Registration Dossier

Administrative data

Description of key information

Oral
- OECD 423, GLP (K1): LD50, rat > 2000 mg/kg bw (2004)


Inhalation
- IHT (7 h), GLP not specified (K2): LC0, rat = 0.00054 mg/L air (1982)


Dermal
- OECD 402, GLP not specified (K2): LD50, rabbit > 2000 mg/kg bw (1980)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Nov - Dec 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP compliant
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Landesanstalt für Pflanzenbau und Pflanzenschutz - Rheinland Pfalz, signed on 24 Sep. 2001
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Füllinsdorf, Switzerland
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 182 g (mean body weight)
- Fasting period before study: at least 16 hours before administration, water was available ad libitum
- Housing: individually in stainless steel wire mesh cages, type DK-III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/100 ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium
- Purity: doubly distilled water


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
2000 mg/kg
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross-pathology
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
without findings or clinical signs
Body weight:
The mean body weights of the administration groups increased throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (2,000 mg/kg, 6 females) examined at termination of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of the test item after oral administration was found to be greater than 2,000 mg/kg body weight in rats.
Executive summary:

The study was performed to assess the acute toxicity following oral administration in Wistar rats in a GLP-compliant study performed according OECD 423 guideline.

Single doses of 2,000 mg/kg body weight of test material preparations in doubly distilled water were given to two administration groups of three fasted female animals, each, by gavage in a sequential manner. After an observation period of 14 days no mortality occurred. Moreover, no clinical signs were observed. The mean body weights of the administration groups increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals of the 2,000 mg/kg administration group examined at the end of the observation period.

Under the conditions of this study, the median lethal dose of the test item after oral administration was found to be greater than 2,000 mg/kg body weight in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Principles of method if other than guideline:
BASF-Test
The inhalation hazard test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (usually 20°C). Groups of rats were sequentially exposed to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted disc in a glass cylinder for different time periods.
No analytical determination of the atmosphere concentrations was performed. The nominal concentration usually can be calculated as quotient of the amount of the test substance weight loss during exposure. Group-wise documentation of clinical signs was performed over the 14 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period in surviving animals.
GLP compliance:
not specified
Test type:
other: Inhalation Risk Test
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Wiga, Sulzfeld, Germany
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 180 - 250 g
- Housing: 3 animals per cage in Becker D III cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 2°C
- Humidity (%): 50+-5 %
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
see: any other informations on materials and methods
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Concentrations:
The dose, based on the a vapor pressure of ca. 0.000044 hPa at 20 °C, computes to ca. 0.00054 mg/l.
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were checked daily for clinical signs
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross-pathology
Statistics:
not applicable
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.001 mg/L air
Exp. duration:
7 h
Remarks on result:
other: All 12 animals exposed to the test material survived.
Mortality:
no deaths, all 12 animals survived the 14 days post exposure
Clinical signs:
other: wiping of the snout
Body weight:
no data
Gross pathology:
without findings
Interpretation of results:
GHS criteria not met
Conclusions:
All 12 animals survived the inhalation risk test, where the animals were exposed to a saturated vapor of the test substance (concentration ca. 0.00045 mg/l) for 7 hours.
Executive summary:

The acute inhalation toxicity was investigated in an Inhalation Risk test with rats (reliability 2). The test was performed in principle as described in OECD test guideline 403 (GLP not specified). It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at 20 °C. Young adult laboratory rats, 6 per sex, were exposed sequentially to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 7 hours. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as 0.000545 mg/l based on the vapor pressure. Group-wise documentation of clinical signs was performed over a 14 day study period. All animals survided inhalative exposure and showed no gross pathology findings. Clinical symptoms soley included wiping of the snout throughout expsoure.

Based on the study findings no acute inhalation toxicity can be concluded for animals expsosed to a saturated vapor of the test item.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
0.54 mg/m³

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
abraded skin, occlusive conditions
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Physical state: liquid
- Analytical purity: no data
- Storage condition of test material: room temperature away from heat and light
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratory Animals, Denver, Pennsylvania, USA
- Age at study initiation: young adults
- Weight at study initiation: males: 2.3-2.5 kg, females: 2.3-3.0 kg
- Fasting period before study: no data, not required
- Housing: individually housed in suspended stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 17 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 °C (65-71 °F)
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of the body surface, abraded skin
- Type of wrap if used: a layer of 8-ply gauze was wrapped around the animal to cover the application site. The animal was then wrapped in an
impervious plastic sleeve, designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and
Elizabethan collars were placed on all animals.


