Fluometuron

Endpoint summary

Description of key information

1. Skin irritation (one single dose) study acute dermal irritation (semi-occlusive), rabbit m/f, EPA FIFRA, Subdivision F, §81-5 (1984) 
     = EEC B.4 (1992): mean skin score < 2
2. Eye irritation (one single dose) study acute eye irritation (singular ocular instillation), rabbit, EPA FIFRA, Subdivision F, §81-4 (1984) 
     = EEC B.5 (1992): mean irritancy score (24, 72 hours) ≤ 0.3

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:

25 to 28 July 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study The experiments were done according to the EPA FIFRA, Subdivision F, §81-5 (1984) = EEC B.4 (1992). USA TSCA, Section HG ‘Primary Dermal Irritation’

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- group of six New Zealand white rabbits (five males/ one female)
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- weight: 2.42 - 3.38 kg
- age:twelve to sixteen weeks old
- free access to mains drinking water and food
- animal room temperature: 17 - 22°C

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

distilled

Controls:

no

Amount / concentration applied:

singl dermal doses: 0.5 g, semi-occluded application of test material, moistened with distilled water

Duration of treatment / exposure:

4 hours

Observation period:

Approximately one hour following the removal of the patches, and 24, 48, and 72 hours later

Number of animals:

six

Details on study design:

PROCEDURE
Approximately twenty-four hours prior to the commencement of the test, each group of six rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of a 0.5g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position by a strip of surgical adhesive tape (BLENDERM: approximate size patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period of four hours.
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
Approximately one hour following the removal of the patches, and 24, 48, and 72 hours later, the test sites were examined for evidence of primary irritation and score according the scale i.e. Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin Texas, "The Appraisal of the safety of the Chemicals in Foods, Drugs and Cosmetics".

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1, 24 h

Score:

0.2

Max. score:

0.2

Reversibility:

no data

Remarks on result:

other: primary irritation index: 0.08

Irritant / corrosive response data:

A very slight erythema was noted in one animal at one and 24 hours after patch removal. No other adverse affects were noted see Table 7.3.1.-01

Table 7.3.1.-01: Individual and mean skin irritation scores

Animal No.	Erythema and Eschar (E) Oedema (O)	Hours
		1	24	48	72
140	E O	0 0	0 0	0 0	0 0
144	E O	0 0	0 0	0 0	0 0
148	E O	1 0	1 0	0 0	0 0
161	E O	0 0	0 0	0 0	0 0
174	E O	0 0	0 0	0 0	0 0
180	E O	0 0	0 0	0 0	0 0
Mean score	E O	- -	0.2 0	0 0	0 0

Interpretation of results:

not classified

Remarks:

Migrated information in accordance with the provisions of regulation 1272/2008 Criteria used for interpretation of results: EU

Conclusions:

In this study the mean skin scores for 24 to 72 hours after removal of the test article were < 2, therefore, in accordance with the provisions of regulation 1272/2008, Annex I, 3.2 , it is proposed fluometuron is not classified as a skin irritant.

Executive summary:

1. A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The study was designed to comply with the requirements of the U.S.A. Environmental Protection Agency (EPA).

 

2. A single 4-hour. semi-occluded application of the test material to the skin of six rabbits produced very slight erythema at one treated skin site, No other adverse skin responses were noted

 

3. The test material produced a primary irritation index of 0.08 and was classified as a mild irritant to rabbit skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

31 July to 04 August 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study The experiments were done according to the EPA FIFRA, Subdivision F, §81-4 (1984) = EEC B.5 (1992). USA TSCA, Section HG ‘Primary Eye Irritation’

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- group of six New Zealand white rabbits
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- weight: 2.54 - 3.09 kg
- age:twelve to sixteen weeks old
- free access to mains drinking water and food
- animal room temperature: 16 - 22°C

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1ml of the test material fluometuron, purity 96.8%

Duration of treatment / exposure:

1, 24, 48, 72 hour

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

six

Details on study design:

Six New Zealand White rabbits each received 0.1ml of the test material (as measured by gently compacting the required volume into an adapted syringe) by a singular ocular instillation without irrigation to the lower everted lid of one eye of each animal. The upper and lower eyelids were held together for about one second immediatly after application, to prevent loss of the test material, and then released.
The left eye remained untreated and was used for control purposes.
Assessment of damage/irritation was made 1, 24, 48 and 72 hours following treeatment. Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

