2,3,4-trihydroxybenzophenone

Endpoint summary

Description of key information

The test item is considered a very mild irritant to skin.  

Based on the observations up to day 7 after treatment, the test item is considered to cause irreversible damage to the cornea and thus, cause serious eye damage.

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:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was conducted according to the Draize protocol (occlusive dressing, 24 h exposure period, abraded and intact test sites). Restrictions of the study: reading time point after 48 h missing, no individual scores, observation period terminated after 72 h

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elkhorn Rabbitry of Watsonville, CA, USA
- Weight at study initiation: 2 - 3 kg
- Housing: Animals were individually housed in hanging wire cages.
- Diet: Approximately 150 g of a commercial rabbit chow (Purina Rabbit Chow Complete Blend); fresh vegetables on occasion.
- Water: UV-purified drinking water, ad libitum.
- Acclimation period: 4 - 5 days

ENVIRONMENTAL CONDITIONS
- Air changes (per hr): air-conditioned rooms

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:

24 h

Observation period:

Reading time points: 24 and 72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: Two unabraded and two abraded test sites were used on the dorsal area of the trunk of each rabbit. The back of each rabbit was clipped free of hair the day before treatment.
- Type of wrap if used: Each application site was covered with a gauze pad and the entire back was wrapped with a rubber dam.

OBSERVATION TIME POINTS: 24 and 72 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritation parameter:

erythema score

Time point:

48 h

Remarks on result:

other: animals were not observed at the 48-h reading time point

Irritation parameter:

edema score

Time point:

48 h

Remarks on result:

other: animals were not observed at the 48-h reading time point

Irritation parameter:

erythema score

Basis:

mean

Remarks:

mean of all 6 animals

Time point:

72 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritation parameter:

edema score

Basis:

mean

Remarks:

mean of all animals

Time point:

72 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritant / corrosive response data:

24 h after the application of the test substance barely perceptible to slight erythema at the treated sites in 4/6 animals were observed. 72 h after treatment a few scattered sites continued to have barely perceptible erythema. No edema was observed in any animal after 24 h and 72 h of observation. The primary irritation score was calculated to be 0.6.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

As worst case assessment the test substance is considered as irritant to the skin.

Conclusions:

The test item is considered a very mild irritant to skin.  

Executive summary:

A study was conducted to evaluate the potential to cause skin irritation. Six male rabbits were treated with undiluted test item. The back of each rabbit was clipped free of hair the day before treatment. Two unabraded and two abraded test sites were used on the dorsal area of the trunk of each rabbit. Each application site was covered with a gauze pad and the entire back was wrapped with a rubber dam. After 24 h the pads and wraps were removed and sites were scored for erythema and edema after 24 and 72 h according to Draize test grading system. 24 h after the application of the test substance barely perceptible to slight erythema at the treated sites in 4/6 animals were observed. 72 h after treatment a few scattered sites continued to have barely perceptible erythema. No edema was observed in any animal after 24 h and 72 h of observation. The primary irritation score was calculated to be 0.6. The test item is considered a very mild irritant to 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:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 02 Oct 2012

Deviations:

yes

Remarks:

(analgesics and anesthetics were not used before instillation of the test substance, no individual scores were given, observation period terminated after 7 days instead of 21 days, no information on the purity of the test substance, non-GLP)

GLP compliance:

no

Species:

rabbit

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elkhorn Rabbitry of Watsonville, CA, USA
- Weight at study initiation: 2 - 3 kg
- Housing: Animals were individually housed in hanging wire cages.
- Diet: Approximately 150 g of a commercial rabbit chow (Purina Rabbit Chow Complete Blend); fresh vegetables on occasion.
- Water: UV-purified drinking water, ad libitum.
- Acclimation period: 4 - 5 days

ENVIRONMENTAL CONDITIONS
- Air changes (per hr): air-conditioned rooms

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

Duration of treatment / exposure:

single application without washing, washing of the eyes after 30 s and 5 min (3 rabbits/group each)

Observation period (in vivo):

Reading time points: 24, 48, 72 and 96 h and 7 days

Number of animals or in vitro replicates:

3 animals per exposure group

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: In two groups, the treated eye was washed 30 s and 5 min after instillation, respectively.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Remarks on result:

other: no individual Draize scores were given in the study report

Irritant / corrosive response data:

Corneal and iridic lesions were observed in all exposure groups beginning at 24 or 48 h after treatment. All rabbits exhibited conjunctival reactions of redness, swelling, and/or discharge. The ocular lesions were present during the first 96 h and in some cases persisted throughout the 1-week study period.
In the animals whose eyes were exposed to the test substance as single application without washing the test substance adhered to the inside of the eyelids during the initial reading time point of 24 h in 3/3 rabbits, persisting as dark material inside the eye lid in 2/3 rabbits. Slight pannus formation was also noted by the end of the study indicating possible permanent damage to the corneas in 3/3 animals in this exposure group.
In the animals whose eyes were exposed to the test substance for 30 s a darkened area was noted in 1/3 rabbits on Day 7. Slight conjunctival redness was also observed in 1/3 animals by the end of the 1-week study in this exposure group.
On day 7 2/3 rabbits of the 5 min wash group had clear eyes and 1 rabbit of the 30 s wash group had normals eyes besides slight conjunctival redness. All 3 rabbits of the no wash group had slight pannus formation.

Other effects:

1 rabbit of the 30 s wash group died on Day 7. Expect for diarrhea, which was present at the beginning of the study, no gross abnormalities were found. Thus, the death is considered unrelated to treatment.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the observations up to day 7 after treatment, the test item is considered to cause irreversible damage to the cornea and thus, cause serious eye damage.

