Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980-08 to 1980-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
comparable to guideline Methode OECD 401
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
3-aminomethyl-3,5,5-trimethylcyclohexan-1-ol

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Source: W. Gassner, Sulzfeld
- Weight at study initiation: 110-130 g
Environmental conditions:
Keeping of animals: diet: Ssniff R 10 pellets;
Water ad libitum;
Room temperature 22°C +/- 1C°C
Light 12 hours per day,
Diet deprived 16 hours before oral application of test substance

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Doses: calculated from volume
- Doses per time period: single dose (gavage)
Doses:
1.6 / 2.0 / 2.5 / 3.2 ml/kg bw
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
yes
Remarks:
4.0 ml Aqua dest/kg bw.
Details on study design:
- Volume administered or concentration: undiluted test substance: 1.6 / 2.0 / 2.5 / 3.2 ml/kg bw, control animals: 4.0 ml Aqua dest/kg bw.
- Post dose observation period: 14 days
EXAMINATIONS: 
- Frequency of observations: The animals were observed for deaths or overt signs of toxicity twice after dosing and subsequently once daily for fourteen days.

central nervous system, lung, heart, heart sac, stomach,  large intestine, small intestine, liver, spleen, kidneys, serosa, lymph  nodes, gonads, perineum
Statistics:
- LD50 calculation: according to Weil, C.S. (Biometrics, 8, 249, 1952)

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2.1 mL/kg bw
95% CL:
>= 1.9 - <= 2.3
Remarks on result:
other: Volume/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 142 mg/kg bw
95% CL:
> 1 938 - < 2 346
Remarks on result:
other: Mass/kg bw
Mortality:
- Time of death: within 24 hours
- Number of deaths at each dose 14 days after substance application: control: 0/10;   1.6 ml/kg: 0/10 ;  2.0 ml/kg: 7/10 ; 2.5 ml/kg: 7/10; 3.2 ml/kg: 10/10;   
- LD50 (14 days) = 2.10 ml/kg    confidence interval: 1.9 - 2.3 ml/kg  
Clinical signs:
increase of locomotive behaviour, piloerection, sedation,  in higher  dose groups also increasing gnawing
Body weight:
Growth rates returned to normal by the end of the post exposure  observation period
Gross pathology:
NECROPSY FINDINGS:
Moderate hyperemia, congestion of liver,  reddening of stomach and bloody intestinal mucosa of dead animals.
No findings at the end of post exposure period.

Any other information on results incl. tables

table of results see under attached background material

Applicant's summary and conclusion

Conclusions:
Treatment related mortality and other sublethal symptoms were observed in rats within the 14 day post-dosing period for the doses used in this acute oral toxicity study. The LD50 (oral) was calculated to be LD50 (14 days) = 2.10 ml/kg.  
Executive summary:

The test item was applied once to 4 dose-groups of rats (5 male and 5 female Sprague Dawley rats per dose-group) in doses of 1.6 / 2.0 / 2.5 / 3.2 ml/kg bw of undiluted test item. Control animals was applied once to 4.0 ml aqua dest/kg bw.

The observation period was 14 days.

In all doses groups a increase of locomotive behaviour, piloerection, sedation,  in higher  dose groups also increasing gnawing was observed beginning 1 h after dosing and lasting 24 hours.

At the highest dose (3.2 ml/kg bw) all animals died within 24 hours after oral application of the test item. Necroscopy findings were moderate hyperemia, congestion of liver,  reddening of stomach and bloody intestinal mucosa. There were no findings at the end of post exposure period.

According to this study the LD50 value (oral) was determined to be 2.1 ml/kg bw in rats for the test item