Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
version December 2001
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
version May 2008
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
Version December 2002
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3a,4,7,7a-tetrahydro-1H-indene
EC Number:
221-260-3
EC Name:
3a,4,7,7a-tetrahydro-1H-indene
Cas Number:
3048-65-5
Molecular formula:
C9H12
IUPAC Name:
3a,4,7,7a-tetrahydro-1H-indene
Constituent 2
Chemical structure
Reference substance name:
4-vinylcyclohexene
EC Number:
202-848-9
EC Name:
4-vinylcyclohexene
Cas Number:
100-40-3
Molecular formula:
C8H12
IUPAC Name:
4-vinylcyclohexene
Constituent 3
Chemical structure
Reference substance name:
Cyclopentadiene
EC Number:
208-835-4
EC Name:
Cyclopentadiene
Cas Number:
542-92-7
Molecular formula:
C5H6
IUPAC Name:
cyclopenta-1,3-diene
Constituent 4
Chemical structure
Reference substance name:
cis-1,2-Divinylcyclobutane
Cas Number:
2422-85-7
Molecular formula:
C8H12
IUPAC Name:
cis-1,2-Divinylcyclobutane
Constituent 5
Chemical structure
Reference substance name:
Ethylbenzene
EC Number:
202-849-4
EC Name:
Ethylbenzene
Cas Number:
100-41-4
Molecular formula:
C8H10
IUPAC Name:
ethylbenzene
Constituent 6
Chemical structure
Reference substance name:
5-vinylnorborn-2-ene
EC Number:
221-259-8
EC Name:
5-vinylnorborn-2-ene
Cas Number:
3048-64-4
Molecular formula:
C9H12
IUPAC Name:
5-vinylbicyclo[2.2.1]hept-2-ene
Constituent 7
Chemical structure
Reference substance name:
Cycloocta-1,5-diene
EC Number:
203-907-1
EC Name:
Cycloocta-1,5-diene
Cas Number:
111-78-4
Molecular formula:
C8H12
IUPAC Name:
cycloocta-1,5-diene
Constituent 8
Chemical structure
Reference substance name:
3a,4,7,7a-tetrahydro-4,7-methanoindene
EC Number:
201-052-9
EC Name:
3a,4,7,7a-tetrahydro-4,7-methanoindene
Cas Number:
77-73-6
Molecular formula:
C10H12
IUPAC Name:
3a,4,7,7a-tetrahydro-4,7-methanoindene,
Constituent 9
Chemical structure
Reference substance name:
3a,4,7,7a-tetrahydro-4-methyl-1H-indene
EC Number:
231-021-5
EC Name:
3a,4,7,7a-tetrahydro-4-methyl-1H-indene
Cas Number:
7413-02-7
Molecular formula:
C10H14
IUPAC Name:
4-methyl-3a,4,7,7a-tetrahydro-1H-indene
impurity 1
Chemical structure
Reference substance name:
Combination of: 6-(cyclohex-3-en-1-yl)bicyclo[2.2.1]hept-2-ene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4-methanonaphthalene 6-vinyl-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethanonaphthalene 2,2'-bi(bicyclo[2.2.1]heptane-5,5'-diene) 3a,4,4a,5,8,8a,9,9a-octahydro-1H-5,8-methanocyclopenta[b]naphthalene 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene
Molecular formula:
C13H18 to C14H18
IUPAC Name:
Combination of: 6-(cyclohex-3-en-1-yl)bicyclo[2.2.1]hept-2-ene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4-methanonaphthalene 6-vinyl-1,4,4a,5,6,7,8,8a-octahydro-1,4-methanonaphthalene 2-vinyl-1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethanonaphthalene 2,2'-bi(bicyclo[2.2.1]heptane-5,5'-diene) 3a,4,4a,5,8,8a,9,9a-octahydro-1H-5,8-methanocyclopenta[b]naphthalene 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene
Constituent 10
Chemical structure
Reference substance name:
4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene OR 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4:5,8-dimethanofluorene
Molecular formula:
C14H18 to C15H18
IUPAC Name:
4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluorene OR 4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4:5,8-dimethanofluorene
Constituent 11
Chemical structure
Reference substance name:
3a,4,4a,5,8,8a,9,9a-octahydro-4,9:5,8-dimethano-1H-benz[f]indene
EC Number:
230-512-1
EC Name:
3a,4,4a,5,8,8a,9,9a-octahydro-4,9:5,8-dimethano-1H-benz[f]indene
Cas Number:
7158-25-0
Molecular formula:
C15H18
IUPAC Name:
3a,4,4a,5,8,8a,9,9a-octahydro-1H-4,9:5,8-dimethanocyclopenta[b]naphthalene
Constituent 12
Reference substance name:
Tetramers of cyclopentadiene and 1,3-butadiene
Molecular formula:
C16H24 to C20H24
IUPAC Name:
Tetramers of cyclopentadiene and 1,3-butadiene
Test material form:
liquid
Details on test material:
Light brown liquid.
Batch number 776809

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200mg/mL for the sighting and main study
- Amount of vehicle (if gavage): 10mL/kg
- Justification for choice of vehicle: solubility considerations
- Lot/batch no. (if required):

MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: sighitng study using one animals each at doses of 300 and 2000mg/kg. In the absence of mortality at 2000mg/kg a further four animals were dosed at this concentration.
Doses:
300mg/kg and 2000mg/kg for range finder. 2000mg/kg for main study.
No. of animals per sex per dose:
Range finder: 1
Main study total: 5 (female only)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily observations, weighing days 1, 8 and 15. Additional observations if toxic signs observed
- Necropsy of survivors performed: yes/no
- Examinations performed: clinical signs, body weight, gross pathology (brain, cecum, duodenum, heart, kidneys, small and large intestine, liver, lungs, bronchi, spleen, stomach, subcutaneous tissue, urinary bladder).
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
None
Clinical signs:
At 2000mg/kg: piloerection and underactivity in 4/5 animals. Resolved within 5 hours but observed again on day 2 (underactivity 4/5 animals, piloerection 2/5 animals). Absent from day 3 onwards.
Body weight:
Low weight seen in one animal on days 8 and 15.
Gross pathology:
No abnormalities noted

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Not classified as harmful under EU implementation of GHS
Executive summary:

In a guideline and GLP fixed dose procedure acute oral toxicity study in rats, no lethality was observed in the 5 females exposed to a single gavage dose of 2000mg/kg during the 14 day observation period. Piloerection and slight underactivity was noted in most animals in the first two days and low body weight gain in a single animal from day 8 onwards. According to this result, this substance THI-TM does not need to be classified for acute toxicity by the oral route.