The RTU-L label directs that 1 day or more before treatment, soil covering buried 

galls should be removed. Any galls larger than a baseball should be largely 

removed by cutting. The EP is painted onto the galls, the cut surfaces (if 

applicable), and 1⁄2-inch of the surrounding healthy bark assuring thorough 

coverage. Retreatment is permitted in 4-6 months if live galls are found. If over 

half of the trunk is galled, any more than half may be treated in 4-6 months. The 

EP is only to be applied to inedible plant parts. Fruit and nuts are not to be used 

for food or feed. 

The literature reports that the acute oral toxicity LD50 of 2,4-xylenol was 3200 

mg/kg for rats and 809 mg/kg for mice (both Toxicity Category III). The dermal 

LD50 was reported as 1040 mg/kg in both rats and mice (Toxicity Category II). 

Skin irritation studies revealed that 2,4-xylenol was corrosive (Toxicity Category 

I) to rabbit skin (Sax and Lewis, 1989). An eye irritation study in rabbits using 

8.5% of each active ingredient found slight eye irritation, which was Toxicity 

Category II (MRID 00138519). A primary dermal irritation study of 2,4-xylenol 

and the RTU-L was conducted with rabbits. 2,4-Xylenol induced necrotic and 

corrosive effects (Toxicity Category I). The RTU-L, with or without m-cresol and 

2,4-xylenol did not cause skin irritation in rabbits and was Toxicity Category IV 

(MRID 00138520). A dermal sensitization study with guinea pigs demonstrated 

that the RTU-L caused sensitization (MRID 00138521). 

A 21-day dermal toxicity study was conducted using rabbits (MRID 00138520). 

The RTU-L (m-cresol and 2,4-xylenol each at 0.46% ai) was applied to abraded 

or intact skin at 1 or 2 ml/kg/day and compared to 2 ml/kg/day of the RTU-L blank 

(EP without the ai’s). After 21 days of dermal exposure, severe dermal damage 

to both abraded and intact skin resulted whether the RTU-L or the formulation 

blank was applied. Hyperplasia of regional lymph nodes and myeloid 

hyperplasia of the bone marrow also occurred. Note that dermal irritation did not 

result (Toxicity Category IV) from the short exposure to the RTU-L in the acute 

dermal toxicity study (MRID 00138520). As a result of the severe skin irritation in 

the 21-day dermal toxicity study testing the EP, a dermal toxicity study testing the 

TGAI was waived in the 1994 RED because it showed the EP was corrosive to 

skin. The acute and 21-day dermal toxicity studies, when taken together, 

indicate that the petroleum distillates in the RTU-L as diluent/solvent are largely 

or wholly responsible for the skin damage. 

The registered uses of 2,4-xylenol are not expected to result in dietary exposure 

or long-term occupational or residential exposure. Therefore, neither a chronic 

nor a cancer study is considered necessary. 

Dietary exposure to 2,4-xylenol residues is not likely to occur given the registered 

use pattern. Also, inhalation exposure of gall painters is not expected due to the 

formulation and application method, i.e., a solution applied by paint brush largely 

outdoors. Therefore, only dermal exposure of applicators could potentially occur. 

In the 1994 RED, a short-term exposure duration was considered to be the only 

likely gall-painting scenario. This is still expected. Given the low concentration 

of 2,4-xylenol in the RTU-L, the low unit exposure, and the lack of dermal 

2
corrosiveness of the petroleum distillate “inert ingredients,” the opportunity for 

human exposures conducive to triggering reproductive or developmental adverse 

effects is quite remote. Therefore, reproductive and developmental toxicity 

studies are not expected to be needed at this time. 

No studies are available to determine the potential mutagenicity of 2,4-xylenol 

and none are not expected to be needed at this time. 

2,4-Xylenol has no food uses registered under FIFRA or uses subject to 

regulation by the Food and Drug Administration (FDA). On 6/11/99, 2,4-xylenol 

was delisted as being “not approved for inert ingredient use, food or nonfood,” in 

a pesticide product (FR Vol. 64, No. 11, p. 31575). No tolerance or tolerance 

exemption has been established under FFDCA for 2,4-xylenol. Human dietary 

exposure to residues of 2,4-xylenol is not expected. Therefore, a dietary (food) 

risk assessment will not be necessary. 

Use of 2,4-Xylenol in the greenhouse is not expected to result in contamination of 

drinking water. Use in the field also is not expected to result in contamination of 

drinking water due to the use pattern and low volume of use. Thus, human 

dietary exposure to residues of 2,4-xylenol in drinking water is not expected. 

Therefore, a dietary (drinking water) risk assessment is not required. 

As the RTU-L label does not restrict use of the product to certified professional 

applicators and as the volume of the product container is 1⁄2 gallon, it is apparent 

that the EP may be purchased and used by residential applicators. Therefore, an 

assessment of residential applicator exposure and risk is appropriate. However, 

the assessment conducted in association with the 1994 RED is considered to 

remain protective of potential residential applicator exposures. Therefore, no 

residential risk assessments are expected to be needed for the 2,4-xylenol 

Registration Review. 

