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Toxicity of the arsenic-based pesticide Monosodium Methane Arsenate (MSMA)

Petition: No. 97

Issue(s): Human health/environmental health, pesticides, and toxic substances

Petitioner(s): Canadian Association of Physicians for the Environment (CAPE)

Date Received: 5 November 2003

Status: Completed

Summary: In this petition, the Canadian Association of Physicians for the Environment (CAPE) expresses concern about the arsenic-based pesticide MSMA, which is used by the forestry industry to control bark beetle. The petitioner asserts that there are new scientific findings on the toxicity of arsenic that need to be considered by the Pest Management Regulatory Agency of Health Canada. Several questions are posed in this petition about MSMA, including questions on re-registration, environmental effects, and human exposure.

Federal Departments Responsible for Reply: Health Canada

Petition

Attachment

Office of the Auditor General and the Commissioner of Environment and Sustainable Development

240 Sparks St.
Ottawa, Ontario
K1A 0G6

Attention: Petitions

Aug 25, 2003

We are submitting a petition under the Auditor General Act, to the Hon. Anne McLellan, Minister of Health, as follows.

From: The Canadian Association of Physicians for the Environment (CAPE)

PETITION

Context

Since July 13, 2001, Dr. Josette Wier, a pediatrician originally trained in France and a member of the Canadian Association of Physicians for the Environment (CAPE), has repeatedly brought to the attention of the Pesticide Management Regulatory Agency (PMRA) her concerns about an application for a permit to use the arsenical pesticide MSMA (Monosodium Methane Arsenate). The BC Ministry of Forests (Morice Forest District) was the applicant for the use of 3,300 kg of arsenic (active ingredient, in the form of MSMA) over a three-year period to "control" bark beetle. Dr. Wier has specifically pointed out that research from the last 3-5 years shows that the assumptions upon which the safety of the product was established no longer hold. This is based on general research and especially on extensive communications from Dr. W.R. Cullen, professor of chemistry at UBC and a world authority on arsenic toxicity. She has repeatedly encouraged the PMRA to get in touch with Dr. Cullen and has forwarded to the PMRA copies of relevant documentation and research materials.

To date, the PMRA has initiated only a single short phone call to Dr. Cullen, of no particular relevance. Furthermore, in a letter to Dr. Wier, dated July 18, 2001 and signed by Mr. Richard Aucoin, Acting Chief Registrar, the agency has stated that an internal review of the data from Drs. Wier and Cullen "had concluded that although the findings are potentially important, these findings are not substantially new in the context of our existing knowledge of arsenic". This statement is in complete contradiction to Dr. Cullen's testimony at the Environmental Appeal Board (EAB) hearing held in Smithers, BC, June 17-21, 2002, where Dr. Wier was the Appellant. His critique of the PMRA letter, sent a week before (June 11, 2002) to the lawyer representing the BC Ministry of Forests, went unchallenged at the hearing. It became very clear that the PMRA had an outdated view of the metabolism of arsenic.

Shortly after the EAB hearing, on July 4, 2002, CAPE informed the PMRA of Dr. Cullen's points. We received, on August 23, 2002, a response from Ms. Wendy Sexsmith of the PMRA, which was in essence a rearranged copy of her June 11, 2002 letter which had been so thoroughly discredited by Dr. Cullen at the hearing. The PMRA, despite clear and very disturbing new data from an unimpeachable source, resolutely maintained the position that NO new information was relevant.

We wrote the PMRA again on September 19, 2002, detailing very precise questions to be answered. Ms. Sexsmith's reply, of November 13, reiterated the inaccurate and completely invalidated notion that "total" arsenic is the relevant indicator, commenting, with surprising and probably unintentional irony, that there is so much of it in the Canadian environment that one should not worry about the effects of adding more! While acknowledging that there has been no monitoring whatsoever of exposure in applicators, and that there is and will be no effort made to monitor small mammal or insect exposure even though such creatures form the basis of the food chain, she nevertheless concludes (without any cited evidence) that "there will be no contamination of dietary or water resources" after MSMA application.

We asked Dr. Cullen to review Ms. Sexsmith's response of November 13, 2002. His evaluation, which is attached to this petition, is at marked variance to that of the PMRA.

We then asked to meet with the Hon. Anne McLellan, Minister of Health, in a letter dated March 14, 2003. We received no response. After five unanswered phone calls over a period of one month to her office, [name withheld], informed Dr. Wier that [name withheld], had decided that CAPE should meet instead with Dr. Claire Franklin, head of the PMRA, with whom we had not previously interacted. A teleconference was duly held with Dr. Franklin on May 6, 2003 but generated the same response as all previous interactions. Dr. Franklin made it crystal clear that she had no intention of altering or modifying the PMRA's position that MSMA was safe to use.

We then again requested a meeting with the Honourable Anne McLellan in an e-mail to [name withheld] of June 11 2003. We pointed out to [name withheld] that we wished to settle this issue before July when injections were to resume. Out of fifteen subsequent phone calls to [name withheld], thirteen were completely ignored. One resulted in an exchange with [name withheld], who said she would pass it on to [name withheld], and as a result of the final one, on July 24, Ms.Wier was informed that [name withheld] had decided that we should not meet with the Minister and that a letter would be forwarded (time unspecified) informing us of the reasons.

