1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Endpoint summary

Description of key information

Guideline-compliant studies of skin and eye irritation in the rabbit are supported by non-guideline studies.  These in vivo studies were performed prior to the validation and adoption of alternative methods.

Test Species/Type	Results	Assessment	Reference
Not stated -	Pencycuron was not a skin irritant.	Supporting study	Thyssen and Lorke (1980)
OECD 404 -	Pencycuron was not a skin irritant.	Key study	Maertins (1989)
Indian guideline - Does not conform to OECD 404	Pencycuron was not a skin irritant.	- no assessment at 48 hours, although a zero response at this timepoint could be assumed.  Result consistent with other studies.	Unknown. (2005)
Not stated (pre-dates OECD TG) -	Pencycuron was not an eye irritant.	Supporting study	Thyssen and Lorke (1980)
OECD 405 -	Pencycuron was not an eye irritant.	Key study	Maertins (1989)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980-03-30 to 1980-05-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was not performed in accordance with OECD 404, because the study report was very concise and essential information was lacking, such as: the test concentration was not indicated, the surface area exposed to the test substance was not indicated, it was unclear whether or not exposure was semi-occlusive, observation period. Therefore, the study could not be properly evaluated.

The study conformed to the recommended guidelines of the US Department of Agriculture (Federal Register, Vol.~' No. 187, p. 27019, 1973). The exposure period was 24 hours.

GLP compliance:

no

Remarks:

older study, predates mandatory GLP

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

not specified

Preparation of test site:

abraded

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

Not specified.

Duration of treatment / exposure:

24

Observation period:

72

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: Unspecified.
- % coverage: Unspecified.
- Type of wrap if used: Unspecified.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Unspecified.
- Time after start of exposure: Unspecified.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 24, 72

SCORING SYSTEM:
- Method of calculation: Fed. Reg. 34, 64, p. 6100)

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0.25

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Interpretation of results:

study cannot be used for classification

Conclusions:

The study is of limited reliability due to deficiencies in design and reporting, but can be used as supporting information. The study is consistent with the key (guideline-compliant) study in demonstrating that pencycuron is not a skin irritant.

Executive summary:

The skin irritation potential of pencycuron was investigated in a non-guideline study in the rabbit. The study is of limited reliability due to deficiencies in design and reporting, but can be used as supporting information. The study is consistent with the key (guideline-compliant) study in demonstrating that pencycuron is not a skin irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-03-14 to 1990-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

See Principles of method if other than guideline.

Principles of method if other than guideline:

The test methods were conducted in accordance with "OECD Guideline for Testing of Chemicals No. 404.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species and Species Justification
The study was performed using rabbits, an animal species recommended in the test guidelines. Healthy, adult albino rabbits (strain: HC:NZW) were used (bred by INTERFAUNA UK LTD.). The state of health of the breed was routinely tested for the most significant specific infective pathogens. If females were used, they were nulliparous and nonpregnant.

Experimental Animal Care
The rabbits were housed in individual cages under standardized conventional conditions (Type III wire cages, tall). Feces pans containing low-dust wood shavings (Type S 8/15; SSNIFF, in Soest, FRB) were located below the cages. These wood shavings were routinely analyzed for contaminants by the Central Office for Experimental Animal Concerns.
Identification of the Animals; The rabbits were identified by individual ear markings (tattooing) and cage I.D. cards.
Acclimatization; 1 day prior to application, the rabbits were examined to determine whether those scheduled for treatment were biologically normal. At least 14 days prior to treatment, the rabbits were clinically examined for diseases and acclimatized in the quarantine station. Shortly after arrival of the animals, feces samples were collected and examined for oocysts of coccidia.
Animal Quarters; All animals of this study were placed in one animal room. For reasons of capacity, rabbits treated with other test substances were also housed in the same animal room. Mix-ups with other animals were avoided by adequate spacing and separation, unambiguous cage and animal identification, and an appropriate scheduling of work.

Climatic Conditions in the Animal Room;
Conditions were adjusted as follows:
Room Temperature: 20° ± 3°C
Relative Humidity: approx. 50%
Light/Dark Cycle: 12 hours, artificial illumination from 6:00 a.m. to 6:00 p.m. MEZ [Middle European Time]
Illumination: approx. 27 watts/m^2 floor area
Air Exchange Rate: approx. 10 times per hour

The humidity and temperature in the animal quarters were recorded continuously using a calibrated thermohygrograph. There were occasional deviations from these conditions, e.g. as a result of the cleaning of the animal room. They had no detectable effect on the outcome of the study.