The only source of exposure contributing to aggregate risk to 2,4-xylenol is the 

residential adult applicator source. As noted above, the 1994 RED assessment 

is protective of aggregate exposure as well. 

Occupational exposure of applicators is possible via the dermal and inhalation 

routes during paint brush treatment of crown galls with the EP in fruit or nut 

orchards or ornamental plantings. Again, the occupational applicator 

assessment conducted in association with the 1994 RED remains protective of 

potential risks. Therefore, no occupational risk assessments are expected to be 

needed for the 2,4-xylenol Registration Review. Label instructions and the 

requirement that handlers wear certain personal protective equipment (PPE) are 

sufficient to protect workers from the localized, irritation effects of exposure to 

2,4-xylenol. 

The primary source of information for this assessment was the September, 1994 

RED. No new toxicity data for 2,4-xylenol have been submitted to the Agency 

since the RED was issued. The purpose of this scoping document is to 

3
determine whether sufficient data are available to support registration review, 

whether new human health assessments are needed to support registration 

review, and to report why the Agency feels it may be appropriate to conduct new 

risk assessments under the registration review process. 

Section 1. Chemical Identity 

Table 1.1 Chemical Identity 

Common Name 2,4-xylenol 

Chemical Name 2,4-dimethylphenol 

Empirical Formula C8H10O 

Molecular Weight 122.17 

PC Code 086804 

CAS Registry Number 105-67-9 

Registration Review Case No. 4098 

Chemical Structure: 

2,4-xylenol is a white, crystalline solid at room temperature with a phenolic odor. 

It melts at 26 °C and boils at 211 °C. It is slightly soluble in water at 25 °C (0.62 

g/100 ml), soluble in organic solvents, and freely soluble in ethanol, chloroform, 

diethyl ether, and benzene. The dissociation constant, pKa, is 10.63. The vapor 

pressure is 0.2 mmHg at 25 °C. 2,4-xylenol has an octanol/water partition 

coefficient, pKo/w, of 2.35. The specific gravity at 20 °C is 0.97 g/ml. 

Section 2. Toxicology 

The toxicity database for 2,4-xylenol, although minimal, is sufficient to permit the 

Agency to conduct a hazard characterization for this Registration Review. No 

additional toxicity data are expected to be needed at this time based on the 2,4-

xylenol volume of use and registered use pattern. 

Acute Toxicity

The literature reports that the acute oral toxicity LD50 of 2,4-xylenol was 3200 

mg/kg for rats and 809 mg/kg for mice (both Toxicity Category III). The dermal 

LD50 was reported as 1040 mg/kg in both rats and mice (Toxicity Category II). 

Skin irritation studies revealed that 2,4-xylenol was corrosive (Toxicity Category 

I) to rabbit skin (Sax and Lewis, 1989). An eye irritation study in rabbits using 

8.5% of each active ingredient found slight eye irritation, which was Toxicity 

4
Category II (MRID 00138519). A primary dermal irritation study of 2,4-xylenol 

and the RTU-L was conducted with rabbits. 2,4-Xylenol induced necrotic and 

corrosive effects (Toxicity Category I). The RTU-L, with or without m-cresol and 

2,4-xylenol, did not cause skin irritation in rabbits and was Toxicity Category IV 

(MRID 00138520). A dermal sensitization study with guinea pigs demonstrated 

that the RTU-L caused sensitization (MRID 00138521). 

Subchronic Toxicity

A 21-day dermal toxicity study was conducted using rabbits (MRID 00138520). 

The RTU-L (m-cresol and 2,4-xylenol each at 0.46% ai) was applied to abraded 

or intact skin at 1 or 2 ml/kg/day and compared to 2 ml/kg/day of the RTU-L blank 

(EP without the ai’s). After 21 days of dermal exposure, severe dermal damage 

to both abraded and intact skin resulted whether the RTU-L or the formulation 

blank was applied. Hyperplasia of regional lymph nodes and myeloid 

hyperplasia of the bone marrow also occurred. Note that dermal irritation did not 

result (Toxicity Category IV) from the short exposure to the RTU-L in the acute 

dermal toxicity study (MRID 00138520). As a result of the severe skin irritation in 

the 21-day dermal toxicity study testing the EP, a dermal toxicity study testing the 

TGAI was waived in the 1994 RED because it showed the EP was corrosive to 

skin. The acute and 21-day dermal toxicity studies, when taken together, 

indicate that the petroleum distillates in the RTU-L as diluent/solvent are largely 

or wholly responsible for the skin damage. 

