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Description of key information

The potential of acute toxicity of Ethoxylated Bisphenol A dimethacrylate was evaluated in two studies (oral & dermal route). No mortality was showed in both studies; the oral and dermal LD50 were higher than 2000 mg/kg in rats.

No data 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
Study period:
27 Aug 2019 - 23 Sep 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl: WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 11 weeks old
- Weight at study initiation: 178 to 199 g.
- Fasting period before study: overnight prior to dosing and until 3-4 hours after administration of the test item
- Housing: group housed (up to 3 animals of the same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany)
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum, throughout the study, except during designated procedures.
- Water: municipal tap-water, ad libitum
- Acclimation period: 5 days before the commencement of dosing

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 21 (18-24)
- Humidity (%): 41-73 (40-70)
- Air changes (per hr): =10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27 Aug 2019 To: 17 Sep 2019
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
TEST ITEM PREPARATION: the test item was administered as received.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight

CLASS METHOD
- Rationale for the selection of the starting dose: based on available toxicity data of the test item, the starting dose level was the one that was likely to produce mortality in at least some of the animals.
- The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as dose level (g/kg) / spec.gravity.
- The dosing formulations were stirred continuously during dose administration.
Doses:
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.
No. of animals per sex per dose:
6 females (2000 mg/kg/)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
* Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day.
* Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
* Animals were weighed individually on day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
Not performed
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
Restless behavior, hunched posture and/or piloerection were noted for the animals between days 1 and 3.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD0 value of Ethoxylated (3) bisphenol A dimethacrylate in Wistar Han rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The objective of this study was to assess the toxicity of the test item when administered in a single dose to female rats at one defined dosage. The study was carried out in compliance with the guidelines described in OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method".


Ethoxylated (3) bisphenol A dimethacrylate was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).


No mortality occurred. Restless behavior, hunched posture and/or piloerection were noted for the animals between Days 1 and 3. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.


The oral LD0 value of Ethoxylated (3) bisphenol A dimethacrylate in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Study is 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
Study period:
10 December 2019 - 02 January 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)
Version / remarks:
2017
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Charles River Deutschland, Sulzfeld, Germany
- 3 females (nulliparous and non-pregnant)
- Age at study initiation: Young adult animals (approximately 10-11 weeks old)
- Weight at study initiation: 194 - 212 g
- Housing: On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.). During the study animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum.
- Water: tap water, ad libitum.
- Acclimation period: at least 5 days

Periodic analysis of the water was performed and feed was analyzed by the supplier for nutritional components and environmental contaminants. It is considered that there were no known contaminants in the feed or water that would interfere with the objectives of the study.

ENVIRONMENTAL CONDITIONS
Temperature (°C): 20 - 21
Humidity (%): 43 - 53
Air changes (per hr): >= 10
Photoperiod (hrs dark/hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
Area of exposure: 18 cm^2
% coverage: approx. 10% of the total body surface
Type of wrap if used: a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages.

REMOVAL OF TEST SUBSTANCE
- Washing: water
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
3 females at 2000 mg/kg bodyweight
Control animals:
not required
Details on study design:
RANGEFINDING STUDY
A range finding study was performed in order to select the dose causing no mortality or significant toxicity to be used in the main study. One animal was dosed at 2000 mg/kg bw.

MAIN STUDY
- Duration of observation period following administration: 14 days
- Frequency of observations: on the day of dosing (at least three times) and once daily thereafter
- Mortality: twice daily
- Body weights: on day 1 (pre-dose), 8 and 15
- Irritation: The skin reactions were assessed approximately 24, 48 and 72 hours after the removal of the dressing and test item. Adjacent areas of untreated skin of each animal served as controls.
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No signs of systemic toxicity were observed.
Body weight:
The body weight gain shown by the surviving animals during the observation period was within the range expected for rats used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
Irritation effects: Very slight erythema was noted in the treated skin-area of one animal on Days 4 and 5 only.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an acute dermal study, performed according to OECD guideline 402 and GLP principles, the dermal LD0 value of Ethoxylated (3) bisphenol A dimethacrylate in Wistar Han rats was determined to exceed 2000 mg/kg bodyweight. As a consequence, Ethoxylated (3) bisphenol A dimethacrylate is not classified according to CLP criteria.
Executive summary:

An acute dermal study was performed according to OECD guideline 402 and GLP principles. Three female rats were exposed at test item concentration of 2000 mg/kg bodyweight and observed for 14 days. No mortality occured. Very slight erythema was noted in the treated skin-area of one animal on Days 4 and 5. No unexpected changes in body weight gain occurred, no clinical signs were observed and no abnormalities were seen at necropsy. These results demonstrate that the dermal LD0 value of Ethoxylated (3) bisphenol A dimethacrylate in Wistar Han rats exceeds 2000 mg/kg bodyweight. As a consequence, Ethoxylated (3) bisphenol A dimethacrylate is not classified according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

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

Additional information

Oral Acute Toxicity study (van Huygevoort 2019)


The objective of this study was to assess the toxicity of the test item when administered in a single dose to female rats at one defined dosage. The study was carried out in compliance with the guidelines described in OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method".


Ethoxylated (3) bisphenol A dimethacrylate was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).


No mortality occurred. Restless behavior, hunched posture and/or piloerection were noted for the animals between Days 1 and 3. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.


The oral LD0 value of Ethoxylated (3) bisphenol A dimethacrylate in Wistar Han rats was established to exceed 2000 mg/kg body weight.


 


Dermal Acute Toxicity study (Van der Wiel 2020)


An acute dermal study was performed according to OECD guideline 402 and GLP principles. Three female rats were exposed at test item concentration of 2000 mg/kg bodyweight and observed for 14 days. No mortality occured. Very slight erythema was noted in the treated skin-area of one animal on Days 4 and 5. No unexpected changes in body weight gain occurred, no clinical signs were observed and no abnormalities were seen at necropsy. These results demonstrate that the dermal LD0 value of Ethoxylated (3) bisphenol A dimethacrylate in Wistar Han rats exceeds 2000 mg/kg bodyweight.

Justification for classification or non-classification

Based on the available data by oral and dermal route, no classification for acute toxicity is required for Ethoxylated (3) bisphenol A dimethacrylate according to the Regulation EC 1272/2008.

Justification: no mortalities were observed in both studies at 2000 mg/kg.

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