SCORING SYSTEM: Draize

Irritation parameter:

other: maximum group mean score

Basis:

mean

Time point:

other: 1, 24, 48, 72 h

Score:

0 - 4

Max. score:

4

Remarks on result:

other: mean irritancy score for the 24 and 72 hours was 0-0.3

Irritation parameter:

overall irritation score

Remarks:

mean irritancy score

Basis:

mean

Time point:

other: 24,72 hours

Score:

>= 0 - <= 3

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: no adverse effects were noted at the 72-hour observation and the study was terminated

Irritant / corrosive response data:

No adverse corneal or iridial effects were noted during the study period.
Minimal conjunctival irritation was noted in all rabbits one hour after treatment and in two treated eyes after 24 hours. No other adverse conjunctival effects were noted see Table 7.3.2.-01

Other effects:

no other effects were recognized

Table 7.3.2.-01: Individual and mean eye irritation scores

 

 

Animal No.	Region of eye	Hours
		1	24	48	72
189	Cornea – degree of opacity area of opacity                        Iris Conjunctiva – redness chemosis discharge	0 0   0 1 1 1	0 0   0 1 0 0	0 0   0 0 0 0	0 0   0 0 0 0
207	Cornea – degree of opacity area of opacity                        Iris Conjunctiva – redness chemosis discharge	0 0   0 1 1 1	0 0   0 0 0 0	0 0   0 0 0 0	0 0   0 0 0 0
168	Cornea – degree of opacity area of opacity                        Iris Conjunctiva – redness chemosis discharge	0 0   0 1 0 0	0 0   0 0 0 0	0 0   0 0 0 0	0 0   0 0 0 0
146	Cornea – degree of opacity area of opacity                        Iris Conjunctiva – redness chemosis discharge	0 0   0 1 0 0	0 0   0 0 0 0	0 0   0 0 0 0	0 0   0 0 0 0
206	Cornea – degree of opacity area of opacity                        Iris Conjunctiva – redness chemosis discharge	0 0   0 1 1 1	0 0   0 0 0 0	0 0   0 0 0 0	0 0   0 0 0 0
182	Cornea – degree of opacity area of opacity                        Iris Conjunctiva – redness chemosis discharge	0 0   0 1 0 0	0 0   0 1 0 0	0 0   0 0 0 0	0 0   0 0 0 0
Mean score	Cornea – degree of opacity area of opacity                        Iris Conjunctiva – redness chemosis discharge	0 0   0 1 0.5 0.5	0 0   0 0.3 0 0	0 0   0 0 0 0	0 0   0 0 0 0

 

Interpretation of results:

not classified

Remarks:

Migrated information According to the provisions of regulation 1272/2008 Criteria used for interpretation of results: EU

Conclusions:

In this study the mean irritancy score for the 24 and 72 hours was 0-0.3. Therefore, fluometuron was only minimally and transiently irritating to the rabbit eye.In accordance with the provisions of regulation 1272/2008, Annex I, 3.3, it is proposed classification is not required. It is proposed fluometuron technical it is not classified as an eye irritant.

Executive summary:

1. A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The study was designed to comply with the requirements of the U.S.A. Environmental Protection Agency (EPA).

 

2. A single application of the test material to the non-irrigated eye of six rabbits produced minimal conjunctival irritation in all treated eyes. No other adverse effects were noted.

 

3. The test material produced a maximum group mean score of 4.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Fluometuron was not irritating to rabbit skin and induced only very slight signs of transient conjunctival irritation one hour after instillation to the eye of rabbits:

A single 4-hour-semi-occluded application of the test material to the skin of six rabbits produced very slight erythema at one treated skin site. A single application of the test material to the non-irrigated eye of six rabbits produced minimal conjunctival irritation in all treated eyes.

No other adverse skin responses were noted.

Table 7.3 : Summary of Irritation studies

Parameter	Species	Result	Reference
Acute skin irritation	Rabbit	Non - irritant	Guest, 1989a (5327)
Acute eye irritation	Rabbit	Non – irritant	Guest, 1989b (5326)

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Irritating properties:

Eyes: All observed reactions were reversible 48 hours and no reaction with a score higher than 1 was observed.

Skin: In acute skin irritation test the mean skin scores for 24 to 72 hours after removal of the test article were < 2. The only observed skin reaction (erythema in one animal) was reversible within 48 hours.

In accordance with the provisions of regulation 1272/2008, Annex I, 3.2 and 3.3, classification as irritant to skin or eyes is not required.