α,α,α',α'-tetramethyl-m-xylene-α,α'-diol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 June 2011 - 20 August 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study does not conform to current guidlines but rather to an older OECD guideline. The study was not conducted in a GLP certified lab. However, the study was audited by the QA unit and appears to be conducted in the "spirit" of GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The study has several deviations from the current guideline.
- The study was performed according to OECD401, a test method that has been banned by OECD in 2002 due to animals welfare reasons. However, this devaiton would not impact the outcome of the study.
- Multiple doses were given. The highest dose given in the study is 10,000 mg/kg bw, the limit dose in 2,000 mg/kg bw. A limit study should have been performed.
- The laboratory has no GLP accreditation. However, it was audited by the QA unit and appears to have been conducted in the "spirit" of GLP.
- The LD50 was calculated using the Horn's method which is not a standard method, and not one of the recommended methods in the guideline. However, no toxicity was noted at the dose of 2150 mg/kg which is approximately the limit dose. Therefore, the LD50 can be stated as being > 2000 mg/kg without the need of statistics.
- It is not mentioned if water/diet is analyzed for contaminants.

GLP compliance:

no

Remarks:

The study was conducted in China for a Chinese registration. The study was not conducted in a GLP certified lab. However, the study was audited by the QA unit and appears to be conducted in the "spirit" of GLP.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α,α,α',α'-tetramethyl-m-xylene-α,α'-diol

EC Number:

217-886-1

EC Name:

α,α,α',α'-tetramethyl-m-xylene-α,α'-diol

Cas Number:

1999-85-5

Molecular formula:

C12H18O2

IUPAC Name:

2-[3-(2-hydroxypropan-2-yl)phenyl]propan-2-ol

Details on test material:

Name: α,α,α',α'-tetramethyl-m-xylene-α,α'-diol
Lot No.: 101155
odourless white solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals were kept in animal room, National Institute of Occupational Health and Poison Control, China CDC (barrier environment, Certificate No.: SYXK(Jing) 2009- 0032). Environmental conditions for animal husbandry are maintained with the 12-h light/dark cycle, the temperature of 20-23℃, and the relative humidity of 40-70%. All animals had free access to sterilized drinking water and irradiation sterilized commercial pellet diets except during exposure (Beijing Keao Xieli Laboratory Diet Co., Ltd. Certificate No.: SCXK(Jing) 2009- 0012). Animals were acclimatized to the laboratory conditions for at least 3d prior to the test.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

1000, 2150, 4640 and 10000 mg/kg bw for female, and 2150, 4640, 10000 and 21500 mg/kg bw for male, respectively.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Forty rats, 20 of each sex, were divided randomly into 4 groups. The exposed dosages were 1000, 2150, 4640 and 10000 mg/kg bw for female, and 2150, 4640, 10000 and 21500 mg/kg bw for male, respectively. The animals were fasted 12h before exposure and were given test substance by gavage with a feeding needle.
The cage side observation has been given. During a 14-day post-exposure period, animals were observed daily, including the onset of signs, recovery and mortality. Individual body weight were measured and recorded on day 3, 7 and 14. Necropsy was performed for the dead rats. On the day 14 of the observation period, all surviving animals were sacrificed and were necThe LD50 and 95% confidence were determined by Horn's method.

Statistics:

The LD50 and 95% confidence were determined by Horn's method.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

4 300 mg/kg bw

Based on:

test mat.

95% CL:

2 950 - 6 260

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

5 010 mg/kg bw

Based on:

test mat.

95% CL:

3 440 - 7 300

Mortality:

See table below.

Clinical signs:

other: Clinical observation: The signs such as, activity decreased, limb weakness, side position, dyspnea, issued open mouth berathing were observed in the higher dose groups (21500 and 10000 mg/kg) animals about 10 minutes after treatment. Death occurred within

Gross pathology:

Such gross pathological findings as pulmonary hemorrhage and congestion of livers were observed in the died rats. No gross pathological changes were observed in the survival animals at necropsy.

Any other information on results incl. tables

Sex	Dose (mg/kg)	Number of tested animals	Number of death	Mortality (%)
Female	10000	5	5	100
	4640	5	3	60
	2150	5	0	0
	1000	5	0	0
Male	21500	5	5	100
	10000	5	5	100
	4640	5	2	40
	2150	5	0	0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 (95% confidence limits): The oral LD50 (95% confidence limits) of the test substance is 4300 (2950-6260) mg/kg for female rats and 5010 (3440-7300) mg/kg for male rats, respectively.

Executive summary:

The objective is to evaluate the acute oral median lethal dose (LD₅₀) of the substance, and research the gross systemic toxicity after oral administration. The acute oral LD50 (95% confidence limits): The oral LD50 (95% confidence limits) of the test substance is 4300 (2950-6260) mg/kg for female rats and 5010 (3440-7300) mg/kg for male rats, respectively.