6H-dibenz[c,e][1,2]oxaphosphorin 6-oxide

Endpoint summary

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:

The experimental work was carried out between 10.11.1997 and 14.11.1997.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Performed to GLP, OECD Guideline followed and no deviations reported

Justification for data waiving:

other:

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: SPF albino rabbits

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Stock Mol:Russian from Møllegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved. The animals were earmarked on arrival.
- Weight at study initiation: 2.3 - 2.6 kg
- Housing: The study took place in animal room No. 2 provided with filtered air at a temperature of 20°C ± 3°C, relative humidity of 55% ± 15% and air changes 10 times/hour. The room was illuminated to give a cycle of 12 hours light and 12 hours darkness. Light was on from 06 to 18 h. During a pre-period of at least one week and throughout the experiment the rabbits were caged individually in PPO cages (floor area: 2576 cm2) with perforated floor.
- Diet (e.g. ad libitum): A pelleted complete rabbit diet “Altromin 2123” from Altromin, D-32791 Lage, Lippe, was available ad libitum. Analyses for major nutritive components and relevant possible contaminants are performed regularly on the diet. Certificates of analysis are retained.
- Water (e.g. ad libitum): The animals had free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth. Analyses for relevant possible contaminants are performed regularly. Certificates of analysis are retained.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10 times/hour
- Photoperiod (hrs dark / hrs light): The room was illuminated to give a cycle of 12 hours light and 12 hours darkness. Light was on from 06 to 18 h.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL undiluted

Duration of treatment / exposure:

Exposure time: 4 hours

Observation period:

1 hour, 24, 48 and 72 hours after the termination of the exposure

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: To each of two 16-layer gauze patches (2.5 x 2.5 cm) 0.5 ml of the test article was applied
- % coverage: No details provided in report
- Type of wrap if used: To each of two 16-layer gauze patches (2.5 x 2.5 cm) 0.5 ml of the test article was applied, and the patches were placed on the appropriate test site on the back of each rabbit. The gauze patches were secured with 2.5 cm wide adhesive Gothaplast tape and fixed with Gothaplast tape, 5 cm width, loosely wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After an exposure time of 4 hours the tape and patches were removed, the test fields were marked and the treated skin was cleaned with mild soap and lukewarm water.
- Time after start of exposure: Patches and tape were removed 4 hours after start of exposure

SCORING SYSTEM: Skin reactions were read 1 hour after removal of patches and washing of treated skin using the scale outlined in the attached report. Reading was also made 24, 48 and 72 hours after termination of exposure. The respective scores for erythema and oedema formation for the 3 readings 24, 48 and 72 hours of each rabbit were summed up separately and divided by 6. The results are the mean scores for erythema and oedema formation of the individual rabbit. The mean scores for erythema and oedema formation in 3 rabbits used were subsequently calculated.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

No skin reactions were observed among the rabbits at any of the readings.

The scores are shown in Table 1 of the attached report.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: EEC commission 93/21/EEC of April 27, 1993

Conclusions:

According to the directive of the EEC commission 93/21/EEC of April 27, 1993 no classification for skin irritation is required for Ukanol DOP.

Executive summary:

The primary skin irritant effect of Ukanol DOP was investigated according to the method recommended in the OECD Guideline No. 404, “Acute Dermal Irritation/Corrosion”, 1992, and EEC Guideline B.4 “Acute Toxicity (Skin Irritation)”, 29.12.1992.                      Three female albino rabbits were exposed to the test article at two skin sites on the back. After 4 hours of exposure the test article was removed and the skin was examined 1, 24, 48 and 72 hours after termination of exposure.   No skin reactions were observed among the rabbits at any of the readings.   Under the experimental conditions described in this report, the mean score for erythema was 0.0 and for oedema 0.0.   According to the directive of the EEC commission 93/21/EEC of April 27, 1993 no classification for skin irritation is required for Ukanol DOP.

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:

Experimental work was carried out between 10.11.1997 and 18.11.1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Performed according to GLP, OECD guidelines followed and no deviations reported

Justification for data waiving:

other:

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: SPF albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Stock: Mol:Russian
- Source: Møllegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved
- Weight at study initiation: 2.1 - 2.4 kg
- Housing: The study took place in animal room No. 2. During a pre-period of at least one week and throughout the experiment the rabbits were caged individually in PPO cages (floor area: 2576 cm2) with perforated floor.
- Diet (e.g. ad libitum): A pelleted complete rabbit diet ''Altromin 2123'' from Altromin, D-32791 Lage, Lippe, was available ad libitum. Analyses for major nutritive components and relevant possible contaminants are performed regularly on the diet. Certificates of analysis are retained.
- Water (e.g. ad libitum): The animals had free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth. Analyses for relevant possible contaminants are performed regularly. Certificates of analysis are retained.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15 (relative humidity)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12 (Light was on from 06 to 18 h)

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml of the test article

Duration of treatment / exposure:

Single application

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

Three females

Details on study design:

Testing procedure:

The day before testing both eyes of the animals were examined with a hand held inspection lamp fitted with white and UV-light and magnifying glass with 2 x magnification to ensure there were no defects or irritation. The examination was performed before and after instillation of Fluorescein. Only the left eye was treated. The right eye remained untreated and served as control.

