)g)

Ethylene oxide is metabolised by hydrolysis to ethylene glycol and conjugation withglutathione (both are considered to be detoxification pathways). The hydrolysis
pathway predominates in larger species such as the rabbit and dog while theconjugation pathway predominates in rodents. A physiologically based
pharmacokinetic (PBPK) model for the dosimetry of inhaled ethylene oxide has
calculated that 80%, 60% and 20% would be metabolized via glutathione conjugationin mice, rats and humans, respectively. This appears to be consistent with the levels of
glutathione S-transferase enzyme (GSTT1) activity (mice>rats>humans); ethyleneoxide is a substrate for the human GSTT1 enzyme. Higher levels of haemoglobin
adducts have been reported in exposed individuals (workers and smokers) with the
GSTT1 ‘null genotype’ (homozygous deletion of the GSTT1 gene) than among thosewith a GSTT1 ‘positive genotype’ (at least one copy of the GSTT1 gene).
(Yong et al, 2001; Fennell and Brown, 2001; Pemble et al, 1994/CICADS 2003)h)Reports on two PBPK models for ethylene oxide in rodents and humans indicate that
ethylene oxide is a direct acting alkylating agent in humans and rodents via the samemode of action (i.e. the quantitative differences between humans and rodents result
from differences in basic physiology rather than mode of action).
(Csandy et al, 2000; Fennel and Brown 2001; Pemble et al, 1994/CICADS 2003)

B.6.8.1.9.2 Acute toxicity, skin and eye irritation and sensitisationa)Five sterilizer operators were exposed accidentally to ethylene oxide at concentrations
high enough to be smelt (odour threshold 1280 mg/m3) for periods up to 0.5 hours.
Two operators suffered headache and diarrhoea which resolved after about 70 hours.
Three operators suffered irritation of the eyes and throat, mouth dryness, pruritus,
headache, vertigo, myasthenia, indigestion and haemolysis which had resolved within
21 days of the exposure. Haemolysis diagnosed on days 9-11 lasted until day 16.
(Deleixhe et al, 1986/IARC 1994)b)Acute effects on the nervous system in nearly all inhalation cases were marked bynausea, recurrent vomiting, and headache. Less frequently reported effects included
decreased consciousness (one case of coma), excitement, sleeplessness, muscular
weakness, diarrhoea, and abdominal discomfort.
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(Capellini and Ghezzi, 1965 and Other workers/WHO, 1985)c)Accidental skin exposure to a 1% aqueous solution, from the waist down, was reported
to result in effects on the nervous system (nausea and repeated vomiting).
(Sexton and Henson, 1949/WHO 1985)d)Burns on the hands were attributed to gloves containing residual traces of ethyleneoxide used for sterilization. Mild skin irritation has been reported after exposure to 1%
aqueous solutions of ethylene oxide. Dermal irritation is characterised by erythema,
oedema and the formation of vesicles and has been observed after contact with
ethylene oxide-sterilized materials and clothing.
(Fisher, 1988/IARC 1994)

e)Skin and eye irritation in sterilizer operators were associated with exposures toethylene oxide at concentrations up to 19.6 mg/m3.
(Bryant et al, 1989/IARC 1994)

f)

Exposure to ethylene oxide can cause irritation of the mucous membranes of therespiratory passages.
(Thiess, 1963/ECHC 2001)g)

Ethylene oxide is a sensitising agent. Type I (mild to severe anaphylactic reactions)and Type IV (contact dermatitis) hypersensitivity reactions have been observed inpatients who received dialysis treatment with equipment that had been sterilized with
ethylene oxide.
(Bommer and Ritz, 1987/IARC)h)Severe respiratory problems due to inflammatory reactions in the trachea and larynx
were reported inpatients who had received endotracheal intubation with tubes sterilisedwith ethylene oxide.
(Mantz et al, 1972 and Other workers/WHO 1985)

B.6.8.1.9.3 Genetic effects

Numerous studies have shown that ethylene oxide induces chromosome aberrations,micronuclei and sister chromatid exchanges in humans and the extent of the damage isrelated to the level and duration of exposure.
a)Increased incidences of sister chromatid exchange have been reported in peripheral
blood lymphocytes of hospital sterilisation workers exposed to 1 ppm ethylene oxide(8 hour TWA) and concentrations between 0.5-25 ppm for various durations.
(Yager at al, 1983; Stolly et al, 1984; Tates et al, 1991a/IARC 1994)b)

Increased incidences of chromosome aberrations have been reported in lymphocytes ofsterilisation workers. It has been stated that ethylene oxide exposures above 9 mg/m3
are required to induce chromosome aberrations.
(Galloway at al, 1986/IARC 1994)46

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008c)Increased incidences of micronuclei have been reported in factory workers, i.e. inlymphocytes at concentrations of 25-720 9 mg/m3, in erythroblasts and polychromaticerythrocytes in bone marrow samples at a concentration of 1 ppm for 0.5 to 8 years andin exfoliated nasal mucosa cells following accidental exposures.
(Tates at al, 1991a; Hodstedt et al, 1983; Sarto et al, 1990/IARC 1994)d)

Mutations at the HPRT locus in circulating lymphocytes of factory workers have beenreported in one study.
(Tates at al, 1991b/IARC 1994)
B.6.8.1.9.4 Neurological effectsa)Several studies in sterilizer operators have associated ethylene exposure withsymptoms of peripheral and central neurotoxicity. In cases of peripheral neuropathy,
the symptoms included numbness in feet and fingers, muscular weakness in the lower
limbs, a reduction in sural nerve velocity, nerve fibre degeneration, and demyelination.
Central nervous system effects were implied on the basis of personality dysfunction
and cognitive impairment.
(Schroder et al, 1985 and Other workers/IARC)b)

Because of a leaking sterilizer, 4 young men were exposed intermittently, for 2-8
weeks, to ethylene oxide at levels of approximately 1000 mg/m3. Three of the men
developed a reversible peripheral neuropathy showing abnormal nerve conduction and,in 2 cases, headache, weakness and decreased reflexes in the extremities,
incoordination, and a wide-based gait. The fourth man developed a reversible acuteencephalopathy with headache, nausea, vomiting, lethargy, recurrent motor seizures,agitation and a diffusely slow electroencephalogram. Following this, 6 more cases
were reported concerning sterilizer operators, suffering from reversible peripheral
neuropathy following ethylene oxide exposure for 0.5-1.5 years.
(Gross et al, 1979/WHO 1985)c)Three people exhibited subacute polyneuropathy with bilateral foot-drop, slowing of
nerve conduction velocity and enervation potential on electromyography as the main
findings. All 3 people had noticed the smell of ethylene oxide regularly at work while
2 persons experienced eye irritation.
(Finelli et al, 1983/WHO 1985)d)

Polyneuropathy was also reported in 3 sterilizer operators. Two of these cases were
described in detail. Sural nerve biopsies revealed axonal degeneration with mild
changes in the myelin sheath and unmyelinated fibres were also involved. Muscle
biopsies showed typical denervation atrophy.
(Kuzuhara et al, 1983/WHO 1985)47

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

B.6.8.1.9.5 Reproductive effectsa)

The rate of spontaneous abortions was significantly higher (P<0.05) in Finish hospital
workers associated with ethylene oxide exposure (20.4%) than in controls (11.3%).
Randomly selected Californian dental assistants (aged 18-39) examined for theoccurrence of spontaneous abortion and pre- (27-37 weeks) and post-term births (≥ 42
weeks) in relation to ethylene oxide exposure. Ethylene exposed women were statedto be 2.7 times more likely to have any of the three adverse effects after adjusting forage.
(Hemminki et al, 1982; Rowland et al, 1996/CICADS 2003)b)

One paper reported an increased risk of spontaneous abortion in Finish women whose
partners had been exposed to ethylene oxide. Paternal exposure was based upon the
job and industry in which the men were employed (no quantitative exposure data).
The number of spontaneous abortions (n=3) and pregnancies (n=10) in the paternalgroup was small and confounding factors, such as previous abortions, alcohol andtobacco consumption were not considered in the analysis.
(Lindbolm et al, 1991/CICADS 2003)

B.6.8.1.9.6 Occupational exposurea)

The health status of 37 male operators from an ethylene oxide-producing plant in the
USA during the period 1953-62 was compared with that of age-matched operatorsfrom other production units. The average employment period was 11 years for
exposed workers and 12 years for controls. The usual average exposure level was
between 9 and 18 mg/m3 with occasional peaks up to 230 mg/m3 for one particular job(collecting a sample of the product). According to the medical records, the health ofthe exposed workers was somewhat better than that of the controls. A physicalexamination and extensive clinical tests did not reveal any exposure-related effects
with the exception of a slightly increased white blood cell count.
(Joyner, 1964/WHO 1985)b)

Chromosomal damage was found in a group of 12 workers from a hospital sterilization
facility in the USA. The maximum exposure concentration measured duringsterilization was 65 mg/m3. Another group of 12 persons, who worked in the adjacent
operating room area, volunteered as representatives of an unexposed or accidentally
exposed group. To ensure adequate control throughout the study, unexposedlaboratory staff members served as a third group. Frequently-reported subjective
complaints indicated irritation of the mouth, throat, and eyes, and effects on the
nervous system, such as headache, nausea, speech difficulty, memory loss, dizzinessand incoordination.
(Garry et al., 1979/WHO 1985)c)

In Belgium, a group of 18 workers, using or distributing the sterilant ethylene oxide,
were compared with a well-matched control group by means of a questionnaire, and byanalyses for urinary retinol-binding protein and albumin, beta-microglobulin, andchromosomal damage in lymphocytes. The overall mean exposure level was 7.6
mg/m3 and the time-weighted average exposure, over a working day, ranged between
0.2 and 95 mg/m3. A significant increase in the incidence of sleeplessness and leg
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cramps was recorded, but not irritation or allergy. These studies did not reveal any
abnormalities with the exception of an increase in sister chromatid exchanges inlymphocytes.
(Wolfs et al, 1983; Laurent et al, 1984/WHO, 1985)d)

In a plant in Bulgaria, 196 workers engaged in the production of ethylene and ethyleneoxides were examined. About 73% of all concentrations of ethylene oxide measured
were 1 mg/m3 or less while 27% were between 1 mg/m3 and 3.5 mg/m3. Significant
increases were found in deviations of the autonomous nervous system and in neurosislike manifestations, especially in female workers but woman may be more prone toneuroses. Because of a mixed exposure was difficult to evaluate the findings.
(Spasovski et al, 1980/WHO, 1985)e)

Haematological changes were reported in a group of 27 workers in an ethylene oxide
manufacturing and processing plant, in Sweden, in 1967. The exposure period varied
from 2 to 20 years, the average length being 15 years. Controls worked with ethyleneoxide in other departments where no leakages were likely. No exposure data werereported. When 2 cases of anaemia were excluded, there was still a significantly
decreased haemoglobin value in exposed workers. There was a 30% increase in thenumber of lymphocytes, and one case of chronic lymphatic leukaemia was noted in the
exposed workers.
(Ehrenberg & Hallstrom, 1967/WHO, 1985)f)

In the Federal Republic of Germany, 279 employees from 8 plants in which alkene
oxides were produced or processed, were examined for morbidity during 1978. They
were employed for an average of 10.8 years. Of these workers, 21 had been involvedin accidents with ethylene oxide. Taking into account age and length of exposure, they
were compared with groups of industrial and clerical workers within the same
company. No abnormalities were found that could be related to ethylene oxide or
propylene oxide. Lymphocytosis and increases in haemoglobin and erythrocyte
volume were attributed to age or smoking. The exposure concentrations were notreported. The workers were also exposed to many other chemicals, some of which
may be carcinogenic for man.
(Stoker & Thiess, 1979/WHO, 1985)g)

Haematological effects were observed among a group of 59 women exposed toethylene oxide released from sterilizers while employed in nine hospitals in the USA
and one hospital in Mexico. Compared with unexposed controls, US workers (exposed
to a mean 8-hour TWA exposure of 0.31 mg/m3 with a range of 0.24-0.55 mg/m3)
exhibited a statistically significant increase in the percentage of lymphocytes and areduction in the percentage of neutrophils in the blood). No statistically significant
effects were found in Mexican workers.
(Schulte et al, 1995/CICADS 2003)h)Haematological effects were not observed in a group of 84 male workers involved in
the manufacture of ethylene oxide and exposed to estimated concentrations of <1.83
mg/m3.
(Currier et al, 1984/CICADS 2003)
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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008i)

Haematological effects were not observed in a group of 36 male workers involved in
the manufacture of ethylene oxide with estimated 8-hour TWA exposures below 0.09
mg/m3.
(van Sittert et al, 1985/CICADS 2003)j)

A study in 46 Israeli hospital workers exposed (at three locations with a mean periodof employment of 6.6 years) to 145- to 210 minutes TWA concentrations of <0.02-0.1
mg/m3 found statistically significant haematological effects compared to 88 nonoccupational exposed controls (matched for age, sex and smoking habits). There wereincreases in the absolute mean numbers of erythrocytes, monocytes and eosinophils,
increases in the haematocrit and reductions in the absolute mean numbers oflymphocytes and platelets.
(Shaham et al, 2000/CICADS 2003)k)Lens opacities and cataracts were assessed in French hospital workers exposed toethylene oxide at concentrations of 0.11 mg/m3 during a 97-minute exposure to 71
mg/m3 during a 2.5 minute exposure. There were no differences between the exposedand control groups in the case of lens opacities. However, cataracts were observed insix exposed people compared to none in the controls (lens opacities have been reported
in monkeys exposed to 100 ppm for up to 24 months).
(Deschamps et al, 1990/CICADS 2003)l)

Following accidental exposure (4 hours/day for 4 days), to concentrations of ethyleneoxide high enough to be smelt, one worker out of five developed persistent nonimmunological asthma, probably induced by extensive epithelial injury which lead
finally to fibrosis (no further information on the outcome).
(Deschamps et al, 1992/IARC 1994)

B.6.8.1.9.7 Case and epidemiological studies

Numerous summaries of case and epidemiological studies are presented in thesubmitted publications (IARC 1994, ECHC 2001 & CICADS 2003).
In epidemiological studies, the most frequently reported association in workers
exposed to ethylene oxide has been with lymphatic and haematopoietic cancer. The
workers studied fell mainly into two groups: i) people using ethylene oxide as asterilant, ii) chemical workers manufacturing (either by the chlorohydrin process ormore recently by the catalytic oxidation of ethylene) or using the compound in otherprocesses. In general, people involved in sterilization are less likely to haveoccupational exposure to other chemicals.

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B.6.8.1.10 Summary and conclusions

Ethylene oxide is an electrophilic agent. It is considered likely that the toxicologicaleffects of ethylene oxide arise primarily from the direct alkylation of macromolecules(e.g. DNA and proteins).
The majority of data for ethylene oxide has been primarily generated using theinhalation exposure route. Only limited data are available for ethylene oxide
administered via the oral route.
Oral exposure
The acute oral LD50 values for ethylene oxide were stated to be 330 mg/kg bw for
male rats and 365 and 280 mg/kg bw for male and female mice, respectively. In a
subacute rat study, the findings included loss of body weight, gastric irritation andslight liver damage. The only long-term rat study (gavage dosing) reported a doserelated increase in the incidence of squamous cell carcinomas in the forestomach at alldose levels tested.
Other routes of exposure (primarily inhalation exposure)
Ethylene oxide is very soluble in blood and the pulmonary absorption is expected to be
rapid and extensive. Excretion is also rapid and occurs mainly via urine while minor
amounts of unchanged parent and labelled carbon dioxide are excreted via the lungs.
Distribution is widespread based on the protein and DNA adducts in various organs
and tissues. Two metabolic pathways have been identified, the hydrolysis of ethyleneoxide to 1,2-ethanediol and conjugation with glutathione to produce S-(2hydroxyethyl)cysteine and N-acetyl- S-(2-hydroxyethyl)cysteine.
Following acute exposure to ethylene oxide, the respiratory system, the nervous systemand the liver and kidneys were identified as target organs. Ethylene oxide is a potent
eye, skin and respiratory irritant and a sensitiser.
In the short-term studies, mortalities and effects on respiratory system, thehaematological system (including bone marrow), the nervous system, ocular lens, liverand kidneys, thymus and spleen and the testes were reported. A dose-related in creasein pulmonary adenoma was also seen in mice after 6 mounts of exposure.
Ethylene oxide is an alkylating agent and is considered to be a mutagen inexperimental animals and humans. It forms DNA adducts and induces gene mutations,chromosome aberrations, cell transformation, unscheduled DNA synthesis, DNA
strand breaks, sister chromatid exchanges, dominant lethal mutations and heritabletranslocations.
The chronic findings in rats included deaths, reduced body weight, inflammatory
lesions of the lungs, nasal cavities, trachea and internal ear and the development of eye
cataracts. There were several reports of haematological changes (including bonemarrow changes) and changes in some serum enzyme activities. Organ weightchanges were also reported. The microscopic findings included lesions in the adrenals

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and atrophy and degeneration of skeletal muscle. No chronic non-neoplastic findings
in mice were reported.
Dose related neoplastic changes were evident in rats and mice following long-term
inhalation exposure. There were significant dose-related increases in several tumour
types of tumours in rats (leukaemia, peritoneal mesotheliomas, brain tumours andsubcutaneous fibroma) and mice (alveolar/bronchiolar carcinoma, malignant
lymphomas of the haematopoietic system, uterine adenocarcinoma and mammary
adenocarcinoma and adenosquamous carcinoma). It is also noteworthy that pituitary
tumours appeared earlier in rats and that an increase in lung tumours was reported inmice after only 6 months of exposure.
Following subcutaneous injections to mice, there was a dose-related increased
incidence of sarcomas at the injection sites. No skin tumours (or skin irritation) were
found in mice after long-term dermal exposure but it was assumed that ethylene oxide
evaporated rapidly from the skin.
The extensive evidence of genotoxicity (in vitro and in vivo effects) andcarcinogenicity (a variety of tumours in rats and mice and the evidence of the early
appearance of certain tumours in rats and mice) indicates that ethylene oxide is apotent genotoxic carcinogen in experimental animals.
In the rat multigeneration study, there were reductions in the number of pups per
litter, the number of implantation sites per female and the number of foetuses born per
implantation site and an increase in the length of the gestation period. An increase inresorptions per litter and per implantation site were also noted in the rat
developmental study together with reduced foetal weight and length and reduced
ossification of sternebrae and skull was observed. In mice, there is clear evidence ofteratogenic activity (severe skeletal malformations) after intravenous injections andevidence that mutagens can induce foetal malformations and death when administeredaround the time of fertilisation. Effects on sperm and reproductive tissues have beenreported in rats and monkeys. There are sufficient data/information to establish that
ethylene oxide is a reproductive toxin that affects fertility and development inexperimental animals (some effects are evident in the absence of maternal toxicity).
There are numerous reports of adverse neurotoxicity in a range of experimental
animals that include effects on reflexes, reduced locomotor activity, ataxia, limb
paralysis, muscle atrophy, axonal degeneration in the limbs and histological alterationsof the medulla oblongata of primates.
The data base for ethylene oxide in rodents and humans indicate that ethylene oxide isa direct acting alkylating agent in humans and rodents via the same mode of action (i.e.
the quantitative differences between humans and rodents result from differences inbasic physiology rather than mode of action).
There are numerous reports of ethylene oxide-induced effects in humans/workers andinclude irritation of the eyes, skin and throat, mouth dryness, pruritus, headache,vomiting, vertigo, myasthenia, indigestion, diarrhoea and haemolysis. Less frequently
reported effects included decreased consciousness (one case of coma), excitement,
sleeplessness, muscular weakness, diarrhoea, and abdominal discomfort. Ethylene
52Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

oxide is also a sensitising agent and induces Type I (mild to severe anaphylactic
reactions) and Type IV (contact dermatitis) hypersensitivity reactions andinflammatory reactions in the trachea and larynx.
Occupational exposures to ethylene oxide have resulted in reports of a wide range ofserious adverse effects that include haematological effects, a possible increase inocular lens cataracts, symptoms of peripheral and central neurotoxicity, increases inchromosome aberrations, micronuclei and sister chromatid exchanges and spontaneousabortions. In addition, ethylene oxide exposure of workers has frequently been
associated with lymphatic and haematopoietic cancer.
In 1994, IARC concluded that there was limited evidence in humans for the
carcinogenicity but there was sufficient evidence in experimental animals for the
carcinogenicity of ethylene oxide. The overall conclusion of IARC 1994 was that
ethylene oxide is carcinogenic to humans (Group 1) when the following evidence wastaken into consideration.
Ethylene oxide is a directly acting alkylating agent that:i) persistently induces dose-related increases in the frequency of chromosome
aberrations and sister chromatid exchange in lymphocytes and micronuclei in bonemarrow cells of workers;ii) has been associated with malignancies of the lymphatic and haematopoietic system
in humans and experimental animals;iii) induces dose-related increases in the frequency of haemoglobin adducts in humans
and dose related increases in the number of adducts in DNA and haemoglobin in
exposed rodents;iv) induces gene mutations and heritable translocations in germ cells in exposedrodents;v) is a powerful mutagen and clastogen at all phylogenetic levels.
B.6.8.2

Adduct formation in experimental animalsa)

The ethylene metabolite, ethylene oxide, reacts with nucleophilic centres in protein andDNA. The haemoglobin adducts N-(2-hydroxyethyl)histidine and N-(2hydroxyethyl)valine have been used as internal dose monitors for the formation of
ethylene oxide from ethylene. In male CBA mice, it has been reported that 7-8% of
inhaled ethylene is metabolised to ethylene oxide. These mice were exposed toethylene at concentrations below 23 mg/m3 (20 ppm) at which first-order kinetics ofmetabolism can be assumed. The value is equal to the alveolar retention of ethylene atsteady state and is similar to the values calculated for rats and humans. The levels of
the haemoglobin-hydroxyethyl valine adduct was determined in Fischer rats andSyrian hamsters exposed for six months to gasoline and diesel exhausts. In hamsters,
the levels of haemoglobin-hydroxyethyl valine adduct increased almost linearly withdose. At the highest dose, the levels were similar in male rats and hamsters and in53

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

female rats and hamsters. The values were about 50-90% of those predicted from dataon mice and indicated that ethylene behaves similarly in these species.
(Ehrenberg et al, 1977; Segerback, 1983/IARC 1994)b)

Ethylene oxide is present in cigarette smoke and smokers have higher haemoglobin
adduct levels (average of 170 pmol/g of globin) than non-smokers (average of 20 pmol/gof globin). The adduct levels in non-smokers indicate widespread backgroundexposures. Ethylene formed endogenously may contribute to this background. The
highest adduct levels have been found in ethylene production workers (up to 16000
pmol/g of globin). Patients treated with cytostatic drugs that transfer hydroxyethylgroups also show elevated adduct levels (e.g. 330 pmol/g of globin for nimustine achloroethyl nitroso urea derivative). Based on the hydroxyethyl valine adduct levels for
smokers (10 cigarettes/day; 120 pmol/g of globin), non-smokers (50 pmol/g of globin)and steriliser operators (0.2-8.5 ppm; median value of 16.2 pmol/g of globin with arange of 5.2-32.7 pmol/g of globin) were reported.
(B-G-G 2003)
B.6.8.3 Human data (Ethylene exposure)B.6.8.3.1 Volunteer studies (ADME)a)

The inhalation pharmacokinetics of ethylene was investigated in human volunteers at
atmospheric concentrations of up to 50 ppm (0.1575 mg/l) by gas uptake in humanvolunteers in a closed spirometer system. The uptake, exhalation and metabolism, canbe described by first-order kinetics. Uptake of ethylene into the body was low.
Clearance due to uptake, which reflected the transfer rate of ethylene from theatmosphere into the body, was 25 litres per hour for a man of 70 kg. This value
represented only 5.6% of the experimentally obtained alveolar ventilation rate of 150
litres per hour. The majority (94.4%) of ethylene inhaled into the lungs was exhaled
again without becoming systemically available via the blood stream.
Maximal accumulation of ethylene in the same man, determined as the thermodynamic
partition coefficient whole body:air was 0.53. The concentration ratio at steady state
was even smaller (0.33), owing to metabolic elimination. Clearance due tometabolism, in relation to the concentration in the atmosphere, was calculated to be
9.3 litres per hour for a man of 70 kg. This indicates that at steady state about 36% ofsystematically available ethylene was eliminated metabolically and 64% waseliminated by exhalation as the unchanged substance, as could be calculated from thevalues of clearance of uptake and of clearance of metabolism. The biological half-life
was 0.65 hr. The alveolar retention of ethylene at steady state was calculated to be 23%. From theoretical considerations of the lung uptake of gases and vapours, it could
be deduced that the low uptake rate of ethylene was due to its low solubility in blood(Ostwald`s solubility coefficient for human blood at 37°C: 0.15). This summary statedthat ethylene gives rise to minute levels of ethylene oxide and that the maximum
conversion of ethylene to ethylene oxide in humans was estimated to be 4 %.
(Filser et al, 1992/OECD:SIDS)

