4,4'-isopropylidenedi-2,6-xylol

Endpoint summary

Description of key information

An acute oral toxicity test on rats (OECD 425) and an acute dermal toxicity test on rats (OECD 402) were conducted under GLP to assess the acute toxicity of TMBPA. Data waiver for acute inhalation toxicity is included.  Under the conditions of the studies, TMBPA was determined to have no significant acute toxicity.

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:

April 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system 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.

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.

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

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).

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

April 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Sprague-Dawley rats were received from Ace Animals, Inc., Boyertown, PA. Animals were approximately 8-9 weeks old and weighed 224-257 g (males) and 186 to 199 g (females) at study start. Females were nulliparous and non-pregnant. Animals were single housed from arrival to termination and were acclimated for 8 days prior to dose administration. Filtered tap water was provided ad libitum by an automatic water dispensing system and feed was provided ad libitum throughout the study. The temperature and humidity were maintained at 20-23°C and 38-66%, respectively. Room lights were on a 12-hour light/dark cycle.

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

On the day prior to application, a group of naïve animals was prepared by clipping the dorsal area and the trunk. After clipping, the animals were examined for health, weighed and the skin checked for any abnormalities. In order to assure adequate contact of the test substance with the skin, the test substance was moistened with distilled water to produce a 70% w/w mixture, which appeared as a dry paste. The test substance mixture (2000 mg/kg body weight) was then applied to a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches by 3 inches (approximately 10% of the body surface). The gauze pad and entire trunk of each animal were wrapped with 3-inch Durapore tape. The rats were then returned to their designated cages. After the 24 hour exposure period, the pads were removed and the test sites were gently cleansed of any residual test substance.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

The animals were observed for mortality, signs of gross toxicity and behavioral changes during the first several hours after application and at least once daily thereafter for 14 days. The animals were observed for signs of erythema and edema after the exposure period according to the Draize Scale for Scoring Skin Reactions. Animals were weighed at Day 0 (prior to dose administration), Day 7 and Day 14 (termination). All animals were euthanized via CO2 inhalation on Day 14 and a gross necropsy was performed. Tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

Statistics: No statistical tests were performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died over the course of this study.

Clinical signs:

No overt signs of toxicity were observed during the course of the study.

Body weight:

All animals gained weight during the post-treatment period.

Gross pathology:

No gross lesions were observed during necropsy.

Other findings:

none

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 dermal 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).

Executive summary:

The acute dermal toxicity of Tetramethyl Bisphenol A (TMBPA; CAS No. 5613-46-7) was determined in a limit test study with male and female Sprague-Dawley rats 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 402 (1987) and EPA OPPTS 870.1200 (1998).

In order to assure adequate contact of the test substance with the skin, the test substance was moistened with distilled water to produce a 70% w/w mixture, which appeared as a dry paste. The test substance mixture (2000 mg/kg body weight) was then applied to the clipped backs of 5 male and 5 female rats. The application site was covered with an occlusive dressing for the 24-hour exposure period, after which the test sits were gently cleansed of any residual test substance. Animals were observed for 14 days post exposure.

 

All animals survived the study, no clinical signs of toxicity were observed and no signs of irritation were seen on the test sites. All animals gained weight during the post-treatment period.

 

Under the conditions of this study, Tetramethyl bisphenol A (TMBPA) was determined to have an acute dermal 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).

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Under the conditions of these studies, Tetramethyl bisphenol A (TMBPA) was determined to have an acute oral LD50 of greater than 2000 mg/kg, and to have an acute dermal LD50 of greater than 2000 mg/kg. In accordance with Column 2 of Annex VIII (8.5), an acute inhalation study does not need to be conducted for substances other than gases if a study is available for the oral route (8.5.1), and at least one other route. As the substance is a solid and a dermal acute toxicity study is also available, the conditions required to justify a data waiver are met.

Justification for classification or non-classification

Based on the observed LD50 of >2000 mg/kg bw in the acute oral and dermal toxicity study, the test substance does not need to be classified according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.