This letter has now arrived; it simply endorses the position taken by the PMRA, without explanation.

From this background, several issues emerge:

1.

The difficulty obtaining a response from the Hon. Minister's office to repeated requests for a meeting with the Minister, and obtaining any sort of substantive response to our concerns or to the evidence presented to her.

2.

The PMRA's unshakeable position that MSMA is safe, despite solid contradictory evidence from one of the most respected Canadian scientific authorities on arsenic toxicity.

3.

The utter opacity of the process for handling requests for interaction with the Minister and with the PMRA.

The following are the questions we seek to have answered:

1.

At what point does a persistent inquiry from a concerned and well-informed citizen on an issue with significant health implications generate a substantive response from the Minister's office?

2.

Does the Minister routinely, and without independent analysis, endorse the PMRA's position that new scientific findings do not challenge the safety of a currently registered pesticide? If not, how is an independent analysis triggered?

3.

We understand that a request for re-registration of a pesticide must come from the Minister. Are there any other ways of triggering a re-registration process, and are any of those available to the public at large?

4.

In this particular case, in which the PMRA's position that MSMA is safe has been flatly contradicted by one of the most respected Canadian scientific authorities on this matter, what process or mechanism is in place to deal with such an outright divergence of opinions? Is the PMRA always presumed to be correct, in the face of any other scientific authority?

5.

Dr. Franklin wrote that the PMRA was not legally obliged to consider testimony provided in a provincial permit appeal. Is the PMRA in fact not obliged to concern itself with Dr. Cullen's rebuttal of their position, simply because it took place in a provincial court and under oath? Is this a general principle?

6.

Again with reference to this particular case, has MMA III ever been measured in applicators that the Minister or the PMRA is aware of?

7.

Regarding the new scientific findings on the metabolism of arsenic, the PMRA states that "although the findings are potentially important, these findings are not substantially new in the context of our existing knowledge of arsenic". Which specific new scientific findings is the PMRA choosing to dismiss? How do these findings not change our understanding of arsenic toxicity? In other words, what is the exact threshold at which new findings about the toxicity of a substance become significant, and how and by whom is it determined?

8.

When was MSMA registered and when was it re-assessed? For which uses is MSMA currently registered? Is forestry use a minor use registration? What exactly is a minor use registration?

9.

What actual evidence does the PMRA possess indicating that the measurement of total arsenic is sufficient to monitor the effects of MSMA?

10.

What measurements are employed by the PMRA, or its delegate, to assess the movement in ecosystems of arsenic derived from applications of MSMA?

11.

What are the effects of MSMA on small mammals, cavity-nesting birds including woodpeckers, or insects, including honey bees?

12.

What are the risks of arsenic exposure and subsequent toxicity arising from a forest fire involving MSMA-treated trees, to both forest firefighters and adjacent communities? What are the relevant arsenic-containing combustion products from the burning of an MSMA-treated tree and what is their toxicity?

13.

What is the potential exposure of a logger cutting, say, 100 treated trees in a day, and breathing smoke from the incineration of their branches? If a logger becomes ill from absorbing toxic levels of arsenic, what system is in place for estimating his or her exposure, monitoring its source, and providing prompt and effective treatment?

14.

Have public health officials been warned of possible dangers associated with either work-related or forest fire-related exposures to MSMA-treated wood?

15.

When is re-registration of MSMA scheduled by the US EPA? If such re-registration is being scheduled earlier than originally planned, does this not imply increasing evidence of hazards associated with this product? If such urgency is warranted in the U.S., of what relevance is the precautionary principle to the PMRA while a re-assessment is being conducted?

16.

If MSMA fails to be re-registered in the US, how long will it take for PMRA to respond to this decision, and what would that response likely be?

17.

Is the PMRA willing to consider evidence regarding the toxicity of MSMA independent of the re-assessment process in the U.S.?

Thank you for your consideration of these matters. We look forward to hearing from you at your earliest convenience.

Sincerely,

[Original signed by Warren Bell]

Warren Bell MD

Canadian Association of Physicians for the Environment
130 Spadina Ave., Ste. 301
Toronto, ON M3V 2L4
416-306-2273

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Attachment

Comments of Dr. William Cullen on MSMA

Current US EPA Position on MSMA

The EPA was recently involved in reevaluating the registration of MSMA. This is a six-phase process. They had completed the risk assessment, phase one, and had sent the document out to the industry for comment. At this stage they became aware of the recent work on methylarsenic compounds and decided to start the process again. So they never got to the public review stage, stage three. At the moment they are in stage one again.

Some background:

The acute and chronic toxicity of inorganic arsenic(III) derivatives has been known for many years, but the fact that the organic arsenic compounds used in medicine, such as Salvarsan, function because they are in the arsenic(III) oxidation state seems to have been overlooked. Also overlooked was the work done at UBC about 20 years ago, showing that methylarsenic oxide and sulfide (arsenic in the III oxidation state) were more toxic to fungi than either inorganic arsenic species or the usually encountered methylarsonic acid and dimethylarsinic acid where the arsenic is in the V oxidation state. The toxicity sequence for arsenic compounds given in the widely quoted review by Cullen and Reimer (1989) shows organoarsenic (III) species as being more toxic than arsenate and more toxic than organoarsenic(V) compounds, but most readers don't notice this.

