Reaction mass of divinylbenzene and ethylstyrene

Endpoint summary

Description of key information

A GLP-study according to OECD guideline 401 is available for DVB-96. In addition, two non-GLP studies equivalent to OECD guideline 401 are available for DVB-HP and DVB-55. The oral LD50 values for different grades of the reaction mass of divinylbenzene and ethylstyrene in rats ranges from >2000 to 4100 mg/kg.

 

Two non-GLP studies equivalent or similar to OECD guideline 403 are available for DVB-55. Based on the available data and considering the exposure conditions (duration and temperature), there is no clear evidence that the LC50 would be smaller than 20 mg/L under normal conditions. The LC50 in rats is greater than 17.6 mg/L.

 

One non-GLP study equivalent to OECD guideline 402 is available for DVB-55. A dermal LD50 of 8000 mg/kg bw was established.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

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 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

To establish the acute oral lethality, varying amounts of the undiluted liquid material were administered to female rats by single dose gavage after an 18-hour food deprivation period.

Doses:

0.5, 1.0, 2.0, 3.98, 7.95 g/kg

No. of animals per sex per dose:

5 female rats/dose

Control animals:

no

Details on study design:

To establish the acute oral lethality, varying amounts of the undiluted liquid material were administered to female rats by single dose gavage after an 18-hour food deprivation period. The animals were weighed before dosing, the day following and at weekly intervals for 2 weeks thereafter and were observed periodically for signs of toxicity.

Statistics:

No data

Sex:

female

Dose descriptor:

LD50

Effect level:

> 3.98 - < 7.95 other: g/kg

Remarks on result:

other: An approximate graphical analysis showed that the value is 4.1 g/kg body weight.

Mortality:

5/5 at 7.95 g/kg, 1/5 at 3.98 g/kg and 0/5 for 2.0, 1.0 and 0.5 g/kg

Clinical signs:

other: other: other: other: Rats given 3.98 or 7.95 g/kg were inactive and fur stained with urine during the first 48 hours after treatment. Death was observed two days after treatment for animals given 7.95 g/kg.

Gross pathology:

No data

Other findings:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

The single dose oral LD50 for DVB-55 in female rats is between 3.98 and 7.95 g/kg body weight. An approximate graphical analysis showed that the value is 4.1 g/kg body weight.

Executive summary:

Female rats were given a single gavage administration of the test substances at doses of 0.5, 1.0, 2.0, 3.98, and 7.95 g/kg and were observed for 14 days. Rats given 3.98 or 7.95 g/kg were inactive and fur stained with urine during the first 48 hours after treatment. Death was observed two days after treatment for animals given 7.95 g/kg. The single dose oral LD50 in female rats is between 3.98 and 7.95 g/kg body weight.  An approximate graphical analysis showed that the value is 4.1 g/kg body weight.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP-study according to OECD guideline 401

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

No data

Doses:

500, 1000 or 2000 mg/kg/day

No. of animals per sex per dose:

5/sex/dose

Control animals:

not specified

Details on study design:

None

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Although the lowest body weight was marked in more than 500 mg/kg/day groups of both sexes and the locomotive activities were decreasing in 2000 mg/kg/day groups of both sexes, no death occurred in any group.

Clinical signs:

other: other: other: other: None

Gross pathology:

No abnormality was found by autopsy.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of DVB-96 in male and female rats is >2000 mg/kg bw.

Executive summary:

The study was conducted in accordance with OECD Guideline 401. The LD50 of DVB-96 in male and female rats is >2000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

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 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Acute oral toxicity tests were conducted on male CDF (Fischer 344 - derived) albino rats (Charles River Breeding Laboratories, Inc., Portage, Michigan), 99-138g.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Rats received the following doses of the undiluted test material by single-dose oral gavage: 630, 1300, 2500 or 5000 mg/kg. The animals were fasted overnight before dosing.