Cleaning. Disinfection, and Pest Control; All surface areas in the animal quarters were cleaned at least once per month and disinfected with Zephirol (1% in water); the floor in the animal quarters was cleaned and disinfected once per week. In so doing, contamination of the feed and contact with the experimental animals were avoided. No pest control was performed in the animal quarters. The water dispensers were cleaned once per week.

Diet;
Feed: standard diet (approx. 100 g to 120 g per animal per day; animals fed once per day in the morning).
Water: Tap water was available to the rabbits ad libitum between 7:00 a.m. and 7:00 p.m.
At the request of the Central Office for Experimental Animal Concerns, the nutrient composition and the contaminant content of the standard diet were checked routinely by taking random samples and analyzing them. These records are archived at the Central Office for Experimental Animal Concerns. The tap water was of drinking water quality (Drinking Water Ordinance dated May 22, 1986, Bundesqesetzblatt [Federal Law Bazettel, Part I, page 760). Results of the analyses of feed and water are archived at BAYER A6. These data provided no evidence of an effect on the study objective. Either approximately 750-ml polycarbonate bottles or automatic water dispensers were used to provide water.

Body Weights
The rabbits were weighed immediately prior to application of the test substance.

State of Health
Only healthy animals that were free of signs were used for the study. No vaccination or treatment of the animals with antibiotics was performed either prior to receipt of the animals or during the acclimatization period or the experimental period.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes

Amount / concentration applied:

6 cm2 of 500mg.

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: contralateral skin areas (approx. 6 x 6 cm) on the flanks
- % coverage: -
- Type of wrap if used: elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
1, 24, 48, and 72 hours, 7 days

SCORING SYSTEM:
- Method of calculation:
The test substance was classified by calculating a primary skin irritation index (see Appendix Ib) by averaging the DRAIZE scores for erythema/eschar formation and edema observed at 24, 48, and 72 hours.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Not relevant: no irritation observed

Other effects:

- Other adverse local effects: none.
- Other adverse systemic effects: none.

Interpretation of results:

GHS criteria not met

Conclusions:

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

Executive summary:

Pencycuron (NTN 19701 Technical) was tested for skin corrosion and irritation potential in the rabbit in a study performed to OECD 404. 0.5 g of the test material was applied to the shorn dorsal skin of three rabbits under semi-occlusive conditions for 4 hours. Residual test material was removed by washing with water. Dermal reactions were scored at 1, 24, 48 and 72 hours; and at 7 days following patch removal, using the Draize scale. No signs of irritation were seen in any rabbit at any time point. Pencycuron was found to be non-irritant under the conditions of this study and does not require classification under CLP for skin corrosion or skin irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980-03-30 to 1980-05-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was not performed in accordance with OECD 405, because the study report was very concise and essential information (e.g. test concentration) was not provided. The eyes were exposed for 5 minutes and 24 hours.

The study conformed to the recommended guidelines of the Department of Health, Education, and Welfare (Fed. Reg. Vol. 22,, No. 83 (1972), p. 8535). The following results were obtained with a 5-minute and a 24-hour period of exposure to the active ingredient in the conjunctival sac of rabbits' eyes (pages 4 - 5).

GLP compliance:

no

Remarks:

older study predates mandatory GLP

Species:

rabbit

Strain:

Chinchilla

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

Not specified.

Duration of treatment / exposure:

5 and 24

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

5 m = 5
24 h = 3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified.
- Time after start of exposure: Not specified.

SCORING SYSTEM: Fed. Reg. 22., 83 (1972), p. 8535

TOOL USED TO ASSESS SCORE: Not specified.

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24/48/72 h

Score:

< 0.15

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: 5 m exposure

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24/48/72 h

Score:

< 0.15

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: 24 h exposure

Irritant / corrosive response data:

Also includes 5 m, 1 h and 7 d timepoints.

Interpretation of results:

study cannot be used for classification

Conclusions:

The study is of limited reliability due to deficiencies in design and reporting, but can be used as supporting information. The study is consistent with the key (guideline-compliant) study in demonstrating that pencycuron is not an eye irritant.

Executive summary:

The eye irritation potential of pencycuron was investigated in a non-guideline study in the rabbit. The study is of limited reliability due to deficiencies in design and reporting, but can be used as supporting information. The study is consistent with the key (guideline-compliant) study in demonstrating that pencycuron is not an eye irritant.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-03-14 to 1990-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

See Principles of method if other than guideline.

Principles of method if other than guideline:

The study was conducted in accordance with "OECD Guideline for Testing of Chemicals No. 405.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species and Species Justification
The study was performed using rabbits, an animal species recommended in the test guidelines. Healthy, adult albino rabbits (strain: HC:NZW) were used (bred by INTERFAUNA UK LTD.). The state of health of the breed was routinely tested for the most significant specific infective pathogens. If females were used, they were nulliparous and nonpregnant.