Recent Conclusions

Recent studies reinforce the conclusion that the methylation of arsenic can not be considered to be a detoxifying process. The methylarsenic(III) species that are necessarily formed in the methylation process are potentially harmful to humans, and their production could result in outcomes such as cancer of the skin, lung, bladder and other organs.

MSMA is the sodium salt of methylarsonic acid. This acid lies on the methylation pathway outlined below, and if ingested, the most likely metabolic process would lead first to the formation of toxic methylarsenic(III) species or, less likely, would result in demethylation to toxic inorganic arsenic(III).

MSMA can be regarded as a precursor to toxic species that are less conveniently synthesized from the already banned inorganic arsenic chemicals. It provides a chemical shortcut.

These conclusions are based on the following:

1.

Studies at the US EPA and at the University of Arizona beginning in the mid 1990s have revealed that methylarsenic(III) species are cytotoxic in a range of cell lines, some human, and are more toxic than inorganic arsenic species, often by factors of a thousand or more.

2.

Studies at the US EPA beginning in the late 1990s have shown that methylarsenic(III) species are genotoxic in some cell lines. The corresponding arsenic(V) derivatives have little or no activity.

3.

The methylation of arsenic in mammals, including humans follows the path:
As(V) ' As(III) ' MeAs(V) ' MeAs(III) ' Me2As(V) ' Me2As(III)

 

and it was widely held that this was a detoxification process because the methylarsenic(V) species, in bold, are not very toxic in animal models and these are the species excreted in urine. However, these are the species that were detected by the commonly used analytical method that was incapable of finding other arsenic species. It is now known that the methylarsenic(III) species, in italics, that are an integral part of the methylation pathway, are present in human urine. They are found to be the major species present in the urine of individuals, e.g. in Mexico, exposed to high levels of arsenic in their drinking water.

4.

It has been known that dimethylarsinic acid, cacodylic acid, is a likely human carcinogen and it is now becoming apparent that the mode of action involves the formation of methylarsenic(III) species, probably the Me2As(III) in the scheme above.

5.

MSMA, an arsenic(V) compound, has been regarded by regulators as a potential source of the likely human carcinogen dimethylarsinic acid, but this was underplayed by regulators. However, if this is accepted then the same metabolic process would proceed through the formation of the much more toxic methylarsenic(III) species not all of which would be further methylated.

Response to the Response to the letter from Dr Warren Bell
With reference to Attachment 1

Level of MMA(III) in forest litter.
I suggest that the author actually read the quoted references, particularly Cullen and Reimer.

There is a vast difference between MSMA on the ground or elsewhere and other arsenic species. The background arsenic level is of no concern here. Think of MSMA as a totally different species that has to be evaluated separately.

If all arsenic species were the same and additions contributed only a little to the background environmental burden, we would still be dealing with calcium arsenate as an agrochemical.

As for methylarsine, it could be formed in an anaerobic environment, flooded soil for example, but I don't think that issue has been raised. What is under discussion is that the MSMA could be reduced to species such as methylarsenic oxide, MeAsO (which is probably MeAs(OH)2) in dilute solution), in the soil or elsewhere. These methylarsenic(III) species are cytotoxic and genotoxic. See comments on the current US EPA position.

Monitoring Data
Sensitive techniques for monitoring arsenic in urine have been available long before 2001. In fact a study done in 1988 is quoted at the end of the paragraph. Most of the material in this paragraph is plain obfuscation. Monitoring can be done if necessary. See comments on the current US EPA position.

Norris article.
Again the main issue is being avoided. Monitoring has not been done, and to say that it was not done because it was assumed that the results would be acceptable is hardly a justification. Prudence alone should suggest that workers handling a toxic compound should be monitored.

Small Mammals' exposure
I am assuming that again the reference to methylarsine is an error as it was in the first paragraph. Some of the studies quoted are old and were made at a time when it would have been difficult to obtain speciation. In fact I doubt the authors would have considered such an enterprise. Total arsenic values are not much use as an indicator of exposure to specific arsenic species. The situation is much different now and there is no excuse for the lack of useful information on, for example, the arsenic species and their concentration in specific organs such as liver, if that is a concern.

Contamination of dietary, water resources, and plants (sic?)
Here again this response shows a complete lack of appreciation of the problem. MSMA is not arsenic. The references are lamentably out of date and irrelevant. For the record quite a lot is known about the arsenic species in mushrooms and there is very little of it which is the same "arsenic" that is in the ground.

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Minister's Response: Health Canada

19 March 2004

Dr. Warren Bell
Canadian Association of Physicians for the Environment
301-130 Spadina Avenue
Toronto, Ontario
M3V 2L4

Dear Dr. Bell:

Further to my acknowledgement letter of December 10, 2003, and in accordance with the requirements of section 22 of the Auditor General Act, I am pleased to provide you with Health Canada's response to the questions raised in your petition concerning the safety assessment of the arsenical pesticide Monosodium Methane Arsenate.

