Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 February 1980 - 27 February 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to methods similar to OECD guideline 401 (limit test) and was performed pre-GLP. A concise description of the protocol is available and results are reported clearly.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
pre-GLP test
Test type:
standard acute method
Limit test:
yes

Test material

1
Chemical structure
Reference substance name:
3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indenyl propionate
EC Number:
272-805-7
EC Name:
3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indenyl propionate
Cas Number:
68912-13-0
Molecular formula:
C13H18O2
IUPAC Name:
3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl propionate
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace animals
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 179 - 298 grams
- Fasting period before study: 16 - 20 hours
- Housing: 5 animals per cage in suspended wire mesh cages (20 x 10 x 7)
- Diet: Fresh Purina rat chow ad libitum
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21 C
- Animal room was reserved exclusively for rodents on acute tests and kept clean.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.0 g/kg (5000 mg/kg) (The dose was based on the sample weight as calculated from the specific gravity)
Doses:
5000 mg/kg body weight
No. of animals per sex per dose:
10 male rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rats were observed 3 - 4 hours after dosing and once daily for 14 days
- Necropsy of survivors performed: yes, all animals were sacrified and examined for gross pathology
- Other examinations performed: mortality, toxicity and pharmacological effects
Statistics:
The LD50 was calculated according to the method of Litchfield, JT Jr & Wilcoxon, F. JPET 96:99, 1949 (if possible).

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed (0/10)
Clinical signs:
All animals had lethargy and piloerection 3 - 4 hours post dosing. Lethargy persisted in all animals to day 1. One instance of oily anogenital area was noted on day 1. Chromorhinorrhea was noted in five or more animals on day 2 and 3. All animals were normal on day 4 until day 12. Isolated instances of ptosis, chromorhinorrhea, diarrhea, piloerection and lethargy were noted on day 13 and 14. Nine animals were normal on day 14.
Gross pathology:
On day 14, internal organs of all animals were normal upon superficial examination.

Applicant's summary and conclusion

Interpretation of results:
other: not acute harmful
Remarks:
according to EU CLP (EC 1272/2008 and its amendments)
Conclusions:
In an acute oral toxicity study with Cyclaprop, all animals survived a dose of 5000 mg/kg bw. It can be concluded that Cyclaprop was not acute toxic by the oral route under the conditions of this test.
Executive summary:

The acute oral toxicity of Cyclaprop was determined in an acute oral toxicity study according to methods similar to OECD401 (limit test). Ten male rats were dosed 5000 mg/kg bw test material by gavage. The rats were observed 3 - 4 hours after dosing and once daily for 14 days. Mortality, toxicity, pharmacological effects and gross pathology were examined.

All animals survived a dose level of 5000 mg/kg bw, resulting in a LD50 > 5000 mg/kg bw. The most prevalent toxic signs were lethargy (persisting to day 1 in all animals), piloerection (3 -4 hrs post-dosing in all animals) and chromorhinorrhea (on day 2 and 3 in five or more animals).All animals were normal on day 4 until day 12. Isolated instances of ptosis, chromorhinorrhea, diarrhea, piloerection and lethargy were noted on day 13 and 14. Nine animals were normal on day 14. After necropsy on day 14, internal organs of all animals normal upon superficial examination.

Based on these results, Cyclaprop does not need to be classified as acute toxic via the oral route in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC, under the conditions of this test.