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Administrative data

Description of key information

 Two acute studies are available on 1,4-butanediylbis[oxy(2-hydroxy-3,1-propanediyl)] diacrylate : one by oral route (200 < LD50 < 2000 mg/kg in rats) and one by dermal route (LD0> 2000 mg/kg in rats). No study is available by inhalation. 

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
adopted 1984
Deviations:
yes
Remarks:
modified according to BGA-modell: "Neue Wege zur Bestimmung der akuten Toxizitaet von Chemikalien" (1991)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr . K . Thomae GmbH, D-W7950 Biberach, FRG
- Age at study initiation: young adult
- Weight at study initiation: 176-190g
- Fasting period before study: >=16h (water ad lib.)
- Housing: individually in stainless steel wire mesh cages, type DK-III
- Diet (e.g. ad libitum): Kliba diet 343 ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: >= 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 or 20g/100ml
- Amount of vehicle (if gavage): 10ml/kg b.w.
- Justification for choice of vehicle: physiological

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000mg/kg b.w. was selected because no toxicity was expected based on physical and chemical characteristics of the test substance.
Doses:
200 mg/kg bw
2000 mg/kg bw
No. of animals per sex per dose:
3 females, 3 males (200 mg/kg)
3 females (2000 mg/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
observations: serveral times on day one, at least once daily thereafter
weighing: once before application, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Sex:
male/female
Dose descriptor:
LD0
Effect level:
200 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD100
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
200 mg/kg: no deaths
2000 mg/kg: all animals died within 4-24h
Clinical signs:
200 mg/kg: no symptoms
2000 mg/kg: poor general state, dyspnoea, apathy, abdominal position, atonia, paresis, cyanosis, diarrhea
Body weight:
200 mg/kg: no effects
2000 mg/kg: no effects
Gross pathology:
200 mg/kg: no effects
2000 mg/kg: general congestion
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study, the LD50 was found to be greater than 200 mg/kg and less than 2000 mg/kg bw.
Executive summary:

A group of 6 fasted animals (3 males and 3 females) was given a single oral dose of test material preparation in aqua bidest at the dose level of 200 mg/kg bw. Another group of 3 females was treated in the same way with a dose of 2000 mg/kg bw.

The animals treated with 200 mg/kg bw did not show any mortality or symptoms. No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Signs of toxicity noted in females treated with 2000 mg/kg bw comprised poor general state, dyspnea, apathy, abdominal position, atonia, paresis, cyanosis and diarrhea. All females treated with 2000 mg/kg bw died 4 hours or 1 day after treatment. Necropsy findings of the animals that died was general congestion.

Under the conditions of this study, the range of LD50 after oral application was found to be greater than 200 mg/kg bw and less than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
200 mg/kg bw
Quality of whole database:
The study is considered as reliable with a klimisch score of 1.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted Feb. 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males app. 8 weeks, females app. 12 weeks
- Weight at study initiation: males: 225 - 251g; females: 203 - 219g
- Fasting period before study: no
- Housing: single housing in Makrolon type III cages
- Diet (e.g. ad libitum): VRF1(P); SDS Sepcial Diets Services, Altrip, Germany
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
semiocclusive
Vehicle:
olive oil
Remarks:
only for the 500mg/kg b.w. group; 2000mg/kg were applied undiluted
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 40cm² (= at least 10% of body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, using warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.71ml/kg b.w. (2000mg/kg); 2.00ml/kg b.w. (500mg/kg)
- Concentration (if solution): undiluted (2000mg/kg); 25g/100mL (500mg/kg)

Duration of exposure:
24h
Doses:
500 mg/kg bw, 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of application, daily thereafter on workdays
- Frequency of weighing: on day 0, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin findings (scored according to Draize 30-60minutes after removal of the dressing and weekly thereafter)
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Systemic effects: none

Local effects in males:
2000 mg/kg: erythema grade 2 on day 1, which decreased to grade 1 on day 2 or 3
500 mg/kg: erythema grade 3 on day 1 in 3 of 5 males which decreased to grade 1 until day 5. Grade 1 or 2 erythema were noted in the other 2 males on days 1 and 2.
All local effects were reversible within 7 days at the latest.

Local effects in females:
2000 mg/kg: erythema grade 3 in 3 of 5 females on day 1 which persisted in two animals until day 6 or 7. Very slight erythema were still noticed on day 10 or day 13 in these animals. Erythema grade 2 which persisted until day 2 or 7 were noted in the remaining 2 females. Incrustations were noted in 4 animals from day 2/3 to day 14.
500 mg/kg: erythema grade 3 on days 1 and 2, which decreased to grade 1 until day 5 or 6.
Body weight:
The mean body weight of the animals increased within the normal range throughout the study period.
Gross pathology:
no abnormalities observed
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test substance after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Executive summary:

In an acute dermal toxicity study (Limit Test), 5 male and 5 female young adult Wistar rats per group were dermally exposed to test groups of 2000 and 500 mg/kg bw of 1,4-butanediylbis[oxy(2-hydroxy-3,1-propanediyl)] diacrylate (undiluted or preparation in olive oil) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semiocclusive dressing for 24 hours. During the 14 day observation period, no mortality occured and no signs for systemic toxicity were recorded. Slight to moderate erythema (grade 1 to 3) were noted, and incrustations occured in females exposed to 2000 mg/kg bw. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted. Accordingly, the acute dermal median lethal dose (LD50) was determined to be higher than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The study is considered as reliable with a klimisch score of 1.

Additional information

Oral acute toxicity study (1993):

An acute toxicity test (toxic class method) according to EU method B.1. modified according to the BGA modell and similar to OECD 423 was performed under GLP conditions in 1993. A group of 6 fasted animals (3 males and 3 females) was given a single oral dose of test material preparation in aqua bidest at the dose level of 200 mg/kg bw. Another group of 3 females was treated in the same way with a dose of 2000 mg/kg bw.

The animals treated with 200 mg/kg bw did not show any mortality or symptoms. No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Signs of toxicity noted in females treated with 2000 mg/kg bw comprised poor general state, dyspnea, apathy, abdominal position, atonia, paresis, cyanosis and diarrhea. All females treated with 2000 mg/kg bw died 4 hours or 1 day after treatment. Necropsy findings of the animals that died was general congestion.

Under the conditions of this study, the range of LD50 after oral application was found to be greater than 200 mg/kg bw and less than 2000 mg/kg bw.

Dermal acute toxicity study (2011):

In an acute dermal toxicity study (Limit Test), 5 male and 5 female young adult Wistar rats per group were dermally exposed to test groups of 2000 and 500 mg/kg bw of 1,4-butanediylbis[oxy(2-hydroxy-3,1-propanediyl)] diacrylate (undiluted or preparation in olive oil) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semiocclusive dressing for 24 hours. During the 14 day observation period, no mortality occured and no signs for systemic toxicity were recorded. Slight to moderate erythema (grade 1 to 3) were noted, and incrustations occured in females exposed to 2000 mg/kg bw. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted. Accordingly, the acute dermal median lethal dose (LD50) was determined to be higher than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate should be classified as Acute tox 4 (H302, oral route) according to the Regulation EC n°1272/2008.

Justification: Since the oral LD50 was greater than 200 mg/kg, but smaller than 2000mg/kg. No signs of toxicity were noted at 200 mg/kg and no mortality occurred, so that it is considered unlikely that half the animals would die when treated with 300 mg/kg.

Because no animals died after dermal application of up to 2000 mg/kg, no classification is required for dermal acute toxicity.