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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 October 1999 - 14 March 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Alcohols, C12-14 (even numbered), propoxylated, aminated
Molecular formula:
C12H27N (C3H6O)n n=1-5, C14H31N (C3H6O)n n=1-4
IUPAC Name:
Alcohols, C12-14 (even numbered), propoxylated, aminated
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: test item provided by sponsor

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: males 8 weeks, females 9 weeks
- Weight at study initiation: 177-193g (dose range), 187-254 (main study)
- Fasting period before study: overnight
- Housing: group housing during acclimation, single housed during study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
- Method of randomisation in assigning animals to test and control groups : based on weight

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30 November 1999 To: 23 December 1999

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: test item is soluble in water
- Lot/batch no. (if required): 0630991047
- Purity: distilled water
Doses:
dose range finding study: 500, 2500, 5000 mg/ kg bw
main study: 1000, 1500, 2000 mg/ kg bw
No. of animals per sex per dose:
dose range finding study: 1 animal/sex/dose
main study: 5 animals/ sex/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded 1 and 4 hours after dosing and once/ day from day 2 to 15. Body weight was recorded on days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: all surviving rats were sacrificen on day 15 and necropsis were perfomed including examination of the extermal body surface, all orifices and the thoracic, pelvic and the abdominal cavities and their contents
Statistics:
Litchfield and Wilcoxon method for confidence limit calculation

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 308.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 100 - <= 1 556.1
Sex:
female
Dose descriptor:
LD50
Effect level:
1 212.4 mg/kg bw
Based on:
test mat.
95% CL:
>= 933.9 - <= 1 574.1
Sex:
male
Based on:
test mat.
Remarks on result:
other: could not be determined with the statistical method used
Mortality:
One of 10 animals died at 1000mg/kg bw and seven of ten animals died at 1500mg/kg bw. All animals were found dead at 2000mg/kg bw by day 5.
Clinical signs:
Decreased activity, decreased body tone, abnormal gait, abnormal stance, piloerection, poor grooming, soft stools and dark areas around the nose and/or eyes were observed in all three dose levels. Dry eyes and hair loss was observed at 1000mg/kg bw with body quivers and right eye closure observed at 1500mg/kg bw with prostration observed at 2000mg/kg bw.
Body weight:
All surviving animals gained waight during the course of the study.
Gross pathology:
No visible lesions were observed in the surviving animals. In the animals found dead lesions of the stomach or intestines predominated. Pale intestines, mottled liver, dark liver and dark discharge from the mouth/ nose and/ or anal area were also seen.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the study the combined LD50 for males and females is 1308.3mg/ kg bw.
Executive summary:

The study evaluated the acute oral toxicity with a 14- day post dose observation period in Sprague Dawley rats.

In a dose ranging study the doses of 500, 2500 and 5000mg/kg bw were tested. Based on the resutls the doses selected for the main study were 1000, 1500 and 2000mg/kg bw.

Three groups of ten rats (5 males and 5 females) were administered a single oral dose. Clinical observations were recorded 1 and 4 hourse post dosing and daily from day 2 to 15. body weights were recorded on days 1, 8 and 15. Surviving animals were euthanised on day 15 and gross necropsy was perfomed.

One of 10 animals died at 1000mg/kg bw and seven of ten animals died at 1500mg/kg bw. All animals were found dead at 2000mg/kg bw by day 5.

Clinical signs included decreased activity, decreased body tone, abnormal gait, abnormal stance, piloerection, poor grooming, soft stools and dark areas around the nose and/or eyes were observed in all three dose levels. Dry eyes and hair loss was observed at 1000mg/kg bw with body quivers and right eye closure observed at 1500mg/kg bw with prostration observed at 2000mg/kg bw.

Necropsis showed in the animals found dead lesions of the stomach or intestines predominated. Pale intestines, mottled liver, dark liver and dark discharge from the mouth/ nose and/ or anal area were also seen. No lesions were observed in the animals surviving to day 15.

Based on the results of the study the combined LD50 for males and females is 1308.3mg/ kg bw (95% CL 1100- 1556.1 mg/kg bw)