2,4,8,10-tetra(tert-butyl)-6-hydoroxy-12H-dibenzo[d,g] [1,3,2]dioxaphosphocin, 6-oxide

Endpoint summary

Description of key information

Skin irritation:

The study was performed in accordance with OECD Guideline for the testing of chemicals: Acute Dermal Irritation/Corrosion (TG 404, adopted July 28, 2015). The test substance was considered to have no irritations to skin in rabbits.

Eye irritation:

The study was performed in accordance with the OECD Guideline for the testing of chemicals: Acute Eye Irritation/Corrosion (TG 405, adopted October 9, 2017). The test subatnce could produce very slight eye irritant reactions in rabbit.

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:

From 2018-06-21 to 2018-06-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Purity: > 99%
Batch No.: 102Z4

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Qingdao Kangda Biological Technology Limited Company
- Age at study initiation: 84 days at arrival and 90 - 91 days at dosing
- Weight at study initiation: 2112.3-2486.1 g at dosing
- Housing: in stainless steel cages (W 70 cm × L 80 cm × H 75 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 -7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.2 - 20.9 °C
- Humidity (%): 47% - 72%
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Ultra-purified water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

3 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm × 2.5 cm
- Type of wrap if used: elastic bandage and medical paper tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test substance was gently wiped off the application site by cotton moistened with tepid water.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- Clinical Observations: once daily throughout the study
- Skin Reactions Examination: at approximate 1, 24, 48 and 72 hours after patches removal
- Body Weights: within 24 hours after arrival, on the day of dosing and on the completion of the final observations of dermal irritation symptoms

SCORING SYSTEM:
- Method of calculation: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Remarks:

mean of three males

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Remarks:

mean of three males

Inidividual skin reactions grading:

Animal ID	Skin reactions	1 h	24 h	48 h	72 h
1100	Erythema/Eschar	0	0	0	0
	Oedema	0	0	0	0
1101	Erythema/Eschar	0	0	0	0
	Oedema	0	0	0	0
1102	Erythema/Eschar	0	0	0	0
	Oedema	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was considered to have no irritations to skin in rabbits.

Executive summary:

The study was performed to assess the acute dermal irritation/corrosion of the test substance in Japanese White rabbits in accordance with OECD Guideline for the testing of chemicals: Acute Dermal Irritation/Corrosion (TG 404, adopted July 28, 2015).

Three male rabbits were used for the study. A quantity of 0.5 g test item was applied to the right side of back skin of each animal for an exposure period of 4 hours. The untreated skin on the left back area of the animal served as the control. Clinical signs were performed once daily throughout the study. The skin sites of each animal for signs of erythema/eschar and oedema were all recorded immediately, and at approximate 1, 24, 48 and 72 hours after patch removal, and all local toxic effects of skin were also fully described and recorded. Individual animal body weights were recorded on the day of dosing and on the completion of final observations of dermal irritation symptoms.

 

No abnormal signs or symptoms were observed in all animals throughout the course of the study. There were no observable abnormalities for three control sites in skin reaction examinations at all observation intervals after patches removal. There were no observable abnormalities for three test sites in skin reaction examinations at approximate 1, 24, 48 and 72 hours after patches removal of the test item. All animals showed expected gains in body weights during the course of the study.

Based on above results, the test substance was considered to have no irritations to skins in rabbits, and was classified as unclassified according to GHS's classification criteria for the skin irritation.

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:

From 2018-06-21 to 2018-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Purity: > 99%
Batch No.: 102Z4

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Qingdao Kangda Biological Technology Limited Company
- Age at study initiation: 84 days at receipt and 90 - 94 days at dosing
- Weight at study initiation: 1899.2 - 2009.1 g at receipt and 2233.4 - 2257.5 g at dosing
- Housing: in stainless wire cages (W 70 cm × L 80 cm × H 75 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 – 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.2 - 20.9 °C
- Humidity (%): 47% - 72%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

72 hours

Details on study design:

TOOL USED TO ASSESS SCORE: binocular loupe

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Remarks:

The mean values of the three animals are 0, 0, 0, respectively.

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Remarks:

The mean values of the three animals are 0, 0, 0, respectively.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Remarks on result:

probability of weak irritation

Remarks:

The mean values of the three animals are 0, 0, 0, respectively. The maximum values of animals No. 1100 and 1102 are 1, 1.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Remarks:

The mean values of the three animals are 0, 0, 0, respectively.

Other effects:

- Clinical Observations: No significant adverse systemic effect was observed in any animal during the study. The animals only showed excessive blinking at immediate observations after dosing.
- Eye Examination: There were no abnormalities for all eyes in eye examinations approximately 24 hours prior to dosing. There were no observable abnormalities in eye examinations for three control eyes at all observation intervals after administrations. The treated eyes of animal No. 1100 and 1102 showed some blood vessels hyperaemic (injected) at 1 hour after administration. All treated eyes showed no eye irritant reactions at 24, 48 and 72 hours after administration.
- Fluorescein Examination: There was no retention of fluorescein for three control and treated eyes at 24 hours before and after dosing.
- Body Weights: All animals showed expected gains in body weights during the study.

Eye reaction scoring:

Animal ID	Eye reactions	1 h	24 h	48 h	72 h
1100	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjunctivae Redness	1	0	0	0
	Conjunctivae Chemosis	0	0	0	0
1101	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjunctivae Redness	0	0	0	0
	Conjunctivae Chemosis	0	0	0	0
1102	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjunctivae Redness	1	0	0	0
	Conjunctivae Chemosis	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test subatnce could produce very slight eye irritant reactions in rabbit.

