Sabtu, 18 Februari 2012
“Sudahlah tu Farah, jangan dikenang perkara yang sudah lepas,” kata ibu sambil menutup televisyen. Aku menonton drama yang disiarkan di TV3 di mana aku memegang watak utama dalam drama tersebut. Drama itulah yang membolehkan aku dicalonkan untuk gelaran Anugerah Pelakon Wanita Popular. Walaupun aku gagal memenangi anugerah tersebut tetapi pencalonan aku cukup bermakna kerana ia telah menaikkan namaku setaraf dengan artis-artis yang lebih ‘established’. Dahulu, aku dikenali sebagai artis wanita yang cantik, berkulit kuning langsat, genit dan lincah. Kemana aku pergi sentiasa mendapat perhatian, ramai lelaki ingin menghampiriku untuk berkenalan. Tetapi hari ini, dengan badanku yang kurus kering, rambut yang hanya segenggam dan muka yang cengkung…. Aduhai, betapa bezanya diriku dulu dan sekarang….
Detik hitam dalam hidupku bermula 5 tahun dahulu apabila pada kemuncak kerjayaku sebagai artis, aku menerima tawaran untuk menjadi duta kecantikan rangkaian produk kecantikan yang agak terkenal. Aku pun mula menggunakan produk tersebut. Walaupun pada mulanya kulit mukaku terasa gatal-gatal, aku tidak menghiraukan sangat kerana aku taksub dengan perubahan pada wajahku. Kulit mukaku kelihatan begitu cantik, putih gebu dan kemerahan. Ramai yang memuji kecantikan wajahku. Aku begitu yakin akan produk yang aku gunakan dan terus mempromosikannya kepada kaum keluarga, sahabat handai dan orang ramai.
Kulit yang pada mulanya gatal menjadi radang dan terus mengelupas. Kulit mukaku semakin tipis tetapi aku masih tidak menghiraukan sangat kerana aku sangka itu tandanya kulit sudah menjadi lebih halus. Mungkin kerana umurku yang masih muda, kesan buruk pada wajahku tidak ketara sehinggalah hampir 3 tahun menggunakan produk kecantikan tersebut. Kulitku mulai kusam dengan warna kulit tidak sekata. Apabila terkena cahaya matahari, kulit mukaku merah menyala seperti udang kena bakar. Pada mulanya kemerahan itu akan reda sendiri tetapi lama kelamaan bahagian yang merah menjadi terbakar. Kulit yang dahulunya licin menjadi berbintik seperti pasir dan dipenuhi tompokan berwarna coklat kehitaman.
Puas aku bertukar produk, mendapat rawatan di salun-salun kecantikan, namun keadaan kulitku bertambah teruk. Yang paling mengecewakan lagi apabila kontrak aku dengan syarikat produk kecantikan tersebut dibatalkan. Aku disuruh perbaiki wajah yang sudah hodoh, walhal produknya yang menyebabkan wajahku menjadi sedemikian rupa! Bagaikan sudah jatuh ditimpa tangga, tiada lagi produser filem yang mahu memberi aku peluang berlakon lagi. Aku masih teringat kata-kata mereka. “Sorry Farah, nanti bila you dah cun macam dulu, contact I balik OK”. Begitulah hidup dunia artis; bila rupa muka dah tak ada, tiada siapa yang nak pandang kita lagi…
Sejak setahun yang lepas, aku kerap mengalami rasa pening dan sakit kepala, sentiasa berpeluh, rasa dahaga, sakit perut dan cirit-birit. Tanggal malam 12 Oktober 2006, setelah seminggu demam panas yang tinggi dan sukar bernafas serta muntah-muntah, Tijah kawan serumahku membawa aku ke HUKM. Aku tidak dibenarkan pulang dan dirawat di wad kecemasan. Keesokan harinya, setelah menjalani pemeriksaan fizikal keatas diriku dan melihat keadaan kulit mukaku yang dipenuhi tompok hitam, sambil mengeleng- gelengkan kepalanya, Dr Rusilah yang merawatku memberitahu kemungkinan besar aku menghadapi masalah keracunanHydroquinon e, kesan daripada produk kecantikan yang telah aku gunakan. Dr Rusilah juga agak risau melihat tahi lalat di pipi kiriku yang mempunyai lingkaran hitam disekelilingnya. Memang aku perasan, tetapi pada sangkaanku ia telah bercantum dengan tumpukan hitam yang sememangnya sedang membesar
Biopsi dilakukan pada tahi lalat tersebut dan setelah laporan makmal diterima, alangkah terkejutnya apabila aku diberitahu menghidap kanser kulit jenis ‘Nodular Melanoma’. Ibu yang sedang menemankanku menangis sekuat hatinya sambil memelukku. Aku terdiam kaku dan tidak mampu bersuara. Aku masih ingat ketika itu perasaanku sedih bercampur geram. Geram kerana terasa diri diperalatkan oleh syarikat produk kecantikan yang hanya mementingkan keuntungan semata-mata. “Apa ituHydroquinone, doktor?” tiba-tiba soalan itu terkeluar dari mulutku.
