Microbial Transformation of Phthalate Esters: Diversity of Hydrolytic Esterases - Environmental Contamination: Health Risks and Ecological Restoration - page 323

Basically,. the. toxicity. of. estrogen-like. PAEs. comes. from. the. action. called.
“estrogen.receptor-mediated.hormone.action.”.The.estrogen.is.bound.to.the.
protein.carrier.to.penetrate.cell.membrane.before.binding.ER..The.estrogen.
dimmer. with. estrogens. binds. with. its. DNA. binding. to. the. domain. of. an.
estrogen-responsive. element. and. regulates. the. gene. expression. with. gen-
eral.transcription.assembly.together.(Mueller.and.Korach.2001)..As.a.result,.
the.endocrine.disruptors.cause.the.endocrine.system.malfunction.and.even.
develop.cancer.(Birkett.2003).
Conjugation. of. ER. and. estrogens. is. closely. related. to. phthalate. ester.
structure,. especially. to. the. length. of. alkyl. chain. and. the. chain. position.
on. benzene. ring. (Nakai. et. al.. 1999).. The. chain. length. up. to. eight. carbons.
exhibits. a. relatively. weaker. potency. to. ER. than. does. the. length. of. three.
to.four.carbons..Furthermore,.for.different.chain.position.isomers.(namely,.
ortho -,. meta -,. and. para -),. the. ortho -PAE. has. higher. afinity. than. meta -. and.
para -PAE;.for.example,. meta -.and. para -dipropyl.phthalate.have.almost.twice.
the. IC 50 . value. (210. and. 147.μM. respectively). than. ortho -dipropyl. phthalate.
(78.8.μM).. Evidence. supported. that. the. ring. hydroxylated. PAEs. may. have.
higher. afinity. to. ER.. The. hydroxylated. PAEs. should. also. be. given. some.
attention. because. hydroxylation. reaction. is. very. common. in. the. environ-
ment.by.organisms.(Toda.et.al..2004).
After. the. Second. World. War,. the. toxicity. of. PAEs. had. been. surveyed.
(Shaffer. et. al.. 1945,. Carpenter. et. al.. 1953,. Harris. et. al.. 1956).. Autian. (1973).
published. a. review. to. recapitulate. the. toxicity. and. health. threats. of. PAEs.
to.human.beings.and.reported.that.the.acute.toxicity.did.not.show.a.severe.
damage.to.the.testing.tissues.or.organisms..The.lethal.dose.(LD 50 ).for.com-
monly.utilized.compounds.like.DMP,.DEP,.and.DEHP.were.1.58-10.0.mL/kg,.
1.0-5.06.mL/kg,.and.10.0-50.0.mL/kg,.respectively..However,.the.chronic.and.
subacute.toxicity.detected.was.shown.to.cause.irritation.to.the.upper.respi-
ratory.tract.of.humans,.particularly.when.its.presence.was.associated.with.
DMP,.DEP,.and.DEHP..The.estrogenic.activity.of.several.PAEs.was.observed.
in vitro ..Such.compounds.were.ranked.for.their.estrogenic.potentialities.in.
the.order:.BBP.>.DBP.>.DIBP.>.DEP.>.DINP.(Harris.et.al..1997).
DEHP.was.conirmed.to.be.causing.possible.hepatocellular.carcinomas.in.
female.rats.and.male.and.female.mice.(National.Toxicology.Program.1982)..
Hepatocellular.carcinomas.and.neoplastic.nodules.induced.in.male.rats.with.
concentration. reaching. 12,000.mg/L. caused. rats'. liver. neoplastic. lesion. as.
well.as.toxic.damage.in.testes.and.pituitary..The.male.rats.exposed.chroni-
cally. to. DEHP. developed. reproductive.damage,. including. hypospermia.in.
the.testis.and.epididymis.(Moore.1996)..The.reproductive.toxicity.was.also.
conirmed. at. a. high. concentration. of. 1.7.g/kg/day. for. 14. days. (Wilkinson.
and.Lamb.IV.1999)..However,.according.a.recent.study.on.the.DEHP.cancer.
risk.assessment,.no.genotoxicity.was.observed.at.a.concentration.level.that.
is.relevant.to.the.human.cancer.development.(Doull.et.al..1999)..The.author.
suggested.that.DEHP.should.not.be.classiied.as.a.likely.carcinogen.based.on.
margin.of.exposure.(MOE).approach.to.the.human.risk.assessment.