Identyfikatory
Warianty tytułu
1,4-Dichlorobenzene : documentation of proposed values of occupational exposure limits (OELs)
Języki publikacji
Abstrakty
1,4-Dichlorobenzen jest ciałem stałym o budowie krystalicznej, bezbarwnym lub białym, o zapachu kamfory, ulegającym sublimacji. Jest stosowany jako insektycyd (głównie w środkach przeciwmolowych), fumigant, a także jako składnik środków dezodoryzujących stosowanych do pomieszczeń oraz odświeżaczy stosowanych w kontenerach na śmieci. W syntezie chemicznej jest stosowany do produkcji siarczku polifenylenu, 1,2,4 trichlorobenzenu, 2,5-dichloroaniliny oraz wielu barwników. Ma również zastosowanie w przemyśle farmaceutycznym. W warunkach narażenia zawodowego 1,4-di-chlorobenzenwchłania się do organizmu głównie przez drogi oddechowe. Ma niewielką toksyczność ostrą. Skutki działania przewlekłego na ludzi obejmują: działanie drażniące na oczy i błony śluzowe górnych dróg oddechowych, pogorszenie parametrów funkcji płuc, zaburzenia funkcji nerek i wątroby. W badaniach na zwierzętach w warunkach narażenia przedłużonego i przewlekłego na 1,4-dichlorobenzen per os zmiany obserwowano głównie w wątrobie oraz u szczurów samców w nerkach. Skutkiem krytycznym przewlekłego narażenia na 1,4-dichlorobenzen drogą inhalacyjną było działanie drażniące objawiające się zmianami w nabłonku jamy nosowej. Nie wykazano istotnego potencjału genotoksycznego 1,4-dichlorobenzenu. W badaniach mutagenności zarówno w warunkach in vitro, jak i in vivo, w większości eksperymentów uzyskano wyniki ujemne. Stwierdzono działanie rakotwórcze 1,4-di-chlorobenzenu na zwierzęta. Po podaniu dożołądkowym u myszy obu płci obserwowano głównie nowotwory wątroby, a u szczurów samców – gruczolakoraki kanalików nerkowych. Za powstawanie nowotworów nerek u szczurów samców narażonych na 1,4-dichlorobenzen jest odpowiedzialny specyficzny niegenotoksyczny mechanizm, nieistotny w przypadku ludzi. Najbardziej istotnymi zmianami nowotworowymi u myszy obu płci stwierdzonymi w wyniku eksperymentu inhalacyjnego były nowotwory wątroby (raki i gruczolaki wątrobowo komórkowe, mięsaki histiocytarne wątroby). Mechanizm powstawania u myszy nowotworów wątroby po podaniu 1,4 dichlorobenzenu drogą pokarmową lub inhalacyjną nie jest dokładnie wyjaśniony, ale na podstawie wyników badań wykazano progowy charakter tego skutku.W badaniach dwupokoleniowych na szczurach narażanych na 1,4-dichlorobenzen per os lub drogą inhalacyjną nie stwierdzono jego wpływu na funkcje rozrodcze zwierząt. 1,4-Dichlorobenzen nie działałem briotoksycznie, fetotoksycznie ani teratogennie. Dla 1,4-dichlorobenzenu zaproponowano wartość NDS wyprowadzoną z wartości NOAEL 10 mg/kg mc./dzień uzyskaną w badaniach na psach, którym związek podawano per os(w kapsułkach) przez 52 tygodnie. Skutkiem krytycznym było działanie hepatotoksyczne substancji. Po uwzględnieniu współczynników niepewności zaproponowano wartość NDS na poziomie 12 mg/m3. Z uwagi na występowanie stężeń pikowych 1,4-dichlorobenzenu w środowisku pracy oraz działanie drażniące zaproponowano ustalenie wartości najwyższego dopuszczalnego stężenia chwilowego (NDSCh) na poziomie 3 razy NDS, czyli 36 mg/m3 Brak jest ilościowych danych dotyczących wchłaniana 1,4-dichlorobenzenu przez skórę, ale na podstawie wyników modelowania oceniono, że wchłanianie substancji przez skórę może być tak samo istotne, jak przy narażeniu drogą oddechową, dlatego zaproponowano notację„skóra”. Ze względu na działanie drażniące zaproponowano również notację„I”. Dostępne dane nie są wystarczające do ustalenia wartości dopuszczalnej w materiale biologicznym (DSB).
1,4-Dichlorobenzene is a solid crystalline substance, colorless or white, with camphor-like odour. It sublimes at room temperature. It is used as insecticide (mainly in the mothballs), as a fumigant and as a component of indoor deodorants and air-fresheners used in dumpsters. 1,4-Dichlorobenzene is used in the synthesis of polyphenylene sul fide,1,2,4trichlorobenzene, 2,5-dichloroaniline and dyes. It is also used in pharmaceutical industry.1,4-Dichlorobenzene is absorbed into the body mainly by inhalation. It has low acute toxicity. Chronic effects in humans include irritation to eyes and mucous membranes of the upper respiratory tract, impaired lung function parameters, impaired kidney and liver function.In prolonged and chronic animal studies changes were observed mainly in a liver. In male rats changes were also observed in kidneys. After chronic exposure to 1,4-dichlorobenzene, changes due to irritation were observed in epithelium of the nasal cavity.1,4-Dichlorobenzene has no significant genotoxic potential. Most in vitro and in vivo mutagenicity studies were negative.1,4-Dichlorobenzene was carcinogenic to animals. Liver tumors were observed in the male and female mice after oral administration of 1,4-dichlorobenzene and after inhalation. The mechanism of liver tumor in mice after administration of 1,4-dichlorobenzene by ingestion or inhalation is not exactly clear but studies indicate the threshold nature of this effect. Adenocarcinomas of the renal tubule were observed in male rats after oral administration of 1,4-dichlorobenzene. Specific genotoxic mechanism, irrelevant for humans, is responsible for kidney tumors in male rats exposed to 1,4-dichlorobenzene.1,4-Dichlorobenzene is not embryotoxic, teratogenic or fetotoxic. There was no impact on reproductive functions of animals in the two-generation study in rats exposed to 1,4-dichlorobenzene by ingestion or by inhalation.A critical effect for exposure to 1,4-dichlorobenzene is hepatotoxic activity. Oral administration of 1,4-dichlorobenzene (in capsules) in dogs for 52 weeks caused changes in liver and NOAEL value obtained from this study was 10 mg/kg/day. On the basis of this NOAEL value, after taking into account uncertainty factors, the MAC (TWA) value of 12 mg/m3and STEL of 36 mg/m3(3 times NDS) were recommended.There is no quantitative experimental data on skin absorption of 1,4-dichlorobenzene, but on the basis of modeling data the “Skin” notation was added because absorption of substances through the skin can be as important as inhalation. It is recommended to label the substance with symbol “I” (irritant).
Czasopismo
Rocznik
Tom
Strony
13--60
Opis fizyczny
Bibliogr. 148 poz., rys., tab.
Twórcy
autor
- Instytut Medycyny Pracy im. prof. dr. med. Jerzego Nofera 91-348 Łódź ul. św. Teresy od Dzieciątka Jezus 8
autor
- Instytut Medycyny Pracy im. prof. dr. med. Jerzego Nofera 91-348 Łódź ul. św. Teresy od Dzieciątka Jezus 8
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