Dengan menarik nafas panjang, Dr Rusilah berkata, “Hydroquinone adalah sejenis bahan
penghakis kulit. Bahan kimia beracun ini juga digunakan dalam pemprosesan filem gambar.
Hydroquinone yang diletakkan pada kulit akan menyebabkan terjadi proses depigmentasi iaitu proses di
mana pigmen dibuang dan ini menyebabkan kulit menjadi lebih cerah.Hydroquinone digunakan sebagai pemutih dalam produk kecantikan keranahydroquinone mampu mengelupaskan kulit bahagian luar dan membenteras pembentukan pigmen melanin yang memberi warna kepada kulit. Pengelupasan ini membuat peradangan serta iritasi kulit sehingga kulit menjadi merah dan terbakar.Hydroquinone juga boleh menyebabkan kerosakan pada buah pinggang, kanser darah atauleu kemia, kanser kulit dan kanser sel hati iaitu hepatocellular adenoma. Walaupun produk kecantikan hanya disapu pada bahagian kulit, namun ia boleh meresap ke dalam kulit dan dibawa ke seluruh bahagian tubuh melalui peredaran saluran darah. Ia juga boleh meresap melalui sistem pernafasan dan mulut. Kandungan bahan ini didapati tinggi di bahagian hati dan buah pinggang”, terang Dr Rusilah dengan panjang lebar.
Setelah enam bulan berlalu dan selesai menjalani rawatan pembedahan serta kemoterapi, laporan
CAT Scan yang dilakukan tempoh hari mengesahkan kanser tidak dikesan di bahagian lain dalam
tubuhku. Dr Rusilah berkata insyaAllah kanserku berjaya dirawat. Walau bagaimanapun aku perlu menjalani pemeriksaan susulan selama 5 tahun untuk memastikan kanser tersebut tidak berulang. Sekarang keadaanku kurus dan rambutku yang dahulu cantik mayang mengurai kini hanya tinggal tipis serta jarang akibat kesan sampingan kemoterapi tetapi aku tetap bersyukur. Aku bersyukur kerana penderitaanku ini sememangnya juga suatu rahmat kerana ia membuka hatiku untuk bertaubat dan mengingati kembali Allah SWT. Aku berterima kasih kerana ibu dan adikku, Leha telah banyak membantuku mengharungi saat-saat genting dalam kehidupanku dan aku berniat akan menjadi seorang insan yang lebih baik.
Esok, bakal kakak ipar Leha, Dr Suriani seorang pakar kulit dari HUKM akan membawaku ke salun Alam Kecantikan Zai’s Beauty Formula. Sebagai seorang wanita, aku tetap mahu memperbaiki kerosakan pada kulit mukaku dan kelihatan cantik kembali. Menurut Dr Suriani sudah lebih 10 tahun dia menggunakan produk Zai’s Beauty Formula dan dia amat berpuas hati. “Ramai doktor wanita dan isteri doktor kenalan Kak Ani menggunakan Zai’s Beauty Formula ciptaan Dr Tunku Zaidar,” terang Dr Suriani padaku. “Produk kecantikan ini paling selamat kerana tiada langsung menggunakan bahan kimia, pewangi, pengawet dan penyatu. Dr Tunku Zaidar menggunakan 100% herba dan cara pembuatan produk ini menggunakan kaedah penapaian. Pengeluaran produk begini terhad kerana proses penapaian mengambil masa berbulan-bulan lamanya. Itulah sebabnya produk kecantikan Zai’s Beauty Formula tidak dapat dikeluarkan dengan banyak dan tiada agen atau stokis dan ia hanya boleh didapati di Salun- salun Alam Kecantikan Zai’s Beauty Formula”. Tak sabar rasanya nak ke sana
The Ugly Side of Beauty
by Judi Vance
by Judi Vance
For ten long years, Judi Vance, author of Beauty to Die For - The Cosmetic Consequence has been voicing a conflicting account on the safety of cosmetics. Her latest endeavor is an Internet community, Cosmetics - Are they worth the risk? The publisher sponsored Web site allows Vance to continue her quest to educate on the subject of cosmetic risks.
