[1S-(1α,2β,3α,5α)]-[2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]methylamine

Endpoint summary

Description of key information

Oral:

In an oral acute toxicity study in rats, an LD50 range of 200 - 2200 mg/kg bw was determined (BASF SE, 1994).

Inhalation/Dermal:

No study on acute inhalation and dermal toxicity was conducted due to the corrosive nature of the test substance.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

German BGA method (1991)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab

Test type:

acute toxic class method

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot No.of test material: 109 + 110/91

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adults
- Weight at study initiation: comparable
- Fasting period before study: ~16 h
- Housing: single-housed in stainless steel wire mesh cages, DK-III
- Diet: ad libitum, standardized animal laboratory diet
- Water: ad libitum, tab water
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4 and 44 g/100 mL
- Justification for choice of vehicle: The test substance was insoluble in water.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

Doses:

200 (male and female animals), 2200 mg/kg (males only)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: General observation and mortalities was made twice each working day and once on weekends and on public holidays. Body weight determination was done shortly before administration (day 0), weekly thereafter and at the end of the study.
- Necropsy of survivors performed: Yes, at the last day of the observation period. Necropsy of all animals that died before as soon as possible.
- Other examinations performed: clinical signs, gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 200 mg/kg bw

Based on:

test mat.

Mortality:

Male animals: 200 mg/kg: no deaths; 2200 mg/kg: 3/3
Female animals: 200 mg/kg: no deaths; 2200 mg/kg: not tested

Clinical signs:

Signs of toxicity noted in the 2200 mg/kg bw dose group were: poor general state, dyspnoea, apathy, excitation, staggering, tremor, twitching, spastic gait, saltatory and flexion spasms, rolling convulsions, piloerection, and salivation.
The male animals of the 200 mg/kg bw dose group exhibited poor general state, dyspnoea, excitation, staggering, spastic gait, and piloerrection. They appeared normal 1 day after application.
The female animals of the 200 mg/kg bw dose group did not show any symptoms.

Body weight:

Male animals (200 mg/kg) : 179 g at study start, 271 g after 13 days
Female animals (200 mg/kg): 169 g at study start, 216 g after 13 days

Gross pathology:

Animals that died: diffuse reddening with blood extravasation into the lumen in the gastro-intestinal tract (2200 mg/kg: 3 males).
Sacrificed animals: no pathological findings noted (200 mg/kg; 3 males and 3 females)

Interpretation of results:

Category 3 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Quality of whole database:

2

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study according to the EEC-Guideline and modified according to BGA-model (1991), a group (3) of fasted young adult male Wistar rats was given a single oral dose of the test substance preparation in olive oil DAB 9 at a dose level of 2200 mg/kg bw. Another group of six fasted animals (3 male/3 female) was treated in the same way with a dose of 200 mg/kg bw.

Signs of toxicity in the 2200 mg/kg bw dose group were poor general state, dyspnoea, apathy, staggering, tremor, twitching, salutatory spasm, rolling convulsion, flexion spasm, and salivation. The male animals of the 200 mg/kg bw dose group exhibited poor general state, dyspnoea, excitation, staggering, spastic gait, and piloerrection. They appeared normal 1 day after application. The female animals of the 200 mg/kg bw dose group did not show any symptoms. The expected body weight gain has been observed in the course of the study. All animals of the 2200 mg/kg bw dose group died within 1 h after application. Necropsy findings of the animals that died was diffuse reddening of the gastrointestinal tract with blood extravasation into the lumen. No abnormalities were noted at necropsy of animals sacrified at the end of the study.

Under the conditions of this study, the range of mortality after oral application was found to be > 200 mg/kg and < 2200 mg/kg bw.

(+)-3-Aminomethylpinan is of moderate toxicity based on the LD50 range of 200 – 2200 mg/kg bw.

 

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

An LD50 of > 200 - < 2200 mg/kg bw was considered for C+L. As a result the substance is considered to be classified as category 3 (acute oral toxicity, H301) under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.