Registration Dossier

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

Non-GLP studies similar to OECD guideline 404 are available for DVB-55 and DVB-HP. The substances were irritating to the skin.

 

Non-GLP studies similar to OECD guideline 405 are available for DVB-55 and DVB-HP. In addition, a published summary of an eye irritation study conducted with an unknown grade of the reaction mass is available. The substances were irritating to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
e study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
semiocclusive
Preparation of test site:
other: shaved, abraded and unabraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
1-2 mL
Duration of treatment / exposure:
unabraded, intact skin - 5 days per week for 2 weeks
abraded skin- daily for 3 days
ear - daily 5 days per week for 2 week
Observation period:
Condition of the skin, at the exposure sites, was assessed and the severity of the reaction recorded daily, 5 days per week, during the esposure period and also at the end of the 3 week study. The animals were weighed at weekly intervals and were frequently observed to detect any changes in behavior and general appearance.
Number of animals:
3
Details on study design:
The abdominal skin of three rabbits was shaved free of hair using a straight razor and barber soap. The animals were rested for several days to permit healing of minute razor abrasions. Fresh amounts of the DVB (1-2 mL) were applied each day to an intact and an abraded exposure site on each animal under an absorbent cotton pad held in place by a cloth bandage taped to the animal's trunk. In the case of the intact skin, the test material was applied 5 days per week for 2 weeks which represents a continuous exposure of 14 days. The exposure to abraded skin was repeated daily for 3 days. Daily applications, 5 days per week for 2 weeks, were likewise made to the inner surface of the rabbit ear. Condition of the skin, at the exposure sites, was assessed and the severity of the reaction recorded daily, 5 days per week, during the exposure period and also at the end of the 3-week study. The animals were weighed at weekly intervals and were frequently observed to detect any changes in behaviour and general appearance.
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal: all animals
Time point:
24/48/72 h
Remarks on result:
other: Slight erythema was observed at the 24-hour observation. Repeated application resulted in slight erythema, very slight necrosis and moderate exfoliation onintact abdominal skin. Moderate necrosis was observed on abraded skin.
Irritation parameter:
edema score
Basis:
animal: all animals
Time point:
24/48/72 h
Remarks on result:
other: Repeated application resulted in slight edema on the intact abdominal skin site.
Irritant / corrosive response data:
Twenty-four hours after the first application, little irritation was seen on the rabbits' ears. Slight erythema was observed at all the abdominal sites at the 24-hour observation. Repeated application resulted in slight erythema, slight edema, very slight necrosis and moderate exfoliation on the ear and intact abdominal skin site. The response at the abraded skin sites was greater in that moderate necrosis was observed. No signs of toxicity other than topical effects were observed during the course of the skin irritation study.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Twenty-four hours after the first application of DVB-55, little irritation was seen. Prolonged skin contact with the test material would likely result in slight redness and slight swelling.
Executive summary:

The abdominal skin of three rabbits was shaved free of hair using a straight razor and barber soap. The animals were rested for several days to permit healing of minute razor abrasions. Fresh amounts of the DVB (1-2 mL) were applied each day to an intact and an abraded exposure site on each animal under an absorbent cotton pad held in place by a cloth bandage taped to the animal's trunk. In the case of the intact skin, the test material was applied 5 days per week for 2 weeks which represents a continuous exposure of 14 days. The exposure to abraded skin was repeated daily for 3 days. Daily applications, 5 days per week for 2 weeks, were likewise made to the inner surface of the rabbit ear. Condition of the skin, at the exposure sites, was assessed and the severity of the reaction recorded daily, 5 days per week, during the exposure period and also at the end of the 3-week study. The animals were weighed at weekly intervals and were frequently observed to detect any changes in behaviour and general appearance.

Twenty-four hours after the first application, little irritation was seen on the rabbits' ears. Slight erythema was observed at all the abdominal sites at the 24-hour observation. Repeated application resulted in slight erythema, slight edema, very slight necrosis and moderate exfoliation on the ear and intact abdominal skin site. The response at the abraded skin sites was greater in that moderate necrosis was observed. No signs of toxicity other than topical effects were observed during the course of the skin irritation study.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Male New Zealand albino rabbits (Langshaw Farms, Augusta, Michigan)
Type of coverage:
other: open (ear), confined (intact abdomen) and confined (abraded abdomen)
Preparation of test site:
other: shaved, abraded and unabraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Ear - 0.1 mL
Abdomen - 0.5 mL
Duration of treatment / exposure:
Ear - ten 0.1 mL applications over a period of 14 days
Abdomen (intact) - ten 0.5 mL applications over a period of 14 days
Abdomen (abraded) - 3 consecutive daily applications
Observation period:
21 days
Number of animals:
1
Details on study design:
A New Zealand albino rabbit was prepared for this test by shaving the hair from the entire abdomen. The animal was rested for several days to allow any abrasions to heal completely and to be sure the skin was suitable for testing. Applications were made as desribed below and reactions and observations were recorded daily during the application period and at various intervals thereafter. Applications were discontinued upon production of an irreversible skin burn.

