Reaction products of ((5E)-5-ethylidenebicyclo[2.2.1]hept-2-ene and (5Z)-5-ethylidenebicyclo[2.2.1]hept-2-ene) and 2-methyl-1,3-butadiene, epoxidized

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-GLP study following a method equivalent to a recognised guideline. Minor deviations not deemed to impact the reliability of the study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Limit test of 2000 mg/kg bw on clipped-abraded skin and occlusive dressing.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.40

Version / remarks:

The principles of the method were in accordance with the US 16 CFR 1500.3 definitions.

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of ((5E)-5-ethylidenebicyclo[2.2.1]hept-2-ene and (5Z)-5-ethylidenebicyclo[2.2.1]hept-2-ene) and 2-methyl-1,3-butadiene, epoxidized

EC Number:

942-422-6

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

Reaction products of ((5E)-5-ethylidenebicyclo[2.2.1]hept-2-ene and (5Z)-5-ethylidenebicyclo[2.2.1]hept-2-ene) and 2-methyl-1,3-butadiene, epoxidized

Test material form:

other: liquid

Details on test material:

- Physical state: liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: Approximately 8 weeks of age.
- Weight at study initiation: Between 1.8 and 2.5 kg
- Housing: The animals were housed in compliance with US 9 CFR Part 3; group housed two per cage in suspended wire mesh cage.
- Diet: rabbit chow ad libitum
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Clipped area was 200 square cm ; abrasions were completed in at least 50% of the exposure sites extending the length of the exposure site. Abrasion was scratching of the stratum corneum but which did not reach derma or produce bleeding.
- % coverage: approximately 10%
- Type of wrap if used: covered with large gauze patches and an impervious material was wrapped snugly around the trunk of each animal. The dressings were removed after twenty-four hours and any excess material was removed and the approximate amount remaining was noted.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposure site was wiped, but not washed, to remove excess material as per US 16 CFR 1500.40.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg based on specific gravity of the test item.
- Constant volume or concentration used: No (volume); Yes (concentration) – test item was tested neat, without vehicle.

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed daily for signs of toxicity, pharmacological effects and for mortalities. Bodyweights were recorded pre-exposure and at the end of the 14 day exposure period (or at mortality).
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: n=10 (females); n=5 non-abraded and n=5 abraded

Mortality:

Non abraded skin (n=5): One (1) mortality on day 11. Pre-mortality clinical signs included lethargy, diarrhea, ptosis, adipsia and anorexia.
Abraded skin (n=5): Two (2) mortalities on day 6 and 13: There were no pre-mortality clinical signs for day 6 mortality. For the day 13 mortality lethargy, ptosis, diarrhea, yellow nasal discharge and emaciation, was observed.

Clinical signs:

other: There were isolated instances of diarrhoea, lethargy and ptosis noted up to day 14 in four survivors.

Gross pathology:

Not performed.

Other findings:

Other observations (such as local responses) were noted within the report.

Any other information on results incl. tables

Table 1. Local Reactions – day 1

Number	Erythema	Oedema
1	1	0
3 *	2	0
5	1	1
7	2	1
9	2	2
2# *	1	0
4# *	1	2
6#	2	3
8#	2	2
10#	1	2

# Abraded skin

* mortality

Note. Scoring consistent with Draize et al.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU criteria not met

Conclusions:

Under the conditions of this study the LD50 was determined to be > 2000 mg/kg in female rabbits.

Executive summary:

The pre-GLP study was performed following a method similar to OECD 402 to assess the dermal toxicity of the test substance to the New Zealand white rabbit. The test substance was evaluated in ten female rabbits. A dose of 2000 mg/kg test substance (undiluted), was applied to the back clipped intact and abraded skin sites of the rabbit under a occlusive dressing for 24 hours. After twenty-four hours and any excess material was removed and the approximate amount remaining was noted. The animals were observed for a 14 day period for signs of toxicity and for mortalities. There were three mortalities during the study. In the intact skin sites on mortality occurred at day 13 with pre-mortality clinical signs including lethargy, diarrhoea, ptosis, adipsia and anorexia. In the abraded sites, two mortalities occurred. There were no pre-mortality clinical signs for day 6 mortality. For the day 13 mortality lethargy, ptosis, diarrhoea, yellow nasal discharge and emaciation, was observed. In the intact sites three of four survivors gained weight during the study. In number 7 survivor there was a slight body weight decline (- 0.1 g) at day 14. In the abraded sites, in number 6 there was a slight body weight decline (- 0.1 g) at day 14. In number 8 survivor there was no weight gain. Isolated instances of diarrhoea, lethargy and ptosis were noted in four survivors although remained generally healthy throughout the observation period. Local effects were very slight to well defined erythema and very slight to moderate oedema. Applicant assessment indicates there was more significant local effects in abraded sites than in intact skin sites at 24 hours. Under the conditions of this study the LD50 was determined to be greater than 2000 mg/kg bw.