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B.6.8.3.2 Occupational exposurea)Personal and stationary monitoring of ethylene in a company where this gas was used
for controlling the ripening of bananas showed air concentrations to be in the range of0.02-3.85 mg/m3 (0.02-3.35 ppm) with an estimated average concentration of 0.35
mg/m3 (0.3 ppm).
(Tornqvist et al , 1989a/IARC)b)

Exposure to fire-fighters during the ‘knockdown’ phase of a fire showed aconcentration of 53 mg/m3 (46 ppm) ethylene; none was detected during the ‘overhaul,
phase. In laboratory studies, ethylene has been detected as a thermal degradation
product of polyethylene and polypropylene.
(Hoff et al, 1982; Jankovic et al, 1991/IARC)c)

In a preliminary study, the miscarriage rate (6/15 pregnancies) in Swedish workers infive local petrochemical plants was higher than 1549 woman from outside the industry.
Ethylene was the main product in four 4/5 of the petrochemical plants. No data were
provided on occupational levels but measurements made in areas surrounding theplants indicated that ethylene was present in concentrations up to 10-fold higher thatthe other main pollutants (propylene, ethane, propane and phenol).
(Axelsson and Molin, 1988/BIBRA Toxicity Profile 1993)d)

A brief abstract notes that there was a higher than expected rate of miscarriage andgynaecological disease among female operatives of a polyethylene plant who were
exposed to ethylene concentrations in the range of about 40-60 ppm and high levels ofnoise.
(Yakubova et al, 1976/BIBRA Toxicity Profile 1993)
B.6.8.3.3 Environmental exposurea)Ethylene concentrations in ambient air and remote rural sites worldwide are generally
in the range of <1-5 µg/m3. In urban and indoor air contaminated with combustion
products, ethylene concentrations range up to 1000 µg/m3.
(Seinfeld, 1989; Colbeck & Harrison, 1985; Sawada & Totsuka, 1986/IARC)b)

Vehicle exhaust emissions make a significant contribution to urban air concentrationsof ethylene. Several authors have monitored traffic emissions which ranged from 93212 mg/km and 9.8-405 5 µg/m3 depending on the site sampled (e.g. urban intersection
or tunnel).
(Bailey et al, 1990a & b; Barrefors & Petersson, 1992/IARC)c)

Smoking is also a significant source of exposure to ethylene (1-2 mg ethylene arereleased per cigarette). The exposure of the average smoker is roughly 10 times thatfrom urban air pollution. In two studies, the ethylene levels in tavern air were 56 and110 µg/m3 while the corresponding outdoor air concentrations at the time were 16 and12 µg/m3.
(Person et al, 1988; Lofroth et al, 1989/IARC)

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Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008d)Plants that normally produce ethylene at 0.6-6 µg/kg fresh weight per hour may
produce up to 120 µg/kg per hour during ripening of fruits and during senescence andloss of leaves.
(Dorffling, 1982; Tille et al 1985/IARC).
B.6.8.3.4 Endogenous formation
Endogenous production of ethylene can be deduced from its exhalation by unexposed
subjects. For a man of 70 kg, a mean production rate of 32 nmol/hour (0.9 µg/hour)
and a corresponding mean body burden of 0.011 nl/ml tissue [equivalent to 0.44
nmol/kg bw or 0.012 µg/kg bw] was calculated for ethylene gas. The amount of
ethylene in the breath of women is increased significantly at the time of ovulation. No
difference was observed in the basal ethylene outputs of non-pregnant and pregnant
women and of men.
(Filser et al, 1992; Harrison, 1981/IARC)
B.6.8.3.5 Adduct formationa)

The haemoglobin adducts N-(2-hydroxyethyl)histidine and N-(2-hydroxyethyl)valine
have been used as internal dose monitors for the formation of ethylene oxide fromethylene in humans. Higher levels of adducts were found in cigarette smokers than in
non-smokers and ethylene and ethylene oxide were considered to be major causes ofthe elevated adduct levels.
(Tornqvist et al, 1986b & 1989a/IARC 1994)b)

Non-smoking fruit store workers exposed occupationally to atmospheric ethylene at
0.023-3.85 mg/m3 (0.02-3.35 ppm) while ripening bananas had levels of 22-65 pmol/g
haemoglobin-(hydroxyethyl valine) whereas non-smoking controls had 12-27 pmol/g
haemoglobin-(hydroxyethyl valine). On the basis of a mean exposure concentration of
0.345 mg/m3 (0.3 ppm), it was estimated that about 3% (range 1-10%) of inhaled
ethylene as metabolized to ethylene oxide. This percentage is in agreement with thealveolar retention at steady state calculated from pharmacokenitics. An increment of
100-120 pmol/g haemoglobin-(hydroxyethyl valine) was estimated for a time-weighted
average exposure (40 hours/week) to 1.15 mg/m3 (1 ppm) ethylene. On the basis of
the relationship between haemoglobin-(hydroxyethyl valine) levels and exposurelevels of ethylene and ethylene oxide, the amount of ethylene metabolised to ethyleneoxide can be calculated; 1 mg ethylene/kg bw is equivalent to a tissue dose of ethyleneoxide of 0.7 x 10-6 mol x h/l (0.03 mg x h/kg bw). This value is in agreement with thevalue of 0.5 x 10-6 mol x h/l that can be calculated from the pharmacokinetic data for
ethylene and ethylene oxide published by Filser et al, 1992.
(Tornqvist et al, 1988 & 1989a; Kautiainen & Tornqvist, 1991; Filser et al, 1992/IARC 1994)

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The following tabulated exposure data was presented in an article reviewing thecurrent position with respect to some biomarkers and volatile organic chemicals(mainly 1,3-butadiene).

Table B.6.5 Haemoglobin adduct levels (N-terminal hydroxyethyl valine) in smokers and nonsmokers and in subjects with occupational exposure.
aControls

Exposure groups
Exposure
concentration
Ethylene (pmol/g globulin)
Occupational
0.3 (0.1-1) ppm

Type of exposureb

Non-smokers
20 (12-27)
Non-smokers
16.1 ± 2.1
Non smokers
63 ± 2.1

Adduct level(average, range)
43 (22-65)

Tobacco smoking

1-25 cigarettes/day

146 (50-335)

Tobacco smoking>15 cigarettes/day

Maternal blood
361 ± 105
New born babies
blood)
147 ± 105

Newborn babies blood
42 ± 18

Ethylene oxide (pmol/g globulin)
14-26
Occupational
Low: 28 ppm/week
84-2070
Key a) Background levels (average, range or mean ± SD). b) See B.6.8.3.5 b above.

The accumulation of stable haemoglobin adducts during prolonged exposure is the resultof daily increments to the adduct level and daily losses due to the removal of the oldest
fraction of the erythrocytes from the circulation. After exposure for a period of timeexceeding 126 days in humans, a steady-state adduct level is attained. Thus, themeasurement of stable adducts gives information on exposure during the months before
blood sampling. Tates et al (1995) studied hydroxyethylvaline adducts in haemoglobinof four workers accidentally exposed to high concentrations of ethylene oxide. The
adduct levels decreased linearly over time and reached background levels after
approximately 110 days. Contrary to protein adducts, DNA adducts are subjected to
repair and their stability varies considerably between cell type. In the absence of
information on adduct stability, DNA adduct measurements give only qualitative
information on exposure.
(http://www.ehponline.org/members/1996/Suppl-5/osterman-golkar-full.html)

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B.6.8.3.6 Residue data for ethylene and its metabolites in potatoesa)Endogenous concentrations of ethylene range between 0.0007-0.15 ppm for nonsprouting potato tubers and 0.1-3ppm for sprouted tubers. It was also stated that
ethylene and its potential metabolites were not identified in treated potatoes at levels
exceeding those found in control potatoes. Residue data for potatoes treated with 4
ppm ethylene for 150 days of storage. The residues, chloroethanol, dichloroethane,bromoethanol, ethylene oxide and ethylene glycol (including its glucoside) residues
were in total less than 0.1 ppm. Residues of ethylene oxide were stated to be <2 ppm(the lower limit of quantitation of the analytical method employed). In addition, theprocessing or cooking of tubers is expected to result in a reduction of volatile residues(e.g. ethylene oxide) by up to 90% (no actual data included in the report).
(HC 2001)b)

The internal levels of dissolved and absorbed ethylene in Anjou pears during ripening
have been determined. No exogenous ethylene was applied in order to establish theendogenous level in the natural ripening process. In pears, the reported internal ethylene
concentrations ranged from 0.02-44.66 µl/l.
(Wang and Mellenthin, 1972)

B.6.9

Medical data and information (IIA 5.9)

The following medical data and information for ethylene was provided. The
data/information in this section has not been assessed by the RMS.
B.6.9.1

Medical surveillance of manufacturing plant personnel (AII 5.9.1)

Personal and stationary monitoring of ethylene in a company where ethylene was used
for controlling the ripening of bananas showed air concentrations to be in the range of0.02 - 3.35 ppm (0.02 - 3.85mg/m3). In a study on exposure of firefighters, samples
taken during the “knockdown” phase of a fire showed a concentration of 46 ppm (53mg/m3) ethylene. A study was carried out among workers at a Swedish petrochemicalplant in order to assess the amounts and effects of ethylene exposure. The study was
carried out in two parts, part one in 1989 and part two in 1993. Eight workers exposed
to high levels of ethylene (4 mg/m3) and 3 workers exposed to lower levels (0.1 - 0.3
mg/m3) were compared to nine controls exposed to 0.01 mg/m3. All exposed workers
showed elevated levels of haemoglobin adducts and adduct formation was doserelated. The results indicated that about 1% of the inhaled ethylene was metabolized toethylene oxide. Part two of the study, which included four workers, was designed tomore accurately determine exposure level, which had a mean of 4.5 mg/m3. The
results confirmed part one, showing that about 1% of inhaled ethylene was metabolised
to ethylene oxide and the maximum fraction to be converted was estimated to be 4%.
There have been two preliminary but independent reports of increased miscarriage
rates among women working in the petrochemical industry. Elevated ethylene
concentrations were mentioned as a possible reason, but this has not been confirmed.
No firm conclusions can be drawn from these reports. A preliminary study found noincrease in lung cancer incidence in 31 workers exposed to ethylene (at unspecified
levels) at a US petrochemical factory. However, due to the limited number of exposed
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drawn. A study of workers at an US petrochemical plant found that an increased riskof developing brain cancer was associated with exposure to (unspecified levels of) a
number of chemicals including ethylene. However, the investigators wereunconvinced that the association reflected a causal relationship (OECD SIDS).
According to Toxnet (Databases in toxicology and environmental health) HSDB, 2003,
it is estimated that 12,280 workers are potentially exposed to ethylene in the U.S.A.
B.6.9.2

Clinical cases and poisoning incidents (IIA 5.9.2)

Symptoms: dizziness, headache, nausea, and loss of co-coordination.
The following are clinical effects of acute exposure to ethylene, reported in the OECDSIDS assessment profile for ethylene:
ACUTE EXPOSURE: Simple asphyxiants displace oxygen from the breathingatmosphere primarily in enclosed spaces and result in hypoxia. Four stages aredescribed, depending on the arterial oxygen saturation:1) INDIFFERENT STAGE (% O2 Saturation: 90%):
Night vision: decreased
2) COMPENSATORY STAGE (% O2 Saturation: 82 to 90%)
1
2.
3.
4.
5.

Respiratory rate: compensatory increase
Pulse: compensatory increase
Night vision: decreased further
Performance ability: somewhat reduced
Alertness: somewhat reduced

Symptoms may begin in those with significant pre-existing cardiac, pulmonary, or
haematological diseases3) DISTURBANCE STAGE (% O2 Saturation: 64 to 82%)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.

Compensatory mechanisms become inadequate
Air hunger
Fatigue
Tunnel Vision
Dizziness
HeadacheBelligerence
Euphoria
Visual acuity: reduced
Numbness and tingling of extremities
Hyperventilation
Poor judgement
Memory loss
Cyanosis59Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Decreased ability for escape from toxic environment4) CRITICAL STAGE (%O2 Saturation: 60 to 70% or less):
1.
2.
-

Deterioration in judgement and coordination may occur in 3 to 5 minutes or lessTotal incapacitation and unconsciousness follow rapidly
All early effects may decrease ability for self-rescue from the toxic environment.
Some agents causing asphyxia are stored and transported in compressed or liquid
form and can cause frostbite on direct skin contact.

CARDIOVASCULAR EFFECTS
1) An increased pulse rate may occur.
2) Cardiac manifestations of prolonged or severe hypoxia may include atrial or
ventricular dysrhythmias, hypotension, myocardial ischemia, myocardial infarction, andeventual aystole.
3) “Sudden sniffing death”, or cardiac arrest, is reported following intentional inhalationof hydrocarbons.
RESPIRATORY EFFECTS
1) Hyperventilation may develop.
2) Cyanosis may occur.
3) Bronchoconstriction and respiratory depression may be seen.
4) Pulmonary oedema and lung congestion may occur.
NEUROLOGIC EFFECTS
1) Various disturbances including headache, dizziness, mood disturbances, numbness ofthe extremities, sleepiness, mental confusion, poor judgement and coordination, andmemory loss may occur.
2) Prolonged or severe hypoxia results in unconsciousness.
3) Prolonged asphyxia may produce CNS injury.
4) Hemiparesis has been reported with volatile substance abuse.
5) Cerebral oedema with brainstem herniation may occur.
6) Seizures have been reported following intentional inhalation.
GASTROINTESTINAL EFFECTS: Nausea, vomiting, and gastrointestinal
haemorrhage may develop
MUSCULOSKELETAL EFFECTS: Rhabdomyolysis and seizures have been reported.
REPRODUCTIVE HAZARDS: Possible consequence of oxygen deprivation in theunborn is controversial. Cerebral palsy, previously thought to be due to acute hypoxia
during labour and/or childbirth, remains poorly understood.
There are also some acute hazard of dermal and ocular frost burns. Toxnet (Databases intoxicology and environmental health) HSDB, 2003, states that acute dermal exposure
may cause frostbite injury. Severe tissue burns have been reported
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B.6.9.3

Exposure of the general population and epidemiological studies (IIA 5.9.3)

Ethylene is ubiquitous in the environment, arising from both natural and man madesources. Major natural sources are emissions from vegetation of all types, where it
functions as a plant hormone. The main anthropogenic sources are combustion of gas,fuel, coal and biomass. The highest exposure to humans is due to ethylene from car
motors. Ethylene had been in general use as an anaesthetic for many years. It has been
replaced by more modern anaesthetics, mostly due to the high explosion risk. Today,elevated exposure of humans is limited to a low number of workers at ethylene
protection plants, and these involved in transport of ethylene. The total global
emission has been estimated to be 18-45 x 106 t/y, of which approximately 74% isreleased from natural sources and 26% from anthropogenic sources. Emission fromfuel oil combustion is equal to approximately 4% of total global emissions (OECD
SIDS).
In an epidemiological study, following exposure to ethylene, no increase in risk ofdeveloping myelomas was noted.
B.6.9.4

Clinical signs, symptoms of poisoning and details of clinical tests (IIA 5.9.4)

Symptoms included dizziness, headache, nausea, and loss of co-coordination. Pleaserefer to sections B.6.9.2 and B.6.9.3.
B.6.9.5

First aid measures (IIA 5.9.5)

Move the victim to fresh air and call the medical emergencies services. Give artificial
respiration if the victim is not breathing or administer oxygen if breathing is difficult.
Remove and isolate contaminated clothing and shoes. In case of contact with liquefied
gas, thaw frosted parts with lukewarm water. In case of burns, immediately cool
affected skin for as long as possible with cold water. Do not remove clothing if
adhering to the skin. Keep the victim warm and quiet. Ensure that medical personnel
are aware of the material involved and take precautions to protect themselves (USDepartment of Transport, 2004).
Inhalation: Move to fresh air. If not breathing, give artificial respiration. If breathingis difficult, give oxygen. Get medical attention immediately.
Skin Contact: Wash affected area extremely thoroughly with soap and water. Seek
medical attention if irritation persists. Remove all contaminated clothing.
Eye Contact: Rinse immediately with copious amounts of tepid water for at least 15
minutes and obtain medical aid.
Ingestion: Not applicable Ethylene is a gas at normal temperature and pressure.
B.6.9.6

Expected effects and duration of poisoning as a function of the type, level andduration of exposure or ingestion (IIA 5.9.6)

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Under environmental conditions, ethylene is a gas; therefore the most probable route ofhuman exposure is via inhalation. There is no evidence to suggest ethylene is an eyeor skin irritant.
Concentrations of less than 20% ethylene in air (25000 ppm) do not cause harmful
effects and are not irritating to the nose, throat or lungs. High concentrations of
ethylene can displace oxygen in air and cause life-threatening asphyxiation. Whenethylene is used as a compressed gas, high concentrations can be generated quickly if aleak occurs.
The normal oxygen concentration in air is 20.9%. At 15-16% oxygen, symptoms of
sleepiness, fatigue, loss of concentration, errors in judgement and confusion aremasked by a state of euphoria, giving a false sense of security and well-being. An
oxygen concentration of 12% or lower can cause unconsciousness quickly and without
warning. In some cases disturbed respiration, abnormal fatigue. Emotional upsets,
nausea, vomiting and inability to move freely may occur. Concentrations below 6%
can result in respiratory collapse and death. If the victim survives, some or all organs,including the central nervous system and brain, may show damage due to oxygen
deprivation.
Marked memory disturbances have also been reported following exposure to 37.5%(37500 ppm) of ethylene for 15 minutes (this effect may have been due to oxygen
deprivation) (CCOHS, 2000).
Animal toxicity information suggests that ethylene will not cause significant healtheffects following long-term exposure.
B.6.10

Summary of mammalian toxicology and proposed ADI, AOEL, ARfD and MAC(drinking water limit) (IIA 5.10)

No oral ADME studies have been submitted or cited; the available data has been
generated using inhalation exposure. A metabolic pathway has not been proposed for
ethylene in mammals.
Following inhalation of radiolabelled parent, absorption appeared to be rapid (withinminutes) but the systemic uptake from the lungs was low. It has been estimated thatapproximately 83% of the ethylene that reaches the lungs is exhaled unchanged while
17% is absorbed. Distribution is widespread throughout the body. In rats, about 2429% of systemically available ethylene is eliminated by metabolism and the remainder
by exhalation of the unchanged substance. Elimination appears to be rapid. Most of
the inhaled ethylene was exhaled unchanged with smaller amounts excreted in urine
and faeces and as exhaled carbon dioxide. Apart from ethylene oxide and its
metabolites [and the urinary metabolite 5-(2-hydroxyethyl)cysteine in mice], there
appears to be little or no information or investigations into other potential metabolitesof ethylene.
Ethylene is not classifiable via the acute inhalation route according to EC criteria(based on cited data). There are insufficient data to classify ethylene via the acuteoral and dermal routes or for skin and eye irritancy and skin sensitisation using thenormal EC criteria. However, based on industrial use and its use as an anaesthetic,
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ethylene gas dose not appear to be classifiable as a skin or eye irritant or a skinsensitiser. It should be noted that liquefied or pressurized ethylene gas can cause
frostbite damage.
No data were submitted for the oral or dermal routes for short-term exposure (or citedfrom the published literature). The available short term repeat dose inhalation studies
reported effects on blood parameters and the nervous system. A 90-day study did notreport any effects at dose levels up to 11.5 mg/l of air, the highest dose tested (thisstudy may have been conducted by IBT under contract to the CIIT (see comments on
carcinogenicity study).
There was no evidence genotoxicity in the in vitro bacterial and chromosome
aberration assays or the in vivo the bone marrow micronucleus assays in rats or mice.
No long-term studies were submitted for the oral route of exposure (or data cited fromthe published literature). Summaries of a single long-term rat inhalation study areavailable in the literature. Generally, the authors of these summaries have concluded
that there no evidence of chronic toxicity in this study and no evidence of compoundinduced carcinogenicity. However, some authors have expressed doubts over thequality and reporting of the study (conducted by the discredited contract laboratory
IBT), the interpretation of the findings in this study (e.g. mononuclear cell leukaemia)
and their relationship to the toxicological effects induced by the metabolite ethyleneoxide. The background to IBT can be found at section 3.1.8 of
http://www.oecd.org/dataoecd/13/15/36045203.pdf ]. IARC (1994) concluded that theevidence of carcinogenicity in experimental animals and humans was inadequate,
however, several workers have stated that the possible carcinogenic risk from inhaling
ethylene should be reconsidered/re-evaluated based on the potential exposure to
ethylene (very high tonnage), the limited database and the metabolism of ethylene toethylene oxide.
The available reproduction data are limited and the quality is equivocal. A
reproductive screen test concluded there was no compound induced parental or foetal
toxicity or developmental toxicity over a single generation (i.e. up to 4 days post
partum) at concentrations up to 5.75 mg/l or 5000 ppm (approximately equivalent to asystemic exposure of 0.575 mg/l or 500 ppm). However, some published data (ofunknown quality) appears to indicate that post-natal development could be adversely
affected at a dose level of 2.62 ppm.
No specific neurotoxicity studies have been submitted for evaluation but there aresome indications of treatment-related effects on the nervous system.
Ethylene is metabolised to ethylene oxide in experimental animals. Two metabolic
pathways have been identified in experimental animals and humans, the hydrolysis of
ethylene oxide to 1,2-ethanediol and conjugation with glutathione to produce S-(2hydroxyethyl)cysteine and N-acetyl- S-(2-hydroxyethyl)cysteine (Fig B.6.3). Since
ethylene oxide can react with chloride ions, and this reaction is acid catalysed, 2chloroethanol might be expected to be a metabolite, especially after oral
administration.

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Ethylene oxide is currently classified by the ECB as a Cat: 2 for carcinogenicity (R45)
and Cat: 2 for mutagenicity (R46). In addition, the literature indicates that ethyleneoxide induces reproductive effects in experimental animals (foetal toxicity in thepresence and absence of maternal toxicity, teratogenicity in mice, sperm effects) andthere is some limited evidence of spontaneous abortions in humans. Ethylene oxide
has also been associated with neurotoxicity and cataracts in the ocular lens. It is also
currently classified by the ECB as Toxic by inhalation (R23) and as an irritant(R36/37/38) and the literature also indicates that it can also induce sensitisation
responses. Chloroethanol, a possible reaction product with chloride in food, is also
currently classified by the ECB as a Cat:2 carcinogen.
Ethylene oxide is an electrophilic agent that alkylates nucleophilic groups in biologicalmacromolecules, i.e. including DNA and protein (e.g. haemoglobin & albumin). It isconsidered likely that the toxicological effects of ethylene oxide arise primarily fromthe direct alkylation of macromolecules. Since ethylene oxide is formed during themetabolism of ethylene (a natural body constituent) both endogenous and exogenous
sources of ethylene and ethylene oxide will contribute to the background alkylation ofmacromolecules. There is extensive evidence of genotoxicity (in vitro and in vivo
effects) and carcinogenicity indicating that ethylene oxide is a potent genotoxic
carcinogen in experimental animals (via oral and inhalation routes).
Endogenous, environmental and man-made sources of ethylene exposure are well
documented in the literature. Ethylene is a natural product of many plants and it isreleased into the atmosphere at various stages of their life cycle. Other major sources
contributing to background levels of ethylene are industrial and volcanic emissions,natural gas, the burning of vegetation, smoking cigarettes, the combustion of fossil
fuels (including vehicle exhaust emissions) and in food materials. Endogenous but
unidentified sources of ethylene exist in man and experimental animals.
Although ethylene is classified as a “simple asphyxiant” and results in asphyxia due tooxygen displacement in enclosed spaces, the extensive list of adverse effects inhumans (B.6.9) indicates that this is an oversimplification and requires further
consideration. Ethylene is metabolised to ethylene oxide, a known genotoxic
carcinogen, and forms adducts with DNA, haemoglobin and other proteins. The U.S.
Department of Labor (Occupational Safety & Health Administration) web site statesthat the health effects of long-term or repeated exposure to ethylene are not known(www.osha.gov). Occupational exposure has been associated with an increased
incidence of reproductive effects and brain tumours in workers in the petrochemicalindustry but the quality of these epidemiological studies was questioned and it was
concluded that there was no convincing evidence of any causal links. However, nonsmoking fruit store workers exposed occupationally to atmospheric ethylene hadhigher levels of haemoglobin adducts compared to non-smoking controls.
No specific occupation exposure limits have been recommended in the UK or in mostdeveloped countries but Switzerland has established a time-weighted averageoccupational limit of 11500 mg/m3 (OECD: SIDS). In Germany, no exposure limit isgiven for ethylene because it is ‘justifiably suspected of having carcinogenic potential’(Deutsche Forschungsgemeinschaft, 1993/IARC 1994).

