**UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**MEMORANDUM SUBJECT**  : Summary

of Ecotoxicity

Data for EPA Reg. # : CAS # : PC Code **FROM** : Mi cha el 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 cy

tokinin Registration Review Decision Document.
**RECOMMENDATIONS AND CONCLUSIONS Executive Summary**  The plant regulator, c yt okinin, 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. Cyt okinin acts as a plant regulator by promoting cell stimulation; increased y

ield; 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 Cy

tokinin Registration Review Document 5905
- LIU 525
- 79
- 1 and 133

- 32
- 4 PC Code 116801 and 11680 2 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 Pesticide s Branch Biopesticide & Pollution Prevention Division (7511P)

The following is the final ecotoxicity assessment for cy

tokinin /kinin in support of Registration Review Decision Document.
**RECOMMENDATIONS AND CONCLUSIONS**

yt okinin, was initially

registered in the United States in 1978 as CYTEX 1) for applications to certain citrus, fruit and vegetable crops. Cyt okinin acts as a plant regulator by promoting cell division; minimizing effects of stress; root stimulation; increased y

ield; increased vegetative growth; and increased tuber firmness. During Phase 4 of the Reregistration Process, the data base for c yt okinin was evaluated and satisfying certain requirements for biochemical pesticides which **OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION**

**August 31, 2012** Cy tokinin Registration Review Document

/31/ 2012

/s/ 08/31/2012

in support of the

yt okinin, was initially

registered in the United States in 1978 as CYTEX ® 1) for applications to certain citrus, fruit and vegetable crops. Cyt okinin

division; minimizing effects of stress; root stimulation; increased y

ield; increased vegetative growth; and increased tuber firmness. yt okinin was evaluated and satisfying certain requirements for biochemical pesticides whichSince the DCI, the Agency's initial position about these data gaps was re

these data requirements, except for 154 information indicates c yt okinin does not cause unreasonable adverse constituents of c yt okinin, 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 re 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 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 h azard and exposure data on th product s , there non - toxic mode of action, result in toxic risk to non

- targets, including th **considers cytokinin use to have a Background**  Cy tokinin is generall y found in higher concentrations in meristematic regions and growing tissues. They

are believed to be sy

nthesized in the roots and translocated via the xyl em to shoots. Cy tokinin biosy

nthesis 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 sy nthetic cy tokinins combined. C ytokinin concentrations continuous growth potential such as roots, y oung leaves, developing fruits, and seeds (Arteca, 1996; Mauseth, 1991; Raven, 1992; Salisbury and Ross, 1992).

**To xicology**  Summaries of the toxicology profile for information cy

tokinin s 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, we re waived because a

yt okinin does not cause unreasonable adverse effects: 1) The principal yt okinin, algae and seaweed, are natural components of fish diets; has a very

low acute mammalian toxici ty ; 3) Cy tokinin is used as a die tary 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 c yt okinin. 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 th ese chemical s . The unique characteristics of th

of action, and biodegradability (low to no persistence) targets, including th reatened and endangered species. **The Agency considers cytokinin use to have a**  **no effect (NE) on endangered/threatened species**  Cy tokinin is generall y found in higher concentrations in meristematic regions and growing tissues. They

are believed to be sy

nthesized in the roots and translocated via the xyl em to shoots. Cy tokinin biosy

nthesis happens through the biochemical modificatio n 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 sy nthetic cy tokinins combined. C ytokinin concentrations are highest in meristematic regions and areas of continuous growth potential such as roots, y oung leaves, developing fruits, and seeds (Arteca, 1996; Mauseth, 1991; Raven, 1992; Salisbury and Ross, 1992).