Thank you for your interest in this matter and I trust this information will prove helpful.

Sincerely,

[Original signed by Pierre S. Pettigrew, Minister of Health, Minister of Intergovernmental Affairs and Minister responsible for Official Languages]

Pierre S. Pettigrew


INTRODUCTION

Health Canada has been requested by the Office of the Auditor General to respond to a series of questions in Environmental Petition no. 97 as they pertain to the mandate and responsibility of Health Canada. Health Canada's Pest Management Regulatory Agency (PMRA) was identified to provide the Petitioner and Office of the Auditor General with detailed responses to the questions and concerns raised in Environmental Petition no. 97.

HEALTH CANADA RESPONSES

Health Canada has reviewed Environmental Petition no. 97 and developed detailed responses to the 17 questions posed in the petition. The questions and their associated responses are provided below.

Question 1:

At what point does a persistent inquiry from a concerned and well-informed citizen on an issue with significant health implications generate a substantive response from the Minister's office?

Response 1:

In striving to improve the health of all of Canada's people, while respecting individual choices and circumstances, the Minister of Health has always maintained and will continue to maintain an open and transparent office for Canadians to voice their concerns. Accordingly, all inquires, whether to the Minister or the Department, are taken seriously and are responded to in as substantive a manner as possible.

Question 2:

Does the Minister routinely, and without independent analysis, endorse the PMRA's position that new scientific findings do not challenge the safety of a currently registered pesticide? If not, how is an independent analysis triggered?

Response 2:

The Pest Management Regulatory Agency (PMRA) has been mandated by the Minister of Health to administer the Pest Control Products Act (PCPA) and to exercise sound scientific judgment. The officials who are employed to carry out that mandate have the scientific expertise to exercise such judgment and provide the Minister with sound advice on which he can and does rely.

With respect to triggering a re-evaluation or a special review of an existing product in light of new scientific findings, please refer to Response 3 on the following page.

Question 3:

We understand that a request for re-registration of a pesticide must come from the Minister. Are there any other ways of triggering a re-registration process, and are any of those available to the public at large?

Response 3:

The PMRA's re-evaluation program is described in Regulatory Directive 2001-03. The purpose of the program is to assess the continued acceptability of older, registered pesticides to human health and the environment. Monosodium methane arsenate is one of the 401 actives registered prior to 1995 that are being re-evaluated. The Re-evaluation Program consists of four distinct (sub) programs. Program 1 includes active ingredients and their end-use products for which a Risk Assessment Document or Reregistration Eligibility Decision (RED) document has been published by the United States Environmental Protection Agency (EPA). These review documents must be of such quality to allow a Canadian regulatory decision to be made without substantial in-house work. Program 2 includes products that require a detailed in-house re-evaluation before a regulatory decision can be made. Program 3 is focussed on pest control products that are scheduled for a new type of reassessment in the US under the Food Quality Protection Act (FQPA). Program 4 is a program of targeted re-evaluations (Special Review or SR) and involves reviews that are triggered by concerns arising from adverse effects reports as well as products where national or international commitment or policies require the PMRA to address a specific aspect of health or environmental safety.

As mentioned in Regulatory Directive 2001-03, opportunity is limited for public input into priority setting for products reviewed under Programs 1 and 3 as these priorities are driven by the availability of US review documents (Programs 1 and 3). A pesticide review under Program 2 or 4 may be triggered by concerns from the public provided that the evidence being presented is new and has scientific merit.

In the case of MSMA, the PMRA considered and included all information on the speciation of arsenic, including the new information provided by Dr. Cullen, in the Agency's risk assessment. This new information did not change the outcome of the risk assessment (i.e., even when speciation and the higher toxicity of certain species is considered, the risks remain acceptable). Accordingly, a special review was not triggered for this product. However, as indicated in Response 15, MSMA is currently under re-evaluation by both the PMRA and the US EPA.

In the future, the new Pest Control Products Act, which was given Royal Assent in December 2002 but has not yet come into force, allows for further stakeholder input into priority setting for re-evaluations. Section 17 of the new Pest Control Products Act states that any person may request a special review of the registration of a pest control product by making a request to the Minister. The Minister initiates a special review if the supporting documents accompanying the request provide reasonable grounds for the Minister to believe that the health or environmental risks are, or its value is, unacceptable.

Question 4:

In this particular case, in which the PMRA's position that MSMA is safe has been flatly contradicted by one of the most respected Canadian scientific authorities on this matter, what process or mechanism is in place to deal with such an outright divergence of opinions? Is the PMRA always presumed to be correct, in the face of any other scientific authority?

Response 4:

The PMRA's position is that when considering the restricted use detailed in the provincial permit, which includes the level of training and the type of protective equipment required for applicators, together with the fact that the specified forestry use of MSMA is a targeted spot application (direct injection into individual trees in infrequent "spots" in the forest), applicator, bystander and environmental exposure should be minimal and, therefore, would not result in unacceptable risk.

It is important to understand that the toxicity (or hazard profile) of a chemical does not by itself, determine risk. It is the amount, duration and route of exposure to the chemical that must also be considered. In the case of MSMA use in Canada, this use is both localized and restricted to individual trees. Together with the additional precautions imposed, the exposure potential and risk to human health and the environment are minimized.