“Not everything we women do in an attempt to enhance our beauty is necessarily good for us.” says Vance “Years ago, in the Elizabethan times, it was fashionable (and aristocratic) to present a pasty white complexion. Women powdered their faces with a mixture including white lead called ceruse, and colored their lips with a reddener containing fucus-red mercuric sulfide. Even though this beauty regime destroyed the outer layer of skin, they continued using these poison palettes well into the 18th century.”
“Today isn’t much different,” Vance concedes. “Thousands of Filipino women expose themselves to the dangers of severe skin disorders and possibly even cancer through their desire to have paler skin. Although the full extent of the dangers of hydroquinone , the active ingredient in the skin bleaching cream are still unknown, U.S. studies have linked it with leukemia, liver damage, and thyroid disorders. Animal studies show that it could cause mutations in developing fetuses.”
“In our quest for beauty we forget that the skin is an organ that serves vital body functions.” She emphasizes that our skin is part of our respiratory system, absorbing oxygen and releasing waste; cooling or heating us in accordance with the outside temperature; creating natural oils to prevent moisture loss and over-hydration and also to protect us from invading microorganisms. The skin also plays a major role in immunity. “Cosmetic use does not respect these bodily functions—it destroys them.”
According to Vance, “most women have no idea that cosmetics could cause harm. They tend to think that the new “miracle” ingredients are coming from years of scientific discovery. Wrong! Most of the ingredients have been around for many years. It’s only now that they have moved from an industrial purpose into the world of beauty. The ultimate wrinkle removers (according to cosmetic ads)—alpha hydroxy acids—have been used for years in the processing of textiles, leather, and metal and also used in cleaning, polishing, and soldering compounds, copper pickling, adhesives, and electroplating.”
Vance, who participates in the upcoming four-part Discovery Channel documentary called “Hope and beauty: the story of cosmetics” says, “cosmetic chemicals are not adequately tested. The cosmetics business is a self-regulated industry and, as quoted by a Health Canada toxicologist, compliance is as low as 30 percent.”
Several months ago, The Centers for Disease Control (CDC) completed a study in relation to the phthalates found in children’s soft plastic toys. The study showed that the particular phthalate used in toys were at rather low levels. However, other phthalates, like the ones used in fingernail polish, were at levels high enough to raise concern. Warnings were then issued advising women not to use nail polish during pregnancy because of the possibility of birth defects.
“Science doesn’t have all the answers,” she says. “There's no scientific agreement on what tests can correctly determine whether someone’s immune or nervous system, or genes have been damaged. Nor is there a consensus on what constitutes a safe level of exposure. Reproductive, developmental and genetic damage is a non-threshold event and the only safe dose is zero. Until, science knows the answers to these baffling questions, avoidance of the suspect chemicals is probably our antidote.
“Some women are becoming wise,” says Vance and cites the onslaught of natural cosmetic products to the marketplace as validation that safety is an issue. Alternatives exist. Education is a must.
email her at firstname.lastname@example.org. Her telephone number in Mexico is 52-1-122-9661.
Hydroquinone Belum Diharamkan
Hydroquinone sebabkan barah!
The available studies on the carcinogenicity of hydroquinone
are summarized in Table 17.
In an NTP study (NTP, 1989; Kari et al., 1992), groups of 65
F-344/N rats of each sex were given hydroquinone (0, 25 or 50 mg/kg
body weight) in deionized water by gavage 5 days/week for up to 103
weeks, and groups of 65 B6C3F1 mice of each sex were administered
0, 50 or 100 mg/kg body weight according to the same schedule. A
15-month interim kill of ten animals from each group showed that the
kidney of male rats was a target organ forthe toxicity (see also
section 7.4), since there was a compound-related increased severity
of nephropathy. The lesions were less severe in female rats, in
which a mild regenerative anaemia was also found (slightly decreased
haematocrit, haemoglobin and erythrocyte count). After termination
of the experiment, a dose-related increase in the incidence of renal
tubular cell adenomas was observed in male rats (controls 0/55, low
dose 4/55, high dose 8/55; P = 0.003). The incidence of adenomas was
closely associated with the severity of chronic nephropathy. No
renal adenomas were observed in animals examined at 15 months, when
the severity of nephropathy was less severe, or in female rats,
which developed nephropathy to a lesser degree. In the male rats,
9/12 adenomas were seen in kidneys with marked nephropathy, two were
seen in animals with moderate nephropathy, and only one was seen in
an animal with mild nephropathy. In the high-dose group single
tubules exhibited tubular cell hyperplasia. No renal tumours were
seen in females. A dose-related increase in the incidence of
mononuclear cell leukaemia was found in female rats (controls 9/55,
low dose 15/55, high dose 22/55) (P < 0.01 in the high-dose group
versus controls). However, this was not observed in the animals
killed at 15 months. The incidence in controls was lower than the
historical control mean incidence but was within the historical
control group range.
