Page 2 of 9 EXECUTIVE SUMMARY

Alkyl imidazoline is registered for use as a n industr ial fuel preservative. Current ly there is one product ( EPA Reg. No. 68708

- 3) that contains alkyl imidazoline (25%) as the active ingredient (ai). The RED for alkyl imidazoline was completed in 199 5 (US EPA, 1995) and the

use was found to be eligible for re

- registration

. No additional uses have been added since the

RED.

The toxicological database for the alkyl imidazoline registration review case has not changed

since the RED was written in 1995. This database is very limited and includes a few acute

tox icity studies, a developmental toxicity study in rats and three mutagenenicity studies. With respect to acute toxicity, a lkyl imidazoline is a severe eye and skin irritant (Tox icity Category I) and is of moderate oral toxicity (Toxicity Category III) . The acute toxicity studies for inhalation toxicity and dermal sensitization were waived due to corrosivity. In the developmental study

, clinical signs of maternal toxicity were observed with a LOEL of 15 mg/kg/day , which was the

lowest dose tested

, and no de velopmental effects were observed at any of the doses tested, including 100 mg/kg/day, the highest dose tested. The mutagen i city studies indicated that alkyl imidazoline did not induce mutations in bacteria, did not cause chromosomal aberrations in

Chine se H amster o varies (CHO) cells and did not induce unscheduled DNA synthesis in primary rat hepatocytes.

Although the toxicological database for alkyl imidazoline is limited, addi tional studies are not required for registration review because the use patt ern is not likely to cause residential, dietary, or drinking water exposures. In addition, the occupational exposures are anticipated to

be minimal because of the existing label requirement for the use of closed delivery systems.

In conclusion, no addi tional toxicology, dietary exposure or occupational/residential exposure studies are required for the registration review of alkyl imidazoline because the use is limited to fuel preservation in industrial facilities that have closed delivery systemsPage 3 of 9 1.0 B ACKGROUND

1 .1 Chemical Identity

The chemical identity of alkyl imidazoline listed in Table 1

.

Table 1

- Chemical Identity of Alkyl Imidazoline

Chemical Name 1

- (2

- hydroxyethyl)

– 2

- alkyl*

- 2

- imidazoline (*as in fatty acids of tall oil)

Common Na me Alkyl imidazoline

PC Code 046609 CAS Registry Number 61791

- 39

- 7

Case No. 3010 Empirical Formula C 22 H 40 N 2 O

Structure

1.2 Chemical and Physical Properties

The physical and chemical properties of alkyl imidazoline that are relevant for human h ealth risk

assessment are listed in Table 2

.

Table 2

- Physical and Chemical Properties of Alkyl Imidazoline

Property Value Reference

Molecular Weight 348 Based on formula

Physical State Liquid US EPA, 1995

Boiling Point >200 C @ 20 mm Hg US EPA, 1995

Water Sol u bility 8 mg/l @ 20 C US EPA, 1995

Octanol/Water Partition Coefficient 28,500 US EPA, 1995

Vapor Pressure < 1 mm Hg

2.0 USE INFORMATION

2.1 Formulation Types and Percent Active Ingredient

T h ere is one product (68708

- 3) that contai n s 25 percent alkyl imidazoline the active ingredient (ai). Th is product is formulated as a Ready

- to

- Use liquid

.Page 4 of 9 2.2 Summary of Registered Uses

Alkyl imidazoline is registered as Nalco 2210 Fuel Oil Treatment ( EPA Reg. No. 68708

- 3) to inhibit sludge formation, disperse existing sludge and to control filter plugging bacteria and fungi in fuel storage tanks and feed lines. The application rate is 10 to 20 ppm a.i. and the applications must be made using closed delivery systems only.

The RED for alkyl imidazoline was completed in 199 5 and the use w as found to be eligible for registration

.

3

. 0 T OXICOLOGY

The toxicological database for the a lkyl imidazoline registration review case is comprised of

studies that were available to the Agency when the RED was written in 199 5 . No additional

studies were submitted after the RED.

3.1 Acute Toxicity

A summary of the acute toxicity findings is included in Table 4

. Alkyl imidazoline is a

severe eye and skin irritant (Tox icity Category I) and is of mode rate oral toxicity (Toxicity Category III)

. The studies for inhalation toxicity and dermal sensitization were waived due to corrosivity.

