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Chemicals Management Plan - Challenge Advisory Panel
Summary Report
From the meetings held October 20 and 27, 2008

Panel members present October 20, 2008: Dr. T. Boadway (Chair), Dr. J. Bend, Dr. C. Brunk, Dr. N. Cherry, Dr. J. Eyles, Dr. S. Findlay, Mr. G. Granville, Ms. L. Lusby, Dr. S. Maguire, Dr. P. Orris, Dr. D. Scott.

Regrets: Dr. G. Muckle

Panel members present October 27, 2008: Dr. T. Boadway (Chair), Dr. J. Bend, Dr. C. Brunk, Dr. S. Findlay, Mr. G. Granville, Ms. L. Lusby.

Regrets: Dr. N. Cherry, Dr. J. Eyles, Dr. S. Maguire, Dr. G. Muckle, Dr. P. Orris, Dr. D. Scott

Outline:

The Challenge Advisory Panel meeting agenda was structured around a key question (see below) provided to the Panel for deliberation, open discussion and debate. Government staff members were present to make a brief presentation, answer questions and clarify information. The question presented concerned procedures and policies applied in the screening assessment determination. At the end of the discussions, Panel members were asked to craft a response to the question.

In the text below, the Government question is quoted in its entirety from the documents provided to the Panel.

Meeting Summary:

Welcome and Introductions:

The Chair welcomed all members and government staff and asked for introductions of government staff.

The first question was addressed at the October 20, 2008 meeting, whereas the second question was addressed at the October 27, 2008 meeting. Despite low attendance at the second meeting, all members present and several members via email agreed that the statement made by the Panel members on October 27th would stand as the opinion of the Panel. There were abstentions via email but no objections to this course.

Panel Discussion

Questions for the Panel – Health Priority

The draft screening assessment for vinyl acetate, a substance in Batch 2 of the Challenge, was released on May 17, 2008. Vinyl acetate was placed in the Challenge as it was classified by the International Agency for Research on Cancer as a carcinogen and met the categorization criteria of greatest potential for human exposure.

At that time, the European Union had published a draft vinyl acetate risk assessment report, which included both a health and an environment component ( EU RAR, 2005). Although the environment component had been adopted by the Scientific Committee on Health and Environmental Risks (March 17, 2006), the health component had not been adopted by the Committee and the likelihood of this occurring was uncertain.

During internal Health Canada review and external peer consultation on the draft screening assessment, reviewers were asked if they considered that the mode of action analysis present in the draft EU RAR was sufficiently elucidated to support a threshold mode of action for carcinogenicity. An external peer reviewer responded that, although the mode of action was well developed for the inhalation route, it was less developed for the oral route. This input was consistent with internal review comments.

The absence of a fully elucidated and accepted mode of action analysis, together with the uncertain status of the draft EU RAR and peer review input, as well as potential exposure through inhalation and oral routes, led to the decision to consider vinyl acetate as a nonthreshold carcinogen in the draft screening assessment. The proposed conclusion of the draft assessment was that vinyl acetate meets the criterion of paragraph 64(c).

As the Government moved from the draft assessment to the final assessment for vinyl acetate, the following factors were considered:

• Advice from some members of the Challenge Advisory Panel, and some public comments on screening assessments in early batches, that the Government’s approach for concluding that a substance was a nonthreshold carcinogen was ‘excessively precautionary’.
  
  
• New data on exposures received during the public comment period that demonstrated negligible exposure to vinyl acetate by the oral route (e.g., no quantifiable migration from food packaging). This supported a focus on the inhalation route of exposure in the final screening assessment, the route for which the mode of action analysis is most robust. It also led to recalculation of exposure estimates via the inhalation route, and decreased estimates of exposure in key scenarios.
  
  
• Updated draft EU risk assessment report (EU RAR, 2008), and information that the RAR will move forward under the previous legal framework, and that a Scientific Committee rapporteur has been assigned (September 2008).
  
  
• Toxicology data not previously examined, but critical to corroborating the mode of action analysis presented in the draft EU RAR.

Health Canada scientists considered the above information, including conducting a critical review of the draft EU Risk Assessment Report, in particular the studies relating to the key events in the proposed mode of action in animals, and concluded that the evidence supports a mode of action for vinyl acetate involving a threshold of exposure for induction of cancer via the inhalation route, the relevant route of exposure to humans.

Therefore, the Department considers that vinyl acetate is considered to be a threshold carcinogen. As such characterization of risk, and the determination of whether vinyl acetate meets the criterion in Section 64(c), will be based on a comparison of exposure potential and effects levels i.e., the magnitude of the margins of exposure.

Question 1 for the Panel

Does the Panel agree that acceptance by a regulatory agency is a necessary condition for overcoming the assumption of no threshold for a mode of action determination in the context of the Challenge?

Considerations:

Within the context of the Ministerial Challenge, when a substance demonstrates effects for which there is a threshold, including threshold carcinogens, the lowest effect levels in the toxicology database for critical endpoints are compared to upper bound estimates of exposure to the general population, to derive margins of exposure. The magnitude of these margins of exposure informs decision-making. In the final screening assessment for vinyl acetate, the margins of exposure increased considerably and are considered adequate for all endpoints.

Therefore, the proposed conclusion of the final screening assessment is that vinyl acetate does not meet the criterion in paragraph 64(c).

Attachment:

•  Final screening assessment report for Acetic acid ethenyl ester (vinyl acetate monomer).

Panel Response to Question 1:

“In the case of vinyl acetate, the Panel agrees that acceptance by a regulatory agency is not a necessary condition for overcoming the assumption of no threshold for a mode of action determination in the context of the Challenge.”

All but one member agreed.

Question 2 for the Panel

Does the Panel agree that the weight of evidence and application of precaution support the conclusion reached by Health Canada that vinyl acetate does not meet the criteria of CEPA Section 64(c)?

Panel Response to Question 2:

“The Panel agrees that the weight of evidence and application of precaution support the conclusion reached by Health Canada that vinyl acetate does not meet the criteria of CEPA Section 64(c), and is therefore not toxic.”