Table 17. Carcinogenicity studies in animals
Species Route of Number of Dosage Time of Result Remarks Reference
exposure animals treatment
Mouse oral 64 or 65 of 50 or 100 103 weeks liver lesions (males), some evidence of NTP (1989);
each sex mg/kg hepatocellular adenomas carcinogenic activity Kari et al.
per group 5 days/week (females) for female mice (1992)
Mouse oral 30 m, 30 f 0.8% in 96 weeks squamous cell hyperplasia of potential of Shibata et al.
the diet the forestomach epithelium; hepatocarcinogenicity (1991)
renal tubular hyperplasia and in male mice
adenomas (males); increased
incidence of liver foci and
Rat oral 65 of each 25 or 50 103 weeks nephropathy (more severe in some evidence of NTP (1989);
sex per mg/kg males), renal tubular cell carcinogenic activity Kari et al.
group 5 days/week hyperplasia and adenomas for male and female (1992)
(males), leukaemia (females) rats
Rat oral 30 m, 30 f 0.8% in 104 weeks renal tubular hyperplasia, potential of renal Shibata et al.
the diet adenomas and epithelial carcinogencity in (1991)
hyperplasia of the renal male rats
papilla (males); decreased
incidence of liver foci
Table 17. (contd).
Species Route of Number of Dosage Time of Result Remarks Reference
exposure animals treatment
Mouse skin 24 m 0.3 ml of 6.7% one skin papilloma (1/24) no initiating Roe & Salaman
application solution; application; activity (1955)
0.3 ml of then three
0.5% croton weeks later,
oil 18 weekly
Mouse skin 50 f 5 mg three 368 days papilloma (7/50), squamous no co-carcinogenic van Duuren &
application times carcinoma (3/50) or tumour-promoting Goldschmidt
weeklya activity; partial (1976)
inhibition of BP
Mouse implantation not stated 2 mg 25 weeks carcinomas (6/19) Boyland et al.
in urinary (1964)
Rat oral 20 f 0.8% in 32 weeks no preneoplastic lesions Kurata et al.
basal dietb or papillomas of the (1990)
Rat oral 15-16 m 0.8% in 51 weeks no increase in forestomach or Hirose et al.
dietc glandular stomach neoplasms (1989)
Rat oral 5 m 8 weeks no proliferative changes Shibata et al.
in forestomach or glandular (1990)
Table 17. (contd).
Species Route of Number of Dosage Time of Result Remarks Reference
exposure animals treatment
Rat oral 7-10 m per 100 mg/kg 7 weeks increased number of liver foci relatively weak Stenius et al.
group diet per dayd decreased number of liver foci inducer of enzyme- (1989)
200 mg/kg compared to the 100 mg/kg altered liver foci
diet per dayd dose
Hamster oral 15 m 0.5% in basal 20 weeks no proliferative changes in Hirose et al.
diet forestomach (1986)
a after initiating dose of benzo[ a] pyrene (BP)
b after initiating with N-butyl-2 N-(4-hydroxybutyl) nitrosamine for four weeks
c one week after 150 mg/kg body weight
d after partial hepatectomy
In male mice centrilobular fatty changes and cytomegaly were
found in the animals killed at 15 months, but these findings were
not seen in mice killed at 2 years. The authors reported that
hydroquinone dosing stopped two weeks before necropsy and that the
microscopic lesions were likely to be reversible after cessation of
treatment. There was a significantly (P=0.0005) increased incidence
of hepatocellular adenomas in female mice given hydroquinone for 2
years (controls 2/55, low dose 15/55, high dose 12/55) and the
incidences of hepatocellular carcinomas were 1/55, 2/55 and 2/55,
respectively. In males the incidence of adenomas was increased in
treated mice but the incidence of hepatocellular carcinomas was
decreased. Preneoplastic changes (anisokaryosis, multinucleated
hepatocytes, and basophilic foci) were increased in high-dose male
mice. Treatment-related, but not statistically significant,
follicular cell hyperplasia of the thyroid gland was observed in
both male and female mice (NTP, 1989; Kari et al., 1992).