Chronic/Carcinogenicity

The registered uses of 2,4-xylenol are not expected to result in dietary exposure 

or long-term occupational or residential exposure. Therefore, neither a chronic 

nor a cancer study is considered necessary. Accordingly, risk assessments are 

not expected to be needed for dietary exposure or for long-term occupational or 

residential exposures regardless of exposure route. 

Reproductive and Developmental Toxicity

Dietary exposure to 2,4-xylenol residues is not likely to occur given the registered 

use pattern. Also, inhalation exposure of gall painters is not expected due to the 

formulation and application method, i.e., a solution applied by paint brush largely 

outdoors. Therefore, only dermal exposure of applicators could potentially occur. 

In the 1994 RED, a short-term exposure duration was considered to be the only 

likely gall-painting scenario. This is still expected. Given the low concentration 

of 2,4-xylenol in the RTU-L, the low unit exposure, and the lack of dermal 

corrosiveness of the petroleum distillate “inert ingredients,” the opportunity for 

human exposures conducive to triggering reproductive or developmental adverse 

effects is quite remote. Therefore, reproductive and developmental toxicity 

studies are not expected to be needed at this time. 

5
Mutagenicity

No studies are available to determine the potential mutagenicity of 2,4-xylenol 

and none are not expected to be needed at this time. 

Section 3. Dietary Exposure 

Food Exposure

2,4-Xylenol has no food uses registered under FIFRA or uses subject to 

regulation by the Food and Drug Administration (FDA). No tolerance or tolerance 

exemption has been established under FFDCA for 2,4-xylenol. Human dietary 

exposure to residues of 2,4-xylenol is not expected due to its low concentration in 

the RTU-L, the low treatment rate, the base-of-trunk/directed treatment, and the 

label restriction against using fruit or nuts for food or feed. Therefore, a dietary 

(food) risk assessment will not be necessary. 

Drinking Water Exposure

Use of 2,4-xylenol in the greenhouse is not expected to result in contamination of 

drinking water. Use in the field also is not expected to result in contamination of 

drinking water due to the use pattern and low volume of use. Thus, human 

dietary exposure to residues of 2,4-xylenol in drinking water is not expected. 

Therefore, a dietary (drinking water) risk assessment is not required. 

Section 4. Residential Exposure

As the RTU-L label does not restrict use of the product to certified professional 

applicators and as the volume of the product container is 1⁄2 gallon, it is apparent 

that the EP may be purchased and used by residential applicators. Therefore, an 

assessment of residential applicator exposure and risk is appropriate. However, 

the assessment conducted in association with the 1994 RED is considered to 

remain protective of potential residential applicator exposures. Therefore, no 

residential risk assessments are expected to be needed for the 2,4-xylenol 

Registration Review. 

Section 5. Aggregate Risk 

The only source of exposure contributing to aggregate risk to 2,4-xylenol is the 

residential adult applicator source. As noted above, the 1994 RED assessment 

is protective of aggregate exposure as well. 

6
Section 6. Occupational Exposure 

Occupational exposure of applicators is possible during paint brush treatment of 

crown galls with the RTU-L in fruit or nut orchards or ornamental plantings. The 

occupational applicator assessment conducted in association with the 1994 RED 

remains protective of potential risks. Therefore, no occupational risk 

assessments are expected to be needed for the 2,4-xylenol Registration Review. 

Label instructions and the requirement that handlers wear certain personal 

protective equipment (PPE) are sufficient to protect workers from the localized, 

irritation effects of exposure to the EP. 

Section 7. Human Incident Reports

No 2,4-xylenol-specific incidents have been reported in the OPP incident 

database. Low-molecular-weight phenols such as 2,4-xylenol have been 

reported as being contact sensitizers (Bruze, M. and Zimerson, E. 1997. Crossreaction patterns in patients with contact allergy to simple methylol phenols. 

Contact Dermatitis. Aug. 37(2):82-6. This report is supported by a dermal 

sensitization study in which the RTU-L was found to be a sensitizer. 

Section 8. Cumulative Risk 

EPA does not have, at this time, available data to determine whether 2,4-xylenol 

has a common mechanism of toxicity with other substances or how to include 

this pesticide in a cumulative risk assessment. For the purposes of this 

Registration Review, EPA has assumed that 2,4-xylenol does not have a 

common mechanism of toxicity with other substances. 

Section 9. Endocrine Disruption 

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. 

7
8

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. 

2,4-Xylenol is not among the group of 58 pesticide active ingredients on the initial 

list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must 

screen all pesticide chemicals. Accordingly, EPA anticipates issuing future 

EDSP test orders/data call-ins for all pesticide active ingredients. 

For 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, 

please visit our website: http://www.epa.gov/endo/. 

Section 10. Overall Conclusions 

The Agency has screened the hazard and exposure databases for 2,4-xylenol 

and does not anticipate that additional toxicity or exposure data will be needed 

for registration review. In addition, the Agency does not expect that additional 

human health risk assessments will be needed to complete the 2,4-xylenol 

Registration Review.