n,n-methylenebismorpholine - Registration of Contram ST-1

New York State Department of Environmental Conservation
Division of Materials Management
Bureau of Pest Management, 9th Floor
Product Registration & Pest Management Alternatives Section
625 Broadway, Albany, New York 12233-7257
Phone: (518) 402-8768 . Fax: (518) 402-9024
Website: http://www.dec.nv.gov
E-Mail: ppr@gw.dec.state.ny.us
VIA UPS
Ms. Jacqueline J,C. Williams
Keller and Heckman, LLP
1001 G Street, N.W. Suite 500 West
Washington, D.C. 20001
Dear Ms. Williams:
Re
August 7,2072
Registration of Contram ST-1 (EPA Reg. No. 52484-3) Which Contains the
New Active Ingredient N,N-methylenebismorpholine (Chemical Code
0s4702)
Joe Martens
Commissioner
The New York State Department of Environmental Conservation (l)epartment) has
reviewed your application, received December 23,2011 with additional data received March 05,
2012 andJuly 3I,2012, to register the new pesticide product Contram ST-1 (EPA Reg. No'
52484-3) in New York State.
The application, which was submitte

Ms. Jacqueline J.C. Williams
On an acute basis, N,N-methylenebismorpholine (the formulated product consists solely
of the active ingredient and hydrolysis byproducts) was not very toxic to laboratory animals by
either the oral or dermal routes of exposure. Although an acute inhalation toxicity study was not
conducted, this active ingredient was assigned Toxicity Category I (highly toxic) given its
hydrolysis to formaldehyde in the presence of water. N,N-methylenebismorpholine was
corrosive to the skin (tested on rabbits) and was assum"d to also be corrosive to eyes (no testing
was conducted), but was not a skin sensitizer (tested on guinea pigs).
Because,of the use pattern, limited toxicity testing of N,N-methylenebismorpholine was
required for the federal registration of Contram ST-1. In a 90-day feeding study in rats, N,Nmethylenebismorpholine
caused microscopic changes to the non-glandular stomach at 50
milligrams per kilogram body weight per day (mglkglday); the no-observed-effect level (NOEL)
was 15 mglkglday. This chemical did not cause developmental toxicity in offspring of pregnant
rats when administered by gavage during organogenesis at 100 mglkg/day, the highest dose
tested. However, maternal toxicity charactenzed by treatment-related stomach effects inclucling
erosion and granular aspect of the stomach occurred at 30 mglkglduy; the NOEL was 10
mglkglday. N,N-methylenebismorpholine was also negative in a number of genotoxicity studies.
The U.S. Environmental Protection Agency (U.S. EPA) waived all other toxicity studies
including chronic toxicity/oncogenicity and developmental/reproductive toxicity studies for
federal rãgistration of Contram ST-1. A search of the toxicological literature did not find any
additional si gnifi cant information.
The U.S. EPA reported the results of an occupational risk assessment for exposures to
formaldehyde from the use of Contram ST-1 in metal working machine shops' N,Nrnethylenetismorpholine
rapidly hydrolyzes to formaldehyde in the presence of water and due to
formiaenyae's high vapor pressure (1 mm Hg), inhalation is the primary route of exposure. For
determining margins-of-.*porrrr. (MOEs) to formaldehyde, the U.S. EPA compared estimated
inhalation exposures to the reference concentration (RfC) of 0.1 parts per million (ppm) adopted
by rhe Integrated Risk Information System (IRIS). The RfC is based on the NOEL of 0.1 ppm
from an observational study with particle board workers (complaints of eye, nose, and throat
irritation at 0.4-1 .0 ppm formaldehyde) and an uncertainty factor of 1. The U.S. EPA estimated
inhalation exposures to formaldehyde from the use of metal working fluids treated with Contram
ST-l in closed and semi-closed máchines from information available in the open literature and
data from a registrant conducted machinist exposure study (machining of cast metal parts using a
water-based metal working fluid), Typical levels of fonnaldehyde in the air generated using
metalworking fluids containing Contram ST-1 at the label application rate of 2,000 pp- a
(approximately 300 ppm free formaldehyde) were esfimated to range from 1'1 x 10-' to 3.3 x 10-'
ppm. These estimates of exposure to fontraldehyde through typical use in a machine shop do not
exceed the U.S. EPA's level of concern (RfC) of 0.1 ppm. .In addition, the U.S. EPA did not
estimate cancer risk from formaldehyde exposure from the labeled use of Contram ST-1 because
it was assumed that the non-cancer risk level of 0.1 ppm would be protective of cancer risk as
well. The U.S. EPA considered risk estimates from exposure to formaldehyde protective of
exposures to the parent N,N-methylenebismorpholine.
There are no chemical specific federal or New York State drinking water/groundwater
standards for N,N-methylenebismorpholine. Based on its chemical structure, this cornpouncl falls
under the 50 microgram per liter fuglQ New York State drinking water standard for "unspecified
organic contaminants" (10 NYCRR Part 5, Public Water Systems).
2.