Experimental Animal Care
The rabbits were housed in individual cages under standardized conventional conditions (Type III wire cages, tall). Feces pans containing low-dust wood shavings (Type S 8/15; SSNIFF, in Soest, FRB) were located below the cages. These wood shavings were routinely analyzed for contaminants by the Central Office for Experimental Animal Concerns.
Identification of the Animals; The rabbits were identified by individual ear markings (tattooing) and cage I.D. cards.
Acclimatization; 1 day prior to application, the rabbits were examined to determine whether those scheduled for treatment were biologically normal. At least 14 days prior to treatment, the rabbits were clinically examined for diseases and acclimatized in the quarantine station. Shortly after arrival of the animals, feces samples were collected and examined for oocysts of coccidia.
Animal Quarters; All animals of this study were placed in one animal room. For reasons of capacity, rabbits treated with other test substances were also housed in the same animal room. Mix-ups with other animals were avoided by adequate spacing and separation, unambiguous cage and animal identification, and an appropriate scheduling of work.

Climatic Conditions in the Animal Room;
Conditions were adjusted as follows:
Room Temperature: 20° ± 3°C
Relative Humidity: approx. 50%
Light/Dark Cycle: 12 hours, artificial illumination from 6:00 a.m. to 6:00 p.m. MEZ [Middle European Time]
Illumination: approx. 27 watts/m^2 floor area
Air Exchange Rate: approx. 10 times per hour

The humidity and temperature in the animal quarters were recorded continuously using a calibrated thermohygrograph. There were occasional deviations from these conditions, e.g. as a result of the cleaning of the animal room. They had no detectable effect on the outcome of the study.

Cleaning. Disinfection, and Pest Control; All surface areas in the animal quarters were cleaned at least once per month and disinfected with Zephirol (1% in water); the floor in the animal quarters was cleaned and disinfected once per week. In so doing, contamination of the feed and contact with the experimental animals were avoided. No pest control was performed in the animal quarters. The water dispensers were cleaned once per week.

Diet;
Feed: standard diet (approx. 100 g to 120 g per animal per day; animals fed once per day in the morning).
Water: Tap water was available to the rabbits ad libitum between 7:00 a.m. and 7:00 p.m.
At the request of the Central Office for Experimental Animal Concerns, the nutrient composition and the contaminant content of the standard diet were checked routinely by taking random samples and analyzing them. These records are archived at the Central Office for Experimental Animal Concerns. The tap water was of drinking water quality (Drinking Water Ordinance dated May 22, 1986, Bundesqesetzblatt [Federal Law Bazettel, Part I, page 760). Results of the analyses of feed and water are archived at BAYER A6. These data provided no evidence of an effect on the study objective. Either approximately 750-ml polycarbonate bottles or automatic water dispensers were used to provide water.

Body Weights
The rabbits were weighed immediately prior to application of the test substance.

State of Health
Only healthy animals that were free of signs were used for the study. No vaccination or treatment of the animals with antibiotics was performed either prior to receipt of the animals or during the acclimatization period or the experimental period.

Vehicle:

not specified

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 µl of test substance (bulk volume) were applied in the conjunctival sac of one eyelid of each of 3 adult rabbits. This is equivalent to an applied weight of about 50 mg of the test substance.

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 days

Duration of post- treatment incubation (in vitro):

Following application, the lids were gently held together for approximately 1 second.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological saline solution
- Time after start of exposure: 24 hours

SCORING SYSTEM:
In evaluating the results, only those findings which persisted for 24 hours or longer are used. The results were classified on the basis of the DRAIZE scores by calculating a primary eye irritation index for the cornea (degree of opacity) and iris as well as for the redness and swelling (chemosis) of the conjunctivae observed at approx. 24, 48 and 72 hours after application and averaging these scores.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Pencycuron was found to be non-irritant under the conditions of this study and does not require classification under CLP for serious eye damage or serious eye irritation.

Executive summary:

Pencycuron (NTN 19701 Technical) was tested for eye irritation potential in the rabbit in a study performed to OECD 405. 0.1 g of the test material was instilled into one eye of three rabbits. Ocular reactions were scored at 1, 24, 48 and 72 hours; and at 7 days following patch removal, using the Draize scale. No signs of irritation were seen in any rabbit at any time point. Pencycuron was found to be non-irritant under the conditions of this study and does not require classification under CLP for serious eye damage or serious eye irritation.

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

Studies in the rabbit show that pencycuron is not a skin irritant.

Studies in the rabbit show that pencycuron is not an eye irritant.

Pencycuron does not have a harmonised classification for skin or eye irritation.  The results of the available studies demonstrate that pencycuron does not require CLP classification for skin corrosion or skin irritation; for serious eye damage or serious eye irritation.