The PMRA recognizes and does not dispute Dr. Cullen's research findings regarding the potential hazards of arsenic. However, as indicated above, hazard is but one component of risk assessment. When the exposure profile for this use of MSMA is factored into the risk assessment, the risks for properly protected workers do not exceed the level of concern.

Question 5:

Dr. Franklin wrote that the PMRA was not legally obliged to consider testimony provided in a provincial permit appeal. Is the PMRA in fact not obliged to concern itself with Dr. Cullen's rebuttal of their position, simply because it took place in a provincial court and under oath? Is this a general principle?

Response 5:

It is the PMRA's understanding that this question relates to an explanation which Dr. Franklin provided in a letter dated June 5, 2003 to Dr. Warren Bell as detailed below. That explanation was in response to certain statements made by Dr. Bell in a letter of May 15, 2003 to Dr. Franklin concerning a conversation they had on May 6th. The statements related to information that had been entered in evidence at an Environmental Appeal Board hearing.

In the response dated June 5, 2003, Dr. Franklin indicated that, "...although PMRA was not legally obliged to consider testimony provided in a provincial permit appeal, [the PMRA] had reviewed the document to consider the testimony and arguments put forth by Dr. Cullen and any other information [that] might be relevant to our risk assessment of MSMA." Dr. Franklin also noted that the PMRA had, on a number of occasions, indicated that the work of Dr. Cullen, although important, does not necessitate a change in the PMRA's conclusions with respect to the acceptability of the risks posed by MSMA. It was further noted that the risks posed by this use of MSMA under a provincial permit remain acceptable and that the PMRA had previously supplied Dr. Wier with detailed information on why, based on the information available, the use of this product poses minimal risk to humans or the environment, including wildlife.

Dr. Franklin's explanation was intended to convey the message that the Agency is not obligated to act on information simply because it was provided as evidence in a legal proceeding. It is the relevance of the information to the carrying out of the statutory responsibilities which determines whether and how it should be relied upon. When considering the full response provided by Dr. Franklin, (indicated above), it is apparent that the suggestion made in Question 5 (i.e., that the PMRA did not "concern itself with Dr. Cullen's rebuttal of their position") does not properly reflect Dr. Franklin's explanation.

Question 6:

Again with reference to this particular case, has MMA III ever been measured in applicators that the Minister or the PMRA is aware of?

Response 6:

Regarding the availability of monitoring data on urinary levels of MMA (III) in applicators, it should be noted that although the methodologies for arsenic speciation have evolved over the years, it is only within the last few years that sensitive techniques for the speciation of arsenic methylation intermediates have been developed and published (Le, 2001). Also, certified reference material has yet to be established for all arsenic species.

Biological monitoring studies are sometimes used as part of the risk assessment process for occupational exposure. While it might be of interest to conduct appropriate biomonitoring and / or bioindicator studies, including speciation analysis, on urine samples from MSMA applicators, how these data should be applied to a science-based risk assessment would then need to be considered. An article by Norris (1985) provided total arsenic measurements from spot urine samples of MSMA and cacodylic acid applicators that had been collected in the 1970s. The worker scenario in the Norris report (tree-thinning) involved the treatment of a much larger number of trees, which is a higher exposure scenario for applicators when compared to applicator treatment of infrequent "spots" for bark beetle control in BC. While the data suggested some level of arsenic exposure, the PMRA agreed with the author's premise that with proper handling techniques and the use of protective gear, applicator exposure levels would be minimised. To our knowledge, no other applicator bio-monitoring studies relevant to the forestry use of MSMA have been conducted to date.

Question 7:

Regarding the new scientific findings on the metabolism of arsenic, the PMRA states that "although the findings are potentially important, these findings are not substantially new in the context of our existing knowledge of arsenic". Which specific new scientific findings is the PMRA choosing to dismiss? How do these findings not change our understanding of arsenic toxicity? In other words, what is the exact threshold at which new findings about the toxicity of a substance become significant, and how and by whom is it determined?

Response 7:

The PMRA has not dismissed any new scientific findings. It is important to recognize that the carcinogenic potential of MSMA in humans remains uncertain and is still being investigated and debated by various scientific experts. For example, a recent report indicated that MMAA did not cause cancer in rats or mice that were exposed to MMAA in their diet for 2 years (Arnold et al., 2003). That being said, the statement referred to in Question 7 regarding the "existing knowledge of arsenic" was based on the knowledge that inorganic arsenic is a known human carcinogen and that from the regulatory perspective, using conservative assumptions, the possibility that MSMA could be carcinogenic was considered when assessing the risk. Once again it is important to keep in mind that the toxicity (including potential carcinogenicity) of a chemical does not by itself, determine risk. It is the amount, duration and route of exposure to the chemical that must also be considered.

Question 8:

When was MSMA registered and when was it re-assessed? For which uses is MSMA currently registered? Is forestry use a minor use registration? What exactly is a minor use registration?

