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

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

227-033-5

EC Name:

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

Cas Number:

5613-46-7

Molecular formula:

C19H24O2

IUPAC Name:

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

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:

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.

Administration / exposure

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.

Results and discussion

Effect levels

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

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 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).