The NTP concluded that there was "some evidence of carcinogenic
activity" of hydroquinone for male F-344/N rats (tubular cell
adenomas of the kidney) and also for female F-344/N rats
(mononuclear cell leukaemia). There was "no evidence of carcinogenic
activity" for male B6C3F1 mice and "some evidence of carcinogenic
activity" for female B6C3F1 mice (hepatocellular adenomas and
Shibata et al. (1991) administered hydroquinone at dietary
levels of 0.% or 8 g/kg to groups of 30 Fischer-344 rats and
B6C3F1 mice of each sex. The rats were dosed for 104 weeks and the
mice for 96 weeks. Average daily intakes were reported to be 351 and
368 mg/kg body weight per day in male and female rats, respectively,
and 1046 and 1486 mg/kg per day in male and female mice,
respectively. No treatment-related clinical signs and no significant
differences in mortality were found between treated and control
animals of either species. The final body weight was significantly
(P < 0.05) lower in treated female rats than in corresponding
controls. In male rats the absolute and relative liver and kidney
weights were significantly (P < 0.01) increased, but in females
this applied only to the relative kidney weights (P < 0.05).
Histologically, chronic nephropathy was seen in both control and
treated groups of male rats. However, treated males were more
severely affected than the controls, while treated females showed
only slight nephropathy. The incidence of epithelial hyperplasia of
the renal papilla was significantly (P < 0.05) increased in treated
male rats as was the incidence of renal tubular hyperplasia (30/30)
and renal tubular adenomas (14/30).
The authors found that renal cell tumour development in male
rats under the long-term influence of hydroquinone was not
associated with alpha2u-globulin nephropathy. The incidence of liver
foci showed a tendency to decrease in treated males. A quantitative
analysis showed a statistically significant (P < 0.05 in males, P<
0.01 in females) reduction in both sexes given hydroquinone. The
authors did not find an increased incidence of mononuclear cell
leukaemia in female rats (personal communication).
In mice, the final body weight was significantly (P < 0.05)
lower in females given hydroquinone; the relative liver and kidney
weights were significantly (P < 0.05) increased. Histologically,
the incidence of squamous cell hyperplasia of the forestomach
epithelium was significantly (P < 0.01) increased in both sexes. A
significant increase in the incidence of renal tubular hyperplasia
(P < 0.01) and three renal cell adenomas were seen in 30 males
given hydroquinone. In treated males the incidence of liver foci and
hepatocellular adenomas (14/30) was also significantly (P < 0.05)
In a study by Roe & Salaman (1955), stock albino mice (24
males, "S" strain) were given a single skin application of 0.3 ml of
a 6.7% solution of hydroquinone in acetone (total dose 20.0 mg).
Three weeks later the mice received 18 weekly applications of 0.3 ml
of 0.5% croton oil in acetone as a promoter on the same area of the
skin. Of the 24 treated animals, two died during the experiment and
one mouse developed a skin papilloma.
In a two-stage carcinogenesis test on mouse skin using
benzo[ a]pyrene (BP) as the initiating agent, no tumour-promoting
activity was shown (Van Duuren & Goldschmidt, 1976). Hydroquinone (5
mg) was applied to mouse skin (50 female ICR/Ha Swiss mice/group;
both positive and negative controls) three times weekly for 368
days, together with 5 µg BP. Hydroquinone showed no potential as a
co-carcinogen when applied simultaneously with BP; in fact, it
partially inhibited BP carcinogenicity.
Implantation of cholesterol pellets containing hydroquinone
into the urinary bladder of mice (strain and sex unspecified) has
been studied by Boyland et al. (1964). The amount of hydroquinone
was 20% in 10 mg cholesterol pellets (2 mg hydroquinone per mouse).
Bladder carcinomas were produced in 6 out of 19 mice (32%) surviving
25 weeks. The incidence of urinary bladder carcinomas in survivors
of the dosed group was significantly (P=0.03) higher than in
controls (11.7%) given cholesterol pellets only. However, the number
of animals surviving the study was low, and the original number of
animals and their sex distribution were not specified.
In a study by Kurata et al. (1990), groups of 20 male
Fischer-344 rats received 0.05% N-butyl- N-(4-hydroxybutyl)
nitrosamine in the drinking-water for four weeks (as initiation)
followed by 8 g hydroquinone/kg in the basal diet for 32 weeks. No
increase in the incidence of preneoplastic lesions or
papillomas/carcinomas of the urinary bladder was observed when
compared to the incidences in rats given nitrosamine alone.