Doses:

630, 1300, 2500 or 5000 mg/kg

No. of animals per sex per dose:

6 male rats/dose

Control animals:

no

Details on study design:

Animals received a single-dose gavage using a calibrated syringe and blunt feeding needle. The animals were fasted overnight and weighed before dosing, the day after dosing, and at 1 and 2 weeks after dosing. The animals were observed closely the day of treatment, then periodically for the 2-week observation period. All survivors were submitted for a gross pathological examination after the 2-week weighing.

Statistics:

The LD50 was calculated by the moving average method of analysis.

Sex:

male

Dose descriptor:

LD50

Effect level:

2 155 mg/kg bw

95% CL:

1 494 - 3 426

Mortality:

Mortality was 0/6, 1/6, 3/6, and 6/6 at 630, 1300, 2500, and 5000 mg/kg, respectively.

Clinical signs:

other: other: other: other: Following dosage, all rats on test were lethargic and had piloerection (rough hair coats). In addition, rats of the 1300-1500 mg/kg groups exhibited decreased food consumption.

Gross pathology:

No treatment related effects were observed upon gross pathological examination of all survivors 2 weeks post-treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

The single-dose oral LD50 for DVB-HP for male rats is 2155 mg/kg.

Executive summary:

A sample of divinyl benzene - HP (70-85%) was submitted to the Toxicology Research Laboratory on April 7, 1980, for acute toxicological evaluation and definition of industrial handling hazards. It is a mixture of meta and para divinyl benzene (70-85%), with the balance ethyl vinyl benzene. It is an ion exchange raw material and has a proposed use in unsaturated polyester formulations. Acute oral toxicity tests were conducted on male CDF (Fischer 344 - derived) albino rats. Animals received a single-dose gavage using a calibrated syringe and blunt feeding needle. The animals were fasted overnight and weighed before dosing, the day after dosing, and at 1 and 2 weeks after dosing. The animals were observed closely the day of treatment, then periodically for the 2-week observation period. Six male CDF (Fischer 344 - derived) albino rats (Charles River Breeding Laboratories, Inc., Portage, Michigan), 99-138g were used. All survivors were submitted for a gross pathological examination after the 2-week weighing.

 

Mortality was 0/6, 1/6, 3/6, and 6/6 at 630, 1300, 2500, and 5000 mg/kg, respectively. Following dosage, all rats on test were lethargic and had piloerection (rough hair coats). In addition, rats of the 1300-1500 mg/kg groups exhibited decreased food consumption. All surviving rats gained weight during the 2-week post-treatment observation period, and no treatment related effects were observed upon gross pathological examination of all survivors 2 weeks post-treatment. The single-dose oral LD50 for male rats is 2155 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

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 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

other: Standard acute method except the exposure duration was 6 hours, instead of the typical 4 hour exposure period used for acute studies, because this study was intended to help set dose levels for a 2-week inhalation study..

Limit test:

yes

Species:

other: rat and mice

Strain:

other: Fischer 344 rats and B6C3F1 mice

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Fischer 344 (F-344) rats (4-weeks of age) and B6C3F1 mice ( 7 weeks of age) were obtained from Charles River Breeding Laboratories Inc., Kingston, NY and Portage, M I , respectively. All animals were 9-10 weeks of age when exposed to DVB-55. Animals were fed Certified Rodent Chow (Purina Co., St. Louis, MO) and water ad libitum except during exposure.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test material was vapourized by metering DVB-55 at a constant rate into a glass J-tube. Heated compressed air passed through the J-tube to volatize the test material prior to entering the chamber. The compressed air was heated with a flameless heat torch (Master FHT-4) to the minimum extent necessary (70-90°C) to completely vapourize the test material. The nominal concentration (ratio of the amount of test material to vapourized to the total amount of air flowing through the chamber) was calculated for each exposure period.

Stainless and glass 157L Rochester-type chambers were used for this study. The chamber airflow was maintained at 30 L/inin. The minimum and maxinium chamber temperature for the 4 exposures ranged from 70-80°F and the relative humidity for the 4 exposures ranged from 34-62%.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

6 h

Concentrations:

Rats - 0 or 5.0 mg/L
Mice - 0, 0.8, 2.3 or 5.0 mg/L

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Details on study design:

Animals were weighed and examined prior to exposure to the test material. Animals were observed during the exposure period and at least daily during the two-week post-exposure period for any exposure related effects. All surviving rats were weighed on the first day after exposure and approximately twice per week during the two-week post-exposure period.

