UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

MEMORANDUM 

SUBJECT: Summary of Ecotoxicity Data for

EPA Reg. #:

CAS #:

PC Code 

FROM: Michael Rexrode, Ph.D., Senior Biologist /s/ 08

Biochemical Pesticides Branch

Biopesticide & Pollution Prevention Division (7511P)

TO: Leonard Cole, 

Biochemical Pesticide

Biopesticide & Pollution Prevention Division (7511P)

ACTION REQUESTED

The following is the final ecotoxicity assessment for cytokinin

Registration Review Decision Document. 

RECOMMENDATIONS AND CONCLUSIONS

Executive Summary

The plant regulator, cytokinin, was initially registered in the United States in 1978 as CYTEX

(EPA Reg. No. 35980-1) for applications to certain citrus, fruit and vegetable crops. Cytokinin 

acts as a plant regulator by promoting cell 

stimulation; increased yield; increased vegetative growth; and increased tuber firmness.

During Phase 4 of the Reregistration Process, the data base for 

determined to be inadequate in satisfying certain requirements for biochemical pesticides which 

include plant regulators. 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM August 31, 2012

Summary of Ecotoxicity Data for Cytokinin Registration Review Document

5905-LIU

 525-79-1 and 133-32-4 

PC Code 116801 and 116802

Rexrode, Ph.D., Senior Biologist /s/ 08/31/

Biochemical Pesticides Branch

Biopesticide & Pollution Prevention Division (7511P)

Leonard Cole, Regulatory Action Leader /s/ 08/31/2012

Biochemical Pesticides Branch

Biopesticide & Pollution Prevention Division (7511P)

The following is the final ecotoxicity assessment for cytokinin/kinin in support of

Registration Review Decision Document. 

RECOMMENDATIONS AND CONCLUSIONS

ytokinin, was initially registered in the United States in 1978 as CYTEX

1) for applications to certain citrus, fruit and vegetable crops. Cytokinin 

acts as a plant regulator by promoting cell division; minimizing effects of stress; root 

stimulation; increased yield; increased vegetative growth; and increased tuber firmness.

During Phase 4 of the Reregistration Process, the data base for cytokinin was evaluated and 

satisfying certain requirements for biochemical pesticides which 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

August 31, 2012

Cytokinin Registration Review Document

/31/2012

/s/ 08/31/2012

in support of the 

ytokinin, was initially registered in the United States in 1978 as CYTEX® 

1) for applications to certain citrus, fruit and vegetable crops. Cytokinin 

division; minimizing effects of stress; root 

stimulation; increased yield; increased vegetative growth; and increased tuber firmness.

ytokinin was evaluated and 

satisfying certain requirements for biochemical pesticides which 
Since the DCI, the Agency's initial position about these data gaps was re

these data requirements, except for 154

information indicates cytokinin does not cause unreasonable adverse 

constituents of cytokinin, algae and seaweed, are natural 

has a very low acute mammalian toxici

feeds; and 4) are expected to have no adverse effects to fish and wildlife.

During development of the reregistration eligibility decision (RED), the data requirements for 

non-target insect testing were rethe previously mentioned rationale for ecological effects (i.e., low acute mammalian toxicity; use 

as a fish and animal food supplement; and lack of expected adverse effects to fish and wild

Therefore, the data are adequate to support the currently registered uses of 

This Reregistration Eligibility Decision reflects a reassessment of all data which were submitted 

in response to the Reregistration Process. 

Agency does not foresee the need for additional ecotoxicity

has waived all hazard and exposure data on th

products, there non-toxic mode of action, 

result in toxic risk to non-targets, including th

considers cytokinin use to have a 

Background

Cytokinin is generally found in higher concentrations in meristematic regions and growing 

tissues. They are believed to be synthesized in the roots and translocated via the xylem to shoots. 

Cytokinin biosynthesis happens through the biochemical modificatio

have been found in almost all higher plants as well as mosses, fungi, bacteria, and also in tRNA 

of many prokaryotes and eukaryotes. Today there are more than 200 natural and synthetic 

cytokinins combined. Cytokinin concentrations 

continuous growth potential such as roots, young leaves, developing fruits, and seeds (Arteca, 

1996; Mauseth, 1991; Raven, 1992; Salisbury and Ross, 1992).