Ms. Jacqueline J.C. Williarns
The available information on the aotive ingredient N,N-methylenebisrnorpholine
indicates that it is corrosive and caused some toxicity in laboratory animals studies. Of greater
concelat, however, is its rapid hydrolysis to formaldehyde, a probable human carcinogen, in the
presence of water. The estimated exposures to fonnaldehyde of workers handling Contrarn ST-1
through operating machinery that uses metalworking fluids treated with this product are
estimated to be in the acceptable range by the U.S. EPA. In addition, the extensive personal
protective equipment (PPE) required by label (coveralls over long-sleeved shirt and long pants,
socks and chemical resistant foot wear, chemical resistant gloves, protective eyewear and a
respirator with organic vapor removing oartridge for open pour systems or access to such a
respirator for closed loading systems) should mitigate exposures and provide adequate MOEs to
workers exposed through metal working operations or handling the concentrated product.
However, the DOH has concerns about worker exposure to formaldehyde through use of
the Contram ST-1 product. The U.S. EPA did not conduct a cancer risk assessment for
inhalation exposure to formaldehyde although an inhalation unit risk of 1.3 x 10-5 per pglrn3
(based on increased incidence of squanrous cell carcinoma in rnale rats) is available and
supported in the U.S. llPA's Integrated l{isk Information System (IIUS) database. Using the
prãvlouslymentioned formaldehycle exposure concentrations (1.1 x 10'3 to 3.3 x 10¡ ppm) and
the inhalation unit risk, a lifetime excess carloer risk range of 2 x 10-6 to 6.25 x 10-6 can be
estimated for exposure to formaldehyde in machine shops. DOII recognizes that these
calculations likely overestimate worker risks and the estimated range is only slightly greater than
the target risk level of 1 x 10-6. Ilowever, DOH has concems about registering a product that
exposes workers to a compound classified by the tl.S. EPA as a "probable human carcinogen"
and considered by the National Toxicology Program (NTP) as "known to be a human
carcinogen." The personal protective equipment required by the Contram ST-1 label should
reduce potential exposure to formaldehyde; however we believe that workers should be aware of
this potential. Therefore, the DOI-I stated that they did not support registration of the Contram
ST-1 product in New York State atlhat tirne, but would be willing to support registration if the
registrant added a statement to the product label, Material Safety Data Sheet (MSDS) or some
other notification provided to workers alerting to the factthat f'ormaldehyde is fonned during the
use of this product.
In response to the conceffrs presented by the DOI-I in a "technical issues" letter dated
June 15, 2012, the registrant submitted a revisecl MSDS. Specifically, Section 10 of the MSDS
has been revised to alert workers to the fact that fonnaldehyde is formed during the use of the
Contram ST-l produot.
REGISTRATION DECISION
When used as labeled, Contram ST-1 has the potential to expose workers to
formaldehyde, which is classified by the U.S. EPA as a "probable human carcinclgen" and
considered by the National Toxicology Program (N'l-P) as "known to be a human catcinogen."
The personal protective equipment required by the Contram ST-1 label should reduce potential
exposure to fonnaldehyde; however the Department believes that workers should be aware of
this potential. With the addition of the revised MSDS, alerting workers to the fact that
J

Ms, Jacqueline i.C. Williams
formaldehyde is formed during the use of this.product, the Department is willing to support
registration of Contram S'f-1 (EPA Reg. No. 52454-3). Overall, the registrant addressed the
DOH's concerns with the revised MSDS.
'l'herefore, the Departmcnt has registered Contram ST-1 (EPA Reg. No. 52484'3)
for usc in New York Statc.
Enclosed are copies of the stamped "Accepted for Registration" label and the New York
State Certificate of Pesticide Registration for the product'
Please note that a proposal by any registrant to register a product that contains N,Nmethylenebismorpholine,
and whose labeled use are likely to increase the potential for signifrcant
impact on humans, nontarget organisms, or the envirorunent, would constitute a major change in
labeling. Such an application must be accornpanied by a new application fee and meet the
requirements listed in Appendix 1.8 of "New York State Pesticide Product Registration
Procedures" (April 2O0g). Such information, as well as forms, can be accessed at our website as
listed in our letterhead
If you have any questions, please contact Ms. Cyndi Crowley, of our Product Registration
and Pest Management Alternatives Section, at (518) 402-8768.
Enclosures
Sincerely,
5zr^-Æ/4'/-¿"1/4Årc
Scott Menrath, P.E.
Director
Bureau of Pest Management
4