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Nitro musks are cogenotoxicants by inducing toxifying enzymes in the rat
V Mersch-Sundermann1, M Emig, A Reinhardt
1Department of Medical Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, Ruprecht-Karls-University of Heidelberg, Germany.
Abstract:
In the present study, musk xylene (MX) and musk ketone (MK) were examined for their potency to induce toxifying enzymes in the liver of Sprague-Dawley rats, using an in vivo/in vitro model. After i.p. application of 10, 20 and 40 mg/day MX and MK over a period of 5 days, 9000 x g liver fractions (S9M) were used to study the toxification of a number of well-known pregenotoxicants in the SOS chromotest, i.e., benzo[a]pyrene (B[a]P), 2-aminoanthracene (2-AA), and aflatoxin B1 (AFB1). The genotoxic potencies of B[a]P, 2-AA and AFB1 in the presence of S9M were compared to those obtained in the presence of S9 fractions of untreated animals (S9O, negative control). S9M fractions derived from MK-treated rats showed an increased potency to toxify B[a]P, 2-AA and AFB1 in comparison to S9O fractions (for instance: TIP[toxifying induction potency] = 70 per nmol AFB1 using 10 mg MK treatment). In comparison, S9M fractions from MX-pretreated rats exhibited an increased genotoxicity only when using 2-AA (TIP = 0.04) and AFB1 (TIP = 61) as pregenotoxicants, but not when using B[a]P. To summarize the results, both MX and MK were strong inducers of toxifying liver enzymes. Therefore, these compounds seem to be cogenotoxicants for a number of well-known pregenotoxicants. Synergistic effects were found when using inducers of toxifying enzymes and pregenotoxicants in the in vivo/in vitro induction model.
Insights
Musk xylene (MX) and musk ketone (MK) act as cogenotoxicants by inducing liver enzymes that increase the toxicity of pregenotoxicants like benzo[a]pyrene and aflatoxin B1. These synthetic musks enhance the harmful effects of other chemicals.
Area of Science:
- Toxicology
- Biochemistry
- Environmental Health
Background:
- Synthetic musks, including musk xylene (MX) and musk ketone (MK), are widely used in consumer products.
- Their potential to induce liver enzymes and influence the toxicity of other compounds is not fully understood.
Purpose of the Study:
- To investigate the potency of MX and MK in inducing toxifying enzymes in Sprague-Dawley rat livers.
- To assess the cogenotoxic effects of MX and MK on known pregenotoxicants using an in vivo/in vitro model.
Main Methods:
- Administration of MX and MK to rats over 5 days.
- Preparation of liver fractions (S9M) from treated rats.
- Assessment of pregenotoxicant (benzo[a]pyrene, 2-aminoanthracene, aflatoxin B1) toxification using the SOS chromotest in the presence of S9M.
Main Results:
- MK-induced S9M fractions significantly enhanced the toxification of benzo[a]pyrene, 2-aminoanthracene, and aflatoxin B1.
- MX-induced S9M fractions increased the toxification of 2-aminoanthracene and aflatoxin B1, but not benzo[a]pyrene.
- Both MX and MK demonstrated strong induction of liver toxifying enzymes.
Conclusions:
- Musk xylene and musk ketone function as cogenotoxicants, potentiating the genotoxicity of certain pregenotoxicants.
- Synergistic effects were observed between inducers of toxifying enzymes and pregenotoxicants in this in vivo/in vitro model.
- These findings highlight the complex toxicological profile of synthetic musks.