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B.6.10.1 Acceptable Daily Intake (ADI)

Although ethylene is an important industrial chemical, there appears to be only alimited number of standard toxicity studies and human epidemiology studies in the
public domain. No oral toxicity studies are available for ethylene. The majority of theavailable data have been generated using inhalation exposure and the various
international regulatory authorities appear to have relied upon the 2-year rat inhalation
study to conclude that ethylene is not a carcinogen. In addition, the cited regulatory
authorities have relied upon metabolism data generated from acute/short-term
inhalation studies to estimate the predicted conversion of ethylene to ethylene oxide.
Since there are insufficient data to set an ADI for ethylene, any approvals for the use ofethylene as a growth regulator used to ripen bananas must be dependant on the residue
levels of ethylene and its metabolites after treatment being no greater than the normal
background rates in potatoes and bananas. The Health Canada (2001) document statesthat analytical data for ethylene and its potential metabolites in ethylene treatedpotatoes were either non-detectable or were at similar levels to any measurable
residues found in controls (no actual exposure levels or analytical results were
included in the document).
No analytical data was submitted for ethylene treated bananas which would
substantiate that the residue levels were equal to or similar to untreated bananas.
Without these relevant residue data, it is not possible to conclude that the use ofethylene for the requested uses would not present an unacceptable risk to humanhealth.
As indicated by the Health Protection Branch of Health Canada in the “Health and
Safety Status Report” for ethylene (May 1994), an acceptable daily intake (ADI) is not
required for ethylene, since it is a naturally occurring chemical produced by fruits andvegetables, including potatoes, during senescence. Ethylene is also a naturally
occurring endogenous chemical in humans and laboratory animals and has been
identified in the air exhaled by unexposed rats and humans. Potential ethylene
metabolites have also been shown to occur naturally. Analytical data for thesemetabolites in treated potatoes showed that residue levels were either non-detectableor were at levels similar to any measurable residues found in controls (Health
Canada, 2001).
B.6.10.2 Acute Reference Dose (ARfD)

There are insufficient data to set an ARfD. Apart from the formation of adducts, there
are no clear obvious effects of acute exposure presented in the literature and therelevant data for oral exposure is sparse or non-existent. Approval is therefore
dependant on the residue levels of ethylene and its metabolites after treatment being nogreater than the normal background rates in bananas.
The following was proposed:
An acute reference dose (ARfD) was not established, since ethylene was considered
unlikely to present an acute hazard. The available literature suggests that there are no
significant treatment-related findings to indicate a concern in acute dietary risk

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assessment. The potential risks to humans from exposure to ethylene are considerednegligible due to low toxicity concerns and the widespread use of ethylene as ananaesthetic with little concomitant toxicity (Health Canada, 2001).
B.6.10.3 Admissible Operator Exposure Level (AOEL)

There is insufficient data to set an AOEL. However, the current occupational exposurelevels and application methods suggest that the use of ethylene is acceptable. However
due to some reports of increased levels of haemoglobin adducts in fruit plant workers,
it is recommended that exposures be kept as low as reasonably achievable e.g. use of
RPE or engineering controls.
B.6.10.4 Maximum Allowable Concentration (MAC: drinking water limit)

There are insufficient data to set a health based limit. The EU limit for theconcentration of any pesticide in drinking water is 0.1 μg/l.

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B.6.10.5 Classification and labelling

B.6.10.5.1 Ethylenea)Current ECB classification
R67
S2
S46

b)

Vapours may cause drowsiness and dizziness.
Keep out of the reach of children
If swallowed, seek medical advice immediately and show this container orlabel.

Proposed classification
Ethylene is converted into ethylene oxide in rats (5-10%) and humans (estimatedvalues of <4%). The data base is inadequate to conclude a robust proposal for theclassification of ethylene for carcinogenicity and reproductive toxicity. However,assuming that humans metabolise ethylene to ethylene oxide, in the absence of data on
ethylene, the classification could take account of the potential ethylene oxide exposure.

c)

Classification of liquefied or pressurised ethylene
Liquefied or pressurized ethylene gas can cause frostbite damage (this may trigger
part of the risk phrase RSh Directive 2003/82/EC).

B.6.10.5.2 Ethylene oxide
Current ECB classification
CAT: 2 carcinogenicity & CAT: 2 mutagenicity
R23
Toxic by inhalation
R36/37/38 Irritating to eyes, respiratory system and skin
R45
May cause cancer
R46
May cause heritable genetic damage
S45
If swallowed or if you feel unwell, seek medical advice immediately(show the label where possible).
S53
Avoid exposure-Obtain special instructions before use.
B.6.10.5.3 1,2-ethanediol (ethylene glycol)
Current ECB classification
R22
S2

Harmful if swallowed
Keep out of reach of children

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B.6.10.5.4 1,2-dichloroethane (ethylene dichloride)
Current ECB classification
CAT: 2 carcinogenicity
R22
Harmful if swallowed
R36/37/38 Irritating to eyes, respiratory system and skin
R45
May cause cancer
S45
In the case of accidents or if you feel unwell seek medical advice
immediately (show the label where possible).
S53
Avoid exposure-Obtain special instructions before use.
B.6.11a Acute toxicity, irritancy and skin sensitisation of the ‘Ethylene’ (IIIA 7.1)

‘Ethylene’ in cylinders contains 60 g/kg ethylene (99.9% purity) and 940 g/kg
nitrogen. A single source is used by all five notifiers (i.e. Air Liquide, Air Products,
Coleacp, Linde Ag and Praxair).
B.6.11.1a Acute oral toxicity in rats (AIII 7.1.1)

No studies submitted.
B.6.11.2a Acute dermal toxicity (AIII 7.1.2)

No studies submitted.
B.6 11.3 Acute inhalation toxicity (AIII 7.1.3)

No studies submitted.
B.6.11.4a Skin irritancy (AIII 7.1.4)

No studies submitted
B.6.11.5a Eye irritancy (AIII 7.1.5)

No studies submitted.
B.6.11.6a Skin sensitisation (AIII 7.1.6)

No studies submitted.
B.6.11.7a Summary of the toxicity of ethylene

Apart from the dangers of asphyxiation in confined spaces and potential frost bite
injury, the potential acute toxicity, irritation and skin sensitisation effects of thisproduct are likely to be limited to those induced by ethylene gas.

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B.6.11.8a Toxicological data on non active substances (IIIA 7.4)

The nitrogen may cause asphyxiation at high concentrations in enclosed spaces due tooxygen deficiency. The symptoms of oxygen deficiency include respiratory difficulty,
ringing in ears, headaches, shortness of breath, wheezing, headache, dizziness,
indigestion, nausea, and at high concentrations, unconsciousness or death may occur.
B.6.11.9a Proposal for classification and labelling

Apart for the observation that liquefied or pressurized ethylene gas can cause frostbite
damage (this may trigger part of the risk phrase RSh Directive 2003/82/EC), noclassification is proposed for the acute toxicity, irritation or skin sensitisation of‘Ethylene’ (a mixture of ethylene and nitrogen).
B.6.12a Dermal absorption studies (IIIA 7.3)

Not applicable.
B.6.13a Toxicological data on non active substances (IIIA 7.4)

There are no hazard warnings on the MSDS that give rise to toxicological concernswith respect to the classification of ‘Ethylene Gas’ (a mixture of ethylene andnitrogen).
B.6.11b Acute toxicity, irritancy and skin sensitisation of ‘Restrain Generator Fuel’ (IIIA
7.1)

The notifier of ‘Restrain Generator Fuel’ states that it contains 96% ethanol (i.e. foodgrade ethanol without any denaturant); the product is used to generate ethylene using acatalytic generator.
B.6.11.1b Acute oral toxicity in rats (AIII 7.1.1)

No studies submitted.
B.6.11.2b Acute dermal toxicity (AIII 7.1.2)

No studies submitted.
B.6 11.3b Acute inhalation toxicity (AIII 7.1.3)

No studies submitted.
B.6.11.4b Skin irritancy (AIII 7.1.4)

No studies submitted.
B.6.11.5b Eye irritancy (AIII 7.1.5)

No studies submitted.
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B.6.11.6b Skin sensitisation (AIII 7.1.6)

No studies submitted.
B.6.11.7b Summary of the toxicity of ‘Restrain Generator Fuel’

The acute toxicity, irritation and skin sensitisation effects of ‘Restrain Generator Fuel’are driven by the ethanol content of the product. For a full evaluation of ethanol,
please refer to the Ethanol Draft Assessment Report.
Ethanol is considered to be of low toxicity via the acute oral, dermal and inhalationalroutes. It is not a skin irritant or a skin sensitiser but there is some evidence thatethanol is an eye irritant and a respiratory irritant. Therefore, ‘Restrain Generator
Fuel’ is classifiable as an eye irritant and a respiratory irritant based on the ethanol
content.
B.6.11.8b Toxicological data on non active substances (IIIA 7.4)

The available data and information on denatured ethanol do not give rise to
toxicological concerns with respect to the classification of ‘Restrain Generator Fuel’.
B.6.11.9b Proposal for classification and labelling

Based on the ethanol content, ‘Restrain Generator Fuel’ is classifiable as given below
in subsection (a). This level of classification for the carcinogenicity, mutagenicity andreproductive toxicity of ethanol is supported by publicly available animal and humandata. Further discussion is presented in the Ethanol Draft Assessment Report. The
current ECB classification is presented below in subsection (b).
a)

Classification currently being considered by the ECB
Hazard symbol(s)TIndication of danger:

Toxic

Risk phrases:
R36/37R45 (CAT 1or 2: Carcinogen)
R46 (CAT 2: Mutagen)
R60 (CAT 1: Reproductive toxin)
R61 (CAT 1: Reproductive toxin)
R64 (CAT 1: Reproductive toxin)

Irritating to eyes and respiratory system.
May cause cancer
May cause heritable damage
May impair fertility
May cause harm to the unborn child
May cause harm to breast-fed babies

Safety phrases:
S2: Keep out of the reach of children.
S53: Avoid exposure-Obtain special instructions before use.
S45: In case of accident or if you feel unwell seek medical advice immediately (showthe label where possible).
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Current ECB classification of ethanol
According to the ECB web site, ethanol is currently unclassified for health effects
Note: The RMS is aware that the International Agency for Research on Cancer (IARC)
is currently preparing an up-dated monograph on the carcinogenic effects of alcohol
which is expected to be published in the near future.

B.6.12b Dermal absorption studies (IIIA 7.3)

In the absence of data, a dermal absorption value of 100% is proposed for the operator
exposure calculations.
B.6.13b Toxicological data on non active substances (IIIA 7.4)

The notifier of ‘Restrain Generator Fuel’ states that this product contains 96% ethanol(i.e. food grade alcohol without a denaturant); therefore, any other minor constituentsare unlikely to give rise to toxicological concerns with respect to classification.
B.6.14

Exposure data (IIIA 7.2)
Ethylene

The supported use of ethylene is as a plant growth regulator, intended for use indegreening and ripening of bananas. It is applied via compressed gas cylinders
containing ethylene and nitrogen or by a catalytic generator. This produces ethylene byconverting liquid fuel (ethanol) to ethylene gas and water vapour. Ethylene is appliedin hermetic ripening rooms. The target concentrations for the two methods ofgeneration are sufficiently similar to allow the major conclusions drawn vis-à-vis the
scenario involving ethylene introduced from gas cylinders to apply to ethylene
produced from ethanol. Exposure to ethanol from handling the product and preparing
the generator equipment is considered in the Draft Assessment Report for ethanol.

Cylinders (ethylene gas)
Generator (ethanol)

Target concentration
600 – 1000 ppm
4 – 1200 ppm

Source of information
GAP table
Label for ‘Ethygen II’

Table 6.14.1 – Comparison of target concentrations achieved with two forms of
ethylene generation
Ethylene is not classifiable via the acute inhalation route according to EC criteria(based on cited data). There are insufficient data to classify ethylene via the acuteoral and dermal routes or for skin and eye irritancy and skin sensitisation using thenormal EC criteria. However, based on industrial use and its use as an anaesthetic,
ethylene gas dose not appear to be classifiable as a skin or eye irritant or a skinsensitiser. Liquefied or pressurized ethylene gas can cause frostbite damage (B.6.10).
There is insufficient data available to set an AOEL for ethylene (B.6.10.3).

73Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Ethylene oxide

Ethylene oxide has been identified as a metabolite of ethylene (B.6.13). Ethylene isconverted into ethylene oxide in rats (5-10%) and humans (estimated values of <4%)This metabolite is of toxicological concern and is therefore considered as part of thisexposure assessment.
Ethylene oxide is currently classified by the ECB as a Cat: 2 for carcinogenicity (R45)
and Cat: 2 for mutagenicity (R46). It is also currently classified by the ECB as Toxic
by inhalation (R23) and as an irritant (R36/37/38) and the literature also indicates thatit can also induce sensitisation responses.

Supported use

A summary of the treatment process is given below ;74

Ethanol addendum - Volume 3, Annex B.7 : Toxicology of reaction & degradation products September 2008

Fig. 6.14.1.1 – A typical banana ripening installation

75

Ethylene- Volume 3, Annex B.6 : Toxicology and Metabolism

December 2007

The gas is released from a number of cylinders and flow controlled by solenoid valves,
one in the supply line after the cylinders and one in the line leading into each room inthe store.

Fig. 6.14.1.2 – Ethylene station and cylinders

Fig. 6.14.1.3 Secondary solenoid valve controlling entry to a store room

(Note the cut-off
valve which can beused if thesecondary solenoid
valve is broken.)76

Ethylene- Volume 3, Annex B.6 : Toxicology and Metabolism

December 2007

The valves are opened by direct digital controllers (DDCs). As the default position ofboth primary and secondary valves is ‘closed’ it is unlikely that ethylene will be
accidentally released. Equipment is also incorporated which reduces the gas pressure
from 200 bar in the supply tanks to 5 bar in the pipes and will alert the operator whenthe ethylene mixture is depleted.
The concentration of ethylene in the application room is monitored continuously andremotely by trained operators, to ensure the concentration remains near the target level
throughout the application period. Typically, these are fully automated (computer
controlled) systems which include automated door-locking mechanisms, which do notallow the doors to be opened when the treatment process is ongoing. Consequently,
persons will not be present during the treatment process.
B.6.14.1 Operator exposure (IIIA 7.2.1)

Potential occupational exposure to ethylene may occur when entering the application
room or its ventilation ductwork (e.g., for repair) after application of ethylene or when
standing near the ventilation exhaust. This exposure scenario is considered underWorker exposure (B.6.14.3).
It is also possible that exposure could occur when handling the cylinders, for instanceduring changeover. The primary route of exposure would be via inhalation. Potential
exposure to high concentrations of ethylene may occur in the event of a leak into an
enclosed space. The proposed label includes precautionary statements regarding proper
handling of the cylinders and gas release system to avoid leaks. Respiratory protection
for entry into an area of unknown ethylene concentration is recommended on the draft
label.
Although the primary route of exposure would be through inhalation, liquefied orpressurized ethylene gas can cause frostbite damage. In industry, however, PPE isnormally worn to mitigate the risk of physical injury which could be caused by theheavy cylinders; gloves and safety footwear are typical. Gas leakages are considered
accidental occurrences and not a risk encountered during normal procedures. However,
eye protection as a precaution is a simple and prudent measure. Taking these factors
and the low acute toxicity of ethylene gas into account, it is therefore recommended
that for handling the gas cylinders the following PPE should be worn:•

Eye protection and suitable protective gloves.

B.6.14.2 Bystander exposure (IIIA 7.2.2)

As the treatment is made indoors in sealed rooms members of the public will not bepresent at the site of application. However, workers, who may not be not directly
involved in the treatment operation, may be working close to areas where a treatment
is taking place and could be exposed via leakages from stores via door seals (the label
states the ripening room should be reasonably air-tight). Bystander exposure could
also occur during the venting of the gas into the atmosphere after treatment.

77Ethylene- Volume 3, Annex B.6 : Toxicology and Metabolism

December 2007

No information is available to quantify these potential sources of exposure for
bystanders.
B.6.14.3 Worker exposure (IIIA 7.2.3)

The automated nature of the treatment process means entry into treatment rooms isprevented until treatment has been completed and the room ventilated. Workers may
then enter the rooms for inspection tasks or maintenance purposes. The exposurelevels experienced by these workers will be largely dependent on the efficient
functioning of the ventilation system.
Personal and stationary monitoring of ethylene in a company where this gas was used
for controlling the ripening of bananas showed air concentrations (after ventilation of
the treatment room) to be in the range of 0.02-3.85 mg/m3 (0.02-3.35 ppm) with anestimated average concentration of 0.35 mg/m3 (0.3 ppm).
(Tornqvist et al , 1989a/IARC)

B.6.14.4 Conclusions

In the absence of appropriate data it is not possible to quantify the exposure to ethylene
which might be experienced by operators handling and changing cylinders, but due tothe design of the systems involved, this is expected to be minimal under normal
circumstances. It is prudent to mitigate any risk of physical injury and from an
accidental release by the use of appropriate PPE (gloves and eye protection). RPE may
be identified as necessary in some circumstances, for example when entering areas
with unknown concentrations of ethylene.
There is uncertainty with regards to the levels of exposure which might be experienced
by bystanders either due to leakages during treatment or during ventilation of thetreatment room and by workers re-entering treated stores after ventilation as only
limited exposure data are available. In a Swedish petrochemical plant (B.6.9.1) elevenworkers exposed to levels of ethylene between 0.1 and 4 mg/m3 showed dose-related
increases in haemoglobin adduct formation. A study of fruit store workers (B.6.8.3.5)
exposed to ethylene concentrations of 0.02-3.35 ppm showed similar increases inadjunct levels in relation to the control subjects. The concentrations which appear tohave produced these effects are similar to the atmospheric concentrations of ethylene
measured in fruit stores where ethylene has been used in the manner proposed(B.6.14.3). The presence of the haemoglobin adducts is evidence that some exposure to
ethylene (and subsequently the oxide) has occurred. The significance of this exposureis unclear. However, there is some evidence that adduct levels occurring in fruit store
workers are similar to the background levels measured in other sections of the
population (refer to Table B.6.5). There is also evidence that dietary intake of ethylene
may involve acute exposure to much higher concentrations than those encountered in
fruit stores after venting; for instance, fully ripe pears may produce internal
concentrations of the order of 40 ppm (Wang and Mellenthin, 1972).

78

Ethylene- Volume 3, Annex B.6 : Toxicology and Metabolism

December 2007

In conclusion, the supported use for fruit ripening involves practical steps to minimise
exposure to ethylene. The actual levels of exposure for fruit store workers are
uncertain. Whilst treatment is essentially an automated, closed, operation, exposurelevels for workers are expected to vary between fruit stores, i.e. some stores will be
more airtight than others and some will be fitted with better ventilation systems.
Member States may wish to investigate these exposure levels further.

79

資料

環 境基 準 に関するテキサス州 委員会： サポート文書最終版
エチレン
2008 年 ４月

Development Support Document
Final, April 15, 2008

Ethylene
CAS Registry Number: 74-85-1

11
３－６

Development Support Document
Final, April 15, 2008

Ethylene
CAS Registry Number: 74-85-1

Prepared by
Neeraja K. Erraguntla, Ph.D.
Toxicology Section

Chief Engineer’s Office___________________________________________________________TEXAS COMMISSION ON ENVIRONMENTAL QUALITY

Ethylene

Page 2TABLE OF CONTENTS
CHAPTER 1 SUMMARY TABLES..........................................................................................................................4
CHAPTER 2 MAJOR USES AND SOURCES.........................................................................................................6
CHAPTER 3 ACUTE EVALUATION......................................................................................................................6
3.1 HEALTH-BASED ACUTE REV AND ESL ...............................................................................................................6
3.1.1 Physical/Chemical Properties and Key Studies ..........................................................................................6
3.1.1.1 Physical/Chemical Properties................................................................................................................................ 6
3.1.1.2 Essential Data and Key Studies............................................................................................................................. 7
3.1.1.2.1 Conolly et al. (1978) ..................................................................................................................................... 7
3.1.1.2.2 Guest et al. (1981)......................................................................................................................................... 7
3.1.1.2.3 Conolly and Jaeger (1977) ............................................................................................................................ 8
3.1.1.2.4 Other Studies Reviewed by TS ..................................................................................................................... 8

3.1.2 Mode-of-Action (MOA) Analysis and Dose Metric .....................................................................................8
3.1.3 Points of Departure (PODs) for the Key Studies ........................................................................................93.1.4 Dosimetric Adjustments ..............................................................................................................................93.1.4.1 Default Exposure Duration Adjustments............................................................................................................... 9
3.1.4.2 Default Dosimetry Duration Adjustments from Animal-to-Human Exposure ...................................................... 9

3.1.5 Critical Effect and Adjustments of the PODHEC ........................................................................................10

3.1.5.1 Critical Effect...................................................................................................................................................... 10
3.1.5.2 Uncertainty Factors (UFs)................................................................................................................................... 10

3.1.6 Health-Based Acute ReV and acute ESL......................................................................................................11
3.1.7 Information from Other Organizations .....................................................................................................11
3.2. WELFARE-BASED ACUTE ESLS ........................................................................................................................123.2.1 Odor Perception........................................................................................................................................123.2.2 Vegetation Effects .....................................................................................................................................123.2.2.1 Summary of Ethylene Induced Vegetative Effects.............................................................................................. 12
3.2.2.2 Summary of Ethylene Induced Effects in Flowering plants ................................................................................ 13
3.2.2.3 Key Studies ......................................................................................................................................................... 14
3.2.2.3.1 The Alberta Canada Study .......................................................................................................................... 14
3.2.2.3.2 Pallas and Kays (1982) Study ..................................................................................................................... 15
3.2.2.4 Derivation of the acuteESLveg ................................................................................................................................ 16

3.3 SHORT-TERM ESL AND VALUES FOR AIR MONITORING EVALUATION ..............................................................17

CHAPTER 4 CHRONIC EVALUATION...............................................................................................................17
4.1 NONCARCINOGENIC POTENTIAL ........................................................................................................................174.1.1 Physical/Chemical Properties and Key Studies ........................................................................................17
4.1.2 MOA Analysis and Dose Metric................................................................................................................18
4.1.3 POD for Key and Supporting Studies........................................................................................................18
4.1.3.1 Default Exposure Duration Adjustments............................................................................................................. 18
4.1.3.2 Default Dosimetry Adjustments.......................................................................................................................... 18

4.1.4 Application of Uncertainty Factors to the PODHEC based on MOA Analysis ...........................................19
4.1.5 Health-Based Chronic ReV and chronicESLnonlinear(nc) ...................................................................................19
4.2 CARCINOGENIC POTENTIAL ...............................................................................................................................20
4.3. WELFARE-BASED CHRONIC ESL ......................................................................................................................214.3.1. Development of Vegetation-Based Chronic ESL (chronicESLveg) ...............................................................214.3.1.1 The Alberta Canada Study .................................................................................................................................. 21
4.3.1.2 Klassen and Bugbee (2002)................................................................................................................................. 22
4.3.1.3 The Reid and Watson Study (1985) .................................................................................................................... 22
4.3.1.4 The Blankenship study (1993) ............................................................................................................................ 22
4.3.1.5 Determination of chronic ESLveg ............................................................................................................................ 22

Ethylene

Page 34.3.1.6 Other Vegetation-Based Studies Reviewed by TS .............................................................................................. 23

4.4 LONG-TERM ESL AND VALUES FOR AIR MONITORING EVALUATION ...............................................................23
CHAPTER 5. REFERENCES..................................................................................................................................23
5.1 REFERENCES CITED IN DEVELOPMENT SUPPORT DOCUMENT ............................................................................23
5.2 OTHER STUDIES AND REFERENCES REVIEWED BY THE TS.................................................................................28

LIST OF TABLES
Table 1. Health - and Welfare-Based Values.................................................................................................................4
Table 2. Chemical and Physical Data ............................................................................................................................5
Table 3. Derivation of the Acute ReV and acuteESL.....................................................................................................11
Table 4: Information on the Plants and Trees included in the Alberta Canada Study .................................................14
Table 5: Information on the Plants Included in the Pallas and Kays Study .................................................................16
Table 6. Derivation of the acuteESLveg......................................................................................................................17
Table 7. Derivation of the Chronic ReV and chronicESL nonlinear(nc) ................................................................................20
Table 8. Derivation of the chronicESLveg ........................................................................................................................23

Ethylene

Page 4

Chapter 1 Summary Tables
Table 1 provides a summary of health- and welfare-based values resulting from an acute and chronicevaluation of ethylene. Table 2 provides summary information of ethylene’s physical/chemical data.