Summaries of the toxicology profile for cy

tokinin are shown in Table 1.0. Based on this s are practically

non - toxic to mammalian species (LD 50 > 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 a vailable 1) The principal components of fish diets; 2) Cy tokinin 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 wild life). yt okinin. This Reregistration Eligibility Decision reflects a reassessment of all data which were submitted ble information for cy

tokinin the data for a new risk assessment and . The unique characteristics of th ese biodegradability (low to no persistence) , will no t **The Agency endangered/threatened species**  **.** Cy tokinin is generall y found in higher concentrations in meristematic regions and growing tissues. They

are believed to be sy

nthesized in the roots and translocated via the xyl em to shoots. n of adenine. Cy

tokinins 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 sy nthetic are highest in meristematic regions and areas of continuous growth potential such as roots, y oung 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 aToxicological Category IV for acute oral (LD 50 > 5,000 mg/kg), Acute Dermal (LD 50 > 5,000 mg/kg), Acute Inhalation (L C 50 > 2.09 mg/L), and De rmal Irritation (non

- irritating). The study on Ey e Irritation showed mild effects and a Toxicology Category I II. **Table 1.0. Acute Toxicological Values for Cytokinin Guideline**  **Study Results**  **Category MRID #**  870.1100 Ac ute Oral (rat) LD 50 > 5,000mg/kg IV 00142864 870.1200 Ac ute Dermal LD 50 > 2,000 mg/kg III 001380 93 870.1300 Ac ute Inhalation Waived 870.2400 Ey e irritation Slight III 00138094 870.2500 Derm al irritation Slight III 00074304 870.2600 Dermal sensitization Waived
**Table 2.0. Acute Toxicological Values for Kinetin**  **Guideline Study**  **Results Category**  **MRID #** 870.1100 Ac ute Oral (rat) LD 50 > 5,000mg/kg IV 45500703 870.1200 Ac ute Dermal LD 50 > 5 ,000 mg/kg IV 45500704 870.1300 Ac ute Inhalation LC50 > 2.09 mg/L IV 45500705 870.2400 Ey e irritation mild III 45500706 870.2500 Derm al irritation Non
- irritating IV 45500707 870.2600 Dermal sensitization Not a contact sensitizer 45500708 Only the four naturally

occurring cy

tokinins, 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 long er) 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 s ynthetic cy tokinin because of low acute mammalian toxicity and very low us e rates (250 grams ai/A), which would not significantl y increase dietary intake over natural consumption in foods. The Agency, will be proposing an exemption from the requirement of a tolerance for certain cy tokinins (zeatin [6

- (4

- hydrox y - 3
- methylbut

- trans - 2
- en yl amino)

- purine], N 6 - methylaminopurine, N 6 - dimethylamino purine, N 6 - isopenten yl

- aminopurine), and s ynthetic cytokinin

-- kinetin [6

- (furfurylamino) purine] for all raw agricultural commodities (RACs). The exemption will apply onl y when application rates do not exceed 250 grams of active ingredient/acre/ye ar. The Agency believes this action does not present any unreasonable risk. It is based on cy tokinin'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 nat urally occurring or sy nthetic, are not expected. **Ecotoxicity** Ecological toxicity

studies on non

- targe t terrestrial and aquatic organisms were waived because available information shows that cy tokinin does not cause unreasonable adverse effects: 1) The pri ncipal constituents of cy tokinin, algae and seaweed, are natural components of fish diets; 2) Cy tokinin has a very

low acute mammalian toxicity ; 3) C yt okinin is used as a dietary supplementin animal feeds; 4) are expected to have no adverse effects to fis h 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 char acteristics of this product, it s non - toxic mode of action, low use volumes (< 2 g/A), and biodegradabilit y (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 Cy tokinin 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). Biol ogy of Plants. New York: Worth. pp. 545
- 572. Salisbury , F. B., and Ross, C. W. (1992). Plant Phy siology . Belmont, CA: Wadsworth. pp. 357

- 407, 531
- 548. USEPA 738
- R
- 95
- 025 Environmental Protection And Toxic Substances December 1995 Agency (7508W) Reregistrat ion Eligibility Decision ( RED )
.