L-α-methylbenzylamine

Endpoint summary

Description of key information

Oral: The median lethal oral  dose  was found to be greater than 300 mg/kg bw and less or equal than 2000 mg/kg bw in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2011-12-05 to 2012-01-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP and guideline compliant study. For read-across justification please refer to IUCLID section 13. Study was performed with the Racemat (DL-alpha-methylbenzylamine). Read across is done to L-alpha-methylbenzylamine, as the substance is expected to behave similar to the racemat with regard to acute toxicity properties. For read-across justification please refer to IUCLID section 13.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(17 December 2001)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(30 May 2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(December 2002)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: 10 weeks
- Weight at study initiation: Mean weight 180.3-209.3 g
- Fasting period before study: 16 hours before administration
- Housing: Single housing, Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30–70
- Air changes (per hr): Central fully air-conditioned
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 15 g /100 mL (300 mg/kg bw )
- Justification for choice of vehicle: Solution in olive oil Ph.Eur.

MAXIMUM DOSE VOLUME APPLIED
An administration volume of 2 mL/kg bw of suitable test item preparation was used to facilitate application.

Doses:

2000 mg/kg bw (undiluted)
300 mg/kg bw ( 15 g/100 mL) (2 administrations)

No. of animals per sex per dose:

3 animals/dose
2 replicates

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observation: At least once daily; Weighing: Day 0, 7, 14
- Necropsy of survivors performed: Yes
- Other examinations performed: Pathology, mortality

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals of the 2000 mg/kg bw test group died immediately after administration. No mortality occurred in both 300 mg/kg bw test groups.

Clinical signs:

other: Because all animals of the 2000 mg/kg bw test group died immediately after administration no clinical signs could be determined. In the first and second test group 300 mg/kg bw following obseravtions were made: · Impaired general state in 5 out of 6

Gross pathology:

The macroscopic pathological findings in the animals of the 2000 mg/kg bw test group revealed red discoloration in all lobes of the lung, dark discoloration of the liver and extensive bleeding in the glandular stomach.
Additionally one of these animals showed edema in all lobes of the lung. There were no macroscopic pathological findings in the animals of both 300 mg/kg bw test groups sacrificed at the end of the observation period.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

Only one GLP and guideline compliant study available.

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

Read across

No data were available for L-alpha-methylbenzylamine. Study was performed with the Racemat (DL-alpha-methylbenzylamine). Read across is done to L-alpha-methylbenzylamine, as the substance is expected to behave similar to the racemat with regard to acute toxicity properties.

Oral

In an acute oral toxicity study performed with the racemat according to the Acute Toxic Class method, doses of 2000 and 300 mg/kg bw of the test item 1-Phenylethylamine (undiluted or preparations in olive oil Ph.Eur) were administered to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 300 mg/kg bw in 6 females) by gavage in a sequential manner. The following test substance-related clinical observations were recorded: 2000 mg/kg (first test group): All animals died immediately after application. Therefore no clinical signs were observed. Macroscopic pathological findings were made in the animals that died: red discoloration and edema in all lobes of lung; dark discoloration of the liver; extensive bleeding in the glandular stomach

At the concentration of 300 mg/kg (both test groups) no mortality occurred . The following clinical oberservation were made: Impaired general state in 5 out of 6 animals; Poor general state in 2 out of 6 animals; Dyspnoea in 5 out of 6 animals; Piloerection in 5 out of 6 animals; Staggering in 1 out of 6 animals; Abdominal position in 1 out of 6 animals; Exsiccosis in 1 out of 6 animals; Reduced feces in all animals. The mean body weight increased within the normal range throughout the study period. There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period. The acute oral LD50 was calculated to be > 300 <= 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
GLP and guideline compliant study.

Justification for classification or non-classification

No data were available for L-alpha-methylbenzylamine. Studies were performed with the racemat (DL-alpha-methylbenzylamine, read across, CAS 618-36-0). Based on the available data for DL-alpha-methylbenzylamine, L-alpha-methylbenzylamine is subject to C&L:

according to Regulation 1272/2008/EC: acute oral tox. 4, H302; acute dermal tox. 4, H312

according to Directive 67/548/EEC: acute oral tox.: R22; acute dermal tox.: R21