2,2,4,4-tetramethylcyclobutane-1,3-diol, mixed isomers

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 22 - March 8, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted under OECD guideline 402 and utilized various GLP assurances

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (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:

2,2,4,4-tetramethylcyclobutane-1,3-diol, mixed isomers

EC Number:

221-140-0

EC Name:

2,2,4,4-tetramethylcyclobutane-1,3-diol, mixed isomers

Cas Number:

3010-96-6

Molecular formula:

C8H16O2

IUPAC Name:

2,2,4,4-tetramethylcyclobutane-1,3-diol

Details on test material:

The test substance, identified as 2,2,4,4-Tetramethyl-I,3-cyclobutanediol, Lot #X2960I-54-5, was received on December 19, 2005 and was further
identified with PSL Reference Number 051219-3H. The test substance consisted of white crystals and was stored at room temperature. Prior to use, the test substance was ground in a coffee mill (Krups Model 203). In order to insure adequate contact with the skin, the sample was applied as a dry paste (75% w!w mixture in mineral oil). Test article purity was 99.6%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number of Animals: I 0
Sex: 5 Males and 5 Females. Females assigned to test were nulliparous and non-pregnant.
Species/Strain: Rats/Sprague-Dawley derived, albino
Age/Body weight: Young adult (I 0 weeks)/males 316-333 grams and females 200-216 grams at experimental start.
Source: Received from Ace Animals, Inc., Boyertown, PA on February 7, 2006.

Housing: The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was
changed at least three times per week.
Animal Room Temperature Range: 20-24°C
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 15 days
Food: Purina Rodent Chow #5012
Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: mineral oil

Details on dermal exposure:

Prior to application, the test substance was ground in a coffee mill then moistened with mineral oil to achieve a dry paste by preparing a 75% w/w mixture. Two thousand mg/kg ofbody weight ofthe test substance was then applied to a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of
approximately 2 inches x 3 inches (approximately I 0% of the body surface). The gauze pad and entire trunk of each animal were then wrapped with
3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated
cages. The day of application was considered Day 0 of the study. After 24 hours of exposure to the test substance, the pads were removed and the
test sites were gently cleansed of any residual test substance.

Duration of exposure:

24 hours

Doses:

2,000 mg/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

On the day prior to application, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial) and the slkin checked for any abnormalities. Ten healthy rats (five males and five females) were
selected for test. Individual doses were calculated based on the initial body weights, taking into account the concentration of the test mixture.
The day of application was considered Day 0 of the study. After 24 hours of exposure to the test substance, the pads were removed and the test
sites were gently cleansed of any residual test substance. Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination). 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. Observations included gross evaluation of skin and fur, eyes and
mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma. All rats were euthanized via C02 inhalation on Day 14. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

Not required as there were no deaths at the single limit dose.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

0/10

Clinical signs:

other: All animals appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse pharmacologic effects, or abnormal behavior.

Gross pathology:

No gross abnormalities were noted for any ofthe animals when necropsied at the conclusion of the 14-day observation period

Applicant's summary and conclusion

Conclusions:

The acute dermal toxicity is >2,000 mg/kg

Executive summary:

An acute dermal toxicity test was conducted with 10 rats (5/sex) to determine the potential for

2,2,4,4 -tetramethyl-1,3 -cyclobutanediol to produce toxicity from a single topical application of 2,000 mg/kg. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for I 4 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

All animals survived, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse pharmacologic effects, or abnormal behavior. No gross abnormalities were noted for any ofthe animals when necropsied at the conclusion ofthe 14 -day observation period. Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 2,000 mg/kg of body weight in male and female rats.