The RTU-L label directs that 1 day or mo re before treatment, soil covering buried galls should be removed. Any galls la rger 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 surr ounding healthy bark assuring thorough coverage. Retreatment is pe rmitted in 4-6 months if live galls are found. If over half of the trunk is galled, any more t han 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 LD 50 of 2,4-xylenol was 3200 mg/kg for rats and 809 mg/kg for mice (both Toxicity Category III). The dermal

LD 50 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 slig ht eye irritation, which was Toxicity Category II (MRID 00138519). A primary der mal 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 st udy with guinea pigs demonstrated

that the RTU-L caused s ensitization (MRID 00138521).

A 21-day dermal toxicity study was c onducted using rabbits (MRID 00138520). The RTU-L (m-cresol and 2,4-xylenol eac h at 0.46% ai) was applied to abraded or intact skin at 1 or 2 ml/kg/day and co mpared 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 wh ether 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 re sult of the severe skin irritation in the 21-day dermal toxicity study testing t he 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 ex posure. 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 so lution applied by paint brush largely outdoors. Therefore, only dermal exposure of applicators could potentially occur. In the 1994 RED, a short-term exposure dur ation was considered to be the only likely gall-painting scenario. This is st ill expected. Given the low concentration of 2,4-xylenol in the RTU-L, the lo w unit exposure, and the lack of dermal

2corrosiveness 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 t he potential mutagenicity of 2,4-xylenol and none are not expected to be needed at this time.

2,4-Xylenol has no food uses register ed under FIFRA or uses subject to regulation by the Food and Dr ug Administration (FDA). On 6/11/99, 2,4-xylenol was delisted as being “not approved for i nert ingredient use, food or nonfood,” in a pesticide product (FR Vol. 64, No. 11, p. 31575). No tolerance or tolerance exemption has been establis hed under FFDCA for 2,4-xy lenol. Human dietary exposure to residues of 2,4-xylenol is not expected. Therefor e, a dietary (food) risk assessment will not be necessary.

Use of 2,4-Xylenol in the gr eenhouse is not expected to re sult 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-xyle nol in drinking water is not expected. Therefore, a dietary (d rinking water) risk assessment is not required.

As the RTU-L label does not restrict us e of the product to ce rtified 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 re sidential applicators. Therefore, an assessment of residential applicator expos ure and risk is appropriate. However,

the assessment conducted in associati on with the 1994 RED is considered to remain protective of potential residentia l applicator exposure s. Therefore, no residential risk assessments are expect ed 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 cr own galls with the EP in fruit or nut orchards or ornamental plantings. Again, the occupational applicator

assessment conducted in association wit h the 1994 RED remains protective of potential risks. Therefore, no occupat ional 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 loca lized, irritation effe cts of exposure to 2,4-xylenol.

The primary source of information for th is assessment was the September, 1994 RED. No new toxicity data for 2,4-xy lenol have been submitted to the Agency since the RED was issued. The purpos e of this scoping document is to

3determine whether sufficient data are ava ilable to support registration review,

whether new human health assessment s are needed to support registration review, and to report why the Agency f eels 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 C 8 H 10 O 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, cr ystalline solid at room tem perature with a phenolic odor.

It melts at 26 °C and boils at 211 °C. It is slightly solubl e in water at 25 °C (0.62 g/100 ml), soluble in organic solvents, and freely soluble in ethanol, chloroform, diethyl ether, and benzene. T he dissociation constant, pK a , is 10.63. The vapor pressure is 0.2 mmHg at 25 °C. 2,4- xylenol has an octanol/water partition coefficient, pK o/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, althou gh minimal, is suffi cient to permit the Agency to conduct a hazard characterizati on 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 LD 50 of 2,4-xylenol was 3200 mg/kg for rats and 809 mg/kg for mice (bot h Toxicity Category III). The dermal

LD 50 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 slig ht eye irritation, which was Toxicity

4Category II (MRID 00138519). A primary der mal 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 st udy with guinea pigs demonstrated

that the RTU-L caused s ensitization (MRID 00138521).

Subchronic Toxicity

A 21-day dermal toxicity study was c onducted using rabbits (MRID 00138520). The RTU-L (m-cresol and 2,4-xylenol eac h at 0.46% ai) was applied to abraded or intact skin at 1 or 2 ml/kg/day and co mpared 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 wh ether 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 re sult of the severe skin irritation in the 21-day dermal toxicity study testing t he 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 ex posure. Therefore, neither a chronic nor a cancer study is considered nece ssary. Accordingly, risk assessments are not expected to be needed for dietary exposu re 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 so lution applied by paint brush largely outdoors. Therefore, only dermal exposure of applicators could potentially occur. In the 1994 RED, a short-term exposure dur ation 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 lo w 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.

5Mutagenicity

No studies are available to determine t he 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 register ed under FIFRA or uses subject to regulation by the Food and Drug Administration (FDA). No tolerance or tolerance exemption has been establis hed under FFDCA for 2,4-xy lenol. 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 f eed. Therefore, a dietary (food) risk assessment will not be necessary.

Drinking Water Exposure

Use of 2,4-xylenol in the gr eenhouse is not expected to re sult 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-xyle nol in drinking water is not expected. Therefore, a dietary (d rinking water) risk assessment is not required.

Section 4. Residential Exposure

As the RTU-L label does not restrict us e of the product to ce rtified professional applicators and as the volume of the produc t container is 1⁄2 gallon, it is apparent that the EP may be purchased and used by re sidential applicators. Therefore, an assessment of residential applicator expos ure and risk is appropriate. However,

the assessment conducted in associati on with the 1994 RED is considered to remain protective of potential residentia l applicator exposures. Therefore, no residential risk assessments are expect ed 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.

6Section 6. Occupational Exposure

Occupational exposure of applicators is pos sible during paint br ush 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 ris ks. Therefore, no occupational risk assessments are expected to be needed for t he 2,4-xylenol Registration Review. Label instructions and the requirement that handlers wear certain personal protective equipment (PPE) ar e sufficient to protect work ers from the localized, irritation effects of exposure to the EP.

Section 7. Human Incident Reports

No 2,4-xylenol-specific incidents ha ve been reported in the OPP incident database. Low-molecular-weight phenols such as 2,4-xylenol have been reported as being contact sensitizers (Bru ze, 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 RT U-L was found to be a sensitizer.

Section 8. Cumulative Risk

EPA does not have, at this time, availabl e 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 a ssessment. 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 Admi nistrator may designate.” The EDSP employs a two-tiered approach to making t he statutorily requi red 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 det ermine 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.

78 Between October 2009 and February 2010, EPA i ssued test orders/data call-ins for the first group of 67 chem icals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pat hways such as food and water, residential activity, and certain post-applicat ion agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

2,4-Xylenol is not among t he 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. Accord ingly, EPA anticipates issuing future

EDSP test orders/data call-ins for a ll 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 t he Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/.

Section 10. Over all Conclusions

The Agency has screened the hazard and ex posure databases for 2,4-xylenol and does not anticipate that additional to xicity or exposure data will be needed for registration review. In addition, the Agency does not expect that additional

human health risk assessment s will be needed to comple te the 2,4-xylenol Registration Review.