5-ethylidene-8,9,10-trinorborn-2-ene, manufacture of, by-products from

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

version December 2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

version May 2008

Test guideline 3

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

Test material information

Constituent 1

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

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

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

Reference substance name:

cis-1,2-Divinylcyclobutane

Cas Number:

2422-85-7

Molecular formula:

C8H12

IUPAC Name:

cis-1,2-Divinylcyclobutane

Constituent 5

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

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

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

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

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

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

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

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:

other: 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.

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.