0.1 ml of the test article was placed in the left eye of the rabbits by gently pulling the lower lid away from the eyeball to form a cup into which the article was dropped. The lids were then gently held together for 1 second. The eyes were examined and the grade of ocular reaction was recorded 1 and 24 hours later. After the first 24 hour reading Fluorescein was instilled. After rinsing with 20 ml 0.9% sodium chloride solution the eyes were examined again using UV-light to detect possible corneal damage. The eyes were also examined 48 and 72 hours as well as 7 days after the treatment. The reactions were scored according to the grades for ocular lesions outlined in the attached report.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 72h

Score:

0.8

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 72h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 7 days

The individual results are shown in Table 1 of attached report.

 

- One hour after application of the test article all three rabbits showed diffuse redness of conjunctivae and discharge with moistening of lids and hairs and considerable area around the eye.

- After 24 hours animal No. 1002 showed slight opacity of cornea on less than the half of the area. With Fluorescein all animals showed slight opacity of cornea on less than the half of the area. Diffuse redness of conjunctivae and discharge with moistening of lids and hairs and considerable area around the eye were observed in all animals. Slight swelling of conjunctivae was observed in animal Nos. 1000 and 1002, whereas animal No. 1004 showed obvious swelling of conjunctivae.

- After 48 hours all animals showed slight opacity of cornea on less than the half of the area. With Fluorescein all animals showed slight opacity of cornea on less than a quarter of the area. Diffuse redness and slight swelling of conjunctivae were observed in all animals. Animal Nos. 1000 and 1002 showed discharge with moistening of lids and hairs and considerable area around the eye, animal No. 1004 showed discharge of lids and hairs just adjacent to lids.

- After 72 hours animal No. 1000 showed slight opacity of cornea on less than the half of the area. With Fluorescein all animals showed no comeal reactions. Furthermore all animals showed diffuse redness and slight swelling of conjunctivae as well as discharge of lids and hairs just adjacent to lids.

- After 7 days no eye reactions due to the application of the test article were seen.

The following mean values were obtained from the data presented in Table 1 of attached report:

cornea opacity                                  0.8

iris lesion                                          0.0

redness of conjunctiva                    2.0

oedema of conjunctiva (chemosis) 1.1

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: According to the directive of the EEC commission 93/21/EEC of April 27, 1993

Conclusions:

According to the directive of the EEC commission 93/21/EEC of April 27, 1993 no classification is required for eye irritation for Ukanol DOP.

Executive summary:

The eye irritant effect of Ukanol DOP was investigated according to the method recommended in the OECD Guideline No. 405, “Acute Eye Irritation/Corrosion”, Feb. 1987, and EEC Guideline B.5 “Acute Toxicity (Eye Irritation)”, 29.12.1992.

Three female albino rabbits were exposed to 0.1 ml of the test article in the left eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours as well as 7 days after dosing.

 

Moderate signs of eye irritation were observed among the rabbits.

The following mean values, based on the results from the 24, 48 and 72 hour readings, were calculated:

 

                                                 Ukanol DOP

cornea opacity                                  0.8

iris lesion                                          0.0

redness of conjunctiva                     2.0

oedema of conjunctiva (chemosis) 1.1

 

According to the directive of the EEC commission 93/21 /EEC of April 27, 1993 no classification is required for eye irritation of Ukanol DOP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation: According to the directive of the EEC commission 93/21/EEC of April 27, 1993 Ukanol DOP shall not be classified as skin irritating.

Justification for selection of skin irritation / corrosion endpoint:
- According to the directive of the EEC commission 93/21/EEC of April 27, 1993 Ukanol DOP shall not be classified as skin irritating.
- No skin reactions were observed among the rabbits at any of the readings.
- The mean score for the test article was 0.0 for erythema and 0.0 for oedema.

Justification for selection of eye irritation endpoint:
The following mean values, based on the results from the 24, 48 and 72 hour readings, were calculated:
 
                                                 Ukanol DOP
cornea opacity                                  0.8
iris lesion                                          0.0
redness of conjunctiva                     2.0
oedema of conjunctiva (chemosis) 1.1
 
According to the directive of the EEC commission 93/21 /EEC of April 27, 1993 Ukanol DOP shall not be classified as eye irritating.