Hirose et al. (1989) examined the promotion activity and the
carcinogenic potential of some dihydroxybenzenes, such as
hydroquinone, in the glandular stomach and forestomach of F-344
rats. Groups of 15-16 male rats were given a single intragastric
dose of 150 mg/kg body weight N-methyl- N'-nitro- N-
nitrosoguanidine (MNNG), followed one week later by powdered diet
containing hydroquinone (8g/kg) or basal diet alone for 51 weeks.
Further groups of 10 and 15 animals, respectively, were administered
the basal diet alone or a diet containing hydroquinone (8 g/kg) for
51 weeks without pretreatment with MNNG. Hydroquinone did not cause
an increased incidence of forestomach or glandular stomach lesions,
either with or without pretreatment with MNNG, in comparison with
the control groups.
In studies performed by Hirose et al. (1986), hydroquinone
did not produce proliferative lesions in the stomach of hamsters.
Male Syrian golden hamsters (15/group, seven weeks old at the
beginning of the study) were given basal diet with hydroquinone (5
g/kg) added or basal diet alone for 20 weeks. The dose was chosen as
approximately a quarter of the LD50. Tissues from forestomach and
glandular stomach showed mild to moderate hyperplasia in the group
given hydroquinone, but at the same incidence as in the controls.
Similar results were obtained by Shibata et al. (1990) in an
8-week oral study using five male F-344 rats. Hydroquinone did not
induce any proliferative changes in the forestomach or the glandular
Hydroquinone has been shown to be a relatively weak inducer of
enzyme-altered foci in rat liver when tested for tumour-promoting
activity in a liver focus test (Stenius et al., 1989). Male
Sprague-Dawley rats (7-10/group) given diethylnitrosamine (30 mg/kg
intraperitoneally) after partial hepatectomy were treated with
hydroquinone (0, 100 and 200 mg/kg per day) in their diet for 7
weeks. At 100 mg/kg there was a significantly (P < 0.01) increased
number of liver foci and an increased focus volume. The 200-mg dose
caused less foci (0.34 ± 0.16 per cm2) than the 100-mg dose (0.65
± 0.25 per cm2), but the incidence was higher than in the control
group (0.08 ± 0.08 per cm2).
A study by Kurata et al. (1990) yielded similar results
concerning the tumour-promoting potential of hydroquinone in rats.
Dietary administration of hydroquinone (8g/kg in basal diet) for 32
weeks, after initiation for four weeks with N-butyl- N-
(4-hydroxybutyl) nitrosamine, caused no preneoplastic lesions or
papillomas of the urinary bladder.
The bone marrow is the target in benzene toxicity; among the
many metabolites of benzene, hydroquinone has received increased
scrutiny as one of the possible contributing factors. Intravenous or
intraperitoneal administration of hydroquinone (100 mg/kg) for three
consecutive days to male C57BL/6 CRIBR mice significantly (P <
0.05) reduced the spleen and bone marrow cellularity, with bone
marrow demonstrating the greatest sensitivity (Wierda & Irons,
1982). Laskin et al. (1989) found that after injection in Balb/c
mice hydroquinone (50 mg/kg) caused a 30-40% decrease in bone marrow
In vitro studies have demonstrated direct myelotoxic effects
of hydroquinone toward mouse bone marrow stromal cells (Gaido &
Wierda, 1984; Gaido & Wierda 1987). Hydroquinone inhibited stromal
cell colony growth along with the ability of these cells to support
granulocyte/monocyte colony formation in co-culture. The bone marrow
stroma predominantly consists of macrophages and fibroblastoid
stromal cells which interact to regulate myelopoiesis. Treatment
with hydroquinone thus results in reduced capacity of the stroma to
In addition to this cytotoxic effect, Wierda & Irons (1982)
found in in vivo studies that hydroquinone also affected the
immune function by reducing the number of progenitor B-lymphocytes
in the spleen and bone marrow in mice, thus demonstrating an
immunosuppressive potential. The rapid generation and maturation of
progenitor B cells renders them highly susceptible to toxic agents
that affect dividing cells. Evidence has accumulated concerning the
effect of hydroquinone on the cellular activity of the immune system
in vitro. Exposure of lymphocytes in vitro to hydroquinone has
been shown to result in a dose-dependent inhibition of RNA synthesis
in the lymphocytes (Post et al., 1985). A hydroquinone
concentration of 1-2 x 10-5 mol/litre inhibited the RNA synthesis
In vitro exposure (one hour) of mouse bone marrow cells to
hydroquinone (10-7-10-5 mol/litre) inhibited the maturation of
B-lymphocytes from pre B-cells after 24 and 48 h in culture (King
et al., 1987). More recent data have demonstrated that
hydroquinone-induced inhibition of pre-B cell maturation results
from toxicity to adherent stromal cells, and that bone marrow
macrophages may be the primary target for hydroquinone
myelotoxicity, rather than fibroblastic stromal cells or pre-B cells
(King et al., 1989; Thomas et al., 1989a). Results also indicate
a dose-related reduction of macrophage interleukin-1 (IL-1)
secretion in cultures of bone marrow macrophages exposed to
hydroquinone (King et al., 1989; Thomas et al., 1989b). IL-1 is
necessary for the induction of interleukin-4 (IL-4), which is
produced by fibroblastic stromal cells and is required for
maturation of pre-B cells to B cells (King et al., 1989).
