UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460  SEQ CHAPTER \h \r 1 

											

																					  OFFICE OF

									PREVENTION, PESTICIDES AND

								 	                TOXIC SUBSTANCES

Date: August 22, 2007

MEMORANDUM

SUBJECT:	Nicotine: Report of the Risk Assessment Review Committee
(RARC2)

FROM:	Matt Lloyd, Recorder

		Risk Assessment Review Committee

		Health Effects Division (7509P)

TO:	Bonnie Cropp-Kohlligian, ORE Assessor/Risk Assessor

		Registration Branch 1

		Health Effects Division (7509P)

THROUGH:	Christine Olinger and Elissa Reaves, Acting Co-Chairs  

		Risk Assessment Review Committee

		Health Effects Division (7509P)

PC Code:	056702

Team Members:	Bonnie Cropp-Kohlligian, ORE/Risk Assessor

			Susan Hummel, Senior Scientist

			Abdallah Khasawinah, Ph.D,  Toxicologist

				

Assessment Type:	Single Chemical, Aggregate

RARC Members:	 Ray Kent, Jess Rowland, Michael Metzger, Thurston Morton,
Christine Olinger, Kelly O’Rourke, Bill Burnam

Other attendees:	 Jill Bloom, Matt Crowley, Jack Housenger, Tina Levine

The RARC recommends that the Team write up the data requirements as OMB
guidance and provide that information to SRRD.  The RARC recommends that
the  Team redo the children’s incidental oral MOEs to provide to SRRD.
  The RARC recommends the following changes be made the document. 

MAJOR ISSUES

Use of Oral Study for Dermal/Inhalation Endpoint Selection 

The RARC recommends that the Team add characterization identifying that
the database has dermal studies but they are inappropriate for selecting
endpoints.  Oral studies should be used for all routes of exposure
because they are more robust to and will be protective of the
developmental effects seen in the dermal developmental study (patch
study). Additionally, characterize the duration of exposure in the oral
study relative to the anticipated exposure durations. 

 

Assessment of Episodic Granular Ingestion Scenario

The RARC recommends that the Team change the assessment episodic
ingestion to the typical one time post application exposure after it has
been applied using the 5g/kg from the acute LD50 study for the product
as a point of departure, based on the observed salivation effects.

Data Call In: Neurotoxicity Study

The RARC recommends that the Team add rationale to require acute
neurotoxicity and subchronic neurotoxicity studies based on neurotoxic
mode of action that may be applicable to the occupational and
residential exposure assessments

Human Sensitivity Issue

The RARC recommends that the Team add additional characterization of
human sensitivity versus rodent sensitivity to explain whether humans
are more sensitive because of the LD50 values provided throughout the
document. The 10X factor for database uncertainty included in the
assessment is protective of the potential for humans being more
sensitive than the standard 10 fold assumption.

 Data Requirements

The RARC recommends that the Team remove the acute oral, dermal,
inhalation, and primary eye irritation studies as data requirements (pg.
57). The RARC recommends that the Team add rationale to require acute
neurotoxicity and subchronic neurotoxicity studies based on neurotoxic
mode of action and a paucity of public literature for use in the
occupational and residential exposure assessments. The RARC recommends
adding neurotoxicity testing to the 21-day dermal and 90-day inhalation
(reduce to 21-day inhalation) studies. The RARC recommends keeping the
developmental and reproductive studies as indicated in the document.

OTHER POINTS OF DISCUSSION

The RARC recommends that the Team move the endocrine disruption summary
to include it in the hazard characterization section and retain only the
boilerplate language in the Endocrine Disruption section 3.3.

The RARC recommends that add the Environmental Justice and Human Studies
section to the executive summary.

The RARC recommends that the Team expand the discussion of the nicotine
forms of alkaloid and salts in Section 2.2/2.3 and add it the to
Physical Chemical properties section of the risk assessment.

The RARC recommends adding additional characterization to justify why no
drinking water assessment has been conducted in the risk assessment.

The RARC recommends that the Team add rationale to explain why the FQPA
does not apply.

The RARC recommends that the Team better describe the story for nicotine
(i.e, exposure and hazard).

The RARC recommends that the Team add characterization for liver effects
since the mode of action is neurotoxic but the POD is based on liver
effects.

The RARC recommends that the Team reconcile the discrepancy for between
the statement that dermal toxicity studies are not available with the
description of the dermal toxicity studies (pg. 27).

The RARC recommends that the Team add characterization of nicotine blood
levels over short- and longer term exposure and toxicity studies (pg.
28).

The RARC recommends the Team alter the label recommendation on
application rates to more appropriate units (pg. 58).

The RARC recommends the Team modify the regulatory history section at
the beginning of the executive summary.

The RARC recommends the Team organize the hazard characterization
section by route of exposure (inhalation, dermal, etc.).

The RARC recommends the Team clarify the extent of the use of nicotine
as a pesticide and the amount sold annually.

The RARC recommends the Team further describe the level of conservatism
used in the residential exposure assessment. 

The RARC recommends the Team further discuss the available incident data
in terms of rate and usage.

The RARC recommends the Team cite a reference for the assumption of rat
consuming 50 mL of water per day for the toxicity study used for the
endpoints (pg. 22).

The RARC recommends the Team consider adding a residential section
(e.g., reconsider the number of air changes per hour) for the post
application assessment because there is nothing on available labels to
preclude a professional application in a private greenhouse where WPS
would not apply (pg. 53).

18) The RARC recommends adding an assessment for occupational handlers
rather than stating that the residential handler portion is protective
of occupational handlers.  The amount handled (e.g., # bags product used
per day) is of primary concern.

Cc:   Ray Kent, Branch Chief, RRB4 

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