Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 12 June, 1986 to 13 September, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study was conducted according to the OECD guideline 401 and EPA OPP 81-1 as well as in compliance with GLP. Deviation: one animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. This deviation does not affect the scientific validity or integrity of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.
Qualifier:
according to
Guideline:
other: Toxic Substances Control Act (TSCA) Health Effects Test Guidelines
Deviations:
yes
Remarks:
One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Physical state: Clear colourless liquid
- Analytical purity: Not specified
- Lot/batch No.: 1422206
- Storage condition of test material: Room temperature, protected from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Portage, Michigan
- Weight at study initiation: 205-262 g
- Fasting period before study: 18 h
- Housing: Individually housed in wire-mesh cages
- Diet: Purina certified rodent chow # 5002, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: Minimum 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): more than 40%
- Photoperiod (h dark/h light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 0.93 mL/kg
Doses:
0, 512, 620, 750 and 908 mg/kg bw .
No. of animals per sex per dose:
Five animals per sex per dose except for the highest dose which has only 5 males.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of clinical observation: 1, 2.5 and 4 h after dosing on Day 0 and subsequently once daily for 14 d.
- Frequency of weighing: On Days 0, 7 and 14
- Necropsy of survivors performed: Yes
- Examinations performed: Clinical signs, body weight and gross pathological examination.
Statistics:
LD50 values and slopes (with 95% confidence limit) were calculated by method of Litchfield and Wilcoxon.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
684 mg/kg bw
Based on:
test mat.
95% CL:
629 - 743
Mortality:
There was no mortality in the 512 mg/kg bw group while 3 out of 10 and 7 out of 10 rats died in the 620 and 750 mg/kg bw groups, respectively. All the five animals died receiving the highest tested dose of 908 mg/kg bw.
Clinical signs:
Four males in the 512 mg/kg bw group had yellowish anogenital staining during early study period and one of these animals had diarrhoea. Several animals in the 620, 750 and 908 mg/kg bw showed anogenital staining, diarrhoea, brown staining around the mouth, respiratory distress, ataxia, lethargy, salivation and hypothermia. Animals in the 908 mg/kg bw also showed clear ocular discharge and tremors.
Body weight:
No effect
Gross pathology:
Changes were observed in the adrenal glands, brain, kidneys, stomach and intestines for more than one and half of all rats died during study. Abnormalities in the liver were found in of 7/15 of the dead rats. No significant changes for all tissues examined for rats that were terminally sacrificed, including control group.

Any other information on results incl. tables

In the range-finding study, all the rats dosed at 1000, 1500 and 2000 mg/kg bw died while rats dosed at 500 mg/kg bw survived.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the test substance in Sprague-Dawley rats was found to be 684 mg test susbtance/kg bw.
Executive summary:

An OECD 401 study was performed to assess the acute oral toxicity of C12-C18 TMAC in Sprague-Dawley rats. Groups of 10 fasted animals (five males and five females per dose except for five males in the highest dose) were administered 0, 512, 620, 750 and 908 mg/kg bw of the test substance (purity not specified) via the oral route. The animals were observed for 14 days after dosing and then sacrificed and subjected to gross pathological examination. There was no mortality in the 512 mg/kg bw group while 3 out of 10 and 7 out of 10 rats died in the 620 and 750 mg/kg bw groups, respectively. All five animals died receiving the highest tested dose of 908 mg/kg bw. The acute oral LD50of the test substance in Sprague-Dawley rats was determined to be 684 mg test substance/kg bw

with 95% confidence limits of 629−743 mg test substance/kg bw . (Naas DJ, 1987).