Modulation of benzene induced toxicity by protein A

Shankar, Uma; Kumar, Ashwani; Rao, G. Sasibhushana; Dwivedi, Prem P.; Pandya, K. P.

doi:10.1016/0006-2952(93)90529-6

Cited by 9 publications

(3 citation statements)

References 35 publications

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“…SPA treatment was associated with increases in glutathione‐S‐transferase. One prior safety study of intravenous SPA in the monkey was found in the published literature . However, this non‐GLP pilot study did not characterize the origin or purity of the SPA utilized for dosing and contained no toxicokinetic information on the plasma exposures attained.…”

Section: Discussionmentioning

confidence: 99%

Studies of the Safety, Pharmacokinetics and Immunogenicity of Repeated Doses of Intravenous Staphylococcal Protein A in Cynomolgus Monkeys

Bernton¹,

Haughey²

2014

Basic Clin Pharma Tox

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Three Good Laboratory Practice safety studies were performed with intravenous injections of highly purified staphylococcal protein A (SPA) in cynomolgus monkeys, in support of a clinical development programme utilizing this protein as an immunomodulator. These studies established a no-observable-adverse-effect level (NOAEL) for up to 12 weekly doses of SPA, as well as toxicokinetic profiles for SPA, evaluation of antiproduct antibodies and biomarkers to better characterize the pharmacodynamic response to SPA. Biomarkers included neopterin, C-reactive protein (CRP), troponin I and the change in the blood absolute lymphocyte count (ALC) 24 hr after SPA dosing. The transient decrease in ALC noted at 24 hr after dosing was similar to that seen in human Phase 1 trials. The majority of active-treated monkeys developed antibodies against SPA. C max was not affected by development of antidrug antibodies (ADAs), and after the first dose was 87 (SD 19) ng/mL, 330 (SD 84) ng/mL and 1191 (SD 208) ng/mL for 5, 25 and 100 lg/kg doses, respectively. The development of ADAs increased plasma clearance of SPA. By the sixth weekly dose, the AUC was decreased by 76%, 54% and 66% for the 5, 25 and 100 lg/kg dose groups, respectively. These results indicate that SPA can be administered intravenously to non-human primates without observable toxicity at weekly doses of up to 100 lg/kg.

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Section: Discussionmentioning

confidence: 99%

Studies of the Safety, Pharmacokinetics and Immunogenicity of Repeated Doses of Intravenous Staphylococcal Protein A in Cynomolgus Monkeys

Bernton¹,

Haughey²

2014

Basic Clin Pharma Tox

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“…Additional research in this area indicates that tumor necrosis factor may provide protection against the inhibitory effects of hydroquinone on human hematopoietic progenitor cells (Colinas, et al, 1995). The research of Shankar, et al (1993) determined that pretreatment with Protein A, a glycoprotein that acts as a multipotent immunostimulant, modulated the toxicity of benzene. Groups of six female albino rats (Swiss Wistar) were injected intraperitoneally with 1.0 mL/kg/body weight (879 mg/kg) benzene once daily for three consecutive days.…”

Section: Interfering With the Mechanism Of Action For Toxic Effectsmentioning

confidence: 99%

ATSDR evaluation of health effects of benzene and relevance to public health

et al. 2008

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As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of portions of the Toxicological Profile for Benzene. The primary purpose of this article is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of benzene. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health.

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“…Unlike leukopenia and lymphocytopenia (174,175), benzene-induced leukemia has only been observed in humans: no satisfactory animal model exists that can consistently reproduce the human disease (176).…”

Section: Renal Tumorsmentioning

confidence: 99%

Potential Health Effects of Gasoline and Its Constituents: A Review of Current Literature (1990-1997) on Toxicological Data

Caprino¹,

Togna²

1998

Environmental Health Perspectives

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We reviewed toxicological studies, both experimental and epidemiological, that appeared in international literature in the period 1990-1997 and induded both leaded and unleaded gasolines as well as their components and additives. The aim of this overview was to select, arrange, and present references of scientific papers published during the period under consideration and to summarize the data in order to give a comprehensive picture ofthe results of toxicological studies performed in laboratory animals (induding carcinogenic, teratogenic, or embryotoxic activity), mutagenicity and genotoxic aspects in mammalian and bacterial systems, and epidemiological results obtained in humans in relation to gasoline exposure. This paper draws attention to the inherent difficulties in assessing with precision any potential adverse effects on health, that is, the risk of possible damage to man and his environment from gasoline. The difficulty of risk assessment still exists despite the fact that the studies examined are definitely more technically valid than those of earlier years. The uncertainty in overall risk determination from gasoline exposure also derives from the conflicting results of different studies, from the lack of a correct scientific approach in some studies, from the variable characteristics ofthe different gasoline mixtures, and from the difficulties of correcdy handling potentially confounding variables related to lifestyle (e.g., cigarette smoking, drug use) or to preeisting pathological conditions. In this respect, this paper highlights the need for accurately assessing the condusive explanations reported in scientific papers so as to avoid the spread of inaccurate or misleading information on gasoline toxidty in nonscientific papers and in mass-media messages.

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Modulation of benzene induced toxicity by protein A

Cited by 9 publications

References 35 publications

Studies of the Safety, Pharmacokinetics and Immunogenicity of Repeated Doses of Intravenous Staphylococcal Protein A in Cynomolgus Monkeys

Studies of the Safety, Pharmacokinetics and Immunogenicity of Repeated Doses of Intravenous Staphylococcal Protein A in Cynomolgus Monkeys

ATSDR evaluation of health effects of benzene and relevance to public health

Potential Health Effects of Gasoline and Its Constituents: A Review of Current Literature (1990-1997) on Toxicological Data

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