REMOVAL OF TEST SUBSTANCE
Following approximately 24 hours of exosure, the wrappings were removed and the test site wiped free of excess test material. After 30 minutes,
dermal observations were made.


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.9 ml/kg bw
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: no, volume appplied according to body weight

Duration of exposure:
24 hours of occlusive exposure on abraded skin
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: viability check: twice a day; observations of pharmacologic and toxicologic signs: 1, 2 and 4 hours after
dosing and daily thereafter for 14 days; body weights at the time of clipping, day of dosing, day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
all animals survived (5 male, 5 female)
Clinical signs:
No abnormalities were noted during the four hours after dosing. Three males exhibited fecal staining at 24 hours and one female exhibited this sign
at 24 hours and on Day 2. One female exhibited decreased food consumption at 24 hours. One female exhibited clear nasal discharge on a single
occasion and clear ocrilar discharge on several occasions. Another female was noted to have an apparent broken leg or lower back on Day 9 and
exhibited soft stool, fecal staining and/or urinary staining, decreased food consumption, decreased activity and/or prostration from Day 9 through
termination.
At the 24-hour dermal observation, the males exhibited well-defined to severe erythema accompanied by very slight or moderate edema. The females exhibited very slight or well-defined erythema accompanied by severe edema.
Body weight:
Four males and three females exhibited slight weight gains during the fourteen-day post-dose observation period. One male and one female
exhibited no net change in weight at Day 14. One female exhibited a slight weight loss at day 7 and an overall weight loss of 0 .7 kg by day 14. This
animal was noted to have a possible broken leg or lower back injury during the second week of study.
Gross pathology:
no findings in 4/10 animals, 6/10 animals with findings which included: 5/10 animals with slightly irregular, slightly diminished or purplish spleen, 2/10 animals mottled pale liver (20%-40%), 2/10 animals with pale kidneys, 1/10 animals with slight fecal staining, 1/10 animals with empty stomach,
1/10 animals with broken leg
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study a single dermal dosing with 2000 mg/kg test substance did not cause mortality of rabbits after treatment of the abraded skin. Therefore, the LD50 of the test item is greater then the tested limit dose.
Executive summary:

Acute dermal toxicity was investigated with 10 albino rabbits (five/sex) treated with a single dose of 2000 mg/kg similar to OECD protocol of guideline 402 (GLP not specified, reliability 2). Single occlusive dosing at a dose volume of 1.9 ml/kg was performed on abraded skin for 24 hours. Under this study conditions no mortality was observed during the observation period of 14 days. Four males and three females exhibited slight weight gains, whereas one male and one female rabbit exhibited no net change in theig bodyweight. One female animal exhibited a weight loss, however, this animal was noted to have a possible broken leg or lower lack injury during the second week of the study. Well defined to severe erythema accompanied by very slight or moderate edema were observed in males after 24 hours. Females exhibited very slight or well-defined erythema accompanied by severe edema. No abnormalities of clinical signs were noted during the four hours after dosing. Three males exhibited fecal staining at 24 hours and one female exhibited this sign at 24 hours and on Day 2. One female exhibited decreased food consumption at 24 hours. One female exhibited clear nasal discharge on a single occasion and clear ocrilar discharge on several occasions. Another female was noted to have an apparent broken leg or lower back on Day 9 and exhibited soft stool, fecal staining and/or urinary staining, decreased food consumption, decreased activity and/or prostration from Day 9 through termination. Six of the tested ten animals had gross pathology findings which included: 5/10 animals with slightly irregular, slightly diminished or purplish spleen,  2/10 animals mottled pale liver (20%-40%), 2/10 animals with pale kidneys, 1/10 animals with slight fecal staining, 1/10 animals with empty stomach, 1/10 animals with broken leg.

Due to the abscence of mortality under the tested conditions of this study no LD50 value was derived.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

There are valid data available for the assessment of the acute oral, dermal and inhalative toxicity of the test substance.