Table 1. Health - and Welfare-Based Values
Short-Term Values
acute

ESLvegConcentration

Notes

1,400 µg/m3 (1,200 ppb) *This value is a sub-thresholdconcentration that is protective of
all crop plants including flowering
plantsShort-Term ESL for Air
Permit Reviews
acute

ESL [1 h](HQ = 0.3)
acute ReV

170,000 µg/m3 (150,000 ppb)
3570,000 µg/m (500,000 ppb)*

(HQ = 1.0)
acute

ESLodorLong-Term Values
chronic

ESLveg

310,000 µg/m3 (270,000 ppb) *Concentration
34 µg/m3 (30 ppb) *Long-Term ESL for Air
Permit Reviews

chronic

ESLnonlinear(nc)chronic

ESLlinear(c)chronic*

50% odor detection threshold
Notes
This value is a thresholdconcentration that is protective of
all crop plants including flowering
plants1,800 µg/m3 (1,600 ppb)

(HQ = 0.3)
chronic ReV(HQ = 1.0)

Critical Effect: hepatic damage inmale Holtzman rats, based on afree-standing NOAEL

6,100 µg/m3 (5,300 ppb) *---ESLnonlinear(c)Critical Effect: hepatic damage inFischer 344 rats based on freestanding NOAEL
No evidence of carcinogenic
potential

Values that may be used for evaluation of air monitoring data

Abbreviations used: ppb, parts per billion; µg/m3, micrograms per cubic meter; h, hour; ESL, Effects
Screening Levels; ReV, Reference Value; acuteESL, acute health-based ESL; acuteESLodor, acute odorbased ESL; acuteESLveg, acute vegetation-based ESL; chronicESLnonlinear(nc), chronic health-based ESL for
nonlinear dose-response noncancer effects, chronicESLlinear(c), chronic health-based ESL for linear doseresponse cancer effects; chronicESLnonlinear(c), chronic health-based ESL for nonlinear dose-response cancer
effect; and chronicESLveg, chronic vegetation-based ESL; HQ, Hazard Quotient.; NOAEL, no-observedadverse-effect level

Ethylene

Page 5

Table 2. Chemical and Physical Data
Parameter

Value

ChemFinder 2004

Molecular Structure

Molecular Formula
Molecular Weight
Physical State
Color

C2H4
28.05
Volatile gas, highly flammable and adangerous fire risk, liquid under pressure
Colorless

Odor

Faint Sweet

CAS Registry Number

74-85-1
Acetene; Elayl; Olefiant Gas; Refrigerant
150; Ethene; UN1038 (refrigerated
liquid), UN1962 (compressed liquid),Athyllen [German], Bicarburrettedhydrogen; Caswell No. 436; EINECS
200-815-3; EPA Pesticide Chemical Code041901; Etileno; HSDB 168
26 g/L- Slightly soluble
Log Pow= 1.13
760 mmHg @ -104°C

Synonyms

Solubility in water
Log Kow or Pow
Vapor Pressure
Relative Vapor Density @32º F (gas; air =1)
Density(liquid) @ Critical
Temperature (48.54 ºF)
Melting Point
Boiling Point
Conversion Factors at
25ºC and 1 atmospherea

ChemFinder 2004
ChemFinder, 2004
ACGIH 2005a,
ACC 2004b
ACGIH 2005a,
ACC 2004b
ACGIH 2005a,
ACC 2004b
ACGIH 2005a,
ACC 2004b

ACC 2004b

ChemFinder 2004
ACC 2004b
Matheson Tri-Gasc

0.975

ACC 2004b

13.36 lb/ft3; 1.786 lb/gal; 0.21 g/cm3

ACC 2004b-169.14°C-103.7°C
1 ppb = 1.15 µg/m3
1 µg/m3 = 0.87 ppb

ChemFinder 2004
ChemFinder 2004
Alberta Environment 2003
Toxicology Section

American Conference of Governmental Industrial Hygienists (ACGIH)
American Chemistry Council (ACC) 2004cMatheson Tri-Gas Material Safety Data Sheetb

ReferenceEthylene

Page 6

Chapter 2 Major Uses and Sources
Ethylene is produced through both natural and anthropogenic activity. Microbes and higher plants
naturally produce ethylene. Ethylene is also released during forest fires and active volcanic events. In
higher plants, ethylene functions as a plant hormone and ethylene production can either increase or
decrease in response to a variety of environmental stressors such as flooding, wounding (e.g., mechanicaland/or pathogenic attack), chemical exposure (e.g., ozone), and mechanical bending (e.g., lodging)(Health Canada 2001).
Ethylene is also produced endogenously in mammals through lipid peroxidation of unsaturated fats,oxidation of free methionine, oxidation of hemin in hemoglobin, and metabolism of intestinal bacteria(Health Canada 2001). However, ethylene production in mammals is only a minor contributor toatmospheric ethylene when compared to the relative contribution from microbial, vegetative, andindustrial sources (Health Canada 2001).
In occupational settings, very high concentrations of ethylene can lower oxygen concentrations and has
been reported to function as an asphixiant (Cavender 1994). Ethylene is primarily used as an intermediatein the production of other chemicals and as an agent to enhance the ripening process of fruits, vegetables,and flowers. Ethylene is also a high-production-volume chemical product of the petrochemical industry,
produced mainly by the steam-cracking of hydrocarbons. Industrial contribution to ambient ethylene isprimarily due to fugitive emissions from stacks, flares, and leaks in pipe fittings that can result in a
discontinuous exposure scenario (Health Canada 2001).
Ambient ethylene is also produced during incomplete combustion of biomass and fossil fuels. While
gasoline itself does not contain ethylene, the combustion of gasoline causes ethylene to be emitted into
the ambient air. A relatively large proportion of ethylene in urban air is due to vehicular traffic emissions(Abeles and Heggestad 1973).

Chapter 3 Acute Evaluation
3.1 Health-Based Acute ReV and ESL
3.1.1 Physical/Chemical Properties and Key Studies
3.1.1.1 Physical/Chemical Properties
Ethylene is a highly-flammable volatile gas that is considered to be a fire hazard at sufficiently highconcentrations. It is a colorless gas with a faint sweet odor, is a liquid under pressure, and is slightly
soluble in water (Chemfinder 2004). The main physical and chemical properties of ethylene aresummarized in Table 2. Ethylene has been reported to be relatively non-toxic, has a low blood-gas
partition coefficient and does not accumulate in the body.

Ethylene

Page 73.1.1.2 Essential Data and Key Studies
The inhalation toxicity studies conducted by Conolly et al. (1978) and Guest et al. (1981) were selected as
key studies to determine the acute Reference Value (ReV) and the acute Effect Screening Level(acuteESL). The study conducted by Conolly and Jaeger (1977) was selected as a supporting study.

3.1.1.2.1 Conolly et al. (1978)
In the Conolly et al. (1978) studies, a group of male Holtzman rats were exposed to 10,000, 25,000, or
50,000 ppm ethylene for 4 h. A second group of rats were administered a combined exposure protocol
with polychlorinated biphenyl (PCB) mixture (300 µmoles of PCB/kg of body weight) via gavage once
daily for 3 days followed by 4 h of inhalation exposure to the various concentrations of ethylene. In
addition, control groups were included with rats exposed to PCB alone.
In the study, hepatic damage was assessed by conducting histopathology of the liver and by measuring
the levels of hepatic enzymes including sorbitol dehydrogenase (SDH) and serum alanine-alphaketoglutarate transaminase (SAKT). Elevated levels of SAKT and SDH are often indicative of liver
damage. The authors reported ethylene concentrations at 10,000 ppm to be hepatotoxic only when the rats
were pre-treated with the PCB mixture. Specifically, rats that were exposed to ethylene after exposure to
PCB mixture were reported to have elevated levels of SDH and the liver of the rats had severe
degenerative necrosis.
The authors reported no increase in hepatic enzymes and no liver damage in rats exposed to ethylene
alone. A no-observed-adverse-effect-level (NOAEL) of 50,000 ppm was determined from the exposuregroup of rats exposed only to ethylene. As the studies did not provide any other toxicological information,such as lowest-observed-adverse-effect-level (LOAEL), the NOAEL will be considered a free-standing
NOAEL.

3.1.1.2.2 Guest et al. (1981)
Guest et al. (1981) also studied the toxicity of ethylene alone and in conjunction with PCBs. For theethylene-only exposure group, the authors exposed Fisher rats for 5 h to 10,000 ppm ethylene. For the
combined exposure (i.e., PCB mixture + ethylene), the authors administered 500 mg/kg PCB mixture via
gavage five days prior to exposing the rats for 5 h to 10,000 ppm of ethylene. Control groups included
rats exposed either to ethylene alone or rats exposed to only the PCB mixture.
Similar to the Conolly et al. studies, Guest et al. (1981) reported no increase in serum enzyme activities
and no necrotic tissue for the ethylene only exposure groups. Exposure only to the PCB mixture, without
subsequent exposure to ethylene, resulted in slight hypertrophy of centrolobular liver cells with nohepatocellular necrosis. However, animals exposed to 10,000 ppm ethylene after pre-treatment with the
PCB mixture, had uniform hepatic centrolobular necrosis. In addition, the authors also reported elevatedhepatic enzyme levels in the combined exposure group (PCB mixture + 10,000 ppm ethylene). As no
LOAEL information was available, a free-standing NOAEL of 10,000 ppm was determined from thegroup exposed only to ethylene.

Ethylene

Page 8The results from the acute exposure studies indicate that very high doses of ethylene coupled with highdoses of the PCB mixture are required to elicit hepatotoxic responses in rats. Guest et al. (1981)
hypothesized that the PCB mixture induced the hepatic mixed-function oxidase (MFO) system that thenresulted in hepatotoxicity in the rats.

3.1.1.2.3 Conolly and Jaeger (1977)
The study conducted by Conolly and Jaeger (1977) was selected as a supporting study. Similar to
Conolloy et al. (1978) studies, Conolly and Jaeger (1977) studied the acute hepatotoxicity of ethylene andother chemicals with and without PCB pre-treatment. Male Holtzman rates were exposed up to 50,000
ppm ethylene. In addition to hepatic injury, the authors also studied the effects of changes inenvironmental parameters (i.e., changes in temperature during exposure and food deprivation. The
authors reported ethylene to be more acutely toxic in rats that were fasted when compared to rats thatwere fed and PCB –pre-treated. The authors attribute depletion of glutathione to be higher in the fasted
rats.

3.1.1.2.4 Other Studies Reviewed by TS
Aveyard and Collins (1997) conducted a reproductive/developmental toxicity screening study with head
only exposures to rats. A total of 10 animals/sex/group were exposed to 5,000 ppm of ethylene for 6
h/day for 2 weeks prior to mating and during the mating period. Female rats were also exposed toethylene until gestational day 20. No effects on weight gain, food intake, fertility, fecundity, sex ratio,
and pup weight or pup growth were reported. This study was described in the Organization for Economic
Co-Operation and Development (OECD) dossier on ethylene.

3.1.2 Mode-of-Action (MOA) Analysis and Dose Metric
Ethylene is metabolically converted to ethylene oxide (EtO) via the cytochrome P-450 pathway (Filser
and Bolt 1983). Concern about the potential toxicity of ethylene stems from the fact that EtO is asuspected human carcinogen and a genotoxicant (ACGIH 2005 and Tornqvist 1994). In addition, EtO is
also a potent alkylating agent and can form adducts by interacting with cellular macromolecules such as
DNA, RNA, and protein (e.g., hemoglobin). Similar adduct formation has been reported on direct
exposure to EtO (ACGIH 2005).
While adducts have been used as biomarkers of DNA damage, their use is controversial. There is some
controversy in regards to whether adduct formation is indicative of exposure, and if adducts can beunequivocally utilized as precursors of diseases such as cancer (Selinski et al. 2000). A few studies
reported the detection of hemoglobin adduct formation on exposure to ethylene. One example is theidentification of hemoglobin adducts (i.e., hydroxyethylvaline adducts) in the serum of fruit storage
workers exposed to approximately 0.3 ppm ethylene (Tornquist et al. 1989). Similar results have also
been reported in plastic industry workers exposed to ethylene (Granath et al. 1996).
Very few human exposure studies using ethylene have been conducted. The majority of ethylene
exposure studies have been conducted using animals. When using animal studies, it is beneficial toextrapolate the risks observed in animals to humans using physiologically-based-pharmacokinetic(PBPK) models. Filser et al. (1992) measured ethylene uptake by exposing 6 human subjects for 2 h incontrolled chambers to 5 and 50 ppm of ethylene. The authors reported 98% of the ethylene to be exhaledEthylene

Page 9unchanged and only 2% of the ethylene was absorbed and metabolized to EtO. Similar to humans, mostof the inhaled ethylene (83%) in rats was exhaled unchanged. Further, the relatively smaller fraction of
ethylene that was actually absorbed was also reported to be eliminated unchanged in rats (Filser and Bolt
1983).
The metabolic conversion of ethylene to EtO has been reported to be a rate-limiting step resulting in only
an insignificant amount of EtO being produced during the process (Bolt and Filser 1987 and Csanady etal. 2000). At 37 ppm ethylene exposure in rats, Bolt and Filser (1987) estimated a 1 ppm equivalent
exposure to EtO in humans, while Csanady et al. (2000) have reported an exposure of 45 ppm ethylene inrats to be equivalent to a 1 ppm EtO exposure in humans.

3.1.3 Points of Departure (PODs) for the Key Studies
A POD of 50,000 ppm based on a free-standing NOAEL was determined from the Conolly et al. studies,and a POD of 10,000 ppm based on a free-standing NOAEL was determined from the Guest et al. (1981)
study. In the toxicity study selected as the key study, data on the exposure concentration of the parent
chemical are available. Since the MOA of the toxic response is not fully understood and data on othermore specific dose metrics are not available (e.g. blood concentration of parent chemical, area underblood concentration curve of parent chemical, or putative metabolite concentrations in blood or target
tissue), the exposure concentration of the parent chemical was used as the default dose metric.

3.1.4 Dosimetric Adjustments
3.1.4.1 Default Exposure Duration Adjustments
In accordance to the ESL Guidelines, a duration adjustment for 1 h is recommended if the data are
obtained from acute toxicity studies with greater than 1 h exposure (TCEQ 2006). However, as thereported PODs in the key studies were relatively very high (i.e., indicative of low toxicity) and because no
adverse effects were observed in the key studies at either the 4 h and/or 5 h study, the Toxicology Section(TS), did not conduct duration adjustments and considered the POD for 1 h to be the same as the POD
determined for exposure durations greater than 1 h (i.e., 50,000 ppm from the Conolly et al. and 10,000
ppm from the Guest et al. (1981) study).
The POD determined from the Conolly et al. studies (50,000 ppm) is higher than the POD determinedfrom the Guest et al. (1981) study and is selected by the TS as the POD to derive a health-based acutereference value (acute ReV) and effects screening level (ESL). The TS selected the higher POD based on
the fact that the key and supporting studies only determined a free-standing NOAEL and on US. EPA’s(2002) definition of a NOAEL,“The highest exposure level at which there are no biologically significant
increases in the frequency or severity of adverse effect between the exposed population and its
appropriate control”. Some effects may be produced at this level, but they are not considered adverse or
precursors to adverse effects”.

3.1.4.2 Default Dosimetry Duration Adjustments from Animal-to-Human Exposure
As no duration adjustments are required, the POD becomes PODADJ and is 50,000 ppm. The PODADJ isthen adjusted to human equivalent POD or PODHEC. Ethylene is relatively non-toxic even at highconcentrations as it does not produce point of entry (POE) respiratory effects and the critical effect isEthylene

Page 10
hepatotoxicity. The TS will consider ethylene as a Category 3 gas and the duration exposure adjustmentsfrom animals to humans will be conducted with the following equation:
PODHEC = PODADJ x ((Hb/g)A / (Hb/g)H)
Where,PODHEC = Point of Departure at Human Equivalent Concentration
PODADJ = Adjusted Point of Departure
Hb/g = Ratio of blood:gas partition coefficient
A = Animal
H = Human
According to USEPA (1994), if the animal blood:gas partition coefficient is greater than the humanblood:gas partition coefficient, a default value of 1 is used for the regional gas dose ratio [(Hb/g)A /(Hb/g)H], (RGDR). Csanady (2000) reported the tissue:air partition coefficients for rat and humans to bevery similar and the blood:gas partition coefficients for rats to be double that of human values. The TS
will therefore conservatively consider a default blood:gas partition coefficient of 1. The PODHEC
calculated based on the Conolly et al. studies is:
PODHEC = PODADJ x (Hb/g)A / (Hb/g)HPODHEC = 50,000 ppm x 1
PODHEC = 50,000 ppm

3.1.5 Critical Effect and Adjustments of the PODHEC
3.1.5.1 Critical EffectPotential hepatotoxicity is the critical effect in the animal studies discussed in Section 3.1.1.2, although
the PODHEC is a free-standing NOAEL, and no adverse effects were noted in any ethylene-only exposuregroup.

3.1.5.2 Uncertainty Factors (UFs)The TS applied the following UFs to the PODHEC of 50,000 ppm to derive an acute Reference Value(acute ReV) under the assumption of a threshold/nonlinear MOA in accordance with the ESL Guidelines(TCEQ 2006). For detailed information on the MOA, please see Section 3.1.2. A interspecies UF of 3 wasapplied to account for extrapolation from animals to humans (UFA), a UF of 10 is applied to account for
intraspecies variability (UFH), and a database UF of 3 was applied to account for deficiencies in the
database (medium database confidence) of the referenced studies (UFD). A total UF of 100 (i.e., 3 x 10 x
3 = 100) was applied to PODHEC of 50,000 ppm.
acute ReV = PODHEC / (UFA x UFH x UFD)
= 50,000 ppm/(3 x 10 x 3)
= 50,000 ppm/100= 500 ppm (500,000 ppb or 570,000 µg/m3)

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A UFA of 3 was used because default dosimetric adjustments from animal-to-human exposure wereconducted which accounts for toxicokinetic differences but not toxicodynamic differences. A UFH of 10
was used to account for potentially sensitive subpopulations, and a UFD of 3 was used because of theavailability of several toxicity studies with a wide range of end points The confidence in the acutedatabase is medium.

3.1.6 Health-Based Acute ReV and acute ESL
As discussed in the previous section, UFs were applied to the POD obtained from the Conolly et al.
studies to derive the acute ReV. The acute ReV was rounded to two significant figures. Rounding to two
significant figures, the 1-h acute ReV is 500,000 ppb (570,000 µg/m3 ) The rounded acute ReV was thenused to calculate the acuteESL using a target hazard quotient of 0.3 (Table 3).
acute

ESL = 0.3 x acute ReV
ESL = 0.3 x 500,000 ppb
acute
ESL = 150,000 ppb (170,000 µg/m3)

acute

Table 3. Derivation of the Acute ReV and acuteESLKey Studies
Study population
Study quality
Exposure Method
Critical Effects
POD (original animal study) NOAELPODADJ (No adjustment necessary)
PODHEC
Exposure Duration
Total Uncertainty Factors (UFs)Interspecies UF
Intraspecies UF

Conolly et al. (1978)
Male Holtzman rats
Medium-highInhalation
Hepatic effects
50,000 ppm (free-standing NOAEL)
50,000 ppm
50,000 ppm (gas with systemic effects based on default
RGDR =1)
4h
100
3
10

LOAEL UF
Incomplete Database UF
Database Quality
acute Rev[1hr] (HQ = 1)

Not applicable3
Medium570,000 µg/m3 (500,000 ppb)

acute170,000 µg/m3 (150,000 ppb)

ESL [1h] (HQ= 0.3)

3.1.7 Information from Other Organizations
The USEPA Office of Prevention, Pesticides and Toxic Substances has reported the maximum exposure
rate to ethylene under current use as a pesticide to be 1000 ppm (USEPA 1992). This limit is for the postharvest exposure of stored commodities (USEPA 1992). The Screening Information Data Set (SIDS)
program operated under the auspices of the Organization for Economic Cooperation and Development
recommends no further testing of ethylene toxicity based on the reports of low toxicity of ethylene and noEthylene

Page 12risk to human health either through direct exposure or through indirect exposure via the environment(OECD SIDS 1994).

3.2. Welfare-Based Acute ESLs
3.2.1 Odor Perception
Ethylene has a sweet odor and taste. The ACGIH (2005) reported odor threshold is 290,000 ppb and isbased on the Amoore and Hautala (1983) study. A 50% odor detection value of 310,000 µg/m3 (270,000ppb) has also been reported by Hellman and Small (1974). Since, Hellman and Small (1974) is includedin the list of acceptable sources for odor threshold values and is listed in Appendix B of the ESL
Guidelines (TCEQ 2006), the acuteESLodor is 310,000 µg/m3 (270,000 ppb).

3.2.2 Vegetation Effects
3.2.2.1 Summary of Ethylene Induced Vegetative Effects
Interest in ethylene research spiked when it was identified to be phytotoxic to greenhouse plants (Crocker
1948). Later, many investigators documented the adverse effects of ethylene on plant species (Darley etal. 1963, Air Quality Criteria for Hydrocarbons 1970) and reported the effects of ethylene to be dependent
on the types of plant species and the stage of plant growth (Tonneijck et al. 2003, Reid and Watson 1985).
Fruits (e.g., apples, oranges, and avocados) release ethylene as they approach maturity which in turnpromotes the ripening of the fruits.
The majority of ethylene research has been conducted in growth chambers and very few studies exist forfield grown plants. Abeles et al. (1992) reported 10 ppb as the threshold concentration for physiologicaleffects from studies in greenhouse experiments with ethylene. However, there is some controversy
regarding the relevance of the threshold concentrations reported by Abeles et al. (1992) to field grownplants. Amongst the issues surrounding the applicability of the results reported by Abeles et al. (1992) isthe fact that greenhouse plants are normally exposed to very high concentrations of ethylene in acontinuous manner. Field grown plants generally experience lower concentrations of ethylene and theexposure pattern is said to be discontinuous (Tonneijck et al. 1999, 2000, and Dueck et al. 2004).
Greenhouse plants are also less hardy when compared to the field-grown plants and, may experience more
adverse effects (Tonneijck et al. 2003).
Ethylene is a plant hormone that is produced naturally at many of the stages of plant growth. As a plant
hormone, ethylene has been reported to regulate both the morphological (e.g., leaf abscission and epinasty(leaf curling)) and physiological effects (e.g., bud formation, inhibition of flowering, photosynthesis,
senescence, sprouting of buds, seed germination, and flower formation). In addition, ethylene canstimulate or inhibit the growth process, influence other plant hormones (e.g., giberillic acid), or itself beinfluenced by other hormones (Grossmann and Hansen 2001).
Tonneijck et al. (2000) reported epinasty or leaf curling in potatoes grown in the vicinity of polyethylene
manufacturing plants. However, the authors reported that the epinasty did not translate to a loss in tuber
yield. In a review on the effects of air-borne volatile organic compounds such as ethylene, Cape (2003)
reported epinasty to be a reversible effect if the exposure ended. Nutritional deficiencies and stress factors(i.e., water stress, temperatures, and diseases) can cause vegetative effects (i.e., leaf and flower

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abscission) that are similar to the effects caused by exogenous ethylene. Also, plants undergoing stress arereported to be more susceptible to ethylene (Munne-Bosch et al. 2004, Guinn 1982, and Jordan et al.
1972). It therefore becomes difficult to differentiate subtle physiological and morphological effects
caused by naturally produced ethylene (i.e., endogenous) versus ambient ethylene (i.e., exogenous).
Fugitive emissions from leaks around industrial facilities and vehicular traffic can create a discontinuous
exposure scenario in the ambient environment. Meteorological factors (i.e., wind direction and velocity)
can further aid in the movement and dispersal of the emissions and result in subsequent exposures tofield-grown plants. During the discontinuous exposure, field-grown plants often have a chance to recoverfrom the exposure. Green-house plants on the other hand are constantly exposed to ethylene fromgenerators that are housed within the green-houses. For this reason, Tonneijck et al. (2003) indicated thatthe field-grown plants may be less responsive to ethylene when compared to the greenhouse plants wherecontinuous exposure is the norm.