Method A (Ear) - Ten 0.1 mL applications of undiluted test material were typically made over a period of 14 days. The applications were left uncovered.

Method B (Intact Abdomen) - The test material (0.5 mL undiluted) was applied under a 1 by 1 inch cotton pad held in place by a cloth bandage taped tothe marginal hair. Ten applications were typically made over a period of 14 days.

Method C (Abraded Abdomen) - An area of skin about 1 by 1 inch is cross-hatched with a sharp hyperdermic neddle to penetrate the stratum corneum but to produce no more than a trace of bleeding. The test material was applied as in Method B. Typically three consecutive daily applications were made which allowed for 3 days of intimate, confined contact with the abraded skin.

Scoring System:
Hyperemia
1. None
2. Very slight
3. Slight pink
4. Moderate pink
5. Red
6. Very red

Oedema
1. None
2. Very slight
3. Slight
4. Moderate
5. Marked
6. Severe

Necrosis
1. None
2. Very slight
3. Superficial
4. Moderate
5. Deep
6. Very deep

Exfoliation
1. None
2. Very slight
3. Slight
4. Moderate
5. Marked
6. Severe

Hair Loss
1. None
2. Very slight
3. Slight
4. Moderate
5. Marked
6. Severe

Scab
1. None
2. Very slight
3. Slight crustation
4. Moderate crustation
5. Marked scab
6. Deep scab

Scar
1. None
2. Very slight
3. Slight
4. Moderate
5. Marked
6. Severe
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 2 - <= 3
Max. score:
6
Reversibility:
fully reversible within: 14 days
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 4 - <= 5
Max. score:
6
Reversibility:
fully reversible within: 21 days
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 3 - <= 5
Max. score:
6
Reversibility:
fully reversible within: 21 days
Remarks:
abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 3 - <= 4
Max. score:
6
Reversibility:
fully reversible within: 10 days
Remarks:
abraded skin
Irritant / corrosive response data:
Repeated contact with this material on unconfined rabbit skin resulted in slight redness, slight swelling, slight exfoliation, and, after 10 applications, a moderate burn which resulted in scar formation. Contact on confined skin resulted in marked redness, slight to moderate swelling, moderate exfoliation, and, after 4 applications, a moderate burn which resulted in scar formation.
Other effects:
None
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Repeated contact with this material on unconfined rabbit skin rsulted in slight redness, slight swelling, slight exfoliation, and, after 10 applications, a moderate burn which resulted in scar formation. Contact on confined skin resulted in marked redness, slight to moderate swelling, moderate exfoliation, and, after 4 applications, a moderate burn which resulted in scar formation.
Executive summary:

A New Zealand albino rabbit was prepared for this test by shaving the hair from the entire abdomen. The animal was rested for several days to allow any abrasions to heal completely and to be sure the skin was suitable for testing. Applications were made to the ear (ten 0.1 mL applications over a period of 14 days), intact abdomen (ten 0.5 mL applications over a period of 14 days), or abraded abdomen (0.5 mL application over 3 consecutive daily applications) and reactions and observations were recorded daily during the application period and at various intervals thereafter. Applications were discontinued upon production of an irreversible skin burn.