Executive summary:

A study was conducted to evaluate the potential to cause eye irritation. 9 male rabbits were treated with a single application of 0.1 g undiluted test item in one eye each. Animals were divided into groups of 3 for different washing procedures. The eyes of one group were not washed and the eyes of the other groups were washed after 30 s or 5 min. Eyes were graded for ocular lesions after 24, 48, 72 and 96 h and 7 days. The test was terminated after 7 days. The grading system according to Draize was used. Corneal and iridic lesions were observed in all exposure groups beginning at 24 or 48 h after treatment. All rabbits exhibited conjunctival reactions of redness, swelling, and/or discharge. The ocular lesions were present during the first 96 h and in some cases persisted throughout the 1-week study period. In the animals whose eyes were exposed to the test substance as single application without washing the test substance adhered to the inside of the eyelids during the initial reading time point of 24 h in 3/3 rabbits, persisting as dark material inside the eye lid in 2/3 rabbits. Slight pannus formation was also noted by the end of the study indicating possible permanent damage to the corneas in 3/3 animals in this exposure group. In the animals whose eyes were exposed to the test substance for 30 s a darkened area was noted in 1/3 rabbits on Day 7. Slight conjunctival redness was also observed in 1/3 animals by the end of the 1-week study in this exposure group. On day 7 2/3 rabbits of the 5 min wash group had clear eyes and 1 rabbit of the 30 s wash group had normal eyes besides slight conjunctival redness. All 3 rabbits of the no wash group had slight pannus formation. 1 rabbit of the 30 s wash group died on Day 7. Expect for diarrhea, which was present at the beginning of the study, no gross abnormalities were found. Therefore, the death is considered unrelated to treatment. Based on the observations up to day 7 after treatment, the test item is considered to cause irreversible damage to the cornea and thus, cause serious eye damage.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A study was conducted to evaluate the potential to cause skin irritation. Six male rabbits were treated with undiluted test item. The back of each rabbit was clipped free of hair the day before treatment. Two unabraded and two abraded test sites were used on the dorsal area of the trunk of each rabbit. Each application site was covered with a gauze pad and the entire back was wrapped with a rubber dam. After 24 h the pads and wraps were removed and sites were scored for erythema and edema after 24 and 72 h according to Draize test grading system. 24 h after the application of the test substance barely perceptible to slight erythema at the treated sites in 4/6 animals were observed. 72 h after treatment a few scattered sites continued to have barely perceptible erythema. No edema was observed in any animal after 24 h and 72 h of observation. The primary irritation score was calculated to be 0.6. The test item is considered a very mild irritant to skin.  

 

Eye irritation

Key study

A study was conducted to evaluate the potential to cause eye irritation. 9 male rabbits were treated with a single application of 0.1 g undiluted test item in one eye each. Animals were divided into groups of 3 for different washing procedures. The eyes of one group were not washed and the eyes of the other groups were washed after 30 s or 5 min. Eyes were graded for ocular lesions after 24, 48, 72 and 96 h and 7 days. The test was terminated after 7 days. The grading system according to Draize was used. Corneal and iridic lesions were observed in all exposure groups beginning at 24 or 48 h after treatment. All rabbits exhibited conjunctival reactions of redness, swelling, and/or discharge. The ocular lesions were present during the first 96 h and in some cases persisted throughout the 1-week study period. In the animals whose eyes were exposed to the test substance as single application without washing the test substance adhered to the inside of the eyelids during the initial reading time point of 24 h in 3/3 rabbits, persisting as dark material inside the eye lid in 2/3 rabbits. Slight pannus formation was also noted by the end of the study indicating possible permanent damage to the corneas in 3/3 animals in this exposure group. In the animals whose eyes were exposed to the test substance for 30 s a darkened area was noted in 1/3 rabbits on Day 7. Slight conjunctival redness was also observed in 1/3 animals by the end of the 1-week study in this exposure group. On day 7 2/3 rabbits of the 5 min wash group had clear eyes and 1 rabbit of the 30 s wash group had normal eyes besides slight conjunctival redness. All 3 rabbits of the no wash group had slight pannus formation. 1 rabbit of the 30 s wash group died on Day 7. Expect for diarrhea, which was present at the beginning of the study, no gross abnormalities were found. Therefore, the death is considered unrelated to treatment. Based on the observations up to day 7 after treatment, the test item is considered to cause irreversible damage to the cornea and thus, cause serious eye damage.

Supporting study

An in vivo eye irritation study in rabbits was conducted according to OECD 405. Three rabbits without ocular abnormalities were used. The test substance (100 mg) was administered to one eye while the other eye served as control. Washing was done 24 h after treatment. The eyes were examined 1, 24, 42 and 72 h after administration. At 24 and 72 h as well as after 7 days, the eyes were also examined for corneal lesions under UV light after instillation of one drop of a 0.01 % fluorescein sodium solution. Lesions in cornea, iris or conjunctivae were graded and all other changes or toxic effects were recorded. One hour after administration the conjunctivae showed definitely injected blood vessels up to a diffuse beefy red color and very light swellings up to swellings with lids about half closed. The iris was sporadically reddend. The cornea showed diffuse up to translucent opacity areas. Additionally, clear-colorless or substance colored eye discharge occurred sporadically during the observation period. Seven days after administration all signs of irritation were reversible. The primary eye irritation test in the rabbit showed that the test item was irritating to the eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritation, the test item requires classification for causing skin irritation Category 2 (H315: Causes skin irritation) and for causing serious damage to the eye Category 1 (H318: Causes serious eye damage) according to Regulation (EC) No 1272/2008 (CLP).