Statistics:

None

Sex:

male/female

Dose descriptor:

LC0

Effect level:

5 mg/L air (nominal)

Exp. duration:

6 h

Remarks on result:

other: rats

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.8 mg/L air (nominal)

Exp. duration:

6 h

Remarks on result:

other: mice

Sex:

male/female

Dose descriptor:

LC100

Effect level:

2.3 mg/L air (nominal)

Exp. duration:

6 h

Remarks on result:

other: mice

Mortality:

Rats: no mortality
Mice: 5 mg/L- 5/5 male and female mice died, 2.3 mg/L- 5/5 males died and 4/5 females died, 0.8 mg/L and controls - no deaths

Clinical signs:

other: Rats (5 mg/L) appeared to be sedated during exposure and had a reddish material around the face (up to 2 days) Mice sedated at ≥2.3 mg/L during exposure and (0.8 mg/L) slightly lethargic at the end of the 6-hr exposure period

Body weight:

In rats, a slight body weight loss was observed following exposure to DVB-55. Two weeks after exposure to DVB-55, the animal weights were comparable to control values.

Mice exposed to 0.8 mg/L DVB-55 had a greater body weight loss (approximately 10%) than control animals immediately after the exposure period. These mice quickly recovered and their body weights were comparable to control values within 2 weeks. No other effects were observed in these animals which were considered to be exposure related.

Gross pathology:

None

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 in rats is greater than 5 mg/L (highest concentration tested in this study).

Executive summary:

Groups of 5 male and 5 female rats were exposed for 6 hours to 0 or 5.0 mg/L divinylbenzene 55 (DVB-55); groups of 5 male and 5 female mice were exposed for the same time period to 0, 0.8, 2.3 or 5.0 mg/L DVB-55.

 

Exposure of rats to 5 mg/L of DVB-55 resulted in sedation during the exposure period with a reddish material around the face for at most 2 days following the exposure period. A slight body weight loss was observed following exposure to DVB-55. Two weeks after exposure to DVB-55, the animal weights were comparable to control values.

 

Mice exposed to 5 mg/L DVB-55 were sedated like the rats but died several hours after the exposure terminated. Similarly, mice exposed to 2.3 mg/L were sedated with 9 out of 10 dying shortly after the exposure terminated. Mice exposed to 0.8 mg/L DVB-55 were slightly lethargic at the end of the 6-hr exposure period and had a greater body weight loss than control animals immediately after the exposure period. These mice quickly recovered and were comparable to control values within 2 weeks. No other effects were observed in these animals which were considered to be exposure related.

Endpoint conclusion

Dose descriptor:

LC50

Value:

17 600 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Twenty-four hours prior to applying the test compound, the entire trunk of twelve rabbits, six males and six females, was clipped free of hair with electric clippers. Doses of 2.0, 3.98 or 7.95 g/kg body weight of the liquid were applied to the skin of the rabbits under a heavy gauge plastic cuff. The cuff was held in place with rubber bands and a cloth bandage taped securely to the marginal hair. At the end of the 24-hour exposure period, the cuffs were removed and the skin was washed with soap and water, rinsed thoroughly and dried with a cloth towel.

Duration of exposure:

24 hours

Doses:

2.0, 3.98 or 7.95 g/kg body weight

No. of animals per sex per dose:

2/sex/dose

Control animals:

no

Details on study design:

The animals were observed for signs of toxicity during the exposure and periodically for two weeks thereafter. Body weights were recorded before and after the 24-hour exposure and at intervals up to 2 weeks post-application or until any initial loss of body weight was regained.

