The no-effect dose of aniline in human subjects and a comparison of aniline toxicity in man and the rat

Jenkins, F. P.; Robinson, J.A.; Gellatly, J.B.M.; Salmond, G.W.A.

doi:10.1016/s0015-6264(72)80147-0

Cited by 94 publications

(45 citation statements)

References 9 publications

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“…In toxicologic studies using experimental animals, the major acute toxic effects of aniline have been reported as methemoglobinemia and hemolysis [12,13]. In chronic toxicity and carcinogenicity studies of rats, the following toxic effects were also observed: suppression of body weight gain [7]; decrease in steroidogenesis and reduced amount of lipid accumulation in the ovaries and adrenal glands [10,16]; hemosiderosis in the liver and kidneys; splenic fibrosis; increased incidence of endometrial stromal polyps, splenic fibrosarcomas, and hemangiosarcomas [6,7,12].…”

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confidence: 99%

Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Okazaki

Yamashita

Sudo

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. The neurotoxicity of aniline and its age-dependent responses were investigated in male rats. Groups of 6 rats, 4-week-old, were treated once with aniline (500, 750 or 1,000 mg/kg) or olive oil by gavage. Additional groups of 6 rats, 7-or 10-week-old, were treated once with 800 mg/kg of aniline or olive oil. Paralytic gait or hindlimb paralysis was observed between post-treatment days 8 and 15 in two out of six rats receiving 1,000 mg/kg of aniline at 4 weeks of age. On post-treatment day 15, spongy change in the white matter of the spinal cord was observed in all rats receiving 750 or 1,000 mg/kg of aniline at 4 weeks of age. The lateral and ventral columns of the thoracic spinal cord were the most severely affected. Spongy change in the facial nerve and spinal trigeminal tracts of pons and medulla oblongata, and mild degeneration of the peripheral nerves was found in 3 out of 6 rats receiving 1,000 mg/kg of aniline. At the ultrastructural level, the spongy change was due to distention of the myelin sheath and splitting of the intraperiod line. Axons were well preserved in the affected nerve fibers. No abnormalities were seen in the neuronal cell bodies. Although transient cyanosis was observed in all rats receiving 800 mg/kg of aniline at 7-or 10-week-old, as well as in rats receiving 750 or 1,000 mg/kg of aniline at 4-week-old, no treatment-related neurobehavioral or morphologic abnormalities were found in the former. These findings demonstrate the neurotoxicity of orally administered aniline for rats, depending upon the age of the animal at the time of administration. KEY WORDS: aniline, hindlimb paralysis, neurotoxicity, rat, spongy change with myelin vacuolation.

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Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Okazaki

Yamashita

Sudo

et al. 2001

The Journal of Veterinary Medical Science

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“…Dotychczas nie okreś-lono toksycznej dawki aniliny. W badaniach z udziałem ochotników znaczący wzrost methemoglobiny odnotowywano przy przyjęciu doustnym 25 mg aniliny [4]. Jako dawkę śmiertelną wskazuje się 15-30 g, jednak opisano śmierć po przyjęciu już 1 g aniliny [5,6].…”

Section: Omówienieunclassified

“…[4]. Cechą charakterystyczną dla zatrucia aniliną jest wówczas obecność wewnątrzerytrocytarnych wtrętów, zwykle połączonych z błoną komórkową krwinki, nazywanych ciałkami Heinza-Erlicha.…”

Section: Omówienieunclassified

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Accidental severe poisoning with methemoglobinogenic substance: A case report

Rośniak-Bąk

Bąk

Winnicka

et al. 2017

Med Pr

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StreszczenieDo regionalnego ośrodka zatruć (ROZ) przyjęto 45-letniego pacjenta z powodu omyłkowego zatrucia pochodną dimetyloaniliny w miejscu pracy. Substancja toksyczna trafiła do organizmu drogą doustną. Podczas hospitalizacji podstawowym sposobem leczenia było podawanie błękitu metylenowego jako klasycznej odtrutki stosowanej w takim przypadku. W trakcie intensywnej opieki i leczenia u pacjenta zaobserwowano masywną hemolizę wewnątrznaczyniową, wymagającą leczenia preparatami krwiopochodnymi, oraz cechy uszkodzenia wątroby w postaci cholestatycznego uszkodzenia wątroby i żółtaczki. W Klinice Toksykologii pacjent przebywał 3 tygodnie. Opisany przypadek wskazuje na możliwość wystąpienia ciężkich powikłań narządowych w przebiegu zatrucia nawet niewielką ilością substancji chemicznej. Med. Pr. 2017;68(6):795-801 Słowa kluczowe: zatrucia, uszkodzenie wątroby, błękit metylenowy, dimetyloanilina, hemoliza, żółtaczka AbstractA 45-year-old male patient was admitted to the Regional Poison Center because of poisoning with dimethyloaniline contained in a toxic resin-curing dimethyl aniline-based formulation ingested inadvertently. Intoxication happened at workplace. The patient was then transferred to the Toxicology Clinic, where he stayed for 3 weeks. During the hospitalization, the primary method of treatment involved administration of methylene blue, which is the antidote of choice in such cases. During the intensive care and treatment of the patient massive intravascular hemolysis was seen. In that case treatment with blood products was required. He also showed signs of liver dysfunction due to cholestatic liver damage and jaundice. The reported case shows that severe organ damage may result from poisoning with even a small amount of the toxicant. Med Pr 2017;68 (6) https://doi.org/10.13075/mp.5893.00572 WSTĘPSubstancje methemoglobinotwórcze stanowią heterogenną grupę związków chemicznych. Znane są ich róż-ne klasyfikacje [1,2], jednak z punktu widzenia lekarza klinicysty najbardziej przydatnym podziałem jest rozróżnienie na substancje w bezpośrednim lub pośred-nim mechanizmie biologicznego działania. W przypadku zatrucia związkami methemoglobinotwórczymi w bezpośrednim mechanizmie działania bardzo szybko ustępują objawy sinicy i niedotlenienia, natomiast w przypadku związków wywołujących methemoglobinemię w mechanizmie pośrednim obserwowane zmiany utrzymują się przez dłuższy czas.Pochodne aniliny blokują możliwość dokomórko-wego transportu tlenu w efekcie utlenienia jonów Fe 2+

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“…The toxicity is manifested by splenomegaly (Khan et al, 1997a(Khan et al, , 1999aCiccoli et al, 1999), elevated erythropoietic activity (Jenkins et al, 1972;Bus and Popp, 1987;Pauluhn, 2004), hyperpigmentation, hyperplasia, fibrosis (Bus and Popp, 1987;Khan et al, 1999aKhan et al, , 1999bKhan et al, , 2003a, and a variety of primary sarcomas after chronic exposure in rats (Goodman et al, 1984;Weinberger et al, 1985;Bus and Popp, 1987). Among various pathophysiological manifestations, fibrosis appears to be an important initiating preneoplastic lesion of the spleen (Khan et al, 1993(Khan et al, , 1995(Khan et al, , 1999a.…”

Section: Introductionmentioning

confidence: 99%

Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

Wang

Ansari

et al. 2008

Toxicology and Applied Pharmacology

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Aniline exposure causes toxicity to the spleen, which leads to a variety of sarcomas, and fibrosis appears to be an important preneoplastic lesion. However, early molecular mechanisms in anilineinduced toxicity to the spleen are not known. Previously, we have shown that aniline exposure results in iron overload and induction of oxidative stress in the spleen, which can cause transcriptional upregulation of fibrogenic/inflammatory cytokines via activation of oxidative stress (OS)-responsive signaling pathways. To test this mechanism, male SD rats were treated with aniline (1 mmol/kg/day via gavage) for 7 days, an experimental condition that precedes the appearance of fibrosis. Significant increases in both NF-κB and AP-1 binding activity was observed in the nuclear extracts of splenocytes from aniline-treated rats as determined by ELISAs, and supported by Western blot data showing increases in p-IκBα, p-p65 and p-c-Jun. To understand the upstream signaling events which could account for the activation of NF-κB and AP-1, phosphorylation patterns of IκB kinases (IKKα and IKKβ) and mitogen-activated protein kinases (MAPKs) were pursued. Our data showed remarkable increases in both p-IKKα and p-IKKβ in the splenocytes from aniline-treated rats, suggesting their role in the phosphorylation of both IκBα and p65 subunits. Furthermore, aniline exposure led to activation of all three classes of MAPKs, as evident from increased phosphorylation of extracellularsignal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK1/2) and p38 MAPKs, which could potentially contribute to the observed activation of both AP-1 and NF-κB. Activation of upstream signaling molecules was also associated with simultaneous increases in gene transcription of cytokines IL-1, IL-6 and TNF-α. The observed sequence of events following aniline exposure could initiate a fibrogenic and/or tumorigenic response in the spleen.

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The no-effect dose of aniline in human subjects and a comparison of aniline toxicity in man and the rat

Cited by 94 publications

References 9 publications

Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Accidental severe poisoning with methemoglobinogenic substance: A case report

Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

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