Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 29 April 2019 to 21 May 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid
EC Number:
948-054-2
Molecular formula:
not applicable - the substance is an UVCB
IUPAC Name:
4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS B.V.,Inc (The Netherlands)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation:
- Fasting period before study: Food removed overnight prior to dosing
- Housing: Makrolon cages with stainless steel mesh lids and furnished with granulated soft wood bedding
- Diet: Rodent 2018C Teklad Global Certified Diet ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity 45 to 65%
- Air changes (per hr): At least eight air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 30% DMSO+70% PEG 400
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Concentration: 30 or 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test item was formulated at concentrations of 30 and 200 mg/mL in the vehicle and administered at a constant dose volume of 10 mL/kg body weight. Solidifying of the test item in a 50°C water bath was used to formulate the test item in the vehicle.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
One animal/dose for the initial sighting test. Four additional animals for the main test.
Control animals:
no
Details on study design:
Details on study design
- Duration of observation period following administration: Fourteen days
- Frequency of observations: Morbidity / mortality inspection occurred twice daily, early and late, during a normal working day and once daily at weekends and public holidays.
- Necropsy of survivors performed: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained. - Other examinations performed: Body weights were recorded on day 0 (prior to dosing), 7, and 14, or at death. Clinical observations were performed 30 minutes and 1, 2, and 4 hours after dosing, then at least once daily for 14 days.

Results and discussion

Preliminary study:
No mortality was observed at 300 and 2,000 mg/kg bw during the sighting test. Therefore, a dose of 2,000 was used for the main test.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical signs of reaction to treatment throughout the study.
Body weight:
The animals showed expected gains in body weight over the observation period.
Gross pathology:
Animal treated at 300 mg/kgw showed minor and unspecific abnormalities at the macroscopic examination at study termination on Day 14, which included a slightly enlarged, fluid-filled uterus.
Minor and unspecific abnormalities were noted in the animals at the macroscopic examination at study termination on Day 14, which included included an enlarged and fluid-filled uterus in one animal treated with 2000 mg/kg b.w., and slimy content of the stomach in three animals treated with 2000 mg/kg b.w..

Any other information on results incl. tables

See attached background material

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Following an acute oral toxicity experiment in rats, it was determined that 4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid (EC 948-054-2) was not acutely toxic via the oral route under the conditions of the study. The LD50 is >2000 mg/kg bw therefore the substance does not meet the criteria for classification according to Regulation 1272/2008.
Executive summary:

The acute toxicity of 4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid (EC 948-054-2) via the oral route was evaluated during a study performed according to the OECD Testing Guideline 420. The study was GLP-compliant.

The fixed dose method was used. One female Wistar rat received by gavage a single dose of 300 mg/kg bw. In the absence of observable toxicity at 300 mg/kg bw, an animal was treated at 2,000 mg/kg bw. Considering that no mortality or clear signs of toxicity were observed, four additional female Wistar rats were treated at 2,000 mg/kg bw.

Following exposure to the test substance, animals were observed for 14 days. Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily until the end of the observation period. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14. At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

It was concluded that 4,4’-isopropylidenediphenol, reaction products with 1-chloro-2,3-epoxypropane, mono, di and triesters with acrylic acid (EC 948-054-2) has a LD50 > 2,000 mg/kg bw via the oral route.