Statistics:

LD50 was calculated in accordance to: Weil CS (1952) . Tables for convenient calculation of median-effective dose (LD50 or ED50) and instructions in their use, Biometries, 8: 249-263.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

8 other: g/kg

95% CL:

4.5 - 11.8

Remarks on result:

other: The LD50 was calculated to be 8.0 g/kg (95% Confidence Limits 4.5 to 11.8 g/kg) with the assumption that a dose of 15.8 g/kg would kill 100% of the animals.

Mortality:

Mortality was observed in two of the four animals at the 7.95 g/kg dosage level. Death of these animals occurred on the third day after dosing. All other animals survived.

Clinical signs:

other: other: other: other: None

Gross pathology:

None

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was calculated to be 8.0 g/kg (95% Confidence Limits 4.5 to 11.8 g/kg).

Executive summary:

An acute dermal study was conducted using methods equivalent to OECD Guideline 402. Twenty-four hours prior to applying the test compound, the entire trunk of twelve rabbits, six males and six females, was clipped free of hair with electric clippers. Doses of 2.0, 3.98 or 7.95 g/kg body weight of the liquid were applied to the skin of the rabbits under a heavy gauge plastic cuff. The cuff was held in place with rubber bands and a cloth bandage taped securely to the marginal hair. At the end of the 24-hour exposure period, the cuffs were removed and the skin was washed with soap and water, rinsed thoroughly and dried with a cloth towel. The animals were observed for signs of toxicity during the exposure and periodically for two weeks thereafter. Body weights were recorded before and after the 24-hour exposure and at intervals up to 2 weeks post-application or until any initial loss of body weight was regained.

 

Mortality was observed in two of the four animals at the 7.95 g/kg dosage level. Death of these animals occurred on the third day after dosing. All other animals survived. Surviving animals lost weight after exposure and returned to starting weight levels slowly. No clinical signs were observed throughout the study. The LD50 was calculated to be 8.0 g/kg (95% Confidence Limits 4.5 to 11.8 g/kg).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 000 mg/kg bw

Additional information

The oral LD50 values for different grades of the reaction mass of divinylbenzene and ethylstyrene in rats ranges from >2000 to 4100 mg/kg. The grades tested cover the highest concentration of divinylbenzene (DVB-96: 96% divinylbenzene and 4% ethylstyrene) and ethylstyrene (DVB-55: 55% divinylbenzene and 45% ethylstyrene). All oral LD50s were greater than 2000 mg/kg.

 

Both acute inhalation studies available for DVB-55 were conducted equivalent or similar to OECD guideline 403 with some deviations regarding the exposure duration and temperature of the vapour. In one study the highest dose tested was 5 mg/L which did not lead to any mortality in rats. However, in mice an LC50 between 0.8 and 2.3 mg/L can be estimated from that study.

In a second study DVB-55 concentrations up to 17.6 mg/L administered over 7 hours at 80°C did not cause any mortality in male rats, whereas 25.7 mg/L administered over 7 hours at 100°C killed 3 of 5 male rats. One of 5 female rats died after 2 hours exposure to 144 mg/L DVB-55 at 130°C. Based on the available data and considering the exposure conditions (duration and temperature), there is no clear evidence that the LC50 would be smaller than 20 mg/L under normal conditions. The LC50 in rats is greater than 17.6 mg/L.

 

A dermal LD50 of 8000 mg/kg bw was established for DVB-55 in a non-GLP study equivalent to OECD guideline 402. This is the only grade of this reaction mass which was tested for acute toxicity via the dermal route. However, DVB-55 contains both components of the reaction mass at equivalent concentrations. Based on the high LD50 for the reaction mass of 55% divinylbenzene and 45% ethylstyrene, it can be concluded that the other grades of the reaction mass (DVB-63 and DVB-HP), containing up to 80% divinylbenzene, are not acutely harmful via the dermal route.

Justification for classification or non-classification

LD50 values for oral and dermal route are greater than 2000 mg/kg/bw and the LC50 value is greater than 17.6 mg/L with no clear evidence for an LC50 value < 20 mg/L. The substance does not need to be classified for acute oral, dermal, or inhalation toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.