CHLOROPHENOL (Identity, Physical and Chemical Properties, Analytical Methods)

Chlorophenols (CPs) are organic chemicals formed from phenol (1-hydroxybenzene) by substitution in the phenol ring with one or more atoms of chlorine.  Nineteen congeners are posible, ranging from monochlorophenols to the fully chlorinated pentachlorophenol (PCB).  Chlorophenols, particularly trichlorophenols (T₃CP), tetrachlorophenols (T₄CP), and PCP, are also available as sodium or potassium salts.

Chlorophenols are solids at room temperature, except for 2-MCP, which is a liquid.  The aqueous solubility of chlorophenols are up to four orders of magnitude more soluble in water than the parent compounds.  The acidity of chlorophenols increases as the number of chlorine substitutions increases.  The n-octanol/water partition coefficients of chlorophenols increases with chlorination, indicating a propensity for the higher chlorophenols to bioaccumulate.  Taste and odour thresholds are quite low.

Technical grade chlorophenol products are heterogeneous mixtures of chlorophenols, unreacted precursors, and a variety of dimeric microcontaminants.  As a result of the semiquantitative nature of the reaction of chlorine with molten phenol, commercial formulations of chlorophenols contain substantial quantities of other chlorophenols.  When the alkaline hydrolysis of chlorobenzenes is used to manufacture chlorophenols, the technical product can contain unreacted chloro-benzene.

A number of other compounds are present as microcontaminants in technical tri- and tetrachlorophenol preparations, as a result of the elevated reaction temperatures used.  These include the polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated phenoxyphenols (“predioxins”), polychlorinated diphenil ethers, polychlorinated benzenes, and polychlorinated biphenils.  Lower chlorophenol preparations do not contain detectable levels of dioxins, presumably because their manufacture does not occur at sufficiently high temperatures.  Tri- and tetrachloro-dibenzo-p-dioxins predominate int T₃CP formulations, while the hexa, hepta, and octa congeners are the major PCDD contaminants in technical T₄CP and PCP.  2,3,7,8-tetra-chlorodibenzo-p-dioxin (2,3,7,8-TCDD) occurs primarily as a contaminant of 2,4,5-T₃CP, though it is present at low µg/litre concentrations in T₄CP, PCP, and Na-PCP.  Chlorophenol formulations contain a similar array of PCDFs.  Phenoxyphenols may comprise as much 1-5% of the formulation.

A large number of sampling and analytical methods have been developed for the determination of chlorophenols in different media.  Sensitive methods, such as gas chromatography, high-performance liquid chromatography, and mass spectrometry are increasingly used.

For further information :

Chlorophenols Other Than Pentachlorophenol; WHO; Geneva; 1989

BIOCHEMISTRY OF TERATOGENESIS

Teratology is the science of birth defects caused by radiation, viruses, and chemicals, including drug.  Xenobiotic chemical species that cause birth defects are called teratogens.  Teratogens affect developing embryos adversely, often with remarkable specificity in regard to effect and stage of embryo development when exposed.  A teratogen may cause a specific effect when exposure occurs on a definite number of days after conception; if exposure occurs only a few days sooner or later, no effect, or an entirely different one, may be observed.  Although mutations in germ cells (egg or sperm cells) may cause birth deffects (e.g. Down’s syndrome), teratology usually deals with defects arising from damage to embryonic or fetal cells.

The biochemical effects of teratogens are varied and, for the most part, not well understood.  In some cases teratogens interfere with DNA synthesis.  Teratogens may alter the function of nucleic acids in cell replications, and adverse effects may result.  Serious defects may arise from either an absence or excess of chromosomes caused by exposure to xenobiotics, an effect that sometimes can be revealed by microscopic examination.  Enzyme inhibition by xenobiotics can be teratogenic.  Xenobiotics that deprive the fetus of essential substrates (for example, vitamins), that interfere with energy supply, or that alter the permeability of the placental membrane may all cause birth defects.

Perhaps the most notorious teratogen is thalidomide, a sedative-hypnotic drug used in Europe and Japan in 1960-1961.  Some infants born to women who had taken thalidomide from days 35 through 50 of their pregnancies were born suffering from amelia or phocomelia, the absence or severe shortening, respectively, of the limbs.  About 10,000 children were affected.

In 1988 the U.S. Food and Drug Administration estimated that Accutane (retionic acid) used as an anti-acne medication may have been responsible for approximately 1,000 birth defects in children born to women taking the drug during the period 1982-1986.  Exposure of the fetus to the drug over a period of only several days can result in birth defects such as severe facial malformations, heart defects, and mental retardation.

