Page 3 of 5

unknown, or no effects outcomes) are reported by registrants as counts called aggregate
summaries and are recorded in a separate module called Aggregate IDS

.

In A ggregate IDS , from January 1, 200 7 to February 22, 2012, there w ere 111 reported minor

incident s involving pendimethalin

.

For the main IDS, from January 1, 200 7 to February 22, 2012

, there w ere 24 reported incidents involving the single chemical pendimethalin in the database . One incident was classified as major severity and 23 incidents were classified as moderate severity

. The incident classified as major severity is described below in Table 1

. Upon further review this inci dent involved more than one product; however, the other products were not identified. In addition, there was one more incident reported that involved pendimethalin and other chemicals. Overall, there are few incidents involving pendimethalin reported to IDS

.

Within the AHS, there are several published investigations relevant to the hazard and exposure characterization of pendimethalin. In 2006, Hou et al. produced a cohort evaluation of pendimethalin users and all cancers combined as well as specific anatomical cancer sites. Using pesticide exposure information collected at enrollment into the study (lifetime use of pesticides

collected 1993

- 1997), and matching with state cancer registries through 2004, authors identified 9,089 cases of can cer among pendimethalin users in the AHS, among 15,285 participants for which pendimethalin use information was available. Overall, authors reported no compelling evidence that pendimethalin use was related to all cancers combined, or with many specific

an atomical cancer sites including prostate cancer and melanoma. Investigators did observe an elevated risk of rectal cancer when comparing the upper tertile of exposure with both the non

exposed and lowest exposed categories (odds ratio (OR) 4.3, 95% confide nce interval (9 5% CI) 1.5, 12.7), p for trend 0.007. Results were similar upon adjustment for personal protective equipment, i.e. , intensity

- weighted lifetime days. However, this result was based upon 19 cases

of rectal cancer which is a relatively small n umber of exposed cases to perform a robust statistical analysis

. Similarly, authors reported 2

- to 3

- fold elevated odds of lung cancer, among those who reported higher pendimethalin use, but trends by exposure category were inconsistent by use of referent group and exposure metric. Prior to this study, Alavanja et al. (2004) also identified a possible link between pendimethalin and lung cancer in a nested case

- control study within the AHS. In that study, authors reported a significantly reduced risk of lung cancer when comparing all AHS participants with the general populations of the respective study states (IA and NC), but identified a 4

- fold significantly increased risk of lung cancer among pendimethalin users (OR 4.4 (95% CI 1.2, 15.4), p for trend 0.003 ). While authors were able to control for the effect of smoking when estimating the association between pendimethalin and lung cancer, authors note all cases of lung cancer identified in the AHS are among current and former smokers. Therefore, authors coul d not rule out a role of residual confounding by smoking in estimating the association. However, it is notable that this potential link with lung cancer has now been observed in two studies within the AHS, at two points in time, using similar data to

measu re exposure and co

- variables including smoking. Within this cohort, authors also reported a significant association between pendimethalin users and pancreatic cancer (OR 3.0 (95% CI 1.3, 7.2), p=0.01) comparing the upper tertile with the no

- exposed group. However, authors note

there was no a priori hypothesis for this association, and many statistical tests were performed and not adjusted in final analyses.Page 4 of 5

In a related AHS study of self

- reported myocardial infarction (MI) or heart attack, authors

observed an association between pendamethalin users and MI (OR 2.5 (95% CI 1.2, 4.9). However this finding was based upon 9 pendamethalin exposed cases of MI. Authors found no association among users of any of the 50 pesticides included in the AHS, but they did rep ort associations with 6 of 27 pesticides evaluated, including pendamethalin. Given the small number of pendimethalin exposed cases of MI, the correlated nature of many pesticides used by cohort members which is difficult to disentangle in statistical analy ses only, and the lack of an a priori hypothesis and no known or hypothesized mechanism of action, these results should be interpreted with caution.

Based on the generally low frequency and severity of incident cases reported for pendimethalin

, there doe s not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk assessment and follow

- up studie s from the AHS will be

evaluated if available at the time of the risk assessment.

.

Table 1 : M ain IDS high severity incidents involving pendimethalin


### Chemical: Pendimethalin 

### PC code:

027401 Human

Incidents

Incident

Number Incident

Date Product

Name Registration

Number City State Exposure Type* Incident Description

022923

- 00004 5/25/2011 PROWL H2O

HERBICIDE 000241

- 00418 WINDBER PA HB Unknown age adult male applied product along with other products (not reported). He experienced pain

and heaviness in his chest. He was hospitalized with unspecified tests

and treatment.
* Severity Categories

na

– not available

H

- A Human Fatality Death (if the person died)

H

- B Human Major Major (if the person alleged or exhibited symptoms which may have been life

- threatening, or resulted in adverse reproductive effects or in residual disability)

H

- C Human Moderate Moderate (if the person alleged or exhibited symptoms more pronounced, more prolonged or of a more systemic nature than minor symptoms; and involved some form of treatment, even though symptoms were not life threatening and the person returned to his/her pre

- exposure state of health with no additional residual disability)

H

- D Human Minor Minor (if the person alleged or exhibited some symp toms, but they were minimally traumatic; the symptoms resolved rapidly and usually involve skin, eye or respiratory irritation)

H

- E Human Unspecified Unspecified (if symptoms are unknown, unspecified or are alleged to be of a delayed or chronic nature tha t may appear in the future)

H Human Undetermined ( an undetermined severity)
from 40 CFR § 159.184

Materials Referenced

Alavanja MC, Dosemeci M, Samanic C, Lubin J, Lynch CF, Knott C, Barker J, Hoppin JA, Sandler DP, Coble J, Thomas K, Blair A. Pesticides and lung cancer risk in the agricultural health study cohort. Am J Epidemiol. 2004 Nov 1;160(9):876

- 85. PubMed PMID: 15496540.

Andreotti G, Freeman LE, Hou L, Coble J, Rusiecki J, Hoppin JA, Silverman DT,Page 5 of 5

Alavanja MC. Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort. Int J Cancer. 2009 May 15;124(10):2495

- 500. PubMed PMID: 19142867; PubMed Central PMCID: PMC2674312.

Dayton SB, Sandler DP, Blair A, Alavanja M, Beane Free man LE, Hoppin JA. Pesticide use and myocardial infarction incidence among farm women in the agricultural health study. J Occup Environ Med. 2010 Jul;52(7):693

- 7. PubMed PMID: 20595914; PubMed Central PMCID: PMC2927225.

Hou L, Lee WJ, Rusiecki J, Hoppin J A, Blair A, Bonner MR, Lubin JH, Samanic C, Sandler DP, Dosemeci M, Alavanja MC. Pendimethalin exposure and cancer incidence among pesticide applicators. Epidemiology. 2006 May;17(3):302

- 7. PubMed PMID: 16452832; PubMed Central PMCID: PMC1513643.