Threshold of toxicological concern (TTC) for developmental and reproductive toxicity of anticancer compounds

Regulatory Toxicology and Pharmacology

Volumn 72, Issue 3, 2015, Pages 602-609

  Stanard, Brad ^a,b   Dolan, David G ^c   Hanneman, William ^b   Legare, Marie ^b   Bercu, Joel P ^c  

^a MEDIMMUNE   (United States)

^b Department of Ecosystem Science and Sustainability   (United States)

^c AMGEN INC   (United States)

Author keywords

Acceptable Daily Exposure (ADE); Anticancer; Antineoplastic; Developmental toxicity; Direct acting; Indirect acting; Permitted Daily Exposure (PDE); Reproductive toxicity; Threshold of toxicological concern (TTC)

Indexed keywords

ABARELIX; ALKYLATING AGENT; ANASTROZOLE; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIBIOTIC; ANTINEOPLASTIC ANTIMETABOLITE; CYTOTOXIC AGENT; DEGARELIX; DNA TOPOISOMERASE INHIBITOR; FULVESTRANT; GEMTUZUMAB OZOGAMICIN; HISTRELIN; HORMONE RECEPTOR BLOCKING AGENT; HORMONE RECEPTOR STIMULATING AGENT; IMMUNOMODULATING AGENT; LETROZOLE; PENTOSTATIN; PHOSPHOTRANSFERASE INHIBITOR; TOPOTECAN; TOREMIFENE; ZOLEDRONIC ACID;

ARTICLE; BODY WEIGHT; BONE MALFORMATION; CARCINOGENICITY; CHRONIC TOXICITY; DEVELOPMENTAL TOXICITY; EMBRYO RESORPTION; ENVIRONMENTAL EXPOSURE; FETUS DEATH; FETUS MALFORMATION; HUMAN; NO-OBSERVED-ADVERSE-EFFECT LEVEL; NONHUMAN; PERINATAL DEATH; PRIORITY JOURNAL; REPRODUCTIVE TOXICITY; THRESHOLD OF TOXICOLOGICAL CONCERN; TOXICOLOGICAL PARAMETERS; ANIMAL; DOSE RESPONSE; DRUG EFFECTS; EMBRYO DEVELOPMENT; FETUS DEVELOPMENT; PROCEDURES; REPRODUCTION; RISK ASSESSMENT; TOXICITY TESTING;

ANIMALIA;

ANIMALS; ANTINEOPLASTIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; EMBRYONIC DEVELOPMENT; FETAL DEVELOPMENT; HUMANS; REPRODUCTION; RISK ASSESSMENT; TOXICITY TESTS;

EID: 84931281953     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2015.05.024     Document Type: Article

References (33)

