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  • Transparency's picture
    Thank you for taking the time to answer my questions, and for clarifying the apparent disconnect between OECD TG 452 and 453. Your explanation is very helpful. I’ve learned a lot from your response, which makes a great deal of sense.

    A bit off topic, but I must say that Seralini's study did pique my and the public's curiosity -- were the rat tumors all caused by old age or by something they consumed? It would be nice to know a definitive answer, especially since some of the tumors appeared well before the end of the rats' life span.

    One final question, I am still perplexed by The Guardian’s statement, “Monsanto used 20 rats of each sex per group in its feeding trials but only analysed 10, the same number as Séralini.” I am not sure what specific feeding trials The Guardian is referring to, but I would think Monsanto would have wanted to study and analyze more than the bare minimum number of rats so as not to make the same apparent mistakes in study design and interpretation. As a layperson, perhaps I am missing something?
  • Community Manager's picture
    Community Manager
    @Transparency, thanks for your continued participation in the discussion on GMO Answers!
  • Transparency's picture
    Also, while I really appreciate the interesting illustrative example, I just want to clarify as a dog owner myself, I don't believe in testing dogs; I find their emotional sensitivity, need for human bonding, and cognitive level of intelligence for the most part incompatible with a sterile, lab testing environment...just my two cents, thanks.
  • Transparency's picture
    Dr. Koch, thank you very much for taking the time to respond to my question. Your very clear explanation, using the Cavalier King Charles spaniel as an example, is very interesting and helped me to better understand how scientists select a breed to study.

    I was prompted to ask this question after reading the following excerpt from the article, “The Way It’s Done”, http://www.cropgen.org./article_492.html: “So Dr. Van Eenennaam was able to conclude that the EFSA document suggests NOT using Sprague-Dawley rats for long term (104 week) feeding studies but rather the Harlan Wistar strain, having 50/sex/treatment group or at least 65/sex/treatment group if using Sprague-Dawley due to their known poor survival…” This article is also featured on GMOanswers.com, and seems to cast significant doubt on use of the SD rat, at least from EFSA’s perspective.

    I definitely follow the quote you share here, as it does make sense: “US (US EPA, 1998; FDA, 2006) and OECD (1995a) regulatory guidelines for the conduct of carcinogenicity studies in rodents specify the use of at least 50 animals per sex per treatment group. In addition, OECD states that 'it is unlikely that a regulatory authority would find a study using a lower core number of animals per sex and per group acceptable for regulatory purposes, since a sufficient number of animals should be used so that a thorough biological and statistical evaluation can be carried out.' (OECD, 1995b). OECD further states that ‘for strains with poor survival such as SD rats, higher numbers of animals per group may be needed in order to maximize the duration of treatment ...’” (Hammond et al., 2013). I also respect your comment, “Séralini study (2012) included only 10 rats/sex/group, and this low number is inadequate to make meaningful comparisons in tumor incidence between groups at the end of a chronic study.”

    However, the following link to an article from “The Guardian” suggests that Seralini based his study on “the toxicity part of OECD protocol no. 453. This states that for a cancer trial you need a minimum of 50 animals of each sex per test group but for a toxicity trial a minimum of 10 per sex suffices.” (http://www.theguardian.com/environment/2012/sep/28/study-gm-maize-cancer). As you are aware, and as the article points out, the Seralini study was not orchestrated to be a carcinogenicity study, but rather a chronic toxicity study, so perhaps Seralini was not so off-base as critics suggest?

    In addition, “The Guardian” states, “Monsanto used 20 rats of each sex per group in its feeding trials but only analysed 10, the same number as Séralini.” Based on this quote, I am unclear as to whether Monsanto’s own tests were adequate or not.

    Given there are ongoing questions surrounding Seralini’s chronic toxicity study -- about its validity or lack thereof – and the fact that many of Seralini’s critics are in the biotech industry, I would hope that biotech companies would make an effort to settle these questions once and for all, by conducting a new 2-year carcinogenicity study following the above-mentioned OECD guidelines.

    Thanks again for your timely response.
    • Michael Koch's picture
      Michael Koch
      While some of the Seralini group’s critics are in the biotech industry, criticism of the study design and interpretation is not limited to the biotech industry. For a brief overview of independent scientific experts who have criticized this study’s design and conclusions please refer to a reply I wrote for another question on this site (gmoanswers.com/ask/why-eu-plans-2-year-carcinogenicity-study-nk603-maize-are-details-feed-trial-same-gilles-eric). It is worth noting many of the critical experts are from food safety authorities from individual EU member states (Belgium, Germany, Denmark, France, Italy, and the Netherlands), the European Food Safety Authority, Food Standards Australia New Zealand, and Health Canada. Independent scientific professional societies such as the European Society of Toxicologic Pathology and the French Society of Toxicologic Pathology also questioned the validity of the study’s results (see Schorsch et al., and Barale-Thomas at the following link: www.sciencedirect.com/science/article/pii/S0278691512005637). To me, this begs the question: Why are so many people, who are familiar with regulatory safety assessments, critical of the Seralini group’s study? The short answer is study design and interpretation; factors which have contributed to the eventual retraction of the paper by the journal (again, please see the link: www.sciencedirect.com/science/article/pii/S0278691512005637 ).

      While you state it is a “chronic toxicity study” the Seralini group never precisely defines it as such. Rather, the group calls their study a “long term toxicity study”; a nebulous term which might mean chronic toxicity or carcinogenicity or something else altogether. This uncertainty is relevant to the discussion because chronic studies are typically conducted for 1 year (OECD TG 452 and 453) and not longer because spontaneous diseases become more prevalent as the animals age. As discussed in my original reply, this spontaneous disease confounds interpretation of the chronic toxicity data because the higher background disease makes it difficult to determine if a lesion was caused by spontaneous disease or toxic effects from the test substance. Indeed, the stand-alone test guideline for a 1 year chronic study (OECD TG 452) recommends testing ≥ 20 animals/sex/group for precisely this reason. However, as you’ve pointed out, OECD TG 453 allows ≥10 animals/sex/group for a combined 1 year chronic toxicity/carcinogenicity study. This apparent disconnect between OECD TG 452 and 453 is addressed in OECD TG 453 as follows:

      “Each dose group (as outlined in paragraph 22) and concurrent control group intended for the chronic toxicity phase of the study should contain at least 10 animals of each sex, in the case of rodents. It should be noted that this number is lower than in the chronic toxicity study TG 452. The interpretation of the data from the reduced number of animals per group in the chronic toxicity phase of this combined study will however be supported by the data from the larger number of animals in the carcinogenicity phase of the study.”

      Thus, ≥10 animals/sex/group for a chronic study is only recommended if there is another ≥50 animals/sex/group being evaluated as part of a combined carcinogenicity study. As there was not a separate larger group of animals used to assess carcinogenicity on the study conducted by Seralini et al., I stand by my original statement that the number of SD rats the group used was not appropriate to draw the conclusions they did. In fact, many of the findings the group considers signs of toxicity are actually well documented, age-related diseases in the animal model they selected for study (Scorsch et al., 2013; Barale-Thomas, 2013; Hard et al., 2013; Hard et al., 2009; Brix et al., 2005; Keenan et al., 1995).
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