3.2.2.2 Summary of Ethylene Induced Effects in Flowering plants
Many investigators consider flowering plants such as petunias (Petunia nyctaginiflora), marigolds(Tagetes erecta), orchids (Cattleya spp), and carnations (Dianthus caryophyllus L.) to be sensitive toethylene (Tonneijck et al. 2003, Posthumus 1983, and Davidson 1949). Leaf senecessence and flower
abscission have been reported to occur due to ethylene exposure (Tonneijck et al. 2003). In addition,
decreased flower size and increased abortion of flower buds in petunias have been used as indicators ofplant response to pollution (Posthumus 1983 and Cape 2004). While petunias have been used as indicator
plants to assess ethylene sensitivity, orchids have been reported to exhibit severe dry sepal injury at
exposures of 100 ppb of ethylene for up to 8 h (Davidson, 1949).
The flowering plant studies are limited by the fact that they often included relatively high ethylene
exposure concentrations (2 to 4 ppm) when compared to what is expected in an ambient setting(Underwood et al. 2005, Onozaki et al. 2004, Woodson et al. 1988). Ambient ethylene levels vary widely.
For example, while the median concentration of ethylene was reported to be 10.79 ppb in 39 US cities
from 1984 – 1985 (Seila et al. 1989), Abeles and Heggestad (1973) reported a maximum value of 700 ppb
of ethylene in Washington DC. In some of the reported flowering plant studies, longer exposure durations(≥ 8 and/or ≥ 12 h) were required before adverse effects could be recorded. In a multi-year study
conducted by Tonneijck et al. (2003), a quantitative relationship between short-term ethylene exposure
and plant response was not adequately addressed. In another short-term exposure study, excised flowering
petunias were exposed to 4 ppm ethylene for 0, 2, 4, 8, or 10 h (Underwood et al. 2005). Similar exposure
protocols with excised flowers were reported in carnations and geraniums (Evensen K 1991). While themore recent ethylene exposure studies in flowering plants included adequate dose-response information,
the inclusion of excised flowers in the exposure protocols in the opinion of TS is not an appropriate
scenario to depict normal vegetation conditions. For this reason, TS has not chosen these flowering plantstudies as key studies for the development of the short-term vegetation ESL.
Woltering and Van Doorn (1988) conducted an extensive assessment of ethylene flower sensitivity
amongst 93 species of plants from 22 plant families. However, the study included high exposure
concentrations (3,405 µg/m3) that are not relevant to ambient conditions. In addition, the reported
exposure durations (22-24 h) were greater than the acute exposure scenarios defined in the ESL
guidelines (TCEQ 2006). As such, the TS have not chosen the study conducted by Woltering and Van
Doorn (1988) as a key study for the development of the short-term vegetation ESL for ethylene.

Ethylene

Page 143.2.2.3 Key Studies
Since ethylene-related vegetative effects have been documented, a short-term vegetative based ESL for
ethylene exposure was determined according to the ESL Guidelines (TCEQ 2006). The Alberta Canada’s
Ethylene Research Project (i.e., The Alberta Canada Study) was identified as a key study and the study
conducted by Pallas and Kays (1982) was identified as a supporting study to develop the vegetation based
acute ESL (acuteESLveg).

3.2.2.3.1 The Alberta Canada Study
The Alberta Canada Study was a multi-stake holder initiative that was jointly sponsored by theProvisional Government and petrochemical industries in Alberta, Canada (Alberta Research Council
2001). The project was initiated to determine the concentration threshold at which short-term exposures toethylene would cause significant effects on vegetative and reproductive parameters in selected cultivars ofagricultural crops of interest to Alberta, Canada. Archambault and Li, the investigators of the Alberta
Canada study, conducted extensive preliminary screening experiments with Ethephon ((2-Chloroethyl)
phosphonic acid) to determine which plant species in each of 3 plant categories (i.e., cereal, legumes, andoilseeds) and 2 tree species were most sensitive to ethylene (Archambault et al. 2006, Archambault and Li
2001, 1999a, and 1999b). In their studies with field crops, sensitivity of seed yield to ethylene was thecritical effect that was used to determine the relative sensitivity of the crop species. However, for the tree
species, sensitivity to ethylene was based on the vegetative characteristics because vegetative
characteristics are important parameters that determine the marketability of seedlings.
Table 4: Information on the Plants and Trees included in the Alberta Canada Study
Category
Plant
SpeciesSensitive Stage ofVegetative Effects
GrowthSpike emerging
CerealBarleyHordeum
stage
vulgare cv.
Harrington
Decrease in photosynthesis,
vegetative effects, andLegumes
Field pea
Pisum sativum Flat pod stage
decreases in seed yield.
cv. Carrera
Oilseeds
CanolaBrassica napus Many flowers open
cv. Quantum
stage
Trees
White spruce Picea gluca
Vegetative growth
Effects on seedgermination, seedling vigor,
Trees
Lodgepole
Pinus Contorta
growth, and seedlingpinemarketability.
Information on the plants and trees included in the Alberta Canada Study is provided in Table 4. All theplants included in the experiment were grown in the greenhouse until the appropriate stage was reached atwhich time they were transferred to exposure chambers and left for one day to acclimate prior to the startof the exposures. Plants were moved back to the greenhouse and grown to maturity after exposures werecompleted. For a detailed description of the treatments and exposure regimens, please see the Alberta’s
Ethylene Crop Research Project Report titled, “Response of Barley, Field peas, Canola, and Treeseedlings to Ethylene Exposure (2001)”.

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Treatments included exposing barley, field pea, canola, white spruce, and lodgepole pine to six
concentrations of ethylene (10, 75, 150, 300, 600, and 1,200 ppb) at four exposure durations (1.5, 3, 6,
and 12 h). In their studies, the investigators defined short-term exposures as being equal to or less than 12
h. In all the experiments, the order of exposures was randomly selected. In addition, the investigators of
the Alberta Canada Study considered the 10 ppb exposure concentration as a background concentration
based on the findings by Reid and Watson (1985), who reported that complete removal of ethylene fromatmosphere would lead to detrimental effects on plant growth.
The investigators of the Alberta Canada Study reported barley from the cereal category, field pea from thelegume category, and canola from the oil seed category to be the most sensitive species in their respective
categories. In addition, the investigators also reported white spruce and lodgepole pine to be the mostsensitive tree species for ethylene exposure.
The investigators conducted analysis of variance (ANOVA) and reported no significant effects on
photosynthetic rates or vegetative, or reproductive effects for all exposure durations (up to 12 h) at all the
exposure concentrations (up to 1,200 ppb) for all the plant species (barley, field peas, and canola). In thecase of the trees (i.e., lodge pine and white spruce), the investigators reported no effects on seedgermination, seedling vigor, growth, or seedling marketability after an exposure to 1,200 ppb of ethylene
for exposure durations up to 12 h. The investigators reported that after short-term exposures (≤ 12 h) theplants and trees recovered from decreases in photosynthesis and growth.
In addition, the investigators also conducted additional statistical analysis (e.g., linear regression) tofurther understand the relationship between several plant parameters and ethylene dose expressed as a
product of ethylene concentration (ppb) and exposure duration (h). The investigators reported a poorcorrelation between the various plant parameters measured and the ethylene dose. In the case of the tree
seeds/seedlings, the investigators reported a poor correlation between germination and ethylene indicatingthat there was no significant dose effect.
However, the Alberta Research Council established a different short-term (i.e., 1-h) Ambient Air Quality
Objective when compared to the results of the Alberta Canada Study. The Alberta Research Council
established a short-term Ambient Air Quality Objective of 1,200 µg/m3 (1,044 ppb) to be protective of allplant species (Alberta Research Council Report 2001).

3.2.2.3.2 Pallas and Kays (1982) Study
Pallas and Kays (1982) studied the effect of ethylene on photosynthesis by exposing leaves of a variety ofplants to 1 microliter per liter (µl/L) or 1,000 ppb of ethylene for 0, 0.25, 0.5, 1, 2, 4, and 6 h (Table 5).
The investigators also reported including a day without treatment between the treatments to measure any“carry-over effects” on photosynthesis. The Pallas and Kays study (1982) is a well-conducted study as theinhibition of photosynthesis was examined in many plants at exposure durations representative of shortterm exposure scenarios. However, in the TS’s opinion, the study is limited because it included only asingle exposure concentration (1,000 ppb). For this reason, the TS considered the Pallas and Kays (1982)
study as a supporting study to develop the acuteESLveg.

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Table 5: Information on the Plants Included in the Pallas and Kays Study
Green bean
Phaseolus vulgaris L. cv. Contender
Pea
Pisum sativum L. cv. Wando
PeanutArachis hypogea L. cv. Florunner
Scarlet runner bean
Phaseolus coccineus L.
Sensitive plant (according to the study authors)
Mimosa Pudica L.
Irish Potato
Solanum tuberosum L.
Sunflower
Helianthus annus L. line CM90RR
White Clover
Trifolium repens L.
Jerusalem artichoke
Helianthus tuberosus L.
Pallas and Kays (1982) reported a wide range of responses in photosynthesis amongst the various
cultivars exposed to ethylene. The net decrease in photosynthesis was dependent both on the genotype ofthe cultivar and the exposure duration. Pallas and Kays (1982) reported a decrease in photosynthesis withan increase in the exposure duration from 0.25 to 6 h in peanuts. In addition, the authors also reported a
net decrease in photosynthesis when Jerusalem artichoke, sunflower, and sweet potato were exposed to
1,000 ppb ethylene for 2.5 h. However, the authors reported no effects on photosynthesis in green bean,scarlet runner bean, pea, Irish potato, or white clover. Amongst the various plant species tested in the
study, peanut cultivars were reported to be relatively more sensitive to ethylene exposure. With anincrease in the duration of exposure, the inhibitory effect on photosynthesis increased, especially forpeanut. Pallas and Kays (1982) reported a 68% decrease in photosynthesis after a 6 h exposure period.
However, the investigators also reported a rapid recovery after short–term exposure durations and theplants did not exhibit any carry-over effect on photosynthesis. The photosynthetic rates after the shortterm exposure treatments (0.5 - 6 h) returned to normal or pre-exposure levels within 24 h following
treatments. Plants in the 6 h treatment required an additional day for recovery. Overall, Pallas and Kays
(1982) concluded the decrease in photosynthesis to be a reversible effect.

3.2.2.4 Derivation of the acuteESLveg
According to the ESL Guidelines, acuteESLveg is set at a threshold concentration for adverse effects (TCEQ
2006). However, the results from the Alberta Canada Study and the Pallas and Kays (1982) study indicatethat short-term exposures (≤ 12 h and/or ≤ 6 h) of plants to ethylene either at 1,200 ppb or 1,000 ppb
respectively to result in no adverse vegetative effects. While the TS acknowledges the absence of adverse
vegetative effects at the reported exposure concentrations and durations in both the key and supporting
studies, TS conservatively recommends a 1-h acuteESLveg of 1,400 µg/m3 (1,200 ppb) as a sub-thresholdconcentration to be protective for all plant species.
The acuteESLveg of 1,400 µg/m3 was rounded to the two significant figures and is based on the results of theshort-term exposures from the Alberta Canada Study (Table 6). In recommending a 1-h acuteESLveg of
1,400 µg/m3 (1,200 ppb), the TS has taken into consideration that the reported exposure concentration(1,200 ppb) was the highest exposure concentration at exposure durations up to 12 h (i.e., 1.5, 3, 6, and 12h) and the limited database of well-conducted ethylene exposure field studies for crops. The proposed
screening value should also adequately protect vegetation from potential intermittent exposures.

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Table 6. Derivation of the acuteESLveg
Study

Alberta’s Ethylene/Crop Research Project Report III

Study population

Barley, field pea, canola, and tree seedlings

Exposure Method

Growth Chambers

Critical Effects

Vegetative effects and decrease in photosynthesis

POD (Sub-Threshold Concentration)

1,400 µg/m3 (1,200 ppb)

Exposure Duration

1.5, 3, 6, 12 hacute1,400 µg/m3 (1,200 ppb)

ESLveg

3.3 Short-Term ESL and Values for Air Monitoring Evaluation
The acute evaluation resulted in the derivation of the following acute values:• acuteESLveg = 1,400 µg/m3 (1200 ppb)
• acute ReV = 570,000 µg/m3 (500,000 ppb)
• acuteESL = 170,000 µg/m3 (150,000 ppb)
• acuteESLodor = 310,000 µg/m3 (270,000 ppb)
The short-term ESL for air permit reviews and air monitoring evaluations is the acuteESLveg of 1,400 µg/m3(1,200 ppb) as it is lower than the acuteESL and the acuteESLodor (Table1). The acute ReV and the acuteESLodor
may also be used for air monitoring evaluations. The acuteESL (HQ = 0.3) will not be used by the TS toevaluate air monitoring data.

Chapter 4 Chronic Evaluation
4.1 Noncarcinogenic Potential
4.1.1 Physical/Chemical Properties and Key Studies
Physical/chemical properties of ethylene are discussed in Chapter 3. Due to the unavailability of chronic
inhalation exposure studies in humans, the TS selected well-conducted animal studies to develop thechronic ReV. A two-year inhalation study conducted by Hamm et al. (1984) was selected as a key study
to determine the chronic ReV. In the study, Hamm et al. (1984) randomly divided 960 Fischer-344 rats
into 4 groups of 120 animals for each sex and exposed them to 0, 300, 1,000, or 3,000 ppm of ethylene
for 6 h/day, 5 days per week for 106 weeks. There were no reports of any chronic toxicity or
oncogenicity at any of the concentrations tested. Comprehensive analysis of various tissues (e.g., kidneyand nasal turbinates) indicated no signs of carcinogenic effects. While a variety of proliferative,
degenerative, and inflammatory lesions were observed in both the control and treatment groups, theauthors reported that these types of lesions are typical of the animal. A discussion on the highconcentrations of ethylene is warranted based on previous findings that 3,000 ppm is the highest
concentration that could be safely studied for long-term chronic studies (CIIT, 1980). Ethylene isEthylene

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explosive when it reaches 3% or higher in air composition. However, for acute exposure experiments,
investigators were able to use higher concentrations of ethylene safely even up to 50,000 ppm (Section
3.1.3.1). Based on safety issues, Hamm et al. (1984) reported 3,000 ppm as the NOAEL for long-term
chronic studies. TS will therefore consider 3,000 ppm as a free-standing NOAEL.
A 90 day sub-chronic study reported by Rhudy et al. (1978) was selected as a supporting study todetermine the chronic ReV. Rhudy et al. (1978) exposed Sprague-Dawley rats to various concentrationsof ethylene (0, 300, 1,000, 3,000, or 10,000 ppm) for 6 h/day, 5 days/week for 14 weeks. The authors
reported no toxic effects related to ethylene exposure on conducting a comprehensive microscopic
analysis of tissue specimens. In addition, the authors also did not report any changes or abnormalities inhematology, clinical chemistry, and urinalysis. A free-standing NOAEL of 10,000 ppm was determinedfrom the Rhudy et al. (1978) study.

4.1.2 MOA Analysis and Dose Metric
The MOA of ethylene is described in detail in Section 3.1.2. For the key and supporting studies, data on
concentration of the parent chemical is used as the default dose metric.

4.1.3 POD for Key and Supporting Studies
The NOAEL reported in the Rhudy et al. (1978) study (10,000 ppm) was higher than the NOAEL
reported in the Hamm et al. (1984) study (3,000 ppm). However, the TS selected the NOAEL (3,000ppm) from the Hamm et al. (1984) study because it was a chronic, rather than a sub-chronic exposure
study.

4.1.3.1 Default Exposure Duration Adjustments
The TS conducted an adjustment from the discontinuous animal exposure regimen to a continuous
exposure regimen with the following equation to determine the PODADJ`. The PODADJ was determined to
be 535.71 ppm (see below).
PODADJ = POD x (D/24 h) x (F/7 d)where:
PODADJ = POD from animal studies adjusted to a continuous exposure scenario
POD= POD from animal studies based on discontinuous exposure scenario
D= Exposure duration, h per day
F= Exposure frequency, days per week
PODADJ = 3,000 ppm x (6/24) x (5/7) = 535.71 ppm

4.1.3.2 Default Dosimetry Adjustments
Similar to section 3.1.4.2, the TS considered ethylene as a Category 3 gas and the duration exposureadjustments from animals to humans was conducted to determine the human equivalent POD or PODHEC
with the following equation:
PODHEC =PODADJ x ((Hb/g)A / (Hb/g)H)
Where:

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PODHEC = Point of Departure at Human Equivalent Concentration
PODADJ = Adjusted Point of Departure
Hb/g= Ratio of blood: gas partition coefficientA= AnimalH= Human
The PODHEC based on the Hamm et al. (19784) study:
PODHEC = PODADJ x (Hb/g)A / (Hb/g)H= 535.71 ppm x 1= 535.71 ppm

4.1.4 Application of Uncertainty Factors to the PODHEC based on MOA
Analysis
TS applied appropriate UFs to derive a Chronic ReV in accordance with the ESL Guidelines (TCEQ
2006). The PODHEC of 535.71 ppm is based on a 2-Year study conducted by Hamm et al. (1984). The
following UFs are applied: A UF of 3 is applied to account for extrapolation from animals to humans(inter-species variability, UFA), a UF of 10 is applied to account for intraspecies variability (UFH), and a
UF of 3 to account for deficiencies in the database (UFA). The total UF was equal to 100 (3 x 10 x 3).
ReV= PODHEC / (UFA x UFH x UFD)
ReV = 535.71 ppm / (3 x 10 x 3);Rev = 535.71 ppm/100
ReV = 5.3571 ppm (5,300 ppb or 6,100 µg/m3) (rounding up to two significant figure)
A UFA of 3 was used because default dosimetric adjustments from animal-to-human exposure wereconducted which account for toxicokinetic differences but not toxicodynamic differences. A UFH of 10
was used to account for potentially sensitive subpopulations, and a UFD of 3 was used because of theavailability of well-conducted chronic and sub-chronic toxicity studies with a wide range of end points
The confidence in the chronic database is medium.

4.1.5 Health-Based Chronic ReV and chronicESLnonlinear(nc)The chronic ReV of 6,100 µg/m3 (5,300 ppb) rounded to two significant figures was used to calculate thechronic
ESLnonlinear(nc) by using the following formula and a hazard quotient (HQ) of 0.3 (Table 7):chronic

ESLnonlinear(nc) = chronic ReV x HQ

= 5,300 ppb x 0.3 = 1,600 ppb (1,800 µg/m3)

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Table 7. Derivation of the Chronic ReV and chronicESL nonlinear(nc)StudyChronic toxicity and oncogenicity bioassay of
inhaled ethylene in Fischer-344 rats
Study population
Fischer-344 rats
Study Quality
MediumExposure Method
Inhalation
Critical Effects
Hepatic damage
POD (original animal study)
3,000 ppm, NOAEL
Exposure Duration
6 h/day, 5 days/wk, 2 years
Extrapolation to continuous exposure (PODADJ)
535.71 ppm
PODHEC535.71 ppm (gas with systemic effects basedon default RGDR =1)
Total UFs
100
Interspecies UF 3
Intraspecies UF 10
LOAEL UF Not Applicable
Subchronic to chronic UF Not Applicable
Incomplete Database UF 3
(Database Quality) (Medium)
Chronic ReV (HQ = 1)
chronic
ESLnonlinear(nc) (HQ = 0.3)

6,100 µg/m3 (5,300 ppb)
1,800 µg/m3 (1,600 ppb)

4.2 Carcinogenic Potential
Concern over the toxicity of ethylene is due to the metabolic conversion of ethylene to EtO which has
been designated as a carcinogen and a genotoxicant (Bolt and Filser 1987). However, the percentage
conversion of ethylene to EtO is insignificant (See Section 3.12). According to the ACGIH reportpublished in 2005, “the potential toxicity due to EtO formation from the metabolic conversion of ethylene
to EtO will not likely pose a cancer risk based on the current knowledge of the significance of adducts”.
In conclusion, ethylene is a relatively non-toxic chemical and is assumed to have a threshold, non-linear
MOA. ACGIH (2005) has designated ethylene as A4 (i.e., it is not classified as a human carcinogen).
The International Agency for Research on Cancer (IARC) (1994) has classified ethylene as a Group 3,
which indicates that it is a not classified as a human carcinogen. The German Commission for theInvestigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has
classified ethylene as a 3B (Deutsche Forschungsgemeinschaft 2004 in ACGIH 2005). The TS has
determined that the data are inadequate for an assessment of human carcinogenic potential by theinhalation pathway.

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Page 214.3. Welfare-Based Chronic ESL
4.3.1. Development of Vegetation-Based Chronic ESL (chronicESLveg)
Four key studies were identified to determine the chronicESLveg. The first study was the Alberta Ethylene
Research Project in which barley, field peas, and canola were exposed to various concentrations of
ethylene for different durations (Alberta Canada Study). The second key study was conducted by Klassen
and Bugbee (2002) in which they evaluated the sensitivity of wheat (Triticum aestivum L.) and rice
(Oryza sativa) to various concentrations of ethylene. The third study was conducted by Reid and Watson(1985) who examined the sensitivity of oats (Avena Sativa L. cv. Random) and canola to chronic
exposure to ethylene. In the fourth key study, Blankenship and colleagues (1993) conducted experiments
to study the effects of continuous low levels of ethylene on growth and flowering of Eastern lily (Lillium
longiflorum Thumb. Culitvar ‘Nellie White’).

4.3.1.1 The Alberta Canada Study
Archambault and Li (2001) wanted to determine the critical duration of exposure and long-term
vegetative effects based on yield when plants are exposed to ethylene during a sensitive stage of growth.
The Alberta Environment (2003) report includes various ethylene exposure scenarios and is discussed
below. For short-term exposure scenarios (less than or equal to 12 h) please see Section 3.4. Two of the
exposure scenarios are discussed below. For a detailed description of the treatments and exposure
regimens, please see the Alberta’s Ethylene Crop Research Project Report titled “Response of Barley,
Field Peas, Canola, and Tree Seedlings to Ethylene Exposure (2001)”.
Exposure Scenario 1:
In this scenario, Archambault and Li exposed barley plants to 50 ppb of ethylene for 0, 3, 6, 12, 18, and24 days, and field peas to 50 ppb of ethylene for 0, 12, 16, 20, 24, and 28 days in growth chambers
according to standard laboratory protocols. In the case of barley, the seed yield decreased by 41% when
the plants were exposed to 50 ppb for 3 days and by 89% when the plants were exposed for 24 days.
However, there were no effects on the above ground and root biomass, plant height, or tiller number after
exposure to 50 ppb for 24 days. Field peas on the other hand were found to be relatively more insensitive
to long-term exposures to ethylene. Exposure of field peas to 50 ppb of ethylene did not result insignificant effects in plant height, number of pods, weight of pods, number of seeds, or seed yield. A
threshold concentration of 50 ppb for long-term exposures was therefore determined from the studies onbarley.
Exposure Scenario 2:
A second exposure protocol included a summary of long-term ethylene exposures in barley, field peas,and canola where barley plants were exposed to a range of ethylene concentrations (10 – 250 ppb). The
investigators reported a 63% reduction in seed yield of barley when barley plants were exposed to 34µg/m3 (30 ppb) for 14 days. A threshold concentration of 34 µg/m3 (30 ppb) for long-term exposures wastherefore determined from the second set of exposure scenarios.

Ethylene

Page 224.3.1.2 Klassen and Bugbee (2002)
Klassen and Bugbee (2002) evaluated the sensitivity of wheat (Triticum aestivum L.) and rice (Oryza
sativa) to continuous ethylene levels ranging from 0 to 1,000 ppb in a growth chamber throughout thegrowing season. The authors reported anthesis (flowering stage) to be the most sensitive period for thecrop plants. Exposures that stopped at the flowering stage were found to have lower reductions in yield.
In this experiment, the authors reported that exposure to 50 ppb of ethylene reduced the yield by 36% in
wheat and 63% in rice, respectively. In addition, plants that were exposed to 1000 ppb were found to becompletely sterile. A threshold concentration of 50 ppb for long-term exposures was therefore determinedfrom the studies on wheat and rice.