Toxicology 

Summaries of the toxicology profile for 

information cytokinins are practically non

(Toxicology Cat. IV); can cause slight acute dermal effects

irritation (Toxicology Cat. III). Studies on kinetin (Table 2.0) show that the compound has a 

Since the DCI, the Agency's initial position about these data gaps was re-evaluated and all of 

these data requirements, except for 154-B-11 Non-target insects, were waived because a

ytokinin does not cause unreasonable adverse effects: 1) The principal 

ytokinin, algae and seaweed, are natural components of fish diets;

has a very low acute mammalian toxicity; 3) Cytokinin is used as a dietary supplement in animal 

4) are expected to have no adverse effects to fish and wildlife.

During development of the reregistration eligibility decision (RED), the data requirements for 

-examined and these data requirements were waived based on 

the previously mentioned rationale for ecological effects (i.e., low acute mammalian toxicity; use 

as a fish and animal food supplement; and lack of expected adverse effects to fish and wild

Therefore, the data are adequate to support the currently registered uses of cytokinin.

This Reregistration Eligibility Decision reflects a reassessment of all data which were submitted 

in response to the Reregistration Process. Based on the available information for 

Agency does not foresee the need for additional ecotoxicity data for a new risk assessment and 

azard and exposure data on these chemicals. The unique characteristics of th

of action, and biodegradability (low to no persistence)

targets, including threatened and endangered species. The Agency 

considers cytokinin use to have a no effect (NE) on endangered/threatened species

Cytokinin is generally found in higher concentrations in meristematic regions and growing 

tissues. They are believed to be synthesized in the roots and translocated via the xylem to shoots. 

Cytokinin biosynthesis happens through the biochemical modification of adenine.

have been found in almost all higher plants as well as mosses, fungi, bacteria, and also in tRNA 

of many prokaryotes and eukaryotes. Today there are more than 200 natural and synthetic 

cytokinins combined. Cytokinin concentrations are highest in meristematic regions and areas of 

continuous growth potential such as roots, young leaves, developing fruits, and seeds (Arteca, 

1996; Mauseth, 1991; Raven, 1992; Salisbury and Ross, 1992).

Summaries of the toxicology profile for cytokinin are shown in Table 1.0. Based on this 

s are practically non-toxic to mammalian species (LD50 > 5,000

(Toxicology Cat. IV); can cause slight acute dermal effects (Toxicology Cat. III), and slight eye 

Studies on kinetin (Table 2.0) show that the compound has a 

evaluated and all of 

re waived because available 

1) The principal 

components of fish diets; 2) Cytokinin 

tary supplement in animal 

During development of the reregistration eligibility decision (RED), the data requirements for 

examined and these data requirements were waived based on 

the previously mentioned rationale for ecological effects (i.e., low acute mammalian toxicity; use 

as a fish and animal food supplement; and lack of expected adverse effects to fish and wildlife). 

ytokinin.

This Reregistration Eligibility Decision reflects a reassessment of all data which were submitted 

ble information for cytokinin the 

data for a new risk assessment and 

. The unique characteristics of these

biodegradability (low to no persistence), will not 

The Agency 

endangered/threatened species.

Cytokinin is generally found in higher concentrations in meristematic regions and growing 

tissues. They are believed to be synthesized in the roots and translocated via the xylem to shoots. 

n of adenine. Cytokinins 

have been found in almost all higher plants as well as mosses, fungi, bacteria, and also in tRNA 

of many prokaryotes and eukaryotes. Today there are more than 200 natural and synthetic 

are highest in meristematic regions and areas of 

continuous growth potential such as roots, young leaves, developing fruits, and seeds (Arteca, 

shown in Table 1.0. Based on this 

> 5,000 mg/kg) 

III), and slight eye 

Studies on kinetin (Table 2.0) show that the compound has a 
Toxicological Category IV for acute oral (LD50 > 5,000 mg/kg), Acute Dermal (LD50 > 5,000 

mg/kg), Acute Inhalation (LC50 > 2.09 mg/L), and Dermal Irritation (non-irritating). The study

on Eye Irritation showed mild effects and a Toxicology Category III.