For further information :

Manahan, Stanley E.; Toxicological Chemistry;

ALGAE MERAH (RED ALGAE)

 Rumput laut (algae laut bentik) yang bernilai ekonomis penting di Indonesia diantaranya adalah jenis Rhodophyta (algae merah).  Algae merah ditandai oleh sifat-sifat sebagai berikut :

• Dalam reproduksinya tidak mempunyai stadia gamet berbulu cambuk.
• Reproduksi seksual dengan karpogonia dan spermatia.
• Pertumbuhan bersifat uniaksial (satu sel di ujung thallus) dan multiaksial (banyak sel di ujung thallus).
• Alat pelekat (holdfast) terdiri dari perakaran sel tunggal atau sel banyak.
• Mempunyai pigmen fikobilin yang terdiri dari fikoeretrin (berwarna merah) dan fikosianin (berwarna biru).
• Bersifat adaptasi kromatik, yaitu mempunyai penyesuaian antara proporsi pigmen dengan berbagai kualitas pencahayaan dan dapat menimbulkan berbagai warna “thalli” seperti : pirang, violet, merah tua, merah muda, coklat, kuning, dan hijau.
• Mempunyai persediaan makanan berupa kanji (floridean starch).
• Dalam dinding selnya terdapat selulosa, agar, karagenan, porpiran, dan furselaran.

Salah satu spesies yang dibudidayakan di Indonesia adalah Eucheuma spp.  Adapun sistematika klasifikasi botani adalah sebagai berikut :

Divisio       : Rhodophyta

Class         : Rhodophyceae

Bangsa      : Gigartinales

Suku          : Solieriaceae

Marga        : Eucheuma

Jenis          : Eucheuma spp.

 Eucheuma spinosum

Eucheuma cottonii

Tidak kurang dari dua puluh jenis Eucheuma dapat dikenal daerah Indo-Pasifik yang terbagi kedalam dua seksi berdasar struktur selnya, yang pertama adalah seksi “axifera” (berstruktur sel memusat) dan yang kedua adalah “unaxifera” (berstruktur sel tidak memusat).  Ciri-ciri umum dari marga ini adalah :

• Thalli (kerangka tubuh tanaman) bulat silindris atau gepeng.
• Berwarna merah, merah-coklat, hijau-kuning, dan sebagainya.
• Bercabang berselang tidak teratur, di atau trikhotomous.
• Mempunyai benjolan-benjolan (blunt nodule) dan duri-duri (spines).
• Substansi thalli “gelatinus” dan atau “kartiagenus” (lunak seperti tulang rawan).

 Beberapa jenis diantaranya terdapat di Indonesia.  Setiap jenis mempunyai nama daerah yang berbeda-beda.  Tetapi secara umum disebut agar-agar.  Khusus untuk Eucheuma spinosum misalnya, di Ujung Pandang disebut agar-agar kasar, di Pulau Seribu dinamakan agar-agar patah tulang, di Sulawesi Tenggara biasa disebut agar-agar kembang, dan di Pulau Seram dinamakan agar-agar geser dan pulu.

Eucheuma umumnya terdapat di daerah tertentu dengan persyaratan khusus.  Kebanyakan tumbuh di daerah pasang-surut (ntertidal) atau pada daerah yang selalu terendam air (subtidal) melekat pada substrat di dasar perairan yang berupa karang batu mati, karang batu hidup, batu gamping, atau cangkang moluska.  Umumnya mereka tumbuh dengan baik di daerah pantai terumbu (reef), karena di tempat inilah beberapa persyaratan untuk pertumbuhannya banyak terpenuhi, antaranya faktor kedalaman, pencahayaan, substrat, dan gerakan air.  Pertumbuhan cenderung lebih baik di daerah dekat batas pasang-surut tahunan terendah.  Biasanya pada kedalaman sekitar 30-50 cm waktu surut terendah.  Habitat khas adalah daerah yang dapat aliran air laut yang tetap, mereka lebih menyukai variasi suhu harian yang kecil dan substrat batu karang mati.  Algae ini tumbuh mengelompok dengan berbagai jenis rumput laut lainnya membentuk populasi campuran.  Pengelompokan ini tampaknya penting dan saling menguntungkan diantaranya dalam hal penyebaran spora.

