Reaction products of 1,4-cyclohexanedimethanol with propylene oxide and ammonia

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-07-04 - 2012-08-06

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Temperature and relative humidity in animal room deviated from the protocol-stated ranges; no impact on outcome or integrity of the study, no effect on health status of the animals

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Temperature and relative humidity in animal room deviated from the protocol-stated ranges; no impact on outcome or integrity of the study, no effect on health status of the animals

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 1,4-cyclohexanedimethanol, propylene oxide and ammonia

Cas Number:

1220986-58-2

Molecular formula:

C11H24N2O

IUPAC Name:

Reaction products of 1,4-cyclohexanedimethanol, propylene oxide and ammonia

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Jeffamine RFD-270 Amine
- Substance type: Colourless liquid
- Physical state: Liquid
- Lot/batch No.: 8802-8-9
- Analytical purity: 92%
- Composition of test material, percentage of components: 0.02 wt% water
- Purity test date: 2010-07-15
- Storage condition of test material: Sample stored in cool, well-ventilated storage area prior to testing

Specific details on test material used for the study:

- Name of test material (as cited in study report): Jeffamine RFD-270 Amine
- Substance type: Colourless liquid
- Physical state: Liquid
- Lot/batch No.: 8802-8-9
- Analytical purity: 92%
- Composition of test material, percentage of components: 0.02 wt% water
- Purity test date: 2010-07-15
- Storage condition of test material: Sample stored in cool, well-ventilated storage area prior to testing

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 weeks at start of dosing
- Weight at study initiation: 196 to 222 grams
- Fasting period before study: Animals were fasted overnight prior to dose administration
- Housing: Animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council "Guide for the Care and Use of Laboratory Animals". Calvert is a USDA registered and fully AAALAC accredited facility.
- Diet (e.g. ad libitum): ad libitum except during fasting
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Study animals were acclimated to their housing for a minimum of 5 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 22°C
- Humidity (%): 28 to 84%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

DOSAGE 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=9. 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 and 2000 mg/kg

No. of animals per sex per dose:

6 rats in total:
2 female rats in the 175 mg/kg dose group
3 female rats in the 550 mg/kg dose group
1 female rat in the 2000 mg/kg dose group

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 up to day 15. Body weights were recorded on the day of dosing (day 1), and on days 8 and 15, or upon death.
- Necropsy of survivors performed: yes, all surviving rats were euthanized by CO2 asphyxiation and necropsied on day 15.

Statistics:

The LD50 was calculated for the main 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:

88.94 - 2 430

Mortality:

175 mg/kg: no mortality observed
550 mg/kg: two of three animals receiving the test article at 550 mg/kg were found dead
2000 mg/kg: the single animal at 2000 mg/kg was as well found dead

Clinical signs:

other: No clinical signs were observed at 175 mg/kg or in the initial surviving animal at 550 mg/kg. Abnormal gait and stance, decreased activity, and decreased body tone were observed in the animal at 2000 mg/kg. In addition to these signs piloerection was obse

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 lesions of the intestines and stomach including fluid-filled red, lining red and a dark red circular lesion.

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 88.94 to 2430 mg/kg).