Benzenemethanol, α-[(1S)-2-(dimethylamino)-1-methylethyl]-α-ethyl-3-methoxy-, (αR)-

Endpoint summary

Description of key information

The oral acute toxicity test with rats (OECD guideline 423) was performed. 

It was noted the death of 3 treated rats at 2000 mg/kg bw, 10 minutes after the test item administration.

The mortalities were preceded by convulsions, during the first minutes of the test.

No mortality occurred in the animals treated with 300 mg/kg bw.

The LD50 (rat, oral) = 500 mg/kg bw.

GHS classification: Acute oral cat 4, H302.

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:

2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 17th, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Directive no 2004/73/EC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Fifteen Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (53940 Le Genest St Isle - France), were used after an acclimatisation period of at least five days.
At the beginning of the study, the animals of the treated group weighed between 181 and 202 g and were 8 weeks old.

Housing:
Three healthy female rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in a conventional air conditioned animal husbandry; the environmental conditions were:
- Temperature: between 19˚C and 23 ˚C
- Relative humidity: between 40% and 68%
- Lighting time: 12 hours daily

Food and drink:
Drinking water (tap-water from public distribution system) and foodstuffs were supplied freely except during treatment period for the food.
Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l’Environnement de Bordeaux (I.E.E.B.).

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The animals of groups 2 and 3, received respectively an effective dose of 2000 mg/kg bw and 300 mg/kg bw of the test item T2955, diluted in olive oil and administered by force-feeding under a volume of 10 ml/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.
The animals of group 1, received, according to the same experimental conditions, the control item (distilled water) under a volume of 2 ml/kg bw.

Doses:

group 1: 0 mg/kg bw (control group, distilled water)
group 2: 2000 mg/kg bw
group 3: 300 mg/kg bw

No. of animals per sex per dose:

group 1: 6 female rats
group 2: 3 female rats
group 3: 6 female rats

Control animals:

yes

Details on study design:

Daily examination:
Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 14 days after administration of the test item.
This examination focuses particularly on a list of symptoms, recorded as ‘present’ or ‘absent’ on the observation sheet.
These observations were compared to control data.
Observations and a mortality report were then carried out every day for 14 days.

Periodical examinations:
The animals were weighed on day D0 (just before administering the test item), then on D2, D7, and D14.
Weight changes were calculated and recorded.

Examination at the end of the test:
On D14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels. Macroscopic observations were entered on individual autopsy sheets.
Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view to microscopic examinations.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 500 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD100

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD0

Effect level:

<= 300 mg/kg bw

Based on:

test mat.

Mortality:

It was noted the death of 3 treated rats at 2000 mg/kg bw, 10 minutes after the test item administration. The mortalities were preceded by convulsions, during the first minutes of the test.
No mortality occurred in the animals treated with 300 mg/kg bw.

Clinical signs:

other: The mortalities were preceded by convulsions, during the first minutes of the test. It was registered in the animals treated at 300 mg/kg bw, from thirty minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated w

Gross pathology:

The macroscopical examination of the animals treated at 2000 mg/kg bw which died during the test did not reveal treatment-related changes.
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 cut-off of the test item T2955 is 500 mg/kg bw by oral route in the rat.

Executive summary:

Summary:

The test item T2955 was administered in a first step to a group of 3 female Sprague Dawley rats at the single dose of 2000 mg/kg bw and in the second step to a group of 6 female Sprague Dawley rats at the single dose of 300 mg/kg bw. The experimental protocol was established according to the official method as defined in the OECD guideline no 423 dated December 17^th, 2001 and the test method B.1 tris of the Directive no 2004/73/EC.

 

It was noted the death of 3 treated rats at 2000 mg/kg bw, 10 minutes after the test item administration. The mortalities were preceded by convulsions, during the first minutes of the test.

No mortality occurred in the animals treated with 300 mg/kg bw.

 

It was registered in the animals treated at 300 mg/kg bw, from thirty minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated with bradypnea (5/6), tremors (1/6), mydrias (4/6), and a decrease of the righting reflex (3/6). The animals recovered a normal activity the 2^ndday of the test.

 

The body weight evolution of the animals treated at 300 mg/kg bw remained normal throughout the study, similar between treated and control animals.

 

The macroscopical examination of the animals treated at 2000 mg/kg bw which died during the test did not reveal treatment-related changes.

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

 

In conclusion, the LD50 cut-off of the test item T2955 is 500 mg/kg bw by oral route in the rat.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw