Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Purity: 98.7%
- Synonym: 4,4’-(1-methylethylidene)-bis(2,6-dimethylphenol)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Five female Sprague-Dawley rats were received from Ace Animals, Inc., Boyertown, PA. Females were nulliparous and non-pregnant, were approximately 9-10 weeks old and weighed 169 to 189 g at study start. Animals were single housed from arrival to termination and were acclimated for 8 to 13 days prior to dosing. Filtered tap water was provided ad libitum throughout the study and feed was provided ad libitum, with the exception of overnight prior to dosing. The temperature and humidity were maintained at 19-21°C and 30-56%, respectively. Room lights were on a 12-hour light/dark cycle.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
A tissue homogenizer was used to facilitate the preparation of a homogeneous mixture of the test substance in water. The test substance was administered as a 35% w/w mixture in distilled water (specific gravity = 1.060 g/mL). Preliminary solubility testing conducted by EPSL indicated mixtures in excess of 35% (i.e. 40% to 70%) were too viscous to be administered properly. Individual doses were calculated based on the initial body weights, taking into account the specific gravity and concentration of the test mixture.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
A limit test was performed. Food was withheld from the animals the night prior to dosing. Animals were administered a single dose of TMBPA by oral gavage at 2000 mg/kg as follows: One animal was dosed at 2000 mg/kg. Since this animal survived, four additional animals were dosed at 2000 mg/kg. Since these four additional animals survived, no additional testing was conducted. After dosing, each animal was returned to their cage and feed and water were provided ad libitum approximately 3 to 4 hours after dosing. All animals were observed for mortality, signs of gross toxicity and behavioral changes at least once daily for 14 days following dosing. Body weights were recorded on Day 0, prior to dose administration, Day 7 and Day 14 (termination). A gross necropsy was performed on all animals at study termination.
Statistics:
No statistical tests were performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no animals died
Clinical signs:
No clinical manifestations of toxicity were observed over the course of the study.
Body weight:
All animals gained weight throughout the study.
Gross pathology:
No gross lesions were observed during necropsy.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the conditions of this study, Tetramethyl bisphenol A (TMBPA) was determined to have an acute oral LD50 of greater than 2000 mg/kg and was assigned Toxicity Category 5 per the OECD Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Executive summary:

The acute oral toxicity of Tetramethyl Bisphenol A (TMBPA; CAS No. 5613-46-7) to female Sprague-Dawley rats was determined in an up-and-down acute oral toxicity study conducted at eurofins/Product Safety Laboratories, Dayton, NJ, USA. The study was conducted in compliance with OECD GLPs and according to the following test guidelines: OECD 425 (2006) and OPPTS 870.110 (2002).

Using the up-and-down procedure, a total of five female rats were dosed via oral gavage with the test substance at a concentration of 2000 mg/kg. A tissue homogenizer was used to facilitate the preparation of a homogeneous mixture of the test substance in water. The test substance was administered as a 35% w/w mixture in distilled water (specific gravity = 1.060 g/mL). Individual doses were calculated based on the initial body weights, taking into account the specific gravity and concentration of the test mixture.

 

No animals died and no clinical signs of toxicity were observed over the course of the study. All surviving animals gained weight throughout the study and no gross findings were observed at the terminal necropsy. 

 

Under the conditions of this study, Tetramethyl bisphenol A (TMBPA) was determined to have an acute oral LD50 of greater than 2000 mg/kg and was assigned Toxicity Category 5 as per the OECD Globally Harmonized System of Classification and Labelling of Chemicals (GHS).