Propylidynetrimethanol, propoxylated, reaction products with ammonia

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-03-01 to 2012-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

Name of test material: Trimethylolpropanepoly(oxypropylene)triamine
EC no.: 500-105-6
CAS no.: 39423-51-3
Physical state: clear colourless liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 1L708
- Composition of test material, percentage of components: 96% primair amine, 0.08 wt%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, 15 to 30°C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan
- Age at study initiation: 9 to 11 weeks at start of dosing
- Weight at study initiation: 195 to 221 grams
- Fasting period before study: overnight
- Housing: Animals were group housed by sex upon receipt and individually housed during the study. No other species were kept in the same room.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum of 5 days prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 24°C
- Humidity (%): 20 to 63%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 1 March 2012 To: 30 March 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

at 175mg/kg dose only (low dose)

Details on oral exposure:

Dose preparation:
The proper amount of the test article was measured according to volume since it was a liquid, and was allocated/dosed neat as received from the Sponsor at 2000 and 550 mg/kg with a pH = 7. The stock bottle was inverted several times prior to dispensing. At 175 mg/kg the test article was dissolved in distilled water (175 mg brought to a volume of 5 mL). The resulting clear liquid had a pH equal to 12.

Doses:

175, 550 or 2000 mg/kg body-weight

No. of animals per sex per dose:

A total of 6 females: 175 (1), 550 (3) and 2000 mg/kg (2)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality checks were made at least once daily. Clinical observations were recorded prior to dosing, as well as at 30 minutes, 4 hours post-dose, and daily thereafter through day 15. Body weights were recorded on the day of dosing (day 1), and on days 8 and 15, or upon death. All surviving rats were euthanized by CO2 asphyxiation and necropsied on Day 15.
- Necropsy of survivors performed: yes

Statistics:

The LD50 was calculated test using the AOT425StatPgm developed by Westat May, 2001.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

95% CL:

123.9 - 3 930

Mortality:

For the dose of 175 mg/kg, no mortality was observed. One of three animals receiving the test article at 550 mg/kg was found dead and both animals at 2000 mg/kg were found dead. All three deaths occurred by the 30 minute observation time point on day 1.

Clinical signs:

other: No clinical signs were observed and all surviving animals appeared normal throughout the study.

Gross pathology:

Terminal necropsy revealed no visible lesions in the surviving animals at 175 and 550 mg/kg. Necropsy of the animals found dead revealed test article visible in the stomach but no other visible lesions.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of this study, the oral LD50 for the test substance in rats was estimated to be 550 mg/kg (95% PL Confidence Interval of 123.9 to 3930 mg/kg). Therefore, the test substance is considered to be classified as category 4 according to the CLP regulation.