Response 8:

The MSMA product was first registered for bark beetle control in 1970. This has been re-examined on previous occasions as proposals for expansion of use or research permits were being considered. Nothing at that time suggested an unacceptable risk with the existing use.

Conifer thinning and bark beetle control are the only registered uses of MSMA in Canada. In addition to these uses, MSMA is currently registered in the U.S. for many other uses, such as on turf, cotton, sugar cane and citrus groves.

Minor Use Registration. Projected sales of some pest control products in Canada may be so low that manufacturers conclude they cannot justify the costs to support Canadian registrations. Therefore, for commercial reasons, such products may not be available for use in this country. Many of these products are regarded as essential to cost-effective pest control, and to the competitiveness and sustainability of agriculture, forestry, aquaculture and other sectors. These products are often referred to as "minor use products". Submissions for registration for these types of products typically occurs via sponsor groups, and more recently Agriculture and Agri-Food Canada has taken on the role of developing the needed data and submitting for registration of these minor use pesticides.

Note, however, the application for registration of the specified MSMA product in forestry was submitted by the registrant United Agri Products, not through the user requested minor use label expansion program.

Question 9:

What actual evidence does the PMRA possess indicating that the measurement of total arsenic is sufficient to monitor the effects of MSMA?

Response 9:

It is not clear whether the petitioner is referring to measurement of arsenic in environmental media or humans. A discussion on each of these issues is provided below.

From an environmental perspective, the distribution and speciation of arsenic in MSMA-treated trees and the target organism have already been investigated (Maclauchlan et al. 1988a, 1988b; Manville et al. 1988; Newton 1986). MSMA-treated trees contain inorganic arsenic (arsenate plus arsenite), monomethylarsonic acid (MMAA) and cacodylic acid (DMAA). Untreated trees also contain these arsenic species, but at lower concentrations. The concentrations and species of arsenic in the target organism (bark beetle) are also being investigated in a current study conducted by Environment Canada, in consultation with the PMRA.

For monitoring arsenic concentrations in soil, the concentration of "total arsenic" (which would include the MMA III component) is most relevant because the arsenic species present in the environment depends entirely on the environmental conditions of the site (i.e., redox potential, pH, biological processes, etc.). Once arsenic residues from decomposing foliage of treated trees are introduced into soil, they enter the "arsenic cycle" and could result in any number of arsenic species dictated by the environmental conditions of the site. If only one or a few arsenic species are monitored, rather than total arsenic, exposure could be underestimated. For national registrations, the PMRA must consider that environmental conditions are variable across Canada and cannot rely on the observed speciation at one particular site. When the estimated or measured concentrations of total arsenic in the soil are comparable to background concentrations, then it is concluded that environmental risks of MSMA used in forestry are comparable to the natural or baseline risk. The PMRA's conclusion, that the predicted negligible increase in arsenic concentrations in soil is comparable to background concentration, is supported by field studies (Newton 1986, Norris et al. 1983).

With regard to monitoring human exposure to arsenic, trivalent species are more unstable intermediates that are not as readily detected or quantified relative to other arsenic metabolites, and there is potential for interconversion. Thus, analysis of one species in the absence of others could underestimate exposure. Accordingly, for regulatory purposes, total arsenic is measured and/or considered when evaluating human exposure.

Question 10:

What measurements are employed by the PMRA, or its delegate, to assess the movement in ecosystems of arsenic derived from applications of MSMA?

Response 10:

The data required from the registrant by the PMRA in a pre-market assessment are generated from controlled laboratory and field studies, which are conducted under approved guidelines and good laboratory practices. They are used to determine the persistence, mobility, and bioconcentration potential of a pesticide and its major transformation products in the environment. The types of data required may vary depending on where the pesticide is used. Some of these studies, such as hydrolysis, photolysis, aquatic and soil metabolism, and terrestrial dissipation, are routinely conducted for all outdoor use pesticides.

Mobility studies attempt to predict the potential of the pesticide to volatilize into the atmosphere, move into ground or surface waters, or bind to soil. Mobility studies, which include leaching, adsorption / desorption, and volatilization, provide information on the mode of transport and eventual destination of the pesticide in the environment. Scientists can predict the degree of pesticide mobility in the soil from data generated from leaching and adsorption / desorption studies.

Field studies, which identify the environmental dissipation processes, assess the transformation, transport, and fate of pesticides under actual use conditions with typically applied pesticide product at representative field sites. These studies characterize the relative importance of each route of dissipation of the pesticide. Data generated from field dissipation studies can provide more realistic estimates (albeit limited in time and space) of the persistence and transport of a pesticide when the product is applied under actual use conditions.

For re-evaluation of a pesticide, the PMRA also reviews published literature. In the case of arsenic, there are very recent comprehensive reviews of the environmental behaviour of inorganic and organic arsenic compounds introduced to the terrestrial environment (including MSMA). The summary of Dost (1995) of the fate of MSMA is a good summary and relevant to the use pattern in question. The reviews by ATSDR (2000) and WHO (2001) do not contradict the conclusions of Dost (1995) on the environmental fate of MSMA.

Question 11:

What are the effects of MSMA on small mammals, cavity-nesting birds including woodpeckers, or insects, including honey bees?