1. Ball D., Blanchard J., Jacobson-Kram D., McClellan R.O., McGovern T., Norwood D.L., Vogel W., Wolff R., Nagao L. Development of safety qualification thresholds and their use in orally inhaled and nasal drug product evaluation. Toxicol. Sci. 2007, 92(2):226-236.
2. Ben-Aharon I., Shalgi R. What lies behind chemotherapy-induced ovarian toxicity. Reproduction 2012, 144:153-163.
3. Bernauer U., Heinemeyer G., Heinrich-Hirsh B., Ulbrich B., Gundert-Remy U. Exposure-triggered reproductive toxicity testing under REACH legislation: a proposal to define significant/relevant exposure. Toxicol. Lett. 2008, 176:68-76.
4. Chabner B.A., Barnes J., Neal J., Olson E., Mujagic H., Sequist L., Wilson W., Longo D.L., Mitsiades C., Richardson P. Chapter 62. Targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies, and cytokines. Goodman and Gilman's The Pharmacological Basis of Therapeutics 2011, 1731-1754. McGraw-Hill Professional, New York. 12th ed. L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds.).
5. Cheeseman M.A., Machuga E.J., Bailey A.B. A tiered approach to threshold of regulation. Food Chem. Toxicol. 1999, 37(4):387-412.
6. Cramer G.M., Ford R.A., Hall R.L. Estimation of toxic hazard-a decision tree approach. Food Cosmet. Toxicol. 1978, 16:255-276.
7. Dolan D.G., Naumann B.D., Sargent E.V., Maier A., Dourson M. Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations. Regul. Toxicol. Pharmacol. 2005, 43(1):1-9. 10.1016/j.yrtph.2005.06.010.
8. EMA, 2014a. Guideline on setting health base exposure limits for use in risk identification in manufacture of different medical products in shared facilities. (accessed 11.01.2015). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/11/WC500177735.pdf.
9. EMA, 2014b. EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Part 1, Chapter 3: Premises and Equipment. (accessed 11.01.2015). http://ec.europa.eu/health/files/eudralex/vol-4/chapter_3.pdf.
10. EMA, 2014c. EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Part 1, Chapter 5: Production (accessed 11.01.2015). http://ec.europa.eu/health/files/eudralex/vol-4/chapter_5.pdf.
11. Food and Drug Administration Food Additives: Threshold of regulation of substances used in food-contact articles: Final rule. Fed. Reg. 1995, 60:36582-36596.
12. International Conference on Harmonisation (ICH), 2014. M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.
13. International Conference on Harmonisation (ICH), 2009a. M3 (R2) Guidance on Nonclincal Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.
14. International Conference on Harmonisation (ICH), 2009b. S9 Nonclincal Evaluation for Anticancer Pharmaceuticals.
15. International Conference on Harmonisation (ICH), 1997a. Q3C: Impurities in New Drug Substances.
16. International Conference on Harmonization on Technical Requirements for Registration of Pharmaceuticals for Human Use., 2000. ICH Harmonized Tripartite Guideline. Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. Q7. Current Step 4 version dated 10 November 2000. . http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/Step4/Q7_Guideline.pdf.
17. International Society of Pharmaceutical Engineers, 2010. Risk-Based Manufacture of Pharmaceutical Products: A Guide to Managing Risks Associated with Cross-Contamination, vol. 7.
18. Kroes R., Galli C., Munro I., Schilter B., Tran L.-A., Walker R., Würtzen G. Threshold of toxicological concern for chemical substances present in the diet: A practical tool for assessing the need for toxicity testing. Food Chem. Toxicol. 2000, 38:255-312.
19. Kroes R., Renwick A.G., Cheeseman M., Kleiner J., Mangelsdorf I., Piersma A., Schilter B., Schlatter J., van Schothorst F., Vos J.G., Würtzen G. Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet. Food Chem. Toxicol. 2004, 42(1):65-83. 10.1016/j.fct.2003.08.006.
20. Kroes R., Renwick A.G., Feron V., Galli C.L., Gibney M., Greim H., Guy R.H., Lhuguenot J.C., van de Sandt J.J.M. Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food Chem. Toxicol. 2007, 45(12):2533-2562. 10.1016/j.fct.2007.06.021.
21. Laufersweiler M.C., Gadagbui B., Baskerville-Abraham I.M., Maier A., Willis A., Scialli A.R., Daston G. Correlation of chemical structure with reproductive and developmental toxicity as it relates to the use of the threshold of toxicological concern. Regul. Toxicol. Pharmacol. 2012, 62(1):160-182. 10.1016/j.yrtph.2011.09.004.
22. Leeman W.R., Krul L., Houben G.F. Reevaluation of the Munro dataset to derive more specific TTC thresholds. Regul. Toxicol. Pharmacol. 2014, 69(2):273-278.
23. Munro I.C., Ford R.A., Kennepohl E., Sprenger J.G. Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern. Food Chem. Toxicol. 1996, 34(9):829-867.
24. Munro I.C., Ford R.A., Kennepohl E., Sprenger J.G. Thresholds of toxicological concern based on structure-activity relationships. Drug Metab. Rev. 1996, 28(1-2):209-217. 10.3109/03602539608994000.
25. NIOSH, 2014. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2014. By Connor TH, MacKenzie BA, DeBord DG, Trout DB, O'Callaghan JP. Cincinnati, OH: U.S. Department of Health and Human Services, Center for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-138 (Supersedes 2012-150).
26. Remesh A. Toxicities of anticancer drugs and its management. Int. J. Basic Clin. Pharmacol. 2003, 1:1-12.
27. SCCS, SCHER, SCENIHR, 2012. Joint Opinion on the Use of the Threshold of Toxicological Concern (TTC) Approach for Human Safety Assessment of Chemical Substances with focus on Cosmetics and Consumer Products (8 June).
28. Tiboni G.M., Marotta F., Rossi C., Giampietro F. Effects of the aromatase inhibitor Letrozole on in utero development in rats. Hum. Reprod. 2008, 23:1719-1723.
29. Trasler J., Doerksen T. Teratogen update: paternal exposures-reproductive risks. Teratology 1999, 60:161-172.
30. Van Ravenzwaay B., Dammann M., Buesen R., Flick B., Schneider S. The threshold of toxicological concern for prenatal developmental toxicity in rabbits and a comparison to TTC values in rats. Regul. Toxicol. Pharmacol. 2012, 64(1):1-8. 10.1016/j.yrtph.2012.06.004.
31. Van Ravenzwaay B., Dammann M., Buesen R., Schneider S. The threshold of toxicological concern for prenatal developmental toxicity. Regul. Toxicol. Pharmacol. 2011, 59(1):81-90. 10.1016/j.yrtph.2010.09.009.
32. Ward J.A., Furr B.J., Valcaccia B., Curry B., Bardin C.W., Gunsalus G.L., Morris I.D. Prolonged suppression of rat testis function by a depot formulation of Zoladex, a GnRH agonist. J. Androl. 1989, 10:478-486.
33. Winkler G.C., Barle E.L., Galati G., Kluwe W.M. Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics. Regul. Toxicol. Pharmacol. 2014, 10.1016/j.yrtph.2014.06.012.