Table 1.0. Acute Toxicological Values for Cytokinin

Guideline Study Results Category MRID #

870.1100 Acute Oral (rat) LD50 > 5,000mg/kg IV 00142864

870.1200 Acute Dermal LD50 > 2,000 mg/kg III 00138093

870.1300 Acute Inhalation Waived

870.2400 Eye irritation Slight III 00138094

870.2500 Dermal irritation Slight III 00074304

870.2600 Dermal sensitization Waived

Table 2.0. Acute Toxicological Values for Kinetin

Guideline Study Results Category MRID #

870.1100 Acute Oral (rat) LD50 > 5,000mg/kg IV 45500703

870.1200 Acute Dermal LD50 > 5,000 mg/kg IV 45500704

870.1300 Acute Inhalation LC50 > 2.09 mg/L IV 45500705

870.2400 Eye irritation mild III 45500706

870.2500 Dermal irritation Non-irritating IV 45500707

870.2600 Dermal sensitization Not a contact 

sensitizer

45500708

Only the four naturally occurring cytokinins, derived from certain algal species, are exempt from 

the requirement of a tolerance when used as a plant growth regulator (40 CFR 180.1042). 

Tolerance exemptions are often based on the results of 90-Day (or longer) feeding and 

developmental toxicity studies submitted to support reregistration. However, it is the Agency's 

opinion that these studies can be waived for naturally occurring and synthetic cytokinin because 

of low acute mammalian toxicity and very low use rates (250 grams ai/A), which would not 

significantly increase dietary intake over natural consumption in foods. The Agency, will be 

proposing an exemption from the requirement of a tolerance for certain cytokinins (zeatin [6-(4-

hydroxy-3-methylbut-trans-2-enylamino)-purine], N6-methylaminopurine, N6-dimethylamino 

purine, N6- isopentenyl- aminopurine), and synthetic cytokinin -- kinetin [6- (furfurylamino) 

purine] for all raw agricultural commodities (RACs). The exemption will apply only when 

application rates do not exceed 250 grams of active ingredient/acre/year. The Agency believes 

this action does not present any unreasonable risk. It is based on cytokinin's low acute 

mammalian toxicity, its low use rates, exposure in the diet from numerous natural plant food 

sources, and minimal exposure in the diet derived from consumption of treated commodities 

under the proposed maximum label use rates. The Agency has concluded that dietary exposure 

risks from consuming commodities treated with cytokinin, either naturally occurring or 

synthetic, are not expected.

Ecotoxicity

Ecological toxicity studies on non-target terrestrial and aquatic organisms were waived because 

available information shows that cytokinin does not cause unreasonable adverse effects: 1) The 

principal constituents of cytokinin, algae and seaweed, are natural components of fish diets; 2) 

Cytokinin has a very low acute mammalian toxicity; 3) Cytokinin is used as a dietary supplement 
in animal feeds; 4) are expected to have no adverse effects to fish and wildlife; and 5) no 

reported incidents. Data waivers were also granted for Nontarget Insect Testing (885.4340) and 

Nontarget Plant Testing (885.4300) in July of 1995 as part of the RED development process 

because of the unique characteristics of this product, its non-toxic mode of action, low use 

volumes (< 2g/A), and biodegradability (low to no persistence). Based on the current use 

patterns, the non-toxic effects to terrestrial and aquatic plants and animals, the Agency finds that 

Cytokinin use is a No Effect to endangered plant and animal species from current registered uses. 

References

Arteca, R. (1996). Plant Growth Substances: Principles and Applications. New York: Chapman 

& Hall. 

Mauseth, J. D. (1991). Botany: An Introduction to Plant Biology. Philadelphia: Saunders. pp. 

348-415.

Raven, P. H., Evert, R. F., and Eichhorn, S. E. (1992). Biology of Plants. New York: Worth. pp. 

545-572.

Salisbury, F. B., and Ross, C. W. (1992). Plant Physiology. Belmont, CA: Wadsworth. pp. 357-

407, 531-548.

USEPA 738-R-95-025 Environmental Protection And Toxic Substances December 1995 Agency

(7508W) Reregistration Eligibility Decision (RED).