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

Endpoint summary

Description of key information

In vitro data are not available; in vivo data predate the adoption of validated in vitro methods.

The key studies for irritation endpoints are as follows:

Skin irritation (OECD 404, GLP, RL1): not irritating (M-075928-02-1, Merkel, 2002)

Eye irritation (OECD 405, GLP, RL1): not irritating (M-075936-01-1, Merkel, 2002)

The supporting studies for irritation endpoints are as follows:

Skin irritation (no guideline, non-GLP, RL2): not irritating (M-087278-01-1, Flucke, 1977)

Eye irritation (no guideline, non-GLP, RL2): not irritating (M-087278-01-1, Flucke, 1977)

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 16 2002 - April 19 2002.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Age: Young adult.

Source: Received from Davidson’s Mill Farm, South Brunswick, NJ on April 4, 2002.

Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.

Animal Room Temperature Range: 19-23°C

Photoperiod: 12 hour light/dark cycle

Acclimation Period: 12 days

Food: Pelleted Purina Rabbit Chow #5326

Water: Filtered tap water was supplied ad-libitum by automatic water dispensing system.

Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

Five-tenths of a gram of the test substance (0.71 g of the test mixture) was placed on a 1 inch x 1 inch, 4-ply gauze pad and applied to one 6 cm^2 intact dose site on each animal.

Duration of treatment / exposure:

4 hours.

Number of animals:

3 rabbits (2 females, 1 male).

Details on study design:

Preparation and Selection of Animals:
On the day before application, a group of animals was prepared by clipping (Oster model #A5-small) the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Only healthy animals without preexisting skin irritation were selected for the test.

Application of Test Substance:
Prior to application, the test substance was moistened with distilled water to achieve a dry paste by preparing a 70% w/w mixture. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3 inch Micropore tape, to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit, and they were returned to their designated cages. After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites gently wiped with water and a clean towel to remove any residual test substance.

Evaluation of Test Sites:
Individual dose sites were scored according to the Draize scoring system at approximately 1, 24, 48 and 72 hours after patch removal. The classification of irritancy was obtained by adding the average erythema and edema scores for the 1, 24, 48 and 72 hour scoring intervals and dividing by the number of evaluation intervals (4). The resulting Primary Dermal Irritation Index (PDII) was classified as follows: 0, Non-irritating, > 0 - 2.0, Slightly irritating, 2.1 - 5.0 Moderately irritating, > 5.0 Severely irritating.

Cage-Side Observations:
The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

Edema

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

Erythema

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Triflumuron was found to be non-irritant under the conditions of this study and does not require classification for skin corrosion or irritation according to the CLP criteria.

Executive summary:

Triflumuron (0.5 g) was applied to the shorn intact skin of 3 rabbits using a 70% (w/w) mixture (test substance/distilled water). The contact period was 4 hours; dermal reactions were scored for up to 72 hours.  No signs of dermal irritation were seen in any rabbit at any time point. Triflumuron was therefore found to be non-irritant under the conditions of this study and does not require classification for skin corrosion or irritation according to the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 24 2002 - April 27 2002.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Age: Young adult

Source: Received from Davidson’s Mill Farm, South Brunswick, NJ on April 19, 2002.

Housing: The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.

Photoperiod: 12 hour light/dark cycle.

Acclimation Period: 5 days.

Food: Pelleted Purina Rabbit Chow #5326

Water: Filtered tap water was supplied ad libitum by automatic water dispensing system.

Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study.

Vehicle:

physiological saline

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A volume of one-tenth of a milliliter (0.08-0.10 g) of the test substance, as received, was instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball.

Duration of treatment / exposure:

Not applicable: treated eyes were not rinsed after exposure

Observation period (in vivo):

1, 24, 48 and 72 hours post-instillation

Number of animals or in vitro replicates:

3 (2 males and 1 female)

Details on study design:

Preparation and selection of animals: Prior to instillation, both eyes of a number of animals were examined using a fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCl) approximately 30 seconds after instillation of the fluorescein. Using a Spectroline® Lamp (compact 4-watt UV Lamp), the eyes were checked for gross abnormalities according to the "Scale for Scoring Ocular Lesions". Only healthy animals without preexisting ocular irritation were selected for test.


Ocular scoring: Ocular irritation was evaluated using a high-intensity white light (Mag Lite) in accordance with the Draize method. The fluorescein dye evaluation procedure was used at 24 hours to verify the absence of corneal damage. In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were noted.

Cage-Side Observations: The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The incidence, severity and reversibility of irritation are detailed below (Table 1 and 2).

Other effects:

All animals appeared active and healthy. Apart from the eye irritation noted below, there were no other signs of gross toxicity.

Table 1: Time post instillation and incidence of irritation (corneal opacity, iritis, conjunctivitis).

Time Post Instillation	Corneal Opacity	Iritis	Conjunctivitis
1 hour	0/3	0/3	3/3 (score 1 each)
24 hours	0/3	0/3	1/3 (score 1)
48 hours	0/3	0/3	0/3
72 hours	0/3	0/3	0/3

 

Table 2: Time post instillation and severity of irritation- mean score. 

Time Post Instillation	Severity of Irritation – Mean Score
1 hour	4
24 hours	0.7
48 hours	0
72 hours	0

Interpretation of results:

GHS criteria not met

Conclusions:

Triflumuron was found to be a minimal and reversible eye irritant under the conditions of this study and does not require classification for eye irritation according to the CLP criteria.

Executive summary:

A primary eye irritation test was conducted with New Zealand albino rabbits to determine the potential for triflumuron to produce irritation from a single instillation via the ocular route. Under the conditions of this study, the test substance is classified as minimally irritating to the eye. A volume of one-tenth of a milliliter (0.08-0.10 g) of the test substance, as received, was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize.  No corneal opacity or iritis was observed during the study. One hour following instillation, all three treated eyes exhibited conjunctivitis. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 48 hours.  Triflumuron was found to be a minimal and reversible eye irritant under the conditions of this study and does not require classification for eye irritation according to the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No dermal reactions were seen in any rabbit at any timepoint in a study of skin irritation. No ocular reactions were seen in any rabbit at any timepoint in a study of eye irritation. There were no clinical signs in an acute inhalation toxicity study, indicating a lack of respiratory irritation. Therefore, triflumuron does not meet the criteria for classification for skin and eye irritation/corrosion according to Regulation (EC) No. 1272/2008.