N-methoxy-1-(2,4,6-trichlorophenyl)propan-2-amine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 November 2013 to 10 December 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

methoxy[1-(2,4,6-trichlorophenyl)propan-2-yl]amine

EC Number:

941-634-6

Cas Number:

1228284-78-3

Molecular formula:

C10H12Cl3NO

IUPAC Name:

methoxy[1-(2,4,6-trichlorophenyl)propan-2-yl]amine

Test material form:

other: liquid

Details on test material:

- Physical state: Brown liquid
- Expiration date of the lot/batch: Recertification date end May 2017
- Storage condition of test material: Room temperature (<30°C), protected from light and humidity

Test animals

Species:

rat

Strain:

other: RccHan:(WIST)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-11 weeks
- Weight at study initiation: 166-203 g
- Fasting period before study: Yes
- Housing: Individually in Type II polypropylene/polycarbonate cages
- Diet: Ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" ad libitum (except overnight prior to dosing and 3 hours after dosing)
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1-22.2
- Humidity (%): 35-68
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12 November 2013 To: 10 December 2013

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000, 550 mg/kg bw

No. of animals per sex per dose:

3 females per dose level

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 mins, 1, 2, 3, 4, 6 hours after dosing, then once daily for 14 days (observations); days -1 (prior to removal of food), 0 (prior to administration), 7 and 14 (body weight).
- Necropsy of survivors performed: Yes

Statistics:

Data was evaluated using the Acute Oral Toxicity (OECD Test Guidelines 425) Statistical Programme (AOT 425 Stat Pgm).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 550 - < 2 000 mg/kg bw

Based on:

test mat.

95% CL:

550 - 2 000

Mortality:

3/3 at 2000 mg/kg bw, 0/3 at 550 mg/kg bw

Clinical signs:

other: Decreased activity (3/3), hunched back (2/3), prone position (3/3), incoordination (2/3), continuous tremors (3/3), piloerection (3/3), decreased respiratory rate (1/3) and cold to touch (1/3) at 2000 mg/kg bw. Hunched back (3/3), incoordination (3/3),

Gross pathology:

No treatment-related effects

Any other information on results incl. tables

Table 1: Mortality data

Dosing sequence / animal number	Dose (mg kg bw)	Outcome
4303	550	Survived
4304	2000	Died on day 2
4305	550	Survived
4306	2000	Died on day1
4307	550	Survived
4308	2000	Died on day 2

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information: H302: Harmful if swallowed

Conclusions:

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test item, CA5204A, was found to be between 550 and 2000 mg/kg bw in female RccHan:(WIST) rats.

Executive summary:

An acute oral toxicity (up and down procedure) study was conducted with 6 animals (female RccHan:(WIST) rats). The starting dose was 550 mg/kg bw. Animals were treated with a single oral (gavage) dose of CA5204A at a dose level of 550 or 2000 mg/kg bw followed by a 14 day observation period. The animals were fasted overnight prior to treatment and food was returned approximately 3 hours after dosing. Surviving animals were observed individually after dosing at 30 minutes, 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1 (prior to removal of food), Day 0 (prior to administration) and weekly thereafter. All surviving animals were examined macroscopically at the end of the observation period. Moreover, the animals found dead were examined macroscopically and body weight was recorded at necropsy. No mortality was observed at the dose level of 550 mg/kg bw. Treatment with CA5204A at the dose level of 550 mg/kg bw caused hunched back (3/3), incoordination (3/3), continuous tremors (2/3), piloerection (3/3) and hyperactivity (2/3). Surviving animals were symptom free from 8 days after the treatment. There were no treatment related body weight changes. Body weights were within the range commonly recorded for this strain and age. There was no evidence of the macroscopic observations in animals dosed at 550 mg/kg bw and terminated on Day 14. Mortality was observed in all three animals on Day 1 or 2 at 2000 mg/kg bw dose level. Treatment with CA5204A at the dose level of 2000 mg/kg bw caused decreased activity (3/3), hunched back (2/3), prone position (3/3), incoordination (2/3), continuous tremors (3/3), piloerection (3/3), decreased respiratory rate (1/3) and cold to touch (1/3).

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test item, CA5204A, was found to be between 550 and 2000 mg/kg bw in female RccHan:(WIST) rats.