Response 11:

Small mammals that inhabit forested areas can be exposed to arsenic by consuming plants that contain arsenic residues. Terrestrial plants may accumulate arsenic by root uptake from the soil and certain species may accumulate substantial levels (ATSDR 2000). Yet even when grown on highly polluted soil or soil naturally high in arsenic, the arsenic level take up by the plants is comparatively low (ATSDR 2000). Therefore, dietary exposure of arsenic to small wild mammals is expected to be low. The lack of expected exposure is supported by field studies, where arsenic residues in small mammals from MSMA-treated areas (Norris 1974, Ghassemi et al. 1981) are comparable to arsenic concentrations in mammals from background sites (Elfving et al. 1979, Ismael and Roberts 1992, Norris 1985).

All insects residing in the tree at the time of application are expected to die (since insects are the target organism). The trap tree approach (pheromone attractant) does not draw species other than the target organism to the insecticide (Dost 1995). Therefore, adverse effects on honeybees are not expected due to lack of exposure. Adverse effects on insects in the soil or on the forest floor are not expected due to the expected negligible increase of total arsenic in the soil relative to background concentrations.

Birds can be exposed to arsenic by excavating insects residing in the treated tree. Woodpeckers are known to obtain insects from standing dead timber, whereas other woodland birds occasionally take insect food from the surface of dead wood. In consultation with the PMRA, Environment Canada is currently researching both exposure (arsenic concentrations and speciation in beetles and in food consumed by nestlings) and effects of MSMA (reproductive success and health) on breeding and nestling woodpeckers.

The impact of MSMA on wildlife was considered prior to its registration in 1970. The outcome of the assessment did not raise any concern that would result in the denial of registration of MSMA. The impact of MSMA on wildlife as a result of forest use was also assessed in 1981 by the U.S. EPA (Ghassemi et al. 1981) and in 1995 by BC Ministry of Forests (Dost 1995). The conclusion in both reviews was that proper use of MSMA in forestry is unlikely to harm wildlife. In the 33 years since MSMA was first registered in Canada, there have not been any reported wildlife incidents. The lack of reported incidents in Canada is attributed to the precise and restricted application of MSMA and the consequent small contribution of arsenic relative to background concentrations.

Question 12:

What are the risks of arsenic exposure and subsequent toxicity arising from a forest fire involving MSMA-treated trees, to both forest firefighters and adjacent communities? What are the relevant arsenic-containing combustion products from the burning of an MSMA-treated tree and what is their toxicity?

Response 12:

The review of MSMA by Dost (1995) included an evaluation of the systemic toxicity and cancer risk as a result of the combustion of MSMA-treated wood under three different scenarios: domestic stove emission, open burning of slash or waste, and burning of mill waste. The risk posed by the burning of MSMA-treated trees as a result of forest fires would also be accounted for in these scenarios. This report concluded that no significant exposures to arsenic would be expected and that there was unlikely to be any increased health risk due to combustion of MSMA-treated trees, specifically. Although this report is several years old and does not include more recent information with respect to the recent research conducted by Dr. Cullen and others, the PMRA considers that this assessment still holds relevance for the forest fire scenario, given the conservative assumptions on which the assessment was based. In addition, the PMRA shares Dost's assertion that the greater hazard would more likely be the exposure to natural combustion products of the wood itself.

Question 13:

What is the potential exposure of a logger cutting, say, 100 treated trees in a day, and breathing smoke from the incineration of their branches? If a logger becomes ill from absorbing toxic levels of arsenic, what system is in place for estimating his or her exposure, monitoring its source, and providing prompt and effective treatment?

Response 13:

With respect to burning treated logs, Dost (1995) has assessed the systemic toxicity and cancer risk as a result of the combustion of MSMA-treated wood under three different scenarios (domestic stove emission, open burning of slash or waste, and burning of mill waste). The eventualities of forest fires and the fuelling of beehive burners with arsenic-contaminated wood would be included in these scenarios. It was concluded that no significant exposures to arsenic would be expected and that there was unlikely to be any increased health risk. Please note that the PMRA does not routinely conduct prospective risk assessments for scenarios of misuse / lack of compliance and does not support the purposeful burning of arsenic-contaminated wood (as with CCA-treated wood). Furthermore, in the environmental appeal [2001PES-003: Josette Wier vs. Deputy Administrator Pesticide Control Act, (Minister of Forests, Morice Forest District, Permit Holder)], the Permit Holder has indicated that MSMA-treated trees are not to be removed and their bark is not burned. The provincial permit for MSMA treatment in the Morice Forest District (Permit No. 402-582-01/03) also requires each individual treated tree to be marked, prior notification that a specified area is to be treated, substantial buffer zones from water and stipulates that only trained and provincially licensed personnel can apply this product. Concerns regarding the lack of compliance with posted areas should be raised with provincial authorities.

Question 14:

Have public health officials been warned of possible dangers associated with either work- related or forest fire exposures to MSMA-treated wood?

Response 14:

See responses to Questions 12 and 13. The PMRA has determined that, based on current information, use of this product in forestry does not pose an unacceptable risk of harm to human health or the environment. As outlined in the provincial permit for MSMA (Permit No. 402-582-01/03) Public Notification is required.