Fan et al. (1989) demonstrated that hydroquinone can inhibit
the natural killer activity of mouse spleen cells in vitro at low
concentrations. Concentrations of 1 x 10-5 mol/litre and 1 x
10-6 mol/litre inhibited 29 and 22% of the activity, respectively.
Lewis et al. (1988b) found that hydroquinone had a selective
effect on macrophage functions important in host defense. At
concentrations of 3-100 µmol/litre, hydroquinone significantly
(P < 0.05) inhibited the release of hydrogen peroxide and at 100
µmol/litre it significantly (P < 0.05) inhibited priming by
interferon for tumour cell cytolysis. Cheung et al. (1989) have
shown a concentration-dependent inhibition of interferon-alpha/ß
production following exposure to hydroquinone in murine L-929 cell
The cytotoxic activity of hydroquinone has been tested on
different tumour cells. Chavin et al. (1980) studied the effect on
melanoma transplants in female BALB/c mice. The incidence of
melanoma transplants was reduced and the survival significantly (P
< 0.0005) increased in mice that received hydroquinone treatment
Vladescu & Apetroae (1983) studied the molecular mechanisms of
antitumour action and the possibilities of using hydroquinone as a
toxic agent against cancer cells. In H 18R tumour-bearing male
Wistar rats treated with hydroquinone (5 mg/kg per day) for seven
days, the catalase activity was markedly depressed in liver, spleen,
blood and H 18R tumour. In vitro studies on tumour and liver
homogenates from normal and tumour-bearing rats showed a marked
inhibition of catalase activity in the tumour, which was less
evident in the liver. The activity was less reduced in normal liver
homogenates. It was suggested that the mechanism of action of
hydroquinone as an antitumour agent is achieved mainly via peroxide
When tested on cultured rat hepatoma cells hydroquinone showed
a dose-dependent cytotoxic activity (Assaf et al. 1987). A dose of
33 mg/litre (300 µmol/litre) caused cellular mortality of 40% after
24 h of incubation and 66 mg/litre (600 µmol/litre) resulted in 100%
Hydroquinone, given as single oral or subcutaneous lethal
doses, causes nonspecific effects on the nervous system such as
hyperexcitability, tremor and convulsions in several experimental
animal species (see section 7.1). Animals given sublethal oral doses
recover within a few days.
These central nervous system stimulation effects were confirmed
in a 90-day oral study on rats (Eastman Kodak Company, 1988) (see
also section 7.3). Male and female weanling rats (CD(SD)BR),
initially seven weeks old, were treated with hydroquinone (20, 64 or
200 mg/kg per day) dissolved in water at a concentration of 5%.
Doses were given by gavage 5 days per week. Functional-observational
battery examinations were performed throughout the study. The
battery included observations of body position, activity level,
coordination of movement and gait, behaviour, presence of
convulsions, tremors, lacrimation, salivation, piloerection,
pupillary dilatation or constriction, respiration, diarrhoea,
urination, vocalization, forelimb/hindlimb grip strength and sensory
function. Tremors and depression of general activity were observed
in both sexes shortly after dosing with 64 or 200 mg
hydroquinone/kg. Functional-observational battery examinations did
not result in any evidence of neurotoxicity as assessed by
quantitative grip strength measurement, brain weight or
neuropathological examination. The NOEL was considered to be 20 mg
hydroquinone/kg body weight.
Otsuka & Nonomura (1963) reported that hydroquinone reversed
curare blockage at neuromuscular junctions in frog sciatic nerve -
sartorius muscle preparations. The authors suggested that this
effect was due to an increased release of transmitter at the
neuromuscular junction induced by hydroquinone.
