1,3-Benzenedimethanamine, N-(2-phenylethyl) derivs.

Endpoint summary

Description of key information

In an acute oral toxicity test, the LD50 was in the range between 500 and 2000 mg/kg. As the submission item turned out to be corrosive, no further acute testing was performed. 

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

Study period:

from 2002-01-29 to 2002-02-14 (experimental phase)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study without deviations, not performed under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Crj: CD(SD)IGS, SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan Co., Ltd.
- Age at study initiation: 5 weeks
- Weight at study initiation: 113 ± 2.5 g (males), 97.0 ± 3.4 g (females)
- Fasting period before study: Rats were fasted overnight. Feeding was restarted three to four hours after dosing.
- Housing: in groups of six to ten in suspended metal wire cages on a rat cage rack equipped with a feed water supply system (Tokiwa Scientific Instrument Co., Ltd.)
- Diet (e.g. ad libitum): free access to a rat pellet diet MF (Oriental Yeast Co., Ltd.)
- Water (e.g. ad libitum): free access to mains water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 55 ± 6
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: from 2002-01-29 to 2002-02-14

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.25, 0.5, 2, 5 and 20 (w/v)% olive oil solutions
- Amount of vehicle (if gavage): 1.0 mL per 100 g body weight
- Justification for choice of vehicle: not reported

MAXIMUM DOSE VOLUME APPLIED: 1.0 mL per 100 g body weight

DOSAGE PREPARATION (if unusual): A prescribed amount of test material was weighed out and diluted with olive oil in order to formulate 0.25 to 20 (w/v)% olive oil solutions as test solutions.

Doses:

25, 50, 200, 500 and 2000 mg/kg

No. of animals per sex per dose:

6 animals per sex and dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed daily for mortality and clinical signs, weighed immediately before dosing and on Days 2, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

500 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: This value is calculated as the geometric mean of the highest test dose without mortalities (500 mg/kg) and the first one with mortality in all test animals.

Mortality:

Male: 25 mg/kg bw; Number of animals: 6; Number of deaths: 0
Male: 50 mg/kg bw; Number of animals: 6; Number of deaths: 0
Male: 200 mg/kg bw; Number of animals: 6; Number of deaths: 0
Male: 500 mg/kg bw; Number of animals: 6; Number of deaths: 0
Male: 2000 mg/kg bw; Number of animals: 6; Number of deaths: 6
Female: 25 mg/kg bw; Number of animals: 6; Number of deaths: 0
Female: 50 mg/kg bw; Number of animals: 6; Number of deaths: 0
Female: 200 mg/kg bw; Number of animals: 6; Number of deaths: 0
Female: 500 mg/kg bw; Number of animals: 6; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 6; Number of deaths: 6

Clinical signs:

other: Males from the 25, 50 and 200 mg/kg dose groups showed no abnormalities. In the 500 mg/kg dose group, all of the six males showed body descent, but five of them recovered two hours after treatment. One animal from the dose group showed body descent and ab

Gross pathology:

The decreased six males and six females from the 2000 mg/kg dose group showed mucosal bleeding in glandular stomach, intestinal tract, and anterior stomach, white anterior stomach mucous membrane, and intestinal tract mucosal colliquation.
No abnormalities were noted in males and females from the 25, 50, 200 and 500 mg/kg dose groups that survived the test period.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test material was in the range between 500 and 2000 mg/kg.

Executive summary:

An acute oral toxicity test of the reaction product of 1,1'-(benzene-1,3 -diyl)bis(methylamine) and styrene was conducted in compliance with the OECD Test Guidelines No. 401 (1987) in the rat.

The reaction product was orally administered by gavage to SD rats (SPF). The tested concentrations lay in the range of 25 to 2000 mg/kg bw and 6 male and 6 female rats were treated per concentration. No abnormalities were detected in animals treated with 200 mg/kg bw or less. Animals treated with 500 mg/kg bw showed clinical signs (body descent, abnormal gait (male), squatting (female), diarrhea, loss of fur), but no abnormalities were observed on Day 3 or later. All animals treated with 2000 mg/kg bw died within 5 hours after application.

The LD50 of the test material was determined to be in the range of 500 and 2000 mg/kg. Accordingly, the reaction product falls into acute toxicity hazard category 4 according to Regulation (EC) No 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

500 mg/kg bw

Quality of whole database:

Klimisch 2, OECD guideline-conform, non GLP.

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

An acute oral toxicity test was conducted in compliance with OECD TG No. 401. The submission item was orally administered by gavage to male and female rats. The acute oral LD50 of the test material was in the range between 500 and 2000 mg/kg bw.

As the submission item turned out to be corrosive, neither the dermal nor the inhalative route of application was tested in an acute toxicity test in accordance with Regulation (EC) 1907/2006, column 2 of Annex VIII.

Justification for selection of acute toxicity – oral endpoint
Valid study, only available data source for acute oral toxicity. The LD50 of the test material was in the range between 500 and 2000 mg/kg.

Justification for selection of acute toxicity – inhalation endpoint
The test item is corrosive to the skin. Therefore, no study on acute inhalation toxicity needs to be conducted in accordance with Regulation (EC) 1907/2006, column 2 of Annex VIII.

Justification for selection of acute toxicity – dermal endpoint
The test item is corrosive to the skin. Therefore, no study on acute dermal toxicity needs to be conducted in accordance with Regulation (EC) 1907/2006, column 2 of Annex VIII.

Justification for classification or non-classification

The acute oral LD50 was determined to be in the range of 500 and 2000 mg/kg in an acute oral toxicity test.

Regulation (EC) No 1272/2008 (CLP): Acute oral toxicity hazard category 4, H302 "Harmful if swallowed".

Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC): Xn; R22 "Harmful if swallowed".