5-vinylnorborn-2-ene

Endpoint summary

Description of key information

Vinyl norbornene is expected to have a relatively low degree of acute toxicity.  Results for VNB are available for all routes of exposure:

Oral LD50: All rat.  male: 5239mg/kg, female: 10567mg/kg

Inhalation LC50: Rat male: 11.2mg/l, female: 12.6mg/l.

Dermal, rabbit LD50: >8ml/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Comparable to guideline study. Well documented study which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: between 200-300 grams

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

Animals were dosed orally by gavage (liquid).

Doses:

1.25, 2.5, 5, 7.1, 10, 19.9 ml/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: daily. Weighed 7 and 14 days after dosing.

Sex:

male

Dose descriptor:

LD50

Effect level:

5 239 mg/kg bw

95% CL:

4 539 - 6 127

Sex:

female

Dose descriptor:

LD50

Effect level:

10 567 mg/kg bw

95% CL:

5 950 - 187 368

Clinical signs:

other: Clinical signs of toxicity were observed in dose groups. At the lowest dose, these were limited to sluggishness and unkemp appearance. At higher doses, also seen were lacrimation, kyphosis, unsteady gait and diarrhea, which appeared within 30-45 min pos

Gross pathology:

The only consistent finding at necropsy of rats that died was mottled dark pink or red lungs. No gross pathology was seen in survivors at necropsy. 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 values indicate a low degree of toxicity. Females had a LD50 value numerically about twice that for males. The marginally significant difference in LD50 values between males and females were due mainly to the greater variability of females to the peroral toxicity of ENB.

Executive summary:

Ballantyne et al (1997) published acute oral LD50 values of ~5200 mg/kg (males) and 10500 mg/kg (females) for vinyl norbornene in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 200 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Comparable to guideline study. Well documented study which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Method not specified

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Vapour produced by metered piston pump delivering liquid into a heated evaporator at 40-50C
- Exposure chamber volume: 1300litre
- Method of holding animals in test chamber:
- Source and rate of air: 250litre/min
TEST ATMOSPHERE
- Brief description of analytical method used: gas sampler and GC/FID every 5 minutes. Nominal concentrations based on mass volume consumed.
- Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1551, 2084, 2365, 2682, 3259 ppm.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: daily. Weighted at 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology.

Sex:

male

Dose descriptor:

LC50

Effect level:

2 231 ppm

95% CL:

1 938 - 2 568

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

2 518 ppm

95% CL:

2 268 - 2 796

Exp. duration:

4 h

Mortality:

Males: 0/5, 1/5, 3/5, 5/5, 4/5 at each dose. For females, none died up to 2365ppm, all died at 2682ppm and above.

Clinical signs:

other: At approximately the LC50 concentration, animals exhibited hind leg paralysis in 7/20 animals post exposure. Hypereactivity, tremors, and convulsions also reported.

Body weight:

Decreased body weight was seen at 2084ppm but not at 1581ppm.

Gross pathology:

No gross pathology was reported..

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The 4-hr LC50 value indicates a moderate degree of vapor toxicity. At these high vapor concentration, signs are predominantly those of a central excitatory nature, particularly hypereactivity, tremors, and convulsions.

Executive summary:

In a reliable study, Ballantyne et al (1997) published acute 4 -hr LC50 values of 2231 ppm (11.2 mg/l) (males) and 2518 ppm (12.6 mg/l) (females) for vinyl norbornene vapor in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

11.2 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Comparable to guideline study. Well documented study which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

. Only two doses given.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products Inc, Denver, PA
- Weight at study initiation: between 2-3 kg
- Housing: singly in wire mesh cages.
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped dorsal trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no. Excess wiped away after occlusive dressings removed.

Duration of exposure:

24 hr

Doses:

8.0, 16 mL/kg

No. of animals per sex per dose:

High dose group 4, low dose group 5.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations. Weighing at 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Mortality:

One male died in the high dose group on day 4.

Clinical signs:

other: Signs of possible systemic effects were few and included almost immediate vocalization on applying the dose, persisting for about 5-15 min. Sluggishness and laboured breathing were seen with a few males. On removal of the occlusive dressing there was som

Gross pathology:

No gross pathology was observed at necropsy in most survivors, although a few had dark or bright red lungs. The one deceased animal showed mottled liver and multiple black foci in the stomach wall.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Undiluted VNB produced slight acute percutaneous systemic toxicity and severe irritancy by single 24-hr contact with skin.

Executive summary:

Ballantyne et al (1997) published an acute (24 -hr occlusive exposure) dermal LD50 value of >16ml/kg (13.8g/kg) for vinyl norbornene in rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

13 800 mg/kg bw

Additional information

There are reliable acute toxicity studies on the substance vinyl norbornene (VNB) by the inhalation route, the oral route and the dermal route. The acute oral LD₅₀value was 5239 mg/kg for male rats and 10567 mg/kg for female rats. The acute inhalation LC₅₀values were 11.2 mg/L for male rats and 12.6 mg/L for female rats. The dermal LD₅₀value was greater than 16ml/kg (13800 mg/kg) for male and female rabbits.

Justification for selection of acute toxicity – oral endpoint
Only available study in dossier

Justification for selection of acute toxicity – inhalation endpoint
Only available study in dossier

Justification for selection of acute toxicity – dermal endpoint
Only available study in dossier

Justification for classification or non-classification

Based on the available animal data, there is sufficient information available to determine that no classification is required for the oral, and dermal routes of acute exposure. Classification as acute toxicity category 4 under the CLP regulation and Xn under directive 67/548 is required for the inhalation route.