Beberapa jenis Eucheuma penting dalam dunia perdagangan internasional sebagai penghasil ekstrak karagenan.  Zat ini adalah suatu fikoloid yang berupa polisakharida.  Contoh senyawa karagenan adalah asam karagenat yang terdiri dari kalsium karagenat dan potasium karagenat.  Prosentase karagenan berkisar antara 54-73% bergantung pada jenis dan lokasi.  Di Indonesia karagenan berkisar antara 61,5-67,5%.  Fraksi pertama larut dalam air panas, yang kedua larut dalam air dingin, sedangkan yang ketiga larut dalam air panas dan air dingin.  Dewasa ini ekstrak karagenan telah meluas pemakaiannya untuk berbagai kebutuhan di berbagai industri.  Misalnya ia berfungsi sebagai penebal, pengemulsi, penstabil, pengental, dan pengikat substansi pada industri makanan, farmasi, kosmetik, tekstil, kertas, keramik, karet, dan lain-lain.  Disamping karagenan, dalam Eucheuma masih terdapat lagi beberapa zat organik lain seperti protein, lemak, serabut kasar, abu, dan air.  Eucheuma spinosum dan Eucheuma cottoniiterutama dari hasil budidaya di Indonesia, kebanyakan untuk komoditi ekspor.  Sedangkan beberapa jenis lainnya di beberapa tempat dimanfaatkan untuk konsumsi dalam negeri sebagai bahan makanan tambahan.

Beberapa jenis Eucheuma spp yang ada di Indonesia beserta sebarannya adalah :

E. spinosum         : P. Seribu, Selat Sunda, Sulawesi Tenggara, Sulawesi Tengah, Maluku, Sumbawa, Riau.

E. edule               : P. Seribu, Bali, Sulawesi Tenggara, Maluku, Sulawesi Tengah.

E. serra               : Bali.

E. cottonii            : Sulawesi Tengah, Maluku, Sumbawa, Sulawesi Tengah.

E. crassum          : Sulawesi Tenggara dan Maluku.

E. urnoldhii          : Bali dan Maluku.

E. leewenii           : Jawa.

E. crustaeforme   : Sulawesi Utara.

E. horizontal        : Sulawesi Selatan.

E. adhaerens       : Maluku.

E. vermiculare     : P. Seribu.

E. dichotomum     : P. Seribu dan Maluku.

E. cervicorne       : Maluku.

E. striatum           : P. Seribu.

E. simplex            : Maluku.

For further information :

Kadi, A. dan Atmadja, W.S.; Rumput Laut (Algae); P3O-LIPI; Jakarta; 1988

BIOCHEMISTRY OF CARCINOGENESIS

Cancer is a condition characterized by the uncontrolled replication and growth of the body’s own cells (somatic cells).  It is now generally believed that many – and perhaps most – cancers are started by the action of synthetic and naturrally occuring chemicals (in some cases viruses cause cancer).  The role xenobiotic chemicals in causing cancer is called chemical carcinogenesis.  It is often regarded as the single most important facet of toxicology and clearly the one that receives the most publicity.

Despite large expenditures of time and money on the subject, the biochemical bases of chemical carcinogenesis are not well understood.  The overall processes for the induction of cancer may be quite complex, involving numerous steps.  It is generally recognized that there are two major steps : an initiation stage followed by a promotional stage.  Chemical carcinogens are often mutagens and it is believed that in many cases cancerous cells result from mutations of normal cells exposed to carcinogens.  This implies that that chemical carcinogens alter DNA in a manner such that an “outlaw cell” is formed that continues to replicate itself and form cancerous tissue.

Chemical carcinogens usually have the ability to form covalent bonds with macromolecular life molecules, especially DNA.  Prominent among these are the alkylating agents which attach alkyl groups – such as methyl (CH₃) or ethyl (C₂H₅) – to DNA.  A similar type of compound, arylating agents, act to attach aryl to DNA.  The alkyl and aryl groups become attached to N and O atoms in the nitrogenous bases that compose DNA.  This leads to alteration in the DNA and it can result in the growth and replication of neoplastic (cancerous) cells.

In order for them to cause cancer, most most cancer-causing substances require metabolic activation and are called precarcinogens or procarcinogens.  The metabolic species actually responsible for carcinogenesis, usually by its interaction with DNA, is termed an ultimate carcinogen.  Some species that are intermediate metabolites between precarcinogens and ultimate carcinogens are called proximate carcinogens.  Carcinogens that do not require biochemical activation are categorized as primary or direct-acting carcinogens.

In some cases chemicals are known to be carcinogens from epidemiological studies of exposed humans.  Animals are used to test for carcinogenicity, and the results can be extrapolated with some uncertainty to humans.  The most broadly applicable test for potential carcinogens is the Bruce Ames procedure, which actually reveals mutagenicity.  The principle of this method is the reversion of mutant histidine-requiring Salmonella bacteria back to a form that can synthesize their own histidine.  The bacteria are inoculated onto a medium that does not contain histidine, and those that mutate back to a form that can synthesize histidine establish colonies which are assayed on the growth medium, thereby providing both a qualitative and quantitative indication of mutagenicity.  The test chemicals are mixed with homogenized liver tissue to simulate the body’s alteration of chemicals (conversion of procarcinogens to ultimate carcinogens).  Up to 90% correlation has been found between mutagenesis on this test and known carcinogenicity of test chemicals.

for further informations :

Manahan, Stanley E.; Toxicological Chemistry;