Question 15:

When is re-registration of MSMA scheduled by the US EPA? If such re-registration is being scheduled earlier than originally planned, does this not imply increasing evidence of hazards associated with this product? If such urgency is warranted in the U.S., of what relevance is the precautionary principle to the PMRA while a re-assessment is being conducted?

Response 15:

MSMA is currently under re-evaluation by both the PMRA and the US EPA. MSMA re-evaluation was initiated by PMRA in 2003 and is now scheduled for completion in Fiscal Year 04/05. EPA is further ahead of the PMRA in their re-evaluation of the organic arsenicals, with a preliminary risk assessment originally scheduled to be released for public comment by the US EPA in early 2002. The US EPA did not meet this deadline and are now scheduled for completion in their Fiscal Year 2004.

The Agency is not aware of any evidence that would support the suggestion that the US EPA's re-registration of MSMA has been scheduled earlier than originally planned. Accordingly, there is no implication of increasing evidence of hazards associated with this product.

Question 16:

If MSMA fails to be re-registered in the US, how long will it take for PMRA to respond to this decision, and what would that response likely be?

Response 16:

The US has many more registered uses for MSMA, including residential uses and uses on food and non-crops. Since it is likely that EPA will complete their re-evaluation ahead of PMRA, should specific concerns be identified in the EPA assessment that apply to the Canadian forestry use, appropriate action will be taken by the PMRA in a time-line that is comparable to that of the EPA. The outcome of the re-evaluation assessment will be available to the public and stakeholders for comment.

Question 17:

Is the PMRA willing to consider evidence regarding the toxicity of MSMA independent of the re-assessment process in the U.S.?

Response 17:

The PMRA considers all available information during the re-evaluation process. Although the PMRA has been involved in scientific discussions with EPA regarding the organic arsenicals, as is the case with other pesticide re-registration decisions, each country is ultimately responsible for their final regulatory decision.

References:

Agency for Toxic Substances and Disease Registry (ATSDR). 2000. Toxicological profile for arsenic. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

Arnold LL, Eldan M, van Gemert M, Capen, C, Cohen S. 2003. Chronic studies evaluating the carcinogenicity of monomethylarsonic acid in rats and mice. Toxicology 190: 197-219.

Dost FN. 1995. Public health and environmental impacts of monosodium methanearsonate as used in bark beetle control in British Columbia. Prepared for Ministry of Forests, Silviculture Practices Branch. Queen's Printer for British Columbia, 47 pp.

Elfving DC, Stehn RA, Pakkala IS, Lisk DJ. 1979. Arsenic content of small mammals indigenous to old orchard soils. Bull Environ Contam Toxicol 21:62-64.

Ghassemi M, Fargo L, Painter, P, Painter P, Quinlivan S, Scofield R, Takata A. 1981. Environmental fates and impacts of major forest use pesticides. EPA Contract no. 68-02-3174. TRW Environmental Division, Redondo Beach, CA. U.S. Environmental Protection Agency, Office of Pesticides and Toxic Substances, Washington, DC.

Ismael A, Roberts RD. 1992. Arsenic in small mammals. Environ Technol 13(11):1091- 1095.

Le XC. 2001. Arsenic speciation in the environment and humans in: Environmental Chemistry of Arsenic, edited by WT Frankenberger, Jr., Marcel Dekker, Inc., New York 95-116.

Maclauchlan LE, Borden JH, D'Auria JM, Wheeler LA. 1988a. Distribution of arsenic in lodgepole pines treated with MSMA. Western Journal of Applied Forestry 3(2): 37-40.

Maclauchlan LE, Borden JH, D'Auria JM, Wheeler LA. 1988b. Distribution of arsenic in MSMA-treated lodgepole pines infested by the mountain pine beetle, Dendroctonus ponderosae (Coleoptera: Scolytidae), and its relationship to beetle mortality. Journal of Economic Entomology 81(1): 274-280.

Manville JF, McMullen LH, Reimer KJ. 1988. Impact and role of monosodium methanearsonate on attack and progeny production by the Douglas-fir beetle (Coleoptera: Scolytidae) in lethal trap trees. Journal of Economic Entomology 81(6): 1691-1697.

Newton M. 1986. Residues from organic arsenical herbicides in chemically thinned forests. Journal of Environmental Quality 15(4): 388-394.

Norris LA. 1985. Exposure of applicators to monosodium methanearsonate and cacodylic acid in forestry. ACS Symposium Series 273: 109-121.

Norris LA. 1974. Studies of exposure of applicators and animals to arsenicals. In Norris LA, The behaviour and impact of organic arsenical herbicides in the forest: Final report on cooperative studies, USDA Forest Service PNW Forest and Range Experiment Station, Corvallis, OR, p 75.

Norris LA, Canutt PR, Neuman JF. 1983. Arsenic in the forest environment after thinning with MSMA and cacodylic acid. Bull Environ Contam Toxicol 30: 309-316.

WHO. 2001. Environmental health criteria 224: Arsenic and arsenic compounds (second edition). Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organization, and the World Health Organization, and produced withing the framework of the Inter-Organization Programme for the Sound Management of Chemicals, 521 pp.