Repeated contact with this material on unconfined rabbit skin resulted in slight redness, slight swelling, slight exfoliation, and, after 10 applications, a moderate burn which resulted in scar formation. Contact on confined skin resulted in marked redness, slight to moderate swelling, moderate exfoliation, and, after 4 applications, a moderate burn which resulted in scar formation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
single exposure, right eye 30 second exposure and then washed, left eye test material instilled and unwashed
Observation period (in vivo):
up to 1 week
Number of animals or in vitro replicates:
3
Details on study design:
Twenty-four hours prior to use, the eyes of three rabbits were examined and established as being without defects or irritation. Approximately 0.1 mL of the liquid material was instilled into the conjunctival sac of the right eye of each of the animals. Following a 30-second exposure period the eye was washed for 2 minutes with tepid, flowing tap water. The liquid material was then instilled in a similar manner into the left eye which was left unwashed. The animals were observed for indications of pain immediately after instillation into each eye. After instillation into the left eye, both eyes were examined for conjunctival irritation, corneal injury and internal effects such as iritis. All eyes were subsequently examined at various intervals up to 1 week post-instillation. At each examination after the first, the eyes were stained with a drop of 5% aqueous fluorescein stain to help evaluate corneal injury. Excess stain was removed by washing in a stream of flowing water.
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal: all animals
Time point:
24/48/72 h
Remarks on result:
other: Conjunctival membranes became slightly inflamed immediately after instillation and were still very slightly affected after 8 days.
Irritation parameter:
cornea opacity score
Basis:
animal: all animals
Time point:
24/48/72 h
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: all animals
Time point:
24/48/72 h
Remarks on result:
other: not reported
Irritation parameter:
chemosis score
Basis:
animal: all animals
Time point:
24/48/72 h
Remarks on result:
other: not reported
Irritation parameter:
other: pain response
Basis:
animal: all animals
Time point:
other: upon instillation
Remarks on result:
other: Moderate pain response observed which appeared to intensify after washing.
Irritant / corrosive response data:
Instillation of DVB-55 into the eyes of rabbits resulted in moderate pain response which appeared to intensify after washing. The conjunctival membranes became slightly inflamed immediately after instillation and were still very slightly affected after 8 days. No effects on the cornea and internal structures of the eye were observed.
Other effects:
No data
Interpretation of results:
other: slightly irritating
Conclusions:
Only slight effects on the conjunctivae were observed after the instillation of DVB-55 into the eyes of rabbits. No effects on the cornea and internal structures of the eye were observed and all effects were resersible within the observation period.
Executive summary:

Twenty-four hours prior to use, the eyes of three rabbits were examined and established as being without defects or irritation. Approximately 0.1 mL of the liquid material was instilled into the conjunctival sac of the right eye of each of the animals. Following a 30-second exposure period the eye was washed for 2 minutes with tepid, flowing tap water. The liquid material was then instilled in a similar manner into the left eye which was left unwashed. The animals were observed for indications of pain immediately after instillation into each eye. After instillation into the left eye, both eyes were examined for conjunctival irritation, corneal injury and internal effects such as iritis. All eyes were subsequently examined at various intervals up to 1 week post-instillation. At each examination after the first, the eyes were stained with a drop of 5% aqueous fluorescein stain to help evaluate corneal injury. Excess stain was removed by washing in a stream of flowing water.

 

Instillation of DVB-55 into the eyes of rabbits resulted in moderate pain response which appeared to intensify after washing. The conjunctival membranes became slightly inflamed immediately after instillation and were still very slightly affected after 8 days. No effects on the cornea and internal structures of the eye were observed.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Male New Zealand albino rabbits (Langshaw Farms, Augusta, Michigan).
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
single exposure, right eye 30 second exposure and then washed, left eye test material instilled and unwashed
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1
Details on study design:
The test procedure consisted of instillation of ~0.1 mL of undiluted test material into the conjunctival sac of the right eye. Following a 30 second exposure period the eye was washed for 2 minutes with tepid, flowing tap water. The test material was then instilled in a similar manner in the left eye which was left unwashed. At various time intervals both eyes were examined for conjunctival irritation, corneal injury and irritation of the iris. The behavior of the animals was observed for indications of pain or discomfort. All eyes were examined following instillation, 1 hour, 24 hours, 48 hours and at intervals of 7 days post-instillation. A drop of 5% aqueous fluorescein was used to help assess corneal injury at the 1-hour reading and at all subsequent readings.

Scoring System:
Immediate Repsonse (Pain)
1. No response
2. Very slight - no more than a few blinks - normal in a minute or so
3. Slight - blinks- tries to open but can't. Reflexes close eye
4. Moderate. Holds eye shut and puts pressure on lids, may rub eye with paw.
5. Severe. Holds eye shut vigorously, rubs eye with paw - may squeal.
6. Very severe. Holds eye shut vigorously. May squeal, claws at eye, jumps, tries to escape.

Conjunctival Response
1. None
2. Very slight. Capillaries prominent. No swelling or general redness.
3. Slight. Conjunctival membranes somewhat inflamed. May be some sclero-corneal inflammation. Similar to response from a mild soap.
4. Moderate. conjunctival membranes inflamed and sore, lids slightly swollen and reddened.
5. Severe. Conjunctival membranes red and swollen. Some pussy exudate; nictitating membrane sore and inflamed.
6. Very severe. conjunctival membranes markedly reddened and swollen. Nictitating membrane edematous. Pussy exudate - eye may be stuck.

Corneal Response (before staining)
1. No response.
2. Very slight haziness.
3. Slight. Cloudy in part.
4. Moderate. Cloudy over whole but not opaque.
5. Severe. Cornea up to 50% opaque.
6. Very severe. Cornea completely opaque.