4.3.1.3 The Reid and Watson Study (1985)
Reid and Watson (1985) conducted a suite of experiments to determine the effect of various
concentrations of ethylene on plant growth in oats (Avena sativa L. cv. Random) and canola (Brassica
campestris L. cv. Candle) plants. Reid and Watson exposed oats for 100 days to 0, 8, 40, 81, and 173µg/m3 of ethylene and canola plants to 0, 12, 40, 173, and 690 µg/m3 of ethylene for 87 days. At the 40µg/m3 concentration, the authors reported per plant floret number to decrease by 26% in oats and per
plant seed yield to decrease by 57%. The authors therefore reported 40 µg/m3 (34 ppb) to be the thresholdconcentration at which negative effects occur.

4.3.1.4 The Blankenship study (1993)
Blankenship and colleagues (1993) studied the effects of continuous, low levels of ethylene on growthand flowering of Easter lily (Lilillum longiflorum) Thumb, cultivar ‘Nellie White’ by exposing Easterlilies to 0, 0.01, 0.05, or 0.1 µl/l (ppm) ethylene for 77 days. The authors reported that the Easter lilies
continuously exposed to 50 ppb (0.05 µl/l) had greater than 50% decrease in dry weight in both shoots
and inflorescences. In addition, both the 50 and 100 ppb exposure groups were unmarketable. The plants
in the 10 ppb were reported to not be affected and were reported to be marketable. Therefore, the reported
threshold concentration for long-term exposure for flowering plants is 50 ppb.

4.3.1.5 Determination of chronic ESLveg
Vegetation-based ESLs are set at the threshold concentration for adverse effects and are determined inaccordance with ESL Guidelines (TCEQ 2006). Amongst all the key studies identified by the TS, thebarley exposure studies (Exposure Scenario 2) reported the lowest threshold concentration of 34 µg/m3(30 ppb). The TS, therefore, determined the chronic ESLveg to be 34 µg/m3 (30 ppb).

Ethylene

Page 23
Table 8. Derivation of the chronicESLveg
Study
Study population
Exposure Method
Critical Effects
POD (Threshold Concentration)
Exposure Duration
chronic
ESLvegAlberta’s Ethylene/Crop Research Project Report
III, 2001 (Exposure Scenario 2)
BarleyGrowth Chambers
63% reduction in seed yield for barley
34 µg/m3 (30 ppb)
14 days
34 µg/m3 (30 ppb)

4.3.1.6 Other Vegetation-Based Studies Reviewed by TS
Among crop plants, vegetative effects of cotton (Gossypium hirsutum) and potato (Solanum tuberosum)
have been studied on exposure to ethylene. Hall et al. (1957) reported extensive plant damage in cotton
plants in the vicinity of a polyethylene manufacturing plant in Texas. The reported ambientconcentrations of ethylene ranged from 0.04 to 30 ppm. In addition to reduction in yield, cotton plants
exhibited leaf abscission, scattered seedling death, vine-like growth habit, and abscission of squares. In a
growth chamber experiment, Heck et al. (1961) exposed cotton to constant levels of 40 or 100 ppb
ethylene for 27 days. While no severe plant injury or death was reported, the authors reported a 25–50%
reduction in yield (Heck et al. 1961). Cotton leaf and fruit abscission were also investigated by Hall et al.
(1957). TS did not consider these studies as key studies because these studies were reported either in areview article or limited dose-response information was presented.

4.4 Long-Term ESL and Values for Air Monitoring Evaluation
The chronic evaluation resulted in the derivation of the following chronic values: chronicESLveg= 34 µg/m3 (30 ppb)
 chronic ReV= 6,100 µg/m3 (5,300 ppb)
chronic

ESLnonlinear(nc)= 1,800 µg/m3 (1,600 ppb )The long-term ESL for air permit reviews and air monitoring evaluations is the chronicESLveg of 34 µg/m3(30 ppb). The chronic ReV of 6,100 µg/m3 (5,300 ppb) may also be used in air monitoring evaluations(Table 1). The chronicESLnonlinear(nc) (HQ= 0.3) will not be used by the TS to evaluate air monitoring data.

Chapter 5. References
5.1 References Cited in Development Support Document
Abeles, FB. 1982. Ethylene as an air pollutant. Agricul For Bul 5:4-12.
Abeles, FB, and HE Heggestad. 1973. Ethylene: an urban air pollutant. J Air Pollut Control Assoc
23: 517-521.
Air Quality Criteria for Hydrocarbons. 1970. US Dept. Of Health, Education, and Welfare, Nat. Air Poll.
Control Admin. Pub. No. AP-64, March 1970.

Ethylene

Page 24
Alberta Environment. 2003. Assessment Report on ethylene for developing ambient air quality objectives.
Publ No. T/691 ISBN No. 0-7785-2498-1 (On-line Edition). Web Site:
http://www3.gov.ab.ca/env/protenf/standards/index.html (accessed October 1, 2007).
Alberta Research Council. 2001. Response of barley, field pea, canola and tree seedlings toethylene exposure. Alberta’s Ethylene Crop Research Project, Report III.
American Chemistry Council (ACC). 2004. Ethylene Product Stewardship Manual.
American Conference of Governmental Industrial Hygienists (ACGIH). 2005. Ethylene: TLV® (2005).
Chemical Substances 7th Edition Documentation ACGIH® Publication #7DOC-264
Amoore, JE, and E Hautala. 1983. Odor as an aid to chemical safety: odor thresholds comparedwith threshold limit values and volatilities for 214 industrial chemicals in the air andwater dilution. J App. Toxicol 3(6):272-290.
Archambault, D, and X Li. 1999a. Report I. Design and Performance of ARC’s ethylene exposuresystem. Alberta Research Council.
Archambault, D, and X Li. 1999b. Report II. The effects of ethephon on barley, wheat, oats, fieldpeas, and canola : A screening test for the determination of ethylene sensitivity. Alberta ResearchCouncil.
Archambault, D, and X Li. 2001. Report III. Response of barley, field pea, canola and tree seedlings
to ethylene exposure. Alberta Research Council.
Archambault, D, X Li, K Foster, et al. 2006. A Screening Test for the Determination of Ethylene
Sensitivity; Environ Monitoring and Assess 115, No. (1-3). pp. 509-530.
Austin, SG, and AR Schnnatter. 1983. A case-control study of chemical exposures and brain tumors
in petrochemical workers. J Occup Med 25(4):313-320.
Aveyard, L, and CJ Collins. 1997. OECD 421 reproduction/developmental toxicity screening study byhead-only exposure: experience with ethylene. Teratology 55:47.
Blankenship, SM, DA Bailey, and JE Miller. 1993. Effects of continuous, low levels of ethylene on
growth and flowering of Eastern lily. Scientia Horticulturae, (53):311-317.
Bolt, HM, and JG Fiser. 1987. Kinetics and disposition in toxicology. Example: carcinogenic risk
estimate for ethylene. Arch Toxicol 60 (1-3):73-76.
Cavender, F. 1994. Aliphatic hydrocarbons. In Patty’s Industrial Hygiene and Toxicology, 4thed., Vol 2B, Chap. 10, pp. 1221 – 1266. [Clayton, G.D.; Clayton, F.E.; Eds. John Wiley& Sons, New York].

Ethylene

Page 25
ChemFinder.com. 2004. ChemFinder.com Database and Internet searching.
http://chemfinder.cambridgesoft.com/result.asp. (accessed September 24, 2007).
Chemical Industry Institute of Toxicology. (1980). A twenty-four month inhalation toxicology study inFischer-344 rats exposed to atmospheric ethylene. Final report. [Report prepared for theChemical Industry Institute of Toxicology by Industrial Biotest Laboratories, Inc., CIIT Docket
No. 12000]. Chemical Industry Institute of Toxicology Research Triangle Park, NC.
Conolly, RB, and RJ Jaeger. 1977. Acute hepatotoxicity of ethylene and halogenated ethylenes after
PCB treatment. Environ. Health Perspect 21: 131-135.
Conolly, RB, RJ Jaeger, and S Szabo. 1978. Acute hepatotoxicity of ethylene, vinyl fluoride, vinyl
chloride, and vinyl bromide,after Arochlor 1254 pretreatment. Exp Mol Pathol 28(1):2533.
Crocker, W. 1948. Growth of plants. New York, Reinhold Publishing Corp. 459 p.
Csanády, GA, B Denk, C Pütz, et al. 2000. A physiological toxicokinetic model for exogenous andendogenous ethylene and ethylene oxide in rat, mouse, and human: formation of 2-hydroxyethyl
adducts with hemoglobin and DNA. Toxicol Appl Pharmaco. 165(1): 1-26, 2000.
Darley, EF et al. 1963. Plant damage by pollution derived from automobiles. Arch Environ Health
6:761-770.
Davidson, OW. 1949. Effects of ethylene on orchid flowers. Proc Amer Soc Hort Sci 53:440-446.
Denk, B, JG Filser, D Oesterle et al. 1988. Inhaled ethylene oxide induces preneoplastic foci in rat
liver. J Cancer Res Clin Oncol. 114: 35-38.
Deutsche Forschungsgemeinschaft. 2004: List of MAK and BAT values 2004, p61. Commission for theInvestigation of Health Hazards of Chemical Compounds in the Work Area, Report 40. WileyVCH Verlad GmBH & Co. KgaA, Weinheim, FRG.
Dueck, Th.A, CJ Van Dijk, C Grashoff et al. 2003. Response of potato to discontinuous exposures ofatmospheric ethylene: results of a long-term experiment in open-top chambers and crop growthmodeling. Atmos Environ 37(12):1645-1654.
Filser, JG, B Denk, M Tornqvist M et al. 1991. Pharmacokinetics of ethylene in man: body burden with
ethylene oxide and hydroxyethylation of hemoglobin due to endogenous and environmental
ethylene. Archives of Toxicology 66(3):157-163.(
Filser, JG, and HM Bolt. 1983. Exhalation of ethylene oxide by rats on exposure to ethylene. Mutat Res
120(1):57-60.
Granath, F, O Rohlen, C Gooransson et al. 1996. Relationship between dose in vivo of ethylene oxide

Ethylene

Page 26
and exposure to ethene studied in exposed workers. Human Exp Toxicol 15(10): 826-633.
Grossmann, K, and H Hansen. 2001. Ethylene triggered abscisic acid: A principle in plant growth
Regulation. Physiol. Plant 113:9-14.
Guest, D, CS Barrow, JA Popp et al. 1981. Effects of Aroclor 1254 on disposition andhepatotoxicity of ethylene in the rat. Toxicol Appl Pharmacol 57(3): 325-334.
Hall, WC, CB Truchelut, CL Leinweber et al. 1957. Ethylene production by the cotton plant and its
effects under experimental and field conditions. Physiol Plant 10:306-316.
Hamm, TE, D Guest, and JG Dent. 1984. Chronic toxicity and oncogenicity bioassay of inhaled
ethylene in Fischer-344 rats. Fundam Appl Toxicol (4): 473-478.
Health Canada. 2001. Proposed regulatory decision document PRDD2001-04 Ethylene, Eco Sprout
Guard. Pest Management Regulatory Agency, 23 pp.
Heck, WW, EG Pires, and WD Hall. 1961. The effects of a low ethylene concentration on the growth ofcotton. J Air.Pollution Control. Assoc. 11: 549-556.
International Agency for Research on Cancer 1994: Ethylene: In: IARC, Monographs on the evaluationof carcinogenic risks to humans, Vol 60, Some industrial chemicals, pp-45-71. IARC, Lyon,
France.
Jordan, WR, Brown, PW Morgan et al. 1972. Water stress enhances ethylene-mediated leaf abscission incotton. Plant Physiol 50: 756-758.
Klassen, SP, and B Bugbee. 2002. Sensitivity of wheat and rice to low levels of atmospheric ethylene.
Crop Sci 42(3): 746-753.
Leffingwell AA, R Waxweiler, V Alexander et al. 1983. Case-control study of gliomas of the brain
among workers employed by Texas City, Texas chemical plant. Neuroepidemiology (2): 179-195.
Matheson Tri-Gas 2004 MSDS http://www.mathesontrigas.com/MSDS/index.aspx. (accessed October 1,2007).
Morgan, PW. 1969. Stimulation of ethylene evolution and abscission in cotton by 2Chloroethanephosphonic acid. Plant Pysiol 44: 37-341.
Munne-Bosch, S, J Penuelas, D Asensio, J Llusia. 2004. Airborne ethylene may alter antioxidant
protection and reduce tolerance of Holm oak to heat and drought stress. Plant Physiol 136:
2937- 2947.
OECD: 1994. SIDS Ethylene. UNEP Publications.
http://www.chem.unep.ch/irptc/sids/oecdsids/74851.pdf. (accessed October 1, 2007).

Ethylene

Page 27
Pallas, JE, and SJ Kays. 1982. Inhibition of photosynthesis by ethylene- A stomatal effect. Plant. Physiol.
70:598-601.
Posthumus, AC. 1983. Higher plants as indicators and accumulators of gaseous air pollution.
Environ Monitor.Assess 3:263-272.
Reid, DM, and K Watson. 1985. Ethylene as an air pollutant. In: Roberts J.A.; Tucker, G.A. (eds.)
Ethylene and Plant Development. Buttersworths, London. pp. 277-286.
Rhudy, RL, DC Lindberg, JW Goode. 1978. Ninety-day sub acute inhalation study with ethylene in
albino rats. Toxicol Appl Pharmacol 45(1):285.
Seila, RL, WA Lonneman, SA Meeks. 1989. Determination of C2 to C12 ambient air hydrocarbons in 39
U. S. cities, from 1984 through 1986. U. S. Environ. Prot. Agency, Off. Res. Dev. [Rep]
USEPA/600/s3-89/058
Selinski S, K Golka, HM Bolt, et al. 2000. Estimation of toxicokinetic parameters in population
models for inhalations studies with ethylene. Environmetrics 11:479-495.
Texas Commission on Environmental Quality (TCEQ). 2006. Guidelines to Develop Effects Screening
Levels, Reference Values, and Unit Risk Factors. Chief Engineer’s Office. RG-442.
Tonneijck AEG, ten Berge WF, Jansen BP, Bakker C. 1999. Epinsastic response of potato toatmospheric ethylene near polyethylene manufacturing plants. Chemosphere 39(10):1617-1628.
Tonneijck, AEG, BP Jansen, C Bakker. 2000. Assessing the effects of atmospheric ethylene on epinasty
and tuber yield of potato (Solanum tubersoum L.) near polyethylene manufacturing plants.
Environ Monitor and Assess 60: 57-69.
Tonneijck, AEG, WF ten Berge, and BP Jansen. 2003. Monitoring the effects of atmospheric ethylene
near polyethylene manufacturing plants with two sensitive plant species. Environ Pollution (123)275-279.
Tornqvist, M. 1994. Is ambient ethene a cancer risk factor? Environ Health Persp 102:157160.
Underwood, BA, DM. Tieman, K Shibuya et al. 2005. Ethylene-regulated floral volatile synthesis inpetunia corollas. Plant Physiol 138(1): 255-266.
United States Environmental Protection Agency (USEPA). 1994. Methods for derivation of inhalationreference concentrations and application of inhalation dosimetry. Washington, DC: U.S.
Environmental Protection Agency. EPA/600/8-90/066F.
United States Environmental Protection Agency (USEPA). 2002. A review of the reference dose andEthylene

Page 28
reference concentration process. EPA/630/P-02/002F. Final Report
Van Gemert, LJ, and AH Nettenbreijer. 1993. Compilation of Odour Threshold Values in Air and Water.
National Institute for Water supply, Voorburg, Netherlands.
Woltering, EJ, and WG Van Doorn. 1988. Role of ethylene in senescence of petals-morphological andtaxonomical relationships. J Exp Bot 39:1605-1616.

5.2 Other Studies and References Reviewed by the TS
Abeles, FB, PW Morgan, and ME Saltveit. 1992. Ethylene in plant biology. 2nd edn. Academic
Press, Inc. San Diego, CA. 414 pp.
Beyer, EM. 1975. Abscission. The initial effect of ethylene is in the leaf blade. Plant Physiol 55: 322327.
Blankenship, SM, and J Kemble. 1996. Growth, fruiting and ethylene binding of tomato plants in
response to chronic ethylene exposure. J of Horti.Sci 71 (1) 65-69.
Guinn, G. 1982. Fruit age and changes in abscisic acid content, ethylene production and abscission rate ofcotton fruits. Plant Physiol. 69(2): 349-352.
Jack, TR, RK McBrien., and B Dowsley. Impact assessment for ethylene emissions at a petrochemicalsite. In: Kanellis AK, Chang C, Kende H, Grierson D. eds. Pp. 283-288. Biology andBiotechnology of the plant hormone Ethylene. Kluwer Academic publishers, Dordrecht,
Netherlands.
Mortensen, LM 1989. Effect of ethylene on growth of greenhouse lettuce at different light andtemperature levels. Sci Horti 39: 97-103.
Registry of Toxic Effects of Chemical Substances Database 2006. Canadian Centre for Occupational
Health and Safety, http://ccinfoweb.ccohs.ca/rtecs/search.html. (accessed October 1, 2007).

資料

米 陸 軍 健康増進・予防医学センター
野 生 生 物に対するエチレンの毒性評価
2008 年 ４月

U.S. Army Center for Health Promotion and Preventive Medicine
JANUARY 2006

Wildlife Toxicity Assessment for
Ethylene

１２
３－7

U.S. Army Center for Health Promotion
and Preventive Medicine

Wildlife Toxicity Assessment for
Ethylene

JANUARY 2006

Prepared byHealth Effects Research Program
Environmental Health Risk Assessment Program

USACHPPM Document No: 37-EJ1138-01Q
Approved for public release; distribution unlimited.

Readiness Thru Health

U
S
C
H
P
P
M

Wildlife Toxicity Assessment for
Ethylene

FINAL REPORTJANUARY 2006

Prepared byHealth Effects Research Program
Environmental Risk Assessment Program

USACHPPM Document No: 37-EJ1138-01Q
Approved for Public Release; Distribution Unlimited

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

Acknowledgements
Key Technical
Authors:

Christopher J. Salice, Ph.D.

USACHPPM; Directorate of Toxicology, Health
Effects Research Program

George Holdsworth, Ph.D.

T N & Associates
124 S. Jefferson Circle
Oak Ridge, TN 37830

Heidi L. Ilg, B.S.

Oak Ridge Institute of Science and Education,
Oak Ridge, TN

Contributors:

Michael J. Quinn, Jr.

Oak Ridge Institute of Science and Education,
Oak Ridge, TN

Outside Reviewers:

Greg Linder

USGS/BRD/CERC
Heron Works Field Office
Entrix, Inc.

John Newstead
Steve Sheffield

Point of Contact
For further information or assistance contact the following:
Mark S. Johnson, Ph.D., D.A.B.T.
U.S. Army Center for Health Promotion and Preventive Medicine
Toxicology Directorate: Health Effects Research Program
ATTN: MCHB-TS-THE, Bldg. E2100
Aberdeen Proving Ground, MD 21010-5403(410) 436-3980 / DSN 584-3980
Mark.s.johnson@us.army.mil

When referencing this document use the following citation:
USACHPPM. 2004. Wildlife Toxicity Assessment for Ethylene. U.S. Army Center for Health
Promotion and Preventive Medicine (USACHPPM) Project Number 37-EJ1138-01Q, Aberdeen Proving
Ground, Maryland.

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WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

Table of Contents
Wildlife Toxicity Assessment for ......................................................................................................... 2
Ethylene ................................................................................................................................................ 2
Acknowledgements............................................................................................................................... 3
Point of Contact .................................................................................................................................... 3
Wildlife Toxicity Assessment for Ethylene.......................................................................................... 5
1. Introduction............................................................................................................................................... 5
2. Toxicity Profile..................................................................................................................................... 5
2.1 Literature Review.......................................................................................................................... 5
2.2 Environmental Fate and Transport................................................................................................ 6
2.3 Summary of Mammalian Toxicity................................................................................................ 7
2.3.1 Mammalian Toxicity - Oral ................................................................................................ 7
2.3.1.1 Studies Relevant for Mammalian TRV Development for Ingestion Exposures .. 7
2.3.2 Mammalian Inhalation Toxicity ......................................................................................... 8
2.3.2.1 Mammalian Inhalation Toxicity – Acute ............................................................. 8
2.3.3.2 Mammalian Inhalation Toxicity – Subchronic.................................................... 8
2.3.3.4 Mammalian Inhalation Toxicity – Chronic......................................................... 9
2.3.3.5 Studies Relevant for Mammalian TRV Development for Inhalation Exposures . 9
2.3.4 Mammalian Inhalation Toxicity – Other .......................................................................... 10
2.3.5 Mammalian Dermal Toxicity............................................................................................ 10
2.4 Summary of Avian Toxicology................................................................................................... 10
2.5 Amphibian Toxicology ............................................................................................................... 10
2.6 Reptilian Toxicology .................................................................................................................. 10
3. RECOMMENDED TOXICITY REFERENCE VALUES..................................................................... 10
3.1 Toxicity Reference Values for Mammals ..................................................................................... 10
3.1.1 TRVs for Ingestion Exposures for the Class Mammalia ................................................... 10
3.1.2 TRVs for Inhalation Exposures for the Class Mammalia.................................................. 10
4. IMPORTANT RESEARCH NEEDS ................................................................................................. 11
5. References........................................................................................................................................... 12
APPENDIX A LITERATURE REVIEW.................................................................................................. 13

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WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

Department of the Army
U.S. Army Center for Health Promotion and Preventive Medicine

Wildlife Toxicity Assessment for Ethylene
CAS No. 74-85-1

January 2006

1. Introduction
Ethylene is a colorless gas that is produced by the petrochemical industry in vast quantities throughout
the world. As summarized by the International Agency for Research on Cancer (IARC), the compound
serves as the "building block" for the production of polyethylene, as well as other important chemicals
and intermediates such as ethylene oxide, ethylene dichloride, ethylbenzene, ethylene glycol, ethanol andvinyl acetate monomer among others (IARC 1994). In medicine, the compound has been used as ananaesthetic when mixed with air. However, the use of this formulation has been largely discontinued
because of the explosive nature of the ethylene-oxygen mixture. The compound is released to theenvironment as a product of burning vegetation, a by-product of petroleum refining, through production
by steam cracking of hydrocarbon feedstocks, incomplete combustion of fossil fuels, in automobile anddiesel exhausts and by sewage treatment plants (HSDB 2001). Ethylene is also produced and emitted by
all plants and hence is present naturally in the environment. Human beings and other mammals also
produce the compound endogenously.
This Wildlife Toxicity Assessment summarizes current knowledge of the toxicological impacts ofethylene on wildlife. Evaluating the toxicity of ethylene is intended to contribute to the derivation of
toxicity reference values (TRVs) that could serve as screening-level benchmarks for wildlife in thevicinity of contaminated sites. The protocol for the performance of this assessment is documented in the
U.S. Army Center for Health Promotion and Preventive Medicine Technical Guide 254, Standard
Practice for Wildlife Toxicity Reference Values (USACHPPM 2000).

2. Toxicity Profile
2.1

Literature Review

Relevant biomedical, toxicological, and ecological databases were electronically searched April 20,
2001 and May 2, 2001, using Dialog to identify primary reports of studies and reviews on the toxicologyof ethylene. Separate searches were carried out linking the compound to mammals, birds, and reptiles
and amphibians (combined). In general, a two-tiered approach was used in which all citations were firstevaluated as titles and “key words in context.” All available abstracts of those articles that were selected
Page 5 of 12

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

in the first tier as possibly relevant to TRV development were then evaluated for relevancy and retention
for evaluation in the second tier. For ethylene, 9 articles were marked for retrieval from 538 initial hits, adisparity arising because the initial sweep captured a substantial number of reports of studies that featured
the use of "ethylene" as part of the name of a large number of other compounds. These were eliminatedin Tier 2 of the selection process. Details of the search strategies and the results of each are documented
in Appendix A.
In addition to Dialog searching, a number of U.S. Army reports were identified in the Defense
Technical Information Center (DTIC). Secondary references and sources of information on ethylene
included the National Library of Medicine’s Hazardous Substances Databank (HSDB 2001) and IARC
monographs (IARC 1979, 1994).

