N-nitrososarcosine limit

I have a client requesting analysis of their DP for the presence of n-nitrososarcosine. The DP contains sarcosine as a precursor to the API, and they are concerned with the potential of forming the associated nitrosamine. I have not found a limit for this compound. Can I use the FDA NDSRI guidance and calculate an associated limit for it based on the predicted carcinogenic potency categorization?

Thanks,

Eric Hill

Hi,

Well, that compound have some level of Carcinogenic Data (how reliable to be determined). Lhasa Carcinogenicity Database - Study Information (lhasalimited.org)

If that do not works, by CPCA this compound ends in Category 4 = 1500 ng/day that makes sense considering the carboxilic acid there.

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Indeed, Nitrososarcosine carcinogenicity data is described in the literature, so you might want to compare the CPCA exercise with the available data as part of the expert review (nitrososarcosine as weak mice liver / rat esophageal carcinogen, nitrososarcosine can decompose to NDMA under certain conditions) to confirm that CPCA is protective (in case CPCA is doable).

Some references:

  • Wogan, G. N., Paglialunga, S., Archer, M. C., & Tannenbaum, S. R. (1975). Carcinogenicity of Nitrosation Products of Ephedrine, Sarcosine, Folic Acid, and Creatinine. Cancer Research (Chicago, Ill.) , 35 (8), 1981–1984.
  • Scanlan, R. A., & Issenberg, P. (1975). N-nitrosamines in foods. CRC Critical Reviews in Food Technology , 5 (4), 357–402. https://doi.org/10.1080/10408397509527180
  • Wainright, T. (1986). chemistry of nitrosamine formation: relevance to malting and brewing. Journal of the Institute of Brewing , 92 (1), 49–64. https://doi.org/10.1002/j.2050-0416.1986.tb04373.x
  • Schrenk, D., Bignami, M., Bodin, L., Chipman, J. K., Mazo, J., Hogstrand, C., (Ron) Hoogenboom, L., Leblanc, J., Nebbia, C. S., Nielsen, E., Ntzani, E., Petersen, A., Sand, S., Schwerdtle, T., Vleminckx, C., Wallace, H., Romualdo, B., Cristina, F., Stephen, H., … Grasl‐Kraupp, B. (2023). Risk assessment of N‐nitrosamines in food. EFSA Journal , 21 (3), e07884-n/a. https://doi.org/10.2903/j.efsa.2023.7884
  • Druckrey, H., Preussmann, R., Ivankovic, S., Schmähl, D., Afkham, J., Blum, G., Mennel, H. D., Müller, M., Petropoulos, P., & Schneider, H. (1967). Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Journal of cancer research and clinical oncology , 69 (2), 103–201. Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten | Journal of Cancer Research and Clinical Oncology
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Hi my self Hema, happy to know about this community as well as join in this huge knowledge gaining site.
as per New updated CPCA guideline N-nitroso sarcosine-limit is 1500 ng/day which under potency category-4 is fine.

May i know the Limit of N,N-dibenzyl nitrous amide as per New CPCA guideline?