Corneal Response (after staining)
1. None
2. Very slight. Few diffuse areas of necrosis. Probably heal in 24-48 hours.
3. Slight. Upt to 50% of eye covered with shallow necrosis. Probably heal O.K.
4. Moderate. 50-100% of eye necrotic but lesions are shallow. Doubtful if vision will be impaired.
5. Severe. Marked necrosis over whole area which may result in loss of eye.
6. Very severe. Eye lost. Heavy necrosis.

Irritation of the Iris
1. No response
2. Very slight.
3. Slight. Just perceptible.
4. Moderate. Definitely perceptible.
5. Severe. Marked change.
6. Very severe. Complete loss of function.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Reversibility:
fully reversible within: 1 hour post exposure
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
6
Reversibility:
other: score of 1 indicates no irritation
Remarks on result:
other: Although 72-hour response not recorded, it was assumed to be 1 as no irritation was observed at any endpoint prior or subsequent to 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
6
Reversibility:
other: score of 1 indicates no irritation
Remarks on result:
other: Although 72-hour response not recorded, it was assumed to be 1 as no irritation was observed at any endpoint prior or subsequent to 72 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
6
Reversibility:
other: score of 1 indicates no irritation
Remarks on result:
other: Although 72-hour response not recorded, it was assumed to be 1 as no irritation was observed at any endpoint prior or subsequent to 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Instillation of this material into the eyes of a rabbit resulted in slight discomfort and transient very slight conjunctival redness. All signs of eye irritation were essentially absent by 1 hour post-exposure. Very slight signs of eye irritation observed after this time were felt to be spontaneous in nature and unrelated to application of the test material.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Instillation of this material into the eyes of a rabbit resulted in slight discomfort and transient very slight conjunctival redness. All signs of eye irritation were essentially absent by 1 hour post-exposure.
Executive summary:

The test procedure consisted of instillation of ~0.1 mL of undiluted test material into the conjunctival sac of the right eye. Following a 30 second exposure period the eye was washed for 2 minutes with tepid, flowing tap water. The test material was then instilled in a similar manner in the left eye which was left unwashed. At various time intervals both eyes were examined for conjunctival irritation, corneal injury and irritation of the iris. The behavior of the animals was observed for indications of pain or discomfort. All eyes were examined following instillation, 1 hour, 24 hours, 48 hours and at intervals of 7 days post-instillation. A drop of 5% aqueous fluorescein was used to help assess corneal injury at the 1-hour reading and at all subsequent readings.

Instillation of this material into the eyes of a rabbit resulted in slight discomfort and transient very slight conjunctival redness. All signs of eye irritation were essentially absent by 1 hour post-exposure. Very slight signs of eye irritation observed after this time were felt to be spontaneous in nature and unrelated to application of the test material.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Both skin irritation studies on DVB-55 and DVB-HP used repeated exposures (4 -10 applications) of the test material. Twenty-four hours after the first application only little irritation was seen. Prolonged or repeated skin contact with the test material on unconfined rabbit skin resulted in slight redness, slight swelling, slight exfoliation, and, after 10 applications, a moderate burn which resulted in scar formation. Contact on confined skin resulted in marked redness, slight to moderate swelling, moderate exfoliation, and, after 4 applications, a moderate burn which resulted in scar formation.

 

Instillation of DVB-HP into the eyes of a rabbit resulted in slight discomfort and transient very slight conjunctival redness. All signs of eye irritation were essentially absent by 1-hour post-exposure. Very slight signs of eye irritation observed after this time were felt to be spontaneous in nature and unrelated to application of the test material. Only slight effects on the conjunctivae were observed after the instillation of DVB-55 into the eyes of rabbits. No effects on the cornea and internal structures of the eye were observed and all effects were reversible within the observation period.

 

The grades tested cover the highest concentration of divinylbenzene (DVB-HP: 80% divinylbenzene and 20% ethylstyrene) and ethylstyrene (DVB-55: 55% divinylbenzene and 45% ethylstyrene).

Justification for classification or non-classification

Based on the slight irritation after a single application of different grades of the reaction mass, a classification as "skin irritant" is recommended for all grades of the reaction mass of divinylbenzene and ethylstyrene. Only slight effects on the conjunctivae were observed after the instillation of different grades of the reaction mass into the eyes of rabbits. No effects on the cornea and internal structures of the eye were observed and all effects were reversible within the observation period. As no scores according to EU criteria have been reported in the study for DVB-55 it is unclear whether the criteria for classification are met or not. Hence, a precautionary classification as "eye irritant" is recommended for all grades of the reaction mass of divinylbenzene and ethylstyrene. Therefore, the substance is classified as Cat 2 (H315: Causes skin irritation) and Cat 2 (H319: Causes serious eye irritation) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.