Table 4

- Acute T oxicity V alues for Alkyl Imidazoline

.

Test (species) Result Toxicity Category

81

- 1 Oral Toxicity ( rat) LD50 (males) = 19 48 mg/kg

LD50 (females) = 1880 mg/kg LD50 (combined) = 1932 mg/kg I II

81

- 2 Dermal Toxicity (rabbit) LD50 > 2000 m g/kg III

81

- 3 Inhalation Toxicity (rat) Waived due to corrosivity I (assumed)

81

- 4 Eye Irritation (rabbit) Severe e ye irritant I

81

- 5 Dermal Irritation (rabbit) S evere skin irritant I

81

- 6 Dermal sensitization (guinea pig) Waived due to corrosivity N/A

3.2 Subchronic and Chronic Toxicity

The following is a summary of the currently available toxicology studies fo r alkyl imidazoline.

a . Subchronic Toxicity

No subchronic studies have been submitted.

b . Chronic T oxicity/Carcinogenicity

No chronic studies have been submitted.Page 5 of 9 c . Developmental Toxicity

D evelopmental T oxicity S tudy in Rats

, MRID 42293008

, R ats we re dosed by oral gavage of EH & S 592 (contains 85 percent alkyl imidazoline) in corn oil at 0, 15

, 65 , and 1 00 mg/kg/day

on gestation days six through 15

. Clinical signs of toxicity (excessive salivation and/or staining of the skin/fur in the anogenital area) were observed at 15 mg/kg/day (i.e. the lowest dose tested). In addition, decreased maternal body weight gain and food consumption were observed at 65 and 100 mg/kg/day and two deaths occurred at 100 mg/kg/day. No developmental toxicity

was observe d at any dose level

. The maternal toxicity L OEL is 15 mg/kg/day (lowest dose tested) based on clinical signs of toxicity and the maternal toxicity NOEL is <15 mg/kg/day (not established)

. The developmental toxicity NOEL is 100 mg/kg/day (highest dose tes ted)

. and the developmental toxicity LOEL is >100 mg/kg/day (not established)

.

d . Mutagenicity

Ames Test

, MRID 422930

- 0 7

. Alkyl imidazoline was tested for the ability to cause mutations

in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100. Alkyl

imidazoline was found to be non

- mutagenic in all five strains with and without metabolic

activation at all concentrations tested (1

- 100 u g/plate )

.

CHO Test, MRID 4 22930

- 05

. Alkyl imidazoline did not induce chromosomal aberration s in Chinese hamster ovary (CHO) cells when tested at concentrations up to cytotoxic levels with and without metabolic (S9) activation. The dose levels were 0, 0.0013, 0.0025, 0.005, and 0.1 ul/ml

w ithout S9 activation

, and 0, 0.0065, 0.013, 0.025, and 0. 05 ul/ml with S9 activation.

Un scheduled DNA S ynthesis

, MRID 422930

- 0 6

. Alkyl imidazoline did not induce unscheduled DNA synthesis in primary rat hepatocyte cultures treated up to cytotoxic levels (0.03 ul/ml). The dose levels used were: 0, 0.001, 0. 003, 0.006, 0.01 and 0.03 ul/ml.

e . Metabolism

No metabolism studies have been submitted.

f. Reproductive Toxicity

No reproductive toxicity studies have been submitted.

g. Neurotoxicity

No neurotoxicity studies have been submitted.

3.3 Toxicology En dpoints

In the human health risk assessment for the RED

, a toxicology endpoint of 15 mg/kg/day, which is the maternal LOEL from the developmental toxicity study, w as used for assessing occupational dermal and inhalation exposures

.Page 6 of 9 4

. 0 DIETARY ASSESSME NT

Dietary Exposure

Dietary exposures to a lkyl imidazoline are not anticipated because of the use pattern which is limited to fuel storage tanks.