2.2

Environmental Fate and Transport

Ethylene is a ubiquitous component of the atmosphere, with concentrations reaching 5 g/m3 at remotesites. However, its concentration can range greater than 1000 g/m3 in urban centers, largely as a resultof vehicle exhaust emissions. Ethylene is produced for a variety of uses in large quantities; about 47
billion pounds were produced in 1995 (Chemical and Engineering News 1996). Industrial release ofethylene to the air is substantial throughout the developed world. IARC (1994) reports an estimated totalindustrial release of 17,400 tons of ethylene in the United States in 1991. A report from the American
Petroleum Institute (Suriano 2003) in support of the EPA Toxic Release Inventory indicates that 1.7
billion pounds of ethylene was released by petroleum refineries in 2000.
Volatilization of soil-borne ethylene is likely, based on the compound's high vapor pressure of
5.2 × 104 and a Henry's Law constant of 2.3 × 10-1 atm-m3/mole at 25oC (HSDB 2001). As listed inTable 1, these and other physical-chemical characteristics also favor volatilization of ethylene from thesurface of marine and freshwater systems. However, although sparingly soluble in water, the compound
has been detected in oceans, lakes, and rivers in and around the United States. For example,
concentrations of ethylene up to 35 nL/L were measured in water samples taken in the Mississippi delta.

Table 1. Summary of Physical-Chemical Properties of Ethylene
CAS No.

74-85-1

Molecular weight

28.05

Color

ColorlessPage 6 of 12

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

Table 1. Summary of Physical-Chemical Properties of Ethylene
Physical state

Gas

Melting point-169oC

Boiling point-103.7oC

Odor

Sweet

Solubility

131 mg/L in water at 20-25 °C
slightly soluble in benzene, ethanol, acetone, soluble indiethyl ether

Partition coefficients:
Log Kow

1.13

Log Koc

2.0–2.5o

5.2 × 104 mm Hg

Vapor pressure at 25 C
Vapor Density

0.978 (air = 1)oHenry's Law constant at 25 C

2.3 × 10-1 atm.m3/mole

Conversion factors

1 ppm = 1.15 mg/m3
1 mg/m3 = 0.87 ppm

Sources: HSDB (2001), IARC (1994)

A number of mechanisms have been suggested for how the chemical is degraded in the environment.
For example, the compound can degrade rapidly in the atmosphere as it reacts with photochemicallyproduced hydroxyl radicals. This process has a half-life of about 1.9 days. Nitrate radicals and ozone
will also cause ethylene degradation, however at a lower rate. Ethylene can also be broken down as aresult of microbial action as determined by pure culture research, however, it is expected to oxidize toethylene oxide which is no metabolized further and may accumulate in the environment (HSDB 2001).
Given the volatility of ethylene, it is unlikely that it would persist in the environment long enough toallow for significant exposures to terrestrial wildlife. In the event that exposure would occur, the most
likely route would be inhalation followed possibly by the dermal route. Importantly, ethylene is readily
converted to ethylene oxide, which is somewhat more stable and could pose some risk to wildlife.

2.3

Summary of Mammalian Toxicity

2.3.1 Mammalian Toxicity - Oral
Given the gaseous nature of ethylene at ambient temperatures and pressures, there are no data on the
toxicological effects of ethylene when administered via the oral route.
2.3.1.1 Studies Relevant for Mammalian TRV Development for Ingestion Exposures
Not applicable.

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WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

2.3.2 Mammalian Inhalation Toxicity
2.3.2.1 Mammalian Inhalation Toxicity – Acute
Due to the fact that ethylene serves as a rapid onset anesthetic, humans and animals have been exposed
to relatively high concentrations without notable long-term adverse effects. For example, rats exposed toethylene at concentrations of up to 500,000 ppm for 5 hours are reported to have suffered no long-term
adverse effects (HSDB 2001). The apparent tolerance to high concentrations of ethylene in animals andhumans has precluded the identification of a reliable compound-specific median lethal concentration(LC50). However, it appears that concentrations of ethylene necessary to induce effective anesthesia comeclose to inducing hypoxia as the proportion of oxygen in the ethylene-air mixture is reduced.
Although there are few if any toxicological consequences of exposure to ethylene via inhalation, theability of the compound to react with biological macromolecules has been demonstrated. For example,
Eide et al. (1995) exposed male Sprague-Dawley rats to ethylene (one of a range of alkenes underinvestigation) at 300 ppm for 12 hours/day on three separate days. Exposure took place in a conicallyshaped steel chamber with a glass door and walls. At termination, aliquots of blood and samples of lung,brain, liver, kidney, and peripheral fat were measured for ethylene. The formation of DNA adducts inliver and lymphocytes were monitored using the 32P-postlabelling technique detected using gas
chromatography/mass spectrometry. N-(2-hydroxyalkyl) valine adducts of hemoglobin and 7alkylguanine adducts of DNA were detected consistently in these experiments, including N-(2hydroxyethyl) valine and 7-ethylguanine when ethylene was used as the test compound.

2.3.2.2 Mammalian Inhalation Toxicity – Subchronic
An experiment by Vergnes and Pritts (1994) used a subacute dosing regime to examine ethylene'sability to induce the formation of micronuclei in the bone marrow of male F344 rats and B6C3F1 mice.
Ten animals/group were exposed to 0, 40, 1000, and 3000 ppm ethylene, 6 hours/day, 5 days/week for 4
weeks, with bone marrow collected 24 hours after the last exposure. Exposure took place in a steel
inhalation chamber with glass windows. Examination of cell smears revealed little if any formation of
micronuclei or polychromatic nuclei in ethylene-exposed groups, although the incidence of thesefeatures was significantly increased in the cells of animals receiving 200 ppm ethylene oxide, a majorcarcinogenic metabolite of ethylene. This finding appears uncharacteristic in view of the likelihood that
ethylene oxide is a metabolite of ethylene. However, the contradiction may have been explained byWalker et al. (2000) who used a similar experimental protocol to show that while both ethylene andethylene oxide induce the formation of N-(2-hydroxyethyl) valine in hemoglobin andN7-(2-hydroxyethyl)guanine in DNA, only ethylene oxide had the ability to increase the frequency ofPage 8 of 12

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

Hprt mutants in splenic T cells. The authors presented evidence to show that the cytochrome
P4502E1-mediated conversion of ethylene to ethylene oxide saturates at levels that are insufficient totrigger the toxic responses that are typical of ethylene oxide exposure.
The Chemical Industry Institute of Toxicology (CIIT) has carried out two full-scale studies on the
toxicology of ethylene, one of which was reported by Rhudy et al. (1978). The protocol featured theexposure of 15 "albino" rats/sex/group to 0, 300, 1000, 3000, or 10,000 ppm ethylene, 6 hours/day, 5days/week for 13 weeks. Ethylene was delivered in unspecified inhalation chambers. During the study
clinical signs, mortality, body weights, and food consumption were monitored daily; clinical chemistry,hematological, and urinalysis parameters were monitored in controls and high dose groups on days 6, 45
and 83; and full necropsies and histopathological evaluations were carried out on all survivors at
termination. However, there were no compound-related differences in treatment groups compared tocontrols in any of the parameters under evaluation.
2.3.3.4 Mammalian Inhalation Toxicity – Chronic
The second CIIT study extended the duration to 24 months for 120 F344 rats/sex/group exposed to 0,300, 1000, or 3000 ppm ethylene (Hamm et al. 1984). Exposure took place in four glass and stainlesssteel chambers. Animals were euthanized on an interim basis after 6, 12, and 18 months, with thesesubjects and all survivors monitored for survival, clinical signs, ophthalmologic characteristics,
hematology, clinical chemistry, and urinalysis. A full suite of histopathological examinations werecarried out in control and high dose groups although, in these as in all other parameters underinvestigation, there appears to have been no compound-related effects.
2.3.3.5 Studies Relevant for Mammalian TRV Development for Inhalation Exposures
The use of high concentrations of ethylene as an anesthetic, with full recovery of faculties on cessationof exposure, is consistent with the negative toxicological results outlined in Sections 2.3.3.1–2.3.3.4.
Taken together, these findings point to the benign nature of the compound in biological systems and argue
against the likelihood that a viable TRV for ethylene can emerge from the overall toxicologicalinformation on the compound. However, the formation of 2-hydroxyethyl derivatives of hemoglobin andguanine shows that ethylene has biochemical activity, most likely mediated through its ethylene oxideintermediate. The disparity between the benign effects of ethylene and the more severe effects ofethylene oxide in toxicological tests has been addressed by Walker et al. (2000) and in a review by Bolt
(1998) who estimated that exposure concentrations of 1000 ppm ethylene would be equivalent to about
7.5 ppm ethylene oxide. By implication, this concentration would probably be below the threshold at
which any toxicological impacts (of ethylene oxide) would become apparent.

Page 9 of 12

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

2.3.4 Mammalian Inhalation Toxicity – Other
Aveyard and Collins (1997) used Organization for Economic Cooperation and Development (OECD)
guideline 421 to test the effects of ethylene on fertility, pregnancy, maternal and suckling behavior, andF1 growth and development in rats (strain unstated) exposed to ethylene. They reported that 10 parental
animals/group were exposed head only to 0, 200, 1000, or 5000 ppm ethylene, 6 hours/day from 2 weeks
prior to mating until gestation day (GD) 20 (males) or day 4 post-partum (females). No animals diedduring treatment, and no compound-related effects were evident on weight gain, food consumption,
fertility, fecundity, litter characteristics, or on pathology or histopathology in either generation.
2.3.5 Mammalian Dermal Toxicity
No data are available.

2.4

Summary of Avian Toxicology

No toxicological data for the effects of ethylene on avian species was located. Ecotoxicologicalresearch on the effects of this compound on birds is recommended.

2.5

Amphibian Toxicology
No toxicological data for the effects of ethylene on amphibian species was located. Ecotoxicologicalresearch on the effects of this compound on amphibians is recommended.

2.6

Reptilian Toxicology
No toxicological data for the effects of ethylene on reptiles was located. Ecotoxicological research on

the effects of this compound on reptiles is recommended.

3. RECOMMENDED TOXICITY REFERENCE VALUES
3.1 Toxicity Reference Values for Mammals
3.1.1 TRVs for Ingestion Exposures for the Class Mammalia
At this time it is not possible to derive a TRV for oral route of exposure for ethylene due to the lackof toxicity data and the gaseous nature of the compound which renders an oral exposure unlikely.
3.1.2 TRVs for Inhalation Exposures for the Class Mammalia
With the use of ethylene in high concentrations as an anesthetic, there is no evidence of
toxicological effects occurring at levels that would be likely in the environment. It is, however, evident
Page 10 of 12

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

that there are toxicological effects through its ethylene oxide intermediate. However, the effects weremolecular in nature and were not linked to more toxicologically relevant endpoints such as tumor
formation, morbidity or death. As a result, a TRV could not be derived for ethylene at this time.

4. IMPORTANT RESEARCH NEEDSThe limited availability of data on the toxicity of ethylene to wildlife species precludes thedevelopment of a TRV. Hence, more studies of the compound and its derivatives are recommended. The
toxicity and biochemical activity of ethylene and ethylene oxide warrant attention to explain therelationship between these compounds. Also, chronic toxicity studies on non-mammalian wildlife such as
birds, reptiles and amphibians are particularly warranted.

Page 11 of 12

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

5.

References

American Chemical Society. 1996. Production by the US Chemical Industry. Chemical and Engineering
News, June 24. http://pubs.acs.org/hotartcl/cenear/960624/prod.html
Aveyard, L, and C.J. Collins. 1997. OECD 421-reproduction/developmental toxicity screening study byhead-only exposure: Experience with ethylene. Teratology 55: 47.
Bolt, H.M. 1998. The carcinogenic risk of ethene (ethylene). Toxicol. Pathol. 26: 454-456.
Eide, I., R. Hagemann, K. Zahlsen et al. 1995. Uptake, distribution and formation of hemoglobin and
DNA adducts after inhalation of C2-C8 1-alkenes (olefins) in the rat. Carcinogenesis 16: 1603-1609.
Hamm, T.E., Jr., D. Guest, and J.G. Dent. 1984. Chronic toxicity and oncogenicity bioassay of inhaled
ethylene in Fischer-344 rats. Fund. Appl. Toxicol. 4: 473-478.
Hazardous Substances Databank (HSDB). 2001. On-line Database. National Library of Medicine.
Washington, DC.
International Agency for Research on Cancer (IARC). 1979. Evaluation of the carcinogenic risk ofchemicals to humans: Ethylene and Polyethylene. 19: 157-186.
International Agency for Research on Cancer (IARC). 1994. Evaluation of the carcinogenic risk ofchemicals to humans: Ethylene. 60: 45-72.
Rhudy, R.L., D.C. Lindberg, J.W. Goode, D.J. Sullivan, and E.J. Gralla. 1978. Ninety-day inhalation
study with ethylene in albino rats. Toxicol. Appl. Pharmacol. 45: 285.
Suriano, R. 2003. Toxic Release Inventory; 1998-2000. American Petroleum Institute, Washington, D.C.
http://api-ep.api.org/filelibrary/Final%20TRI%2000%20May03.pdf
U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM). 2000. Standard
Practice for Wildlife Toxicity Reference Values, Technical Guide 254.
Vergnes, J.S., and I.M. Pritts. 1994. Effects of ethylene on micronucleus formation in the bone marrow ofrats and mice following four weeks of inhalation exposure. Mutat. Res. 324: 87-91.
Walker V.E., K-Y Wu, P.B. Upton et al. 2000. Biomarkers of exposure and effect as indicators ofpotential carcinogenic risk arising from in vivo metabolism of ethylene to ethylene oxide.
Carcinogenesis 21: 1661-1669.

Page 12 of 12

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENEAPPENDIX A
LITERATURE REVIEW
Separate searches in DIALOG (three in all) were carried out on ethylene on April 20, 2001, and on
May 2, 2001.
In the first search the following files were scanned:
File 155 MEDLINE, File 156 TOXLINE, File 5 BIOSIS, File 10 AGRICOLA, File 203 AGRIS, File 399
Chemical Abstracts, File 77 Conference Papers Index, File 35 Dissertation Abstracts, File 40
ENVIRONLINE, File 68 Environmental Bibliography, File 76 Life Sciences Collection, File 41 Pollution
Abstracts, File 185 Zoological Record, File 6 NTIS, File 50 CAB, File 144 PASCAL, File 34
SCISEARCH, and File 434 SCISEARCH.
The search strategy for Amphibians & Reptiles:♦ Chemical name, CAS numbers♦ AND (amphibi? or frog or frogs or salamander? or newt or newts or toad? or reptil? or crocodil? oralligator? or caiman? snake? or lizard? or turtle? or tortoise? or terrapin?)♦ AND (reproduc? or diet or dietary or systemic or development? or histolog? or growth orneurological or behav? or mortal? or lethal? or surviv? or (drinking()water))♦ NOT glycol♦ RD (reduce duplicates)♦ NOT dibromide♦ NOT dichloride♦ NOT (human? or culture? or subcutaneous or vitro or gene or inject? or tumo? or inhalation or carcin?
or cancer?)
The search strategy for Birds:♦ Chemical name, CAS numbers♦ AND chicken? or duck or duckling? or ducks or mallard? or quail? or (japanese()quail?) or coturnixor (gallus()domesticus) or platyrhyn? or anas or aves or avian or bird? or (song()bird?) or bobwhite?
or (water()bird) or (water()fowl)♦ AND (reproduc? or diet or dietary or systemic or development? or histolog? or growth orneurological or behav? or mortal? or lethal? or surviv? or (drinking()water))Appendix A /page 13

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE♦ NOT (human? or culture? or subcutaneous or vitro or gene or inject? or tumo? or inhalation or
carcin? or cancer?)♦ RD (reduce duplicates)♦ NOT dibromide or dichloride♦ NOT dibromide♦ NOT dichloride
The search strategy for Laboratory Mammals:♦ Chemical name, CAS numbers♦ AND (rat or rats or mice or mouse or hamster? or (guinea()pig?) or rabbit? or monkey?)♦ AND (reproduc? or diet or dietary or systemic or development? or histolog? or growth orneurological or behav? or mortal? or lethal? or surviv? or (drinking()water))♦ NOT (human? or culture? or subcutaneous or vitro or gene or inject? or tumo? or inhalation or
carcin? or cancer?)/ti,de♦ NOT (meeting()poster)♦ NOT (meeting()abstract)♦ NOT (conference()proceeding?)♦ RD (reduce duplicates)♦ NOT (patient? or cohort? or worker? or child? or infant? or women or men or occupational)♦ NOT (glycols or polymer or poly or tetraacetic or tetraacetate or dichlorides)♦ NOT EDTA
♦ NOT (dimethanesulphonate? or dimethanesulfonate? or diamine? or EDS)
♦ AND LA=English
The search strategy for Wild Mammals:♦ Chemical name, CAS numbers♦ And (didelphidae or opossum? or soricidae or shrew? Or talpidae or armadillo? or dasypodidae orochotonidae or leporidae) or canidae or ursidae or procyonidae or mustelidae or felidae or cat or catsor dog or dogs or bear or bears or weasel? or skunk? or marten or martens or badger? or ferret? orAppendix A /page 14

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE

mink? Or aplodontidae or beaver? or sciuridae or geomyidae or heteromyidae or castoridae or
equidae or suidae or dicotylidae or cervidae or antilocapridae or bovidae arvicolinae or
mycocastoridae or dipodidae or erethizontidae or sigmodon? or (harvest()mice) or (harvest()mouse)or microtus or peromyscus or reithrodontomys or onychomys or vole or voles or lemming?
♦ AND (reproduc? or diet or dietary or systemic or development? or histolog? or growth orneurological or behav? or mortal? or lethal? or surviv? or (drinking()water))♦ NOT (human? or culture? or subcutaneous or vitro or gene or inject? or tumo? or inhalation or
carcin? or cancer?)/ti,de♦ NOT (meeting()poster?)♦ NOT (meeting()abstract?)♦ NOT (conference()proceedings?)♦ NOT (patient? or cohort? or worker? or child? or infant? or women? or men? or occupational?)♦ RD (reduce duplicates)♦ NOT steriliz?
♦ NOT oxide
When the search retrieved an appreciable number of hits, keywords in context were reviewed to minimize
costs before any abstracts were downloaded (Tier 1). However, when only a limited number of studies
were identified by the search, the abstracts were downloaded at the time of the search (Tier 2).
The second search examined the same files as the first but used the following structure:
For Laboratory Animals♦ CAS Number♦ AND (rat or rats or mice or mouse or hamster? or (guinea()pig?) or rabbit? or monkey?)♦ AND (reproduc? or diet or dietary or systemic or development? or histolog? or growth orneurological or behav? or mortal? or lethal? or surviv? or (drinking()water))♦ RD (reduce duplicates)
The third search examined the following databases
File 155 Medline, File 156 Toxline, File 535 Thomas Register Online, File 76 Life Sciences Collection,
File 185 Zoological Record Online, File 5 Biosis Reviews.
For Birds
Appendix A /page 15

WILDLIFE TOXICITY ASSESSMENT FOR ETHYLENE♦ CAS Number♦ AND (chicken? or duck or duckling? or ducks or mallard? or quail? or (japanese()quail?) or coturnixor (gallus()domesticus) or platyrhyn? or anas or aves or avian or bird? or (song()bird?) or bobwhite?
or (water()bird) or (water()fowl))♦ RD (Reduce Duplicates)
For Wild Mammals♦ CAS Number♦ AND (didelphidae or opossum? or soricidae or shrew? Or talpidae or armadillo? or dasypodidae orochotonidae or leporidae) or canidae or ursidae or procyonidae or mustelidae or felidae or cat or catsor dog or dogs or bear or bears or weasel? or skunk? or marten or martens or badger? or ferret? ormink? Or aplodontidae or beaver? or sciuridae or geomyidae or heteromyidae or castoridae or
equidae or suidae or dicotylidae or cervidae or antilocapridae or bovidae arvicolinae or
mycocastoridae or dipodidae or erethizontidae or sigmodon? or (harvest()mice) or (harvest()mouse)or microtus or peromyscus or reithrodontomys or onychomys or vole or voles or lemming?)♦ RD (Reduce Duplicates)
For Amphibians/Reptiles♦ CAS. Number♦ AND (amphibi? or frog or frogs or salamander? or newt or newts or toad? or reptil? or crocodil? oralligator? or caiman? snake? or lizard? or turtle? or tortoise? or terrapin?)♦ RD (reduce duplicates)
As noted in Section 2.1, 538 hits on ethylene were obtained in the initial searches, of which 9 wereselected for retrieval.

Appendix A /page 16

資料

３－８
１３

国 立 労 働 生 活 研 究 所 ： スウェーデン労働基準の科学的基礎 13．
（抜粋）エチレンのコンセンサス・レポート
１９９６年１２月

National Institute for Working Life
December 11, 1996

Scientific Basis for Swedish Occupational Standards
XVIII

Consensus Report for EtheneConsensus Report for Ethene

December 11, 1996

Physical and chemical data. Occurrence
CAS No:Systematic name:
Synonyms:
Formula:Molecular weight:
Density:
Boiling point:
Vapor pressure:
Melting point:
Explosion threshold:Distribution coefficient:
Conversion factors:

74-85-1ethylene
acetene, elayl, olefiant gas
CH2=CH2
28.05
0.98 (air = 1)
- 104 °C
4270 kPa (0 °C)- 169 °C
2.75 vol % in air (100 kPa; 20 °C)
log POW = 1.13 (octanol/water)
1 ppm = 1.15 mg/m3
1 mg/m3 = 0.87 ppm

Ethene at room temperature is a colorless gas with a sweet odor and taste. The reported
odor threshold is 290 ppm (333.5 mg/m3) (1, 26). The gas dissolves readily in water,acetone, ethanol and benzene. Ethene is stable under normal pressure and temperature
conditions, but may polymerize at higher pressure and temperature.
Ethene is used primarily in the production of polyethylene and ethylene oxide / ethylene
glycol. It is also used as a raw material in the production of other chemical substances.
Ethene is used to accelerate the ripening of fruit. (It is formed naturally by ripening fruit.)
There are virtually no data on occupational exposure to ethene in connection withproduction of the substance. It is usually produced in closed systems. In one study (17) it
is estimated that during the years 1941 to 1947 the exposure level for ethene aroundproduction of ethylene oxide was about 600 mg/m3. Measurements of occupational
exposure to ethene in warehouses where the gas is used to control the ripening of bananas
showed air concentrations ranging from 0.02 to 3.85 mg/m3, with a mean value of 0.35
mg/m3 (28). In a study of firemen, it was found that they were exposed to ethene in somephases of fighting fires (20).

10Uptake, biotransformation, excretion
Six volunteers were exposed to 0, 5 or 50 ppm ethene (0, 5.75 or 57.5 mg/m 3) for twohours. Most (94.4%) of the inhaled ethene was immediately exhaled. Calculations based on
clearance of uptake and metabolic clearance indicated that alveolar retention at steady state
was 2% and the biological half time was 0.65 hours (12). From theoretical calculations ofgas uptake in the lungs, it can be concluded that the low uptake of ethene is due to its low
solubility in blood.
Ethene can be detected in exhaled air of unexposed persons. Women exhale more etheneat the time of ovulation. The biochemical origin of this endogenously produced ethene has
not been explained, but four theories have been proposed: lipid peroxidation, enzymecatalyzed oxidative breakdown of methionine, oxidation of hemoglobin, and metabolism inintestinal bacteria (18).
Two hemoglobin adducts, N-(2-hydroxyethyl)histidine (HOEtHis) and N-(2hydroxyethyl)valine (HOEtVal), have been used as dose measures for formation of
ethylene oxide from ethene.
Exposure to ethene at concentrations of 10 to 20 ppb (11.5 to 23 µg/m3) has been
associated with an increase of adducts (HOEtVal) amounting to 4 – 8 pmol/g Hb at steadystate (29). Fruit store workers exposed to 0.02 to 3.35 ppm ethene (0.023 to 3.85 mg/m3)
had adduct (HOEtVal) levels of 22 to 65 pmol/g Hb; levels in unexposed controls were 12
to 27 pmol/g Hb (28). The adduct level due to endogenous ethylene alone is estimated to beabout 12 pmol/g Hb (12).
It has been estimated from adduct data that about 2 to 3% of inhaled ethene ismetabolized to ethylene oxide (14, 28). Exposure to 1 ppm ethene (1.15 mg/m3) for 40
hours/week is calculated to increase the adduct level by 100 to 120 pmol/g Hb (9).
Mice were exposed to 17 ppm (22.3 mg/m3) 14C-labeled ethene for one hour. Four hours
later radioactivity was found primarily in kidneys and liver, with lesser amounts in testes
and brain. A 48-hour urine sample contained S-(2-hydroxyethyl)cysteine, indicating thatthe ethene had been metabolized to ethylene oxide (8). Fischer-344 rats that were exposed
to 10,000 ppm (11,500 mg/m3) radioactively labeled ethene for 5 hours eliminated most of
the radioactivity as exhaled ethene, while smaller amounts were excreted in urine and feces
or exhaled as CO2. Minor amounts of radioactivity were found in blood, liver, intestinesand kidneys. The amounts of radioactivity in urine and CO2 were higher in animals that had
been pre-treated with Aroclor (a commercial PCB mixture), which indicates that ethene
metabolism can be stimulated by substances that induce the mixed function oxidase system(15).
When Sprague-Dawley rats were exposed to between 0.1 and 80 ppm (0.12 and 92
mg/m3) ethene, they eliminated 24% of available ethene by biotransformation and 76% byexhalation of unchanged ethene. The alveolar retention at steady state was 3.5% and thebiological half time was 4.7 minutes (12). Metabolism was saturated at concentrations
above 80 ppm (92 mg/m3), with a maximum metabolism rate (Vmax) of 0.24 mg/hour x kg
body weight (11).

