UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: December 22, 2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Paclobutrazol: Response to Registrant Comments from Syngenta on the 

Preliminary Human Health Risk Assessment (September 11 , 2013; DP Barcode: 

D394230). 

PC Code: 1 25601 

Decision No.: 486346 

Petition No.: NA 

Risk Assessment Type: NA 

TXRNo.: NA 

MRID No.: NA 

DPBarcode: D417021 

Registration No.: 100-1014 

Regulatory Action: Registration Review 

Case No.: 7002 

CAS No.: 76738-62-0 

40CFR: NA 

FROM: Sheila Piper, Risk Assessor ~huLw Q,~ f'lf'l ~ lltlf\. 

Monica Hawkins, Ph.D., M.P.H., Environmental e~lth Scie tist v-- 't? 

Nancy McCarroll, Ph.D., Geneticist/Toxicologist 

Risk Assessment Branch VI 

THROUGH: Donna 

Risk Assessme

Davis, Acting 

nt Branch 

Branch 

VI 

Chief~~~ 

Health Effects Division 

TO: Khue Nguyen, Chemical Review Manager 

Neil Anderson, Branch Chief 

Risk Management and Implementation Branch I 

Pesticide Re-evaluation Division (7508P) 

HED has received comments on the review of the preliminary human health risk assessment for 

Registration Review September 11, 2013 ; DP Barcode: D394230 (EPA-HQ-OPP-2006-0109-

0021 ). 

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EPA's Statement: The studies available for consideration of paclobutrazol toxicity provide a 

comprehensive database; however, there are three outstanding studies according to revised 40 

CFR Part 158 Toxicology Data Requirement. These studies include an acute neurotoxicity 

(ACN) study, a subchronic neurotoxicity (SCN) study, and an immunotoxicity study (D. Smegal, 

TXR0056149, 01/03/ I2). The registrants have recently submitted the final A CN study report to 

the Agency. The Agency plans to review and inc01porate the ACN into the revised Registration 

Review risk assessment. In addition, as specified in the 2012 HASPOC memo, the Agency will 

reevaluate the need for an SCN based on the results of the ACN. 

Syngenta's Comment: As noted by the EPA review, Syngenta has submitted an ACN study 

with paclobutrazol in rats (Rached, 2013; MRID 49148701 ). Based on the lack of evidence of 

neurotoxicity with paclobutrazol in the guideline ACN study, Syngenta believes that the 

requirement for a SCN study should be waived. Also, the full database of paclobutrazol, which 

now includes an ACN study, supports a conclusion that a SCN study would not add to the safety 

profile of paclobutrazol, and should not be required. Regarding the possible need for an 

immunotoxicity study with paclobutrazol, Syngenta will submit a waiver request, which 

evaluates the potential for immunotoxicity with paclobutrazol in accordance with the waiver 

criteria published by EPA (US EPA, 2013b). This evaluation supports a position that an 

immunotoxicity study with paclobutrazo1 is not needed, considering the lack of any evidence for 

effects on the immune system in the existing database of studies with paclobutrazol. 

EPA's Response: The registrant has submitted an acceptable/guideline ACN study, previously 

identified as a data gap, and that study has been incorporated into the most recent risk assessment 

(D4 15247, Dec X, 2014). In addition, based on the weight of the evidence (WOE) approach 

used by HASPOC at the meeting, which was held February 27, 2014, it was recommended that 

the subchronic neurotoxicity, the subchronic inhalation and the immunotoxicity studies can each 

be granted data waivers (Leshin, 2014, TXR # 0056914). 

EPA's Statement: The restricted entry interval (REI) listed on the existing paclobutrazollabels 

is based on the acute toxicity ofthe technical material. Paclobutrazol is classified as Toxicity 

Category 1/.for acute dermal toxicity and Toxicity Category JI!.for eye and skin irritation. It is 

not a dermal sensitizer (Category IV). In accordance with the Worker Protection Standard 

(WPS), acute Toxicity Category III and II chemicals require a 24- or 12- hour REI, respectively. 

Furthermore, based on the occupa.tional post-application assessment, most post-application 

dermal risk estimates do not exceed HED 's level of concern (MOEs > I 000). Based on the acute 

derma/toxicity, the 12-hour REI that appears on the current paclobutrazollabels may not be 

adequate and should be revisited. 

Syngenta 's Comment: Syngenta requests that EPA replace the citations and descriptions of 

older acute toxicity studies from 1982 (Appendix A2.1) with the new studies submitted in 2012 

with the current production source material of paclobutrazol technical. As a result, the wording 

that discussed results of the older acute dermal toxicity study should be removed, and the final 

EPA conclusions that paclobutrazol is in EPA Toxicity Category III overall (signal word 

Caution) should be inserted. Therefore, the current Restricted Entry Interval of 12 hours is 

supported by the acute toxicity data. 

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EPA's Response: EPA concurs with Syngenta's comment and will revised the REI 

recommendation in HED's latest revised risk assessment accordingly. 

EPA's Statement: Residential handler exposures to the existing uses ofpaclobutrazol may 

occur to adults via the dermal and inhalation route. All residential handler dermal exposure 

scenarios do not exceed HED 's level of concern (MOEs ~I 000) except for 

mixing/loading/applying with a belly grinder (MOE= 790). 

Syngenta's Comment: Syngenta notes that according to the US EPA SOPs, it should be 

assumed that a product registered for use on turf grass is likely to be used on home lawns or by 

homeowners unless a specific statement on the label indicates the product is only to be used in 

non-residential settings. In this case, Syngenta labels for paclobutrazol products specifically 

state, ''Do not apply to residential turf" Therefore, Syngenta respectfully believes this 

statement is restrictive enough that residential post-application risk assessments for use sites 

other than golf courses are not necessary. There are no granular products in the Syngenta 

portfolio for paclobutrazol, and therefore Syngenta believes that the belly grinder applications 

are of not of concern. 

EPA's Response: Paclobutrazol is not registered for homeowner use on residential lawns. A 

residential handler assessment was not conducted as part of the revised paclobutrazol risk 

assessment. A residential post-application assessment was performed as use of paclobutrazol in 

parks and golf courses is expected to result in residential post-application exposure. HED has 

incorporated these changes into HED's latest revised risk assessment document (S. Piper, 

0415247, 12/22/2014). 

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