Executive summary:

The study was performed to assess the acute eye irritation/corrosion of the test substance in Japanese White rabbits in accordance with the OECD Guideline for the testing of chemicals: Acute Eye Irritation/Corrosion (TG 405, adopted October 9, 2017).

Three male rabbits were used for the study. Each animal was administered with 0.1 g of the test item into the right eye. Untreated left eye served as the control. Immediately after administration of the test item, the initial reaction was observed and recorded. Test animals were routinely observed and recorded for clinical signs of pain and/or distress and any adverse systemic effects except eye twice daily for 3 days after administration of the test item, with a minimum of 6 hours between observations. Both eyes of animals were examined by a binocular loupe at approximate 1, 24, 48 and 72 hours after administration. The ocular reactions and any other lesions in the eye were recorded at each examination. Fluorescein stain examination was used at approximate 24 hours after administration. Ocular lesions (cornea, iris, conjunctivae redness and chemosis) for treated eye of each animal were scored and recorded at each examination. Mean scores of ocular lesions at approximate 24, 48 and 72 hours after administration were calculated for treated eyes. Individual animal body weights were recorded on the day of dosing and the completion of the final symptom observations of eye irritation.

 

No significant adverse systemic effect was observed in any animal during the study. The animals only showed excessive blinking at immediate observations after dosing. There were no abnormalities for all eyes in eye examinations approximately 24 hours prior to dosing. There were no observable abnormalities in eye examinations for three control eyes at all observation intervals after administrations. The treated eyes of animal No. 1100 and 1102 showed some blood vessels hyperaemic (injected) at 1 hour after administration. All treated eyes showed no eye irritant reactions at 24, 48 and 72 hours after administration. There was no retention of fluorescein for three control and treated eyes at 24 hours before and after dosing. Body Weights: All animals showed expected gains in body weights during the study.

 

Based on above results, the test substance could produce very slight eye irritant reactions in rabbit, and was classified as unclassified according to GHS's classification criteria for the eye irritation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The study was performed to assess the acute dermal irritation/corrosion of the test substance in Japanese White rabbits in accordance with OECD Guideline for the testing of chemicals: Acute Dermal Irritation/Corrosion (TG 404, adopted July 28, 2015).

Three male rabbits were used for the study. A quantity of 0.5 g test item was applied to the right side of back skin of each animal for an exposure period of 4 hours. The untreated skin on the left back area of the animal served as the control. Clinical signs were performed once daily throughout the study. The skin sites of each animal for signs of erythema/eschar and oedema were all recorded immediately, and at approximate 1, 24, 48 and 72 hours after patch removal, and all local toxic effects of skin were also fully described and recorded. Individual animal body weights were recorded on the day of dosing and on the completion of final observations of dermal irritation symptoms.

 

No abnormal signs or symptoms were observed in all animals throughout the course of the study. There were no observable abnormalities for three control sites in skin reaction examinations at all observation intervals after patches removal. There were no observable abnormalities for three test sites in skin reaction examinations at approximate 1, 24, 48 and 72 hours after patches removal of the test item. All animals showed expected gains in body weights during the course of the study.

Based on above results, the test substance was considered to have no irritations to skins in rabbits, and was classified as unclassified according to GHS's classification criteria for the skin irritation.

Eye irritation:

The study was performed to assess the acute eye irritation/corrosion of the test substance in Japanese White rabbits in accordance with the OECD Guideline for the testing of chemicals: Acute Eye Irritation/Corrosion (TG 405, adopted October 9, 2017).

Three male rabbits were used for the study. Each animal was administered with 0.1 g of the test item into the right eye. Untreated left eye served as the control. Immediately after administration of the test item, the initial reaction was observed and recorded. Test animals were routinely observed and recorded for clinical signs of pain and/or distress and any adverse systemic effects except eye twice daily for 3 days after administration of the test item, with a minimum of 6 hours between observations. Both eyes of animals were examined by a binocular loupe at approximate 1, 24, 48 and 72 hours after administration. The ocular reactions and any other lesions in the eye were recorded at each examination. Fluorescein stain examination was used at approximate 24 hours after administration. Ocular lesions (cornea, iris, conjunctivae redness and chemosis) for treated eye of each animal were scored and recorded at each examination. Mean scores of ocular lesions at approximate 24, 48 and 72 hours after administration were calculated for treated eyes. Individual animal body weights were recorded on the day of dosing and the completion of the final symptom observations of eye irritation.

 

No significant adverse systemic effect was observed in any animal during the study. The animals only showed excessive blinking at immediate observations after dosing. There were no abnormalities for all eyes in eye examinations approximately 24 hours prior to dosing. There were no observable abnormalities in eye examinations for three control eyes at all observation intervals after administrations. The treated eyes of animal No. 1100 and 1102 showed some blood vessels hyperaemic (injected) at 1 hour after administration. All treated eyes showed no eye irritant reactions at 24, 48 and 72 hours after administration. There was no retention of fluorescein for three control and treated eyes at 24 hours before and after dosing. Body Weights: All animals showed expected gains in body weights during the study.

 

Based on above results, the test substance could produce very slight eye irritant reactions in rabbit, and was classified as unclassified according to GHS's classification criteria for the eye irritation.

Justification for classification or non-classification

Skin irritation/corrosion:

Mean scores at 24, 48 & 72 hours for erythema and oedemas were all 0 for 3 test animals.

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.2.2, this substance should not be classified forthe Skin irritation/corrosion endpoint.

Serious eye damage/eye irritation:

Mean scores of cornea opacity, iris, conjunctivae redness and conjunctivae chemosis of three treated eyes were all 0 at 24, 48 and 72 hours after administrations.

 Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.3.2, this substance should not be classified for the Serious eye damage/eye irritation endpoint.