2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-03-27 to 2002-04-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

1

Reference substance name:

2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

EC Number:

264-980-3

EC Name:

2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

Cas Number:

64628-44-0

Molecular formula:

C15H10ClF3N2O3

IUPAC Name:

3-(2-chlorobenzoyl)-1-[4-(trifluoromethoxy)phenyl]urea

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female (nulliparous and nonpregnant) Wistar Hanover (Crl: WI[Glx/BRL/HAN]GS BR) rats from Charles River Laboratories, Inc., (Raleigh, NC) were used in this study. These animals were approximately 11 weeks of age when treatment was administered.
Feed and Water. Feed (PMI Certified Rodent Diet 5002 in "meal" form, St. Louis, MO) and tap water (Kansas City Missouri municipal water, dispensed by automatic watering system) were provided continuously for ad libitum consumption during the acclimation period and throughout the study. Feed and water were periodically sampled and analyzed for a variety of potential impurities. The results of these analyses were unremarkable. Contaminant concentrations outlined in the Certification Profile for Purina Mills Certified Lab Chows (PMI Nutrition International, 1998) were used as a general standard by which to gauge acceptable levels of contaminants in the feed.

Examination and Acclimation. Upon receipt, animals were examined. No animals were sacrificed due to general appearance and/or abnormal behavior. Those animals considered acceptable were then placed into individual cages and acclimated to their ambient laboratory conditions (set for a temperature of 19-25ºC, relative humidity 30-70%, 12-hr light/dark cycles, 12 air changes /hour) for seven days prior to placement on the study. For the holding period, animal care personnel observed the animals at least once daily for moribundity and mortality.

Care and Housing. While on study, rats were individually housed in suspended stainless steel cages. The cages and cage racks were thoroughly cleaned and disinfected before arrival of the animals. Deotized Animal Cage Board was used in the bedding trays and changed at least two times weekly. The cages, feeders and racks were replaced at least once every two weeks with clean, disinfected equipment. The room was disinfected at least once every two weeks.

Randomization. Randomization by weight stratification utilized software from INSTEM Computer Systems (Stone, Staffordshire, UK). Following seven days of acclimation, animals were weighed. All animals placed on study were within 20% of the mean of all available animals.
These animals were randomly assigned to a control group, or to a single dose group (per sex) in order that, groups had equivalent body weights when treatment was initiated.

Administration / exposure

Type of coverage:

semiocclusive

Details on dermal exposure:

The dermal route of exposure was employed in general accordance with the test guidelines for an acute limit test dermal toxicity study, based on this being a possible route of human exposure.
The hair from the scapulae (shoulders) to the wing of the ileum (hipbone) and half-way down the flank on each side of the animal was removed using Oster electric clippers equipped with a number 40 blade. Animals were clipped approximately 24 hours before the first dose was administered and as necessary thereafter, depending on hair growth. Care was taken during clipping to avoid abrading the skin. The dose site was distinguished from the surrounding untreated skin by marking with a felt-tip marker. Animals were treated with the test material Triflumuron as received (neat), administered as a single dose for a duration of 24 hours. Dose amounts (mg/kg body weight) were based on individual body weight measurements determined on day 0. The appropriate quantity of dose was moistened with 25ul of deionized water and applied directly onto an area of the back of the animal, representing approximately 10% of it’s total surface areab. A two-ply gauze pad with plastic backing was applied over the treatment site and secured with hypoallergenic tape. The gauze was further secured with Vetrap© (Animal Care Products/3M, St. Paul, MN) bandage, which was also secured with tape.

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw/day

No. of animals per sex per dose:

6

Control animals:

yes, concurrent no treatment

Details on study design:

All animals were fitted with Elizabethan collars (EJAY International, Glendora, CA), which served to reduce animal access to the dose site and thereby reduce ingestion of the test substance, and returned to their cages.
After approximately 24 hours post-dosing (minimum), the bandages and gauze were removed and the dose site was wiped using paper towels dampened with tap water to remove as much of the residual test substance as feasible without damaging the skin. Animals were sacrificed 14 days after dosing. Both controls and treated rats were treated in an identical manner with the exception that the control group did not receive test substance.
Clinical Signs, Body Weights. Cage-side observations were conducted at least once daily for mortality or moribundity. No animals were sacrificed due to moribundity. Detailed physical examinations for clinical signs were carried out twice daily on three days (0, 1 and 2) and once daily for the remaining portion of the in-life phase of the study. These examinations were performed at approximately the same time each day. Body weights were determined on day 0, and on days 7 and 14.
Gross Pathology. Animals were sacrificed by CO2 asphyxiation and subjected to a gross necropsy examination.

Statistics:

Descriptive statistics were generated by Datatox software (Stone, Staffordshire, UK).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

no mortality occurred.

Clinical signs:

other: other: Lacrimal and nasal staining, in the form of red discharge, in control and the 5000 mg/kg dose groups, were attributed to the animals wearing Elizabethan collars, which interfere with normal rodent preening, and were not considered to be compound-re

Gross pathology:

There were no gross observational findings at necropsy. No evidence of systemic toxicity was found.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The  acute dermal LD50 of triflumuron was found to be >5000 mg/kg bw under the conditions of this study.

Executive summary:

Triflumuron technical formulated in deionized water was administered to 6 fasted male and female CD-1 rats by single gavage at 5000 mg/kg bw/day. Control animals were treated with deionized water only (10 mL/kg bw). Rats were observed for 14 days. The administration of triflumuron technical did not elicit any mortality or treatment-related findings in clinical signs, body weight and macroscopic pathology. The acute dermal LD₅₀ of triflumuron technical was found to be >5000 mg/kg bw under the conditions of this study.