11When Sprague-Dawley rats were exposed for 21 hours to ethene levels exceeding 1000ppm (1150 mg/m3) the amount of ethene absorbed per unit of time was constant (2). When
Fischer-344 rats were exposed to 600 ppm (690 mg/m3) ethene, the blood level of ethyleneoxide rose rapidly during the first five to ten minutes and then dropped to a level thatremained constant during the remainder of the 60-minute exposure. The level ofcytochrome P-450 in liver declined steadily during the experiment (22). This was taken to
indicate that during metabolism of ethene the phenobarbital-induced form of cytochrome P450 is destroyed by transformation of the cytochrome heme to an abnormal porphyrin (23).
Sprague-Dawley rats were exposed to 300 ppm (345 mg/m3) ethene 12 hours/day forthree consecutive days: the concentration of ethene was low in all examined organs 12hours after the last exposure. However, the levels of hemoglobin adducts and of 7alkylguanine in lymphocytes and liver were elevated, indicating the formation of ethyleneoxide (10).
Hemoglobin adduct (HOEtVal) levels of about 100 pmol/g Hb have been measured inseveral strains of rats, mice and hamsters after exposure to ethene (18). Calculations basedon animal data indicate that uptake of 1 mg ethene per kg body weight corresponds to atissue dose of ethylene oxide amounting to 0.03 mg x hour/kg body weight. This value
agrees with the one calculated for human uptake (32).
Toxic effects
Ethene is not irritating to eyes or skin (4). People exposed to a concentration of 37.5% in
air for 15 minutes experienced some memory disturbance, and 50% in air results in loss of
consciousness due to oxygen deprivation (4).
Mice repeatedly exposed to concentrations resulting in loss of consciousness showed nohistopathological changes in kidneys, adrenal glands, heart or lungs (24). The
concentration was described as ”atmosphere in which the partial pressure of oxygen was 20
per cent and ethylene 90 per cent.”
Fischer-344 rats exposed to 10,000 ppm (11,500 mg/m3) ethene for 5 hours showed no
toxic effects (15). Nor were toxic effects observed in Sprague-Dawley rats with ethene
exposures up to 10,000 ppm (11,500 mg/m3) 6 hours/day, 5 days/week in a 90-day study(25), or in Fischer-344 rats with exposures up to 3000 ppm (3450 mg/m3) in a two-year
study (16). This absence of toxicity may be due to saturation of ethene metabolism (18).
Rats pre-treated with Aroclor and 24 hours later exposed to ethene concentrations of
10,000, 30,000 or 57,000 ppm (11,500, 34,500 or 65,550 mg/m3) for 4 hours had dosedependent effects on liver, indicated by elevated serum levels of sorbitol dehydrogenase
and alanin-α-ketoglutarate transaminase and by the histological observation of centrilobular
necrosis (5, 6, 15).
Mutagenicity, carcinogenicity, teratogenicity
Ethene caused no mutations in tests with Salmonella typhimurium (TA 100), either with orwithout metabolic activation (34). Ethene induced no micronuclei in the bone marrow of12

rats and mice exposed to up to 3000 ppm (3450 mg/m3) 6 hours/day, 5 days/week for fourweeks (33).
The DNA adduct 7-(2-hydroxyethyl)guanine (7-HOEtGua) was found in levels of 2 to 6
nmol/g DNA in lymphocytes from untreated Sprague-Dawley rats (13) and in DNA fromseveral different tissues from Fischer-344 rats and B6C3F1 mice (35). After mice were
exposed for eight hours to 11 ppm (12.9 mg/m3) radioactively labeled ethene, 7-alkylationof guanine could be demonstrated in DNA from liver, spleen and testes: 0.17 nmol/g DNA
was measured in liver; 0.098 in spleen and 0.068 nmol/g DNA in testes, which was lessthat 10% above the background level (27).
Groups of Fischer-344 rats (120 of each sex) were exposed to 0, 300, 1000 or 3000
ppm (0, 345, 1150 or 3450 mg/m3) ethene 6 hours/day, 5 days/week for up to 24 months.
Rats were sacrificed and examined after 6, 12, 18 and 24 months. There was no differencein survival between exposed rats and controls. Histological comparisons of the high-dosegroup and the controls revealed no indications of any exposure-related toxicity and noelevated incidence of tumors (16).
Groups of Sprague-Dawley rats (both sexes) were exposed to 0 or 10,000 ppm ethene (0or 11,500 mg/m3) 8 hours/day, 5 days/week for three weeks. One week later the animals
were given polychlorinated biphenyls (unspecified), 10 mg/kg body weight, by gavage
twice a week for 8 weeks. The animals were then sacrificed and examined for ”ATPasedeficient foci.” There was no difference between the ethene-exposed animals and controls.
(When ethylene oxide was used as a positive control, there was a pronounced increase offoci.) (7)According to the IARC (18), it is not possible to determine whether ethene iscarcinogenic to either man or experimental animals (”inadequate evidence”) and ethene has
therefore been placed in Group 3: ”unclassifiable as to its carcinogenicity to humans.” Asfor the metabolite ethylene oxide, in the judgement of the IARC (19) there is ”limited
evidence” that it is carcinogenic to humans and ”sufficient evidence” that it is carcinogenic
to experimental animals, and in the overall assessment ethylene oxide is therefore placed inGroup 1: ”carcinogenic to humans.”
In a theoretical presentation (29, 30, 31) it is postulated that ethene might cause cancer
via activation to ethylene oxide which then binds to DNA, and that the consequent risk ofcancer in Sweden due to ethene in city air would be equivalent to 30 cases per year (at an
average exposure of 1.8 mg/m3).
One study reports 6 miscarriages among 15 pregnant women who were working in apetrochemical industry. This rate was higher than that for 1,549 women who were living inthe surrounding area. The main product was ethene (350,000 tons/year), but the women
were also exposed to other substances including ethylene oxide, vinyl chloride andphthalates. No exposure data are given, but measured ethene concentrations in air outside
the plant were on average 10 to 15 ppb (2).

13Dose-response / dose-effect relationships
There are no data that can be used as a basis for calculating a dose-effect or dose-response
relationship for human exposure to ethene. Occupational exposures of 0.023 to 3.5 mg/m3
have resulted in elevated formation of hemoglobin adducts (28). Data from animal studies
are summarized in Table 1.
Table 1. Effects of ethene inhalation on experimental animals.
________________________________________________________________________
Duration
Species
Effects
Ref.
mg/m3________________________________________________________________________
12.9
92
3450
3450
11,50011,50011,500

8 hours
6 hours
28 days
2 years
5 hours
90 days
24 hoursMouse
7-alkylation of guanine in DNA
27
Rat
Saturation of ethene metabolism
11
Mouse
No increase in micronuclei
33
Rat
No toxic effects
16
Rat
No toxic effects
15
Rat
No toxic effects
25
Rat (pre-treated Liver effects
5, 6with Aroclor)________________________________________________________________________
Conclusions
Judging from available data on toxicity to humans, the critical effect of exposure to etheneis its effect on the central nervous system. (Ethene has been used as an anesthetic.) Fromanimal data it can be observed that, if the animals have been enzyme-induced, effects on theliver may be the critical ones.
It has been debated whether exposure to ethene can give rise to toxic effects and/or
cancer caused by the metabolite ethylene oxide. In its 1981 report, the Criteria Group statedthat the critical effects of exposure to ethylene oxide were the mutagenic, cytogenetic andcarcinogenic effects, and that cytogenetic effects of ethylene oxide were seen at
occupational exposures of about 2 mg/m3 (21).
References
1.

Amoore J E, Hautala E. Odor as an aid to chemical safety: Odor thresholds compared with threshold
limit values and volatilities for 214 industrial chemicals in air and water dilution. J Appl Toxicol
1983;3:272-290.
2. Axelsson G, Molin I. Outcome of pregnancy among women living near petrochemical industries in
Sweden. Int J Epidemiol 1988;17:363-369.
3. Bolt H M, Filser J G, Störmer F. Inhalation pharmacokinetics based on gas uptake studies. V.
Comparative pharmacokinetics of ethylene and 1,3-butadiene in rats. Arch Toxicol 1984;55:213-218.
4. Cavender F. Aliphatic hydrocarbons. In: Clayton G D, Clayton F E, eds. Patty’s Industrial Hygiene
and Toxicology, Vol iiB, 4th ed. NewYork: Wiley-Interscience Publ, 1994:1221-1266.

14

5.

Conolly R B, Jaeger R J. Acute hepatotoxicity of ethylene and halogenated ethylenes after PCB
treatment . Environ Health Perspect 1977;21:131-135.
6. Conolly R B, Jaeger R J, Szabo S. Acute hepatotoxicity of ethylene, vinyl fluoride, vinyl chloride, andvinyl bromide after Aroclor 1254 pretreatment. Exp Mol Pathol 1978;28:25-33.
7. Denk B, Filser J G, Oesterle D, Deml E, Greim H. Inhaled ethylene oxide induces preneoplastic foci in
rat liver. J Cancer Res Clin Oncol 1988;14:35-38.
8. Ehrenberg L, Osterman-Golkar S, Segerbäck D, Svensson K, Calleman C J. Evaluation of genetic
risks of alkylating agents. III. Alkylation of haemoglobin after metabolic conversion of ethene toethene oxide in vivo. Mutat Res 1977;45:175-184.
9. Ehrenberg L, Törnqvist M. Use of biomarkers in epidemiology: quantitative aspects. Toxicol Lett
1992;64/65:485-492.
10. Eide I, Hagemann R, Zahlsen K, et al. Uptake, distribution, and formation of hemoglobin and DNA
adducts after inhalation of C2-C8 1-alkenes (olefins) in the rat. Carcinogenesis 1995;16:1603-1609.
11. Filser J G. The closed chamber technique – uptake, endogenous production, excretion, steady-statekinetics and rates of metabolism of gases and vapors. Arch Toxicol 1992;66:1-10.
12. Filser J G, Denk B,Törnqvist M, Kessler W, Ehrenberg L. Pharmacokinetics of ethylene in man; bodyburden with ethylene oxide and hydroxyethylation of hemoglobin due to endogenous and environmental
ethylene. Arch Toxicol 1992;66:157-163.
13. Föst U, Marczynski B, Kasemann R, Peter H. Determination of 7-(2-hydroxyethyl)guanine with gas
chromatography/mass spectrometry as a parameter for genotoxicity of ethylene oxide. Arch Toxicol
1989;Suppl.13:250-253.
14. Granath F, Westerholm R, Peterson A, Törnqvist M, Ehrenberg L. Uptake and metabolism of ethenestudied in a smoke-stop experiment. Mutat Res 1994;313:285-291.
15. Guest D, Barrow C S, Popp J A, Dent J G. Effect of Aroclor 1254 on disposition and hepatotoxicity of
ethylene in the rat. Toxicol Appl Pharmacol 1981;57:325-334.
16. Hamm T E Jr, Guest D, Dent J G. Chronic toxicity and oncogenicity bioassay of inhaled ethylene inFischer-344 rats. Fund Appl Toxicol 1984;4:473-478.
17. Hogstedt C, Rohlén O, Berndtsson S, Axelson O, Ehrenberg L. A cohort study of mortality and cancer
incidence in ethylene oxide production workers. Br J Ind Med 1979;36:276-280.
18. IARC. Ethylene. Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Industrial
Chemicals. 1994;60:45-71.
19. IARC. Ethylene oxide. Monographs on the Evaluation of Carcinogenic Risks to Humans: Some
Industrial Chemicals. 1994:60;73-159.
20. Jankovic J, Jones W, Burkhart J, Noonan G. Environmental study of firefighters. Ann Occup Hyg
1991;35:581-602.
21. Lundberg P, ed. Scientific Basis for Swedish Occupational Standards. III. Arbete och Hälsa 1982;24:6267.
22. Maples K R, Dahl A R. Levels of epoxides in blood during inhalation of alkenes and alkene oxides.
Inhalat Toxicol 1993;5:43-54.
23. Ortiz de Montellano P R, Beilan H S, Kunze K L, Mico B A. Destruction of cytochrome P-450 byethylene. Structure of the resulting prosthetic heme adduct. J Biol Chem 1981;256:4395-4399.
24. Reynolds C. Propylene, ethylene, nitrous oxide and ether: some comparative investigations. Anest
Analg 1927;6:121-124.

15

25. Rhudy R L, Lindberg D C, Goode J W, Sullivan D J, Gralla E J. Ninety-day subacute inhalation study
with ethylene in albino rats. Toxicol Appl Pharmacol 1978;45:285 (abstract).
26. Ruth J H. Odor thresholds and irritation levels of several chemical substances: A review. Am Ind Hyg
Assoc J 1986;47:A142-A151.
27. Segerbäck D. Alkylation of DNA and hemoglobin in the mouse following exposure to ethene andethene oxide. Chem Biol Interact 1983;45:139-151.
28. Törnqvist M Å, Almberg J G, Bergmark E N, Nilsson S, Osterman-Golkar S M. Ethylene oxide dosesin ethene-exposed fruit store workers. Scand J Work Environ Health 1989;15:436-438.
29. Törnqvist M, Ehrenberg L. Approaches to risk assessment of automotive engine exhausts. IARC Sci
Publ 1990;104:277-287.
30. Törnqvist M, Ehrenberg L. On cancer risk estimation of urban air pollution. Environ Health Perspect
1994;102 Suppl 4:173-181.
31. Törnqvist M, Kautiainen A. Adducted proteins for identification of endogenous electrophiles. Environ
Health Perspect 1993;99:39-44.
32. Törnqvist M, Kautiainen A, Gatz R N, Ehrenberg L. Hemoglobin adducts in animals exposed togasoline and diesel exhausts. 1. Alkenes. J Appl Toxicol 1988;8:159-170.
33. Vergnes J S, Pritts I M. Effects of ethylene on micronucleus formation in the bone marrow of rats andmice following four weeks of inhalation exposure. Mutat Res 1994;324:87-91.
34. Victorin K, Ståhlberg M. A method for studying the mutagenicity of some gaseous compounds in
Salmonella typhimurium. Environ Mol Mutagen 1988;11:65-77.
35. Walker V E, Fennel T R, Upton P B, Skopek T R, Prevost V,Shuker D E G, Swenberg J A.
Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA
following repeated exposures of rats and mice. Cancer Res 1992;52:4328-4334.

16

資料

１４

馬鈴しょ萌芽抑制効果に対するエチレン濃度限界に関する試験（平成 20 年秋～21 年夏、酪農学園大学）
１．目的
加工用馬鈴しょの貯蔵中の萌芽を抑制し、国産馬鈴しょの周年供給体制を確立することを目的とし、エチレンによる芽の生長抑制効果と加工適性維持のための限界エチレン処理濃度を求めるために、代表的な 2 品種を用いて貯蔵試験を行った。
２．試験方法１）供試材料
平成 20 年、帯広市川西産「きたひめ」、「スノーデン」を用いた。
２）エチレンの供給方法および濃度
ガス置換デシケータを利用したエチレン供給貯蔵基礎実験装置（参考資料１）を用いて 10
月 28 日から貯蔵試験を開始した。
３）貯蔵方法無処理区も同様の貯蔵容器（デシケータ）を用いた（参考資料１を参照）。
貯蔵温度は 8℃とし、エチレン濃度はこれまでの試験において 4ppm で十分な効果が得られることが明らかになっているため、その 5 倍濃度の処理区として 20ppm と設定し、無処理区として 0ppm 区を設定した。
４)測定項目
貯蔵環境の温度、湿度、エチレン濃度については、貯蔵期間中継続して測定した。品質については、10月28日、12月26日、2月16日、3月20日、4月24日、5月29日、7月3日に測定した。
(1)恒温室内温湿度
恒温室内温度、湿度をデーターロガーを用いて測定した。
(2)貯蔵容器（デシケータ）内エチレン濃度、二酸化炭素濃度
ガスタイトシリンジにより貯蔵容器の上下2箇所から容器内ガスを採取し、ガスクロマトグ
ラフを用いてエチレン濃度および二酸化炭素濃度を測定した。
(3)試料質量、水分含量
電子天秤を用いて試料質量を測定し、質量減少率を求めた。水分含量は70℃24時間恒温乾燥法により求めた。
(4)芽の長さ5mm以下、5mm以上の芽の塊茎当たりの個数、塊茎毎の最長芽の長さ、塊茎当たりの芽の質量を測定した。
(5)糖含量HPLCを用いてショ糖、ブドウ糖、果糖含量を測定した。

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(6)硬度
レオメータを用い、直径2mmの円筒状プランジャを50mm/sの速度で貫入させて荷重を測定した。
(7)ポテトチップカラー
試料を約1mmの厚さにスライスし、180℃のサラダオイルで約120秒間フライし、その色をア
グトロンメーターを用いて測定した。

30

30

25

25

20

20

15

エチレン濃度(ppm)

エチレン濃度(ppm)

３．結果
図 1～2 に貯蔵中エチレン濃度の推移を示す。
「きたひめ」「スノーデン」の初期のエチレン処理区において、急激な濃度の上昇があったが、これはコンプレッサの不調により空気の供給が停止したためである。また、このとき無処理区においてもエチレンが一時的に検出された。これ以外ではいずれもほぼ設定どおりに制御することができた。貯蔵開始当初は 1 時間換気、5 時間休止のサイクルで換気及びエチレンの供給を行っていたが、特に、エチレン区において CO 2 濃度の上昇が見られたため、2 時間換気、4 時
間換気に変更することにより CO 2 濃度は 0.1％以下に抑えることができ、以後このサイクルで
行った。

KH-0
KH-20

10

SD-20

10
5

5

0

0
10/19

SD-0

15

11/8

11/28

12/18

1/7

1/27

2/16

10/19

3/8

日
図１ 貯蔵中エチレン濃度の推移（きたひめ）

11/8

11/28

12/18

1/7
1/27
日
図２ 貯蔵中エチレン濃度の推移（スノーデン）

2/16

3/8

図 3～4 に、塊茎毎の最長芽の長さの平均値の推移を示す。
いずれの品種においても 2 月 16 日の時点で萌芽が見られ、特に、無処理区において芽の伸長が大きかった。
貯蔵終了時点でいずれの品種においてもエチレン処理区では芽の長さが 20mm 以下に抑制さ
れた。
150
KH-0
KH-20

芽の長さ(mm)

100

50

0
10/28

12/27

2/25

4/26

6/25

日
図3 最長芽の長さの推移（きたひめ）

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8/24

150
SD-0
SD-20

芽の長さ(mm)

100

50

0
10/28

12/27

2/25

4/26
6/25
日
図4 最長芽の長さの推移（スノーデン）

8/24

図 5～6 に、還元糖含量の推移を示す。
いずれの品種も貯蔵初期に還元糖が増加し、その後低下する傾向にあり、貯蔵末期に再び増加する傾向もみられた。
0.4
KH-0

還元糖含量(g/100gFW)

KH-20

0.2

0.0
10/19

12/18

2/16

4/17

6/16

8/15

6/16

8/15

日
図5 還元糖含量の推移（きたひめ）
0.4

還元糖含量(g/100gFW)

SD-0
SD-20

0.2

0.0
10/19

12/18

2/16

4/17
日

図6 還元糖含量の推移（スノーデン）-3-

図 7～8 に、ポテトチップカラーの推移を示す。
還元糖含量の推移を反映し、貯蔵初期にポテトチップカラーが低下し、その後回復する傾向にあるが、「きたひめ」は低下の度合いが小さい。
また、貯蔵末期に低下する傾向にあった。いずれも 20ppm のエチレン処理においてもポテト
チップカラーの大きな低下はなく、5 月下旬頃までは原料としての利用に耐える加工適性を保
っていた。

60

アグトロン値(-)

50

40

KH-0

30

KH-20

20
10/19

12/18

2/16

4/17

6/16

8/15

日
図7 チップカラーの推移（きたひめ）

60

アグトロン値(-)

50

40
SD-0

30
SD-20

20
10/19

12/18

2/16

4/17
日

6/16

8/15

図8 チップカラーの推移（スノーデン）

４．要 約
エチレンによる芽の生長抑制効果と加工適性維持のための限界エチレン処理濃度を求めるために代表的な 2 品種を用いて貯蔵試験を行った。
エチレン濃度 20ppm で貯蔵を行った場合においても、芽の伸長は抑えられ、ポテトチップカ
ラーの顕著な低下はなかった。

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資料

１５

エチレン処理による馬鈴しょの残留性に関する試験（平成 20 年秋～21 年夏、酪農学園大学、十勝農業試験場）
１．目

的

エチレン処理した馬鈴しょの中のエチレン残留量が通常の食品中に含まれるエチレン量を超えることがないこと等を裏付けるために、エチレン処理した馬鈴しょの長期貯蔵後のエチレン処理区と無処理区の塊茎中のエチレン濃度を調査する。
２．試験方法○.酪農学園大学
１）供試品種：「きたひめ」、「スノーデン」、「トヨシロ」
２）試験期間：平成 20 年秋～21 年夏３）エチレン：無処理区 0ppm、処理区は 4ppm、20ppm
４）試験実施：4 月 24 日、5 月 30 日５）その他は参考試料 2 に示す。
○JA 士幌町（試験実施、試験担当は十勝農業試験場）
１）供試品種：「きたひめ」、「スノーデン」、「トヨシロ」
２）試験期間：平成 20 年秋～21 年夏３）エチレン：無処理区 0ppm、処理区は 8ppm
４）試験実施：4 月 23 日、6 月 25 日
５）その他は参考資料 3 に示す。
○カルビーポテト（株）（参考）
１）供試品種：「スノーデン」
２）試験期間：平成 20 年秋～21 年夏３）エチレン：無処理 0ppm、処理区 4ppm
４）試験実施：4 月 20 日５）その他は種略-1-

３．エチレン濃度の分析方法
酪農学園大学および JA 士幌町（十勝農試）でエチレン処理した馬鈴しょ 2 塊茎とスペーサ
ーをラミネートフィルム袋に入れてヒートシールして密閉した（写真 1）。
フィルムにゴムパッチを貼付し注射針を刺し、真空ポンプにて内部の空気を完全に排気し（写真 2､3）、馬鈴しょ重量 300g に対し 1,000mL の空気を再度入れて封入した（写真 4）。
封入後、24 時間経過した時点（写真 5）で内部の空気をガスタイトシリンジでサンプリング
してガスクロマトグラフ（写真 6）にてエチレン濃度を測定した。

写真１．ビニールパック

写真 2．真空ポンプによる脱気写真 3.真空状態

写真 4．一定量の空気を入れる

写真 5．空気を入れて 24 時間保管

写真 6．ガスクロ

４．結果

表 1 に示す。
酪農学園大学において処理した馬鈴しょは、芽をすべて取り除いたのちに残留性試験を行ったが、その他の機関において処理したものについては、芽が付いたままの状態で試験に供試した。
酪農学園大学において処理した馬鈴しょでは、4 月 24 日の「きたひめ」20ppm 処理区においてのみエチレンが検出された。
JA 士幌町において処理した馬鈴しょでは、4 月 23 日の試料では無処理区においてのみエチ
レンが検出された。6 月 25 日においては、「トヨシロ」の無処理区を除いてエチレンが検出されたが、その他は無処理区の方が濃度が高かった。
カルビーポテト（株）において処理した馬鈴しょは、いずれもエチレンは検出されなかった。
本試験に用いた方法では、内生エチレンと処理に使用したエチレンの区別は出来ないが、ほとんどの場合エチレンが検出されないか、検出されても無処理区より濃度は低く、残留性は無いと判断できる。

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