Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
09 June 2011 - 20 August 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has deviations and the information in the report is incomplete. Nevertheless it is sufficient for assessment of acute oral toxicity.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: The Guidelines for the Testing of Chemicals (State Environmental Protection Administration of China, 2004.5, 401, Acute Oral Toxicity Test)
Deviations:
no
GLP compliance:
no
Remarks:
The laboratory has no GLP accreditation (nevertheless the project plan and the report were audited by the Quality Assurance Unit)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- 135-156g Wistar rats, SPF grade, were supplied by Vital River Lab Animal Technology Co., Ltd
- 12-h light/dark cycle
- temperature of 20-23°C
- relative humidity of 40-70%
- All animals had free access to sterilized drinking water and irradiation sterilized commercial pellet diets except during exposure
- Animals were acclimatized to the laboratory conditions for at least 3 days prior to the test.
- Fasting period: 12 hours before esposure

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

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
4 300 mg/kg bw
Based on:
test mat.
95% CL:
2 950 - 6 260
Sex:
male
Dose descriptor:
LD50
Effect level:
5 010 mg/kg bw
Based on:
test mat.
95% CL:
3 440 - 7 300
Clinical signs:
The signs such as, activity decreased, limb weakness, side position, dyspnea, issued open mouth breathing were observed in the higher dose groups (21500 and 10000 mg/kg) about 10 minutes after treatment. Death occurred within 4 hour after exposure. The rats in the
4640 mg/kg dose group showed slighter signs and the number of deaths was less than the higher dose groups above. No toxic signs and death occurred in the 2150 and 1000 mg/kg dose groups. The survival animals recovered within 24 hours after exposure.
Gross pathology:
At 10000 mg/kg, pulmonary hemorrhage and congestion of the liver were observed in 5/5 females; and at 4640 they were observed in 3/5 females.At 21500 mg/kg and 10000 mg/kg, pulmonary hemorrhage and congestion of the liver were observed in 5/5 males; and at 4640 they were observed in 2/5 males.
No gross pathological changes were observed at necropsy at 2150 mg/kg and 1000 mg/kg dose groups.

Any other information on results incl. tables

Sex Dose (mg/kg) Mortality
Female 10000 5/5
4640 3/5
2150 0/5
1000 0/5
Male 21500 5/5
10000 5/5
4640 2/5
2150 0/5

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
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.Taking into consideration both males and females, the LD 50 is aoproximately 4655 mg/kg.
Executive summary:

The acute oral toxicity of a,a,a',a'-tetramethyl-m-xylene-a,a'-diol was evaluated in Wistar rats according to OECD N°401 guideline (Acute Toxic Standard Method), but not in compliance with GLP. Groups of 5 male and 5 female Sprague Dawley rats were given a,a,a',a'-tetramethyl-m-xylene-a,a'-diol in corn oil by oral exposure at doses of 464, 1000, 2150 and 4640 mg/kg for female and 1000, 2150, 4640 and 10000 mg/kg for male . Following treatment, rats were observed daily and weighted on days 3, 7 and 14 . A gross necropsy examination was performed at the time of scheduled euthanasia (Day 14).

 

The signs such as activity decreased, limb weakness, side position, dyspnea, issued open mouth breathing were observed in the higher dose groups (21500 and 10000 mg/kg) about 10 minutes after treatment. Death occurred within 4 hour after exposure (mortality was observed from 4640 mg/kg both in males and in females). The rats in the 4640 mg/kg dose group showed slighter signs and the number of deaths was less than the higher dose groups above. No toxic signs and death occurred in the 2150 and 1000 mg/kg dose groups. The survival animals recovered within 24 hours after exposure.

At necropsy, pulmonary hemorrhage and congestion of the liver were observed in dead animals only.

 

The results indicate that 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. Taking into consideration both males and females, the LD 50 is aoproximately 4655 mg/kg.