 

Oral

In a standard acute test, according to OECD guideline 423 and in compliance with GLP, six female Wistar rats were treated with 2000 mg/kg bw tripropylene glycol diacrylate under standardized conditions (2004). The animals were observed for 14 d, necropsy was performed even with the survivors. No deaths occurred, the LD50 is > 2000 mg/kg bw for female rats. No clinical signs of toxicity were reported. The mean body weights of the administration groups increased throughout the study period and no macroscopic pathologic abnormalities were noted in the animals examined at termination of the study.

Other reliable study findings are available and support the key finding.

In an oral toxicity study, 5 male and 5 female Sprague-Dawley rats were administered 5000 mg/kg bw of the test material under standardized conditions (1982, realibility 2). The animals were observed for 14 d, necropsy was performed even with the survivors. One male animal died on day 2 and one female animal died on day 1, in total 2/10 animals died, the LD50 is >5000 mg/kg bw for female rats. Dyspnoe, apathy, staggering, scrubby fur, salivation and a generally bad general condition were observed. The mean body weight increased within the normal range during the study period. At gross necropsy an acute dilatation of the prechambers of the heart, acute congestive hyperanemia, as well as vascula injections in the stomach/intestine were seen in the animals that died during the study and the intestine was atonic. In the sacrificed animals the gastroesophageal vestibule was thickened in the stomach and a sporadic agglutination of the gastroesophageal vestibule with the peritoneum was seen.

In two further studies, both similar to OECD 401, rats were administered 5000, 6400, 8000 and 10000 mg/kg bw and 3500, 5000, 7000, 10000 and 14200 mg/kg bw, respectively under standardized conditions (1980, 1984, both reliability 2). In both studies the LD50 was 6800 mg/kg bw for male and female rats.

 

Inhalation

The acute inhalation toxicity was investigated in an Inhalation Risk test with rats (1982, reliability 2). The test was performed in principle as described in OECD test guideline 403 (GLP not specified) with an atmosphere saturated with vapors of the volatile components of a test substance at 20 °C. Young adult laboratory rats, 6 per sex, were exposed sequentially to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 7 hours. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as 0.00054 mg/l based on the vapor pressure. Group-wise documentation of clinical signs was performed over a 14 day study period. All animals survided inhalative exposure and showed no gross pathology findings. Clinical symptoms soley included wiping of the snout throughout exposure. The gross necropsy of all animals was inconspicuous.

Based on the study findings no acute inhalation toxicity can be concluded for animals exposed to a saturated vapor of the test item.

Dermals

Acute dermal toxicity was investigated with 10 albino rabbits (five/sex) treated with a single dose of 2000 mg/kg similar to OECD protocol of guideline 402 (1980, GLP not specified, reliability 2). Single occlusive dosing at a dose volume of 1.9 ml/kg was performed on abraded skin for 24 hours. Under this study conditions no mortality was observed during the observation period of 14 days. Four males and three females exhibited slight weight gains, whereas one male and one female rabbit exhibited no net change in their bodyweight. One female animal exhibited a weight loss, however, this animal was noted to have a possible broken leg or lower lack injury during the second week of the study. Well defined to severe erythema accompanied by very slight or moderate edema were observed in males after 24 hours. Females exhibited very slight or well-defined erythema accompanied by severe edema. No abnormalities of clinical signs were noted during the four hours after dosing. Three males exhibited fecal staining at 24 hours and one female exhibited this sign at 24 hours and on Day 2. One female exhibited decreased food consumption at 24 hours. One female exhibited clear nasal discharge on a single occasion and clear ocular discharge on several occasions. Another female was noted to have an apparent broken leg or lower back on Day 9 and exhibited soft stool, fecal staining and/or urinary staining, decreased food consumption, decreased activity and/or prostration from Day 9 through termination. Six of the tested ten animals had gross pathology findings which included: 5/10 animals with slightly irregular, slightly diminished or purplish spleen,  2/10 animals mottled pale liver (20%-40%), 2/10 animals with pale kidneys, 1/10 animals with slight fecal staining, 1/10 animals with empty stomach, 1/10 animals with broken leg.

Due to the absence of mortality under the tested conditions of this study no LD50 value was derived.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No mortality occurred at the limit dose of 2000 mg/kg bw via the oral and dermal route. As a result, the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.

Since an inhalation hazard tests with rats exposed to a saturated vapor atmosphere of the test item for 7 h revealed no mortality and only transient clinical signs, there is no indication given to classify the substance according to EU or GHS requirements for its acute inhalation toxicity. It is stressed, that due to the high reactivity of the substance, aerosols should not be inhaled.