Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 February 1980 - 7 March 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to methods similar to OECD guideline 402 (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 402 (Acute Dermal 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:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Ace animals
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 2.1 - 2.8 kg
- Fasting period before study: no fasting
- Housing: 2 animals per cage in suspended wire mesh cages (30 x 18 x 8)
- Diet: Fresh Purina rabbit chow ad libitum
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21 C

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 200 cm2
- % coverage: approximately 10% of the body surface
- Type of wrap if used: gauze patches secured with adhesive tape (trunks of animals wrapped with impervious material)
-Abrasion: in the even numbered rabbits, abrasions were made (abrasions scratched the stratum corneum but did not reach the derma or produce bleeding)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): exposure site was wiped, not washed, to remove excess material
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.0 g/kg (5000 mg/kg bw)
- Constant volume or concentration used: yes

Duration of exposure:
24 hours
Doses:
5000 mg/kg bw (dose based on sample weight as calculated from specific gravity)
No. of animals per sex per dose:
First, two rabbits were exposed. If no deaths occured, eight additional animals were dosed at 5000 mg/kg bw.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Dermal reactions were scored 24 hours after removal of the patch by the Draize scoring system. The rabbits were observed daily for 14 days.
- Necropsy of survivors performed: yes, all animals were exmained for gross pathology.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Rabbits were observed for signs of toxicity, pharmacological effects and moratlity. Body weight were recorded pretest and in the survivors at 14 days.

Results and discussion

Preliminary study:
Two rabbits were dosed 5000 mg/kg bw. No mortality occured.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died at day 14 (mortality 1/10)
Clinical signs:
At day 1, 7 animals showed very slight erythema, 1 animal showed well defined erythema and 1 animal showed moderate to severe erythema, 4 animals showed slight edema.
Body weight:
There was no significant change in body weight.
Gross pathology:
At necropsy, the animal that died on day 14 showed pronounced / many liver nodules and slight / scattered scaly skin. One other animal also showed slight / scattered scaly skin.
The internal organs of all survivors were normal upon superficial examination.
Other findings:
The animal that died at day 14, showed lethargy from day 5 until day 8 and at day 12 and 13. At day 7, 8, 12 and 13 this animal had diarrhea.
Four other animals showed lethargy during the study. The lethargy remained just for one day and all the animals recovered. One animal showed tachypnea at day 5 and 6.
Most animals were generally healthy throughout the test period.

Any other information on results incl. tables

Individual body weights and skin grades

 Rabbit number Dose volume (cc)  Weight (kg) day 0  Weight (kg) day 14  Erythema score  Edema score 
 1 12.6  2.7  2.9 
 2 (abraded) 12.2  2.6  3.0 
 3 13.1  2.8  3.1 
 4 (abraded) 10.3  2.2  1.9 
 5* 9.8  2.1  2.0 
 6 (abraded) 10.3  2.2  2.3 
 7 11.7  2.5  2.7 
 8 (abraded) 13.1  2.8  3.2 
 9 11.7  2.5  2.9 
 10 (abraded) 13.1  2.8  3.0 

* dead on day 14

Applicant's summary and conclusion

Interpretation of results:
other: Not acute harmful
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments)
Conclusions:
In an acute dermal toxicity study, one animal died after a dosage of 5000 mg/kg bw test material on the abdomen of 10 rabbits. The LD50 of the test material is > 5000 mg/kg bw. Based on these results, Cyclaprop, is not considered to be acute toxic via the dermal route.
Executive summary:

New Zealand White rabbits, 7 males and 3 females, were used to determine the acute dermal toxicity of Cyclaprop. The abdominal fur of the animals was clipped and abrasions were made in five (even numbered) animals. The rabbits were dosed at 5000 mg/kg bw. The test material was applied under gauze patches and secured with adhesive tape. After 24 hours of skin contact the wrappings were removed. Dermal reactions were scored after 24 hours using the Draize scoring system and the animals were observed daily for 14 days.

One death occurred, resulting in a LD50 > 5000 mg/kg bw. Most animals were generally healthy throughout the test period. The skin reactions were nonexistent to slight (one surviving animal with scaly skin) and body weight changes were within expected limits. All animal were normal upon necropsy, only one animal, dead on day 14, had liver nodules and scaly skin.

Based on these results, Cyclaprop does not need to be classified as acute toxic via the dermal 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.