Drinking Water Exposure

Drinking water exposures to a lkyl imidazoline are not anticipated because of the u se pattern which is limited to low concentration applications to fuel storage tanks. Because alkyl imidazoline has an octanol water coefficient of 28,500 it will partition to the oil phase of the treated fuel and it will remain in the oil phase if the t reated fuel contaminates drinking water. It is likely therefore, the oil itself will contaminate the drinking water and cause odor and taste problems long before alkyl imidazoline will reach significant levels. For example, if water is

contaminated with fuel oil at a rate of 10 ppm, the concentration of alkyl imidazoline would be

0. 0 00 2 ppm. (i.e. 80 ppm Nalco 2210 in fuel oil x 20% a.i. in Nalco 2210 x 10 ppm fuel in water

= 0.00 0 2 ppm alkyl imidazoline in water).

5

. 0 OCCUPATIONAL/RESIDEN TIAL EXPOSURE

Occupational Exposures

O ccupational handler exposures were assessed in the RED for the mixing and loading for the fuel preservation use. The MOEs were calculated for “total exposures” based on the addition of the dermal and inhalation exposures and wer e assessed using the oral endpoint of 15 mg/kg/day along with a dermal absorption factor of 100 percent and a daily fuel treatment volume of 10,000 gallons. All of the MOEs exceeded the target MOE of 100 and were not considered to be of

concern.

No occ upational exposure assessments are needed if the current label requirement for closed system use is maintained.

Residential Exposures

Residential exposures to alkyl imidazoline are not anticipated because it is registered for use only in industrial fuel storage facilities.

6

. 0 AGGREGATE AND CUMULATIVE EXPOSURE

In examining aggregate exposure, EPA takes into account the available and reliable information concerning exposures to pesticide residues in food and drinking water, a s well as

non

- occupationa l (i.e. residential) pesticide exposures

. In the case of alkyl imidazoline, anPage 7 of 9 aggregate risk assessment is not needed because of the limited use pattern which is not likely to result in dietary, drinking water or residential exposures.

With respect to cumulative exposure, u nlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to alkyl imidazoline and any other substances and alkyl imidazoline does not appear to produce a toxic metabolite produced by other substances. For the purposes of this registration review, therefore, EPA has not assumed that alkyl imidazoline has a common mechanism of toxicity with other substances. For inform ation regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

7

. 0 INCIDENTS

There are no human incidents reported in the OPP incident database that are associated with alkyl imidazoline exposure.

8

. 0 TOLERANCES

There are no tolerances or exemptions from tolerances for alkyl imidazoline

. A lkyl

imidazoline is not approved for use as an indirect food additive

.

9

. 0 ENDOCRINE DISRUPTION EFFECTS

As required under FFDCA section 408(p), EPA has developed the Endocrine Dis ruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine ef fects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal

systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the potentia l for human exposure through pathways such as food and water, residential activity, and certain post

- application agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors. Alkyl

imidazoline is not among t h e group of 58 pesticide active ingredients on the initial list to bePage 8 of 9 screened under the EDSP

. Under FFDCA S e ction 408 (p), the Agency must screen all pesticidal chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call

- ins f or al l pesticide active ingredients. F urther information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, is

available on the website: http://www.epa.gov/endo/.

10

. 0 ANTI CIPATED DATA NEEDS

10.1 Toxicology Studies

No toxicology studies are needed if the current label requirement for closed system use is

maintained.

10.2 Exposure Studies

No exposure studies are needed if the current label requirement for closed system use is

maintained. A product use study is required, however , to verify that the assumptions regarding drinking water exposure are correct

. A justification for this study is provided in Appendix A.

1 1

. 0 REFERENCE S

US EPA, 199 5

. Reregistration Eligi bility Decision ( RED) for Alkyl Im i dazolines

, June 199 5

, http://www.epa.gov/pesticides/reregistration/status.htmPage 9 of 9 

### Appendix A

- Justifications for the Human Health Studies Needed for Alkyl Imidazoline Registration Review

Study Title: Product Use

Guideline Number: 875.1700 1) What is the value of the study? Product use information is a description of how the product is actually applied; it is not a field study. A description of ho w this product is used would provide for a comprehensive realistic assessment of its potential applications.

2) How would the data be used?

The product use information will be used to define and characterize the exposure scenarios that

will be assessed in the risk assessment

.

3) How could the data affect the risk assessment? A complete description of product use would ensure that the risk assessment is inclusive of the types of exposures occurring during use and that these exposures are accurately assess ed

.

4) What is triggering the need for this data? The need for a risk assessment under Registration Review in turn necessitates that the risk assessor understand how the product is used

.