Until recently, exposure to hydroquinone has not been
associated with nephrotoxicity. Nephrotoxicity has not been reported
following either occupational exposure to hydroquinone or acute
exposures in humans. Carlson & Brewer (1953) gave human volunteers
daily hydroquinone doses of 300 or 500 mg/day for periods of up to
20 weeks without effects on urinalysis parameters. Exposure of five
male mixed-breed dogs to 100 mg hydroquinone/kg per day for 26 weeks
had no effect on urinalysis parameters or renal histopathology
(Carlson & Brewer, 1953). Christian et al. (1976) reported that
exposure of Carworth rats to hydroquinone in the drinking-water at
concentrations of up to 10 g/litre (6 rats of each sex per group for
8 weeks) or up to 4 g/litre (20 rats of each sex per group for 15
weeks) resulted in slight changes in kidney weight but no
histopathological changes. Carlson & Brewer (1953) also reported no
evidence of renal histopathological changes in Sprague-Dawley rats
fed diets containing 10g hydroquinone/kg for 104 weeks.
NTP (1989) reported that oral gavage of hydroquinone (0, 25,
50, 100, 200 or 400 mg/kg) in corn oil for 13 weeks resulted in
toxic nephropathy in F-344 rats at the two highest dose levels (200
mg/kg: 7/10 males, 6/10 females; 100 mg/kg: 1/10 females). Oral
gavage of 0, 25 or 50 mg/kg in water for 15 months resulted in an
increased incidence of chronic nephropathy in male F-344 rats (25
mg/kg: 5/5 males; 50 mg/kg: 6/10 males). When male F-344 rats were
dosed at 0, 25 or 50 mg/kg for two years, there was an increased
severity of chronic progressive nephropathy in 20/55 animals given
50 mg/kg. At a dosage level of 50 mg/kg for either 15 months or 2
years, male rats had heavier relative kidney weights.
Shibata et al. (1991) also reported that F-344 rats developed
chronic nephropathy when fed 8g hydroquinone/kg diet for 2 years.
Male rats showed increased relative and absolute kidney weight, as
well as an increased severity of chronic nephropathy (14/30
animals). Female rats showed an increased relative kidney weight,
but only a minimal increase in severity of chronic nephropathy in
Boatman et al. (1992) reported on the urinalysis changes
observed in male and female F-344 rats and Sprague-Dawley rats given
single doses of 0, 200 or 400 mg hydroquinone/kg in water by oral
gavage. B6C3F1 mice were examined after receiving doses of 0 or
350 mg/kg in a similar fashion. The placement of venous catheters in
F-344 rats increased their response to hydroquinone. At 400 mg/kg,
male and female F-344 rats, but not Sprague-Dawley rats, displayed
pronounced enzymuria and glucosuria, which resolved in 72-96 h. At
200 mg/kg, enzymuria and glucosuria were present in female F-344
rats but not males. Epithelial cell counts in the urine were
statistically significantly increased (P < 0.05) at 400 mg/kg
(male and female F-344 rats only) and 200 mg/kg (female F-344 rats
only). Statistically significant (P < 0.05) decreases in
osmolality were reported at 400 mg/kg for F-344 (both sexes) and
female Sprague-Dawley rats. Diuresis (ml urine/h) was statistically
significant (P < 0.005) only for female F-344 rats at 200 mg/kg
and 400 mg/kg. Although differences were observed in some of the
urinary parameters measured, mice were generally not responsive to
To characterize the early development of renal toxicity in
rats, cell proliferation was quantified within the proximal (P1, P2
and P3) and distal tubular segments of the kidney in rats given 0,
2.5, 25 or 50 mg hydroquinone/kg by oral gavage. Male and female
F-344 rats were treated for 1, 3 or 6 weeks, and male Sprague-Dawley
rats were treated for 6 weeks. At 6 weeks, an 87% increase in cell
proliferation was measured in the P1 segment, a 50% increase in the
P2 segment, and a 34% increase in the P3 segment from kidneys of
male F-344 rats dosed with 50 mg/kg. Urinalysis indicated increased
enzymuria in this same dose group, and mild histological changes
were present in the kidneys. Animals examined at other time points
or from other dose groups were not affected by hydroquinone.
The increased incidence of renal adenomas only in male F-344
rats (NTP, 1989) has led to speculation that the tumours observed
may be related to alpha2u-globulin-induced nephropathy. This
mechanism of action for induction of kidney tumours does not appear
to be relevant for hydroquinone as none of the studies cited above
has reported finding evidence of hyalin droplet nephropathy
following subacute, subchronic or chronic hydroquinone exposure.
Glutathione metabolites, which are at least partially formed in
the liver and transported to the kidney, are reported to be involved
in the nephrotoxicity observed. Some of the potential glutathione