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EXECUTIVE SUMMARY

Alkyl imidazoline is registered for use as an industrial fuel preservative. Currently 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 1995 (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 

toxicity studies, a developmental toxicity study in rats and three mutagenenicity studies. With 

respect to acute toxicity, alkyl imidazoline is a severe eye and skin irritant (Toxicity 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 developmental effects were observed at any of the doses tested, 

including 100 mg/kg/day, the highest dose tested. The mutagenicity studies indicated that alkyl 

imidazoline did not induce mutations in bacteria, did not cause chromosomal aberrations in 

Chinese Hamster ovaries (CHO) cells and did not induce unscheduled DNA synthesis in primary 

rat hepatocytes.

Although the toxicological database for alkyl imidazoline is limited, additional studies are 

not required for registration review because the use pattern 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 additional 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 systems
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1.0 BACKGROUND

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 Name Alkyl imidazoline

PC Code 046609

CAS Registry Number 61791-39-7

Case No. 3010

Empirical Formula C22H40N2O

Structure

1.2 Chemical and Physical Properties

The physical and chemical properties of alkyl imidazoline that are relevant for human health 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 Solubility 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

There is one product (68708-3) that contains 25 percent alkyl imidazoline the active 

ingredient (ai). This product is formulated as a Ready-to-Use liquid.
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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 1995 and the use was found to be eligible 

for registration. 

3.0 TOXICOLOGY

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

studies that were available to the Agency when the RED was written in 1995. 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 (Toxicity Category I) and is of moderate oral toxicity (Toxicity 

Category III). The studies for inhalation toxicity and dermal sensitization were waived due to 

corrosivity.

Table 4 - Acute Toxicity Values for Alkyl Imidazoline. 

Test (species) Result Toxicity Category 

81-1 Oral Toxicity (rat) LD50 (males) = 1948 mg/kg

LD50 (females) = 1880 mg/kg

LD50 (combined) = 1932 mg/kg

III

81-2 Dermal Toxicity (rabbit) LD50 > 2000 mg/kg III

81-3 Inhalation Toxicity (rat) Waived due to corrosivity I (assumed)

81-4 Eye Irritation (rabbit) Severe eye irritant I

81-5 Dermal Irritation (rabbit) Severe 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 for alkyl imidazoline.

a. Subchronic Toxicity

No subchronic studies have been submitted.

b. Chronic Toxicity/Carcinogenicity

No chronic studies have been submitted.
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c. Developmental Toxicity

Developmental Toxicity Study in Rats, MRID 42293008, Rats were dosed by oral gavage of 

EH & S 592 (contains 85 percent alkyl imidazoline) in corn oil at 0, 15, 65, and 100 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 observed at any dose level. The maternal toxicity LOEL 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 tested).

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

d. Mutagenicity

Ames Test, MRID 422930-07. 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 ug/plate). 

CHO Test, MRID 422930-05. Alkyl imidazoline did not induce chromosomal aberrations 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 

without S9 activation, and 0, 0.0065, 0.013, 0.025, and 0.05 ul/ml with S9 activation. 

Unscheduled DNA Synthesis, MRID 422930-06. 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 Endpoints 

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, was used for assessing 

occupational dermal and inhalation exposures.
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4.0 DIETARY ASSESSMENT

Dietary Exposure

Dietary exposures to alkyl imidazoline are not anticipated because of the use pattern which is 

limited to fuel storage tanks.

Drinking Water Exposure

Drinking water exposures to alkyl imidazoline are not anticipated because of the use 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 treated 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 

0.0002 ppm. (i.e. 80 ppm Nalco 2210 in fuel oil x 20% a.i. in Nalco 2210 x 10 ppm fuel in water 

= 0.0002 ppm alkyl imidazoline in water).

5.0 OCCUPATIONAL/RESIDENTIAL EXPOSURE

Occupational Exposures

Occupational 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 were 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 occupational 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, as well as

non-occupational (i.e. residential) pesticide exposures. In the case of alkyl imidazoline, an 
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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, unlike 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 information 

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. Alkyl 

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 Disruptor 

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 effects 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 potential 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 the group of 58 pesticide active ingredients on the initial list to be 
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screened under the EDSP. Under FFDCA Section 408 (p), the Agency must screen all pesticidal 

chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. Further 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 ANTICIPATED 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.

11.0 REFERENCES

US EPA, 1995. Reregistration Eligibility Decision (RED) for Alkyl Imidazolines, June 1995,

http://www.epa.gov/pesticides/reregistration/status.htm
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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 how 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 assessed.

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.