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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-07-18 - 2012-08-21

Reliability:

2 (reliable with restrictions)

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

temperature and relative humidity ranges were broader than specified by the guideline, no impact on the outcome of the study; age range 7 to 9 weeks instead of 8-24 weeks, no impact on the outcome or integrity of the study

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

temperature and relative humidity ranges were broader than specified by the guideline, no impact on the outcome of the study; age range 7 to 9 weeks instead of 8-24 weeks, no impact on the outcome or integrity of the study

GLP compliance:

yes

Test type:

standard acute method

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:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan
- Age at study initiation: 7 to 10 weeks
- Weight at study initiation: 184 to 300 grams
- Fasting period before study: no data
- Housing: Animals were group housed by sex upon receipt and individually housed upon assignment to study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Study animals were acclimated to their housing for a minimum of five days prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 25°C
- Humidity (%): 30 to 84%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: > = 10%
- Type of wrap if used: The test article was applied on an intact skin site for each animal, covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape for 24 (± 0.5) hours.

REMOVAL OF TEST SUBSTANCE
Post-exposure, the site was unwrapped and wiped appropriately (with gauze and water) to remove residual test article.

TEST MATERIAL
Dosage levels were calculated on a mg/kg basis for each individual animal based on body weight. For the liquid test article, the dose was adjusted for test article relative density (1.04 g/mL).

Duration of exposure:

24 ± 0.5 hours

Doses:

One group of ten animals (5/sex) received the test article at 2000 mg/kg (2.1 mL/kg). A full definitive test was performed and three groups of ten (5/sex) received the test article at 50 (5 mL/kg), 200 (5 mL/kg), and 1000 mg/kg (1 mL/kg).

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Morbidity: once daily
Clinical observations: Clinical observations were recorded immediately after unwrap and daily thereafter through day 15. At the time of clinical observations, the dose site was also evaluated for dermal irritation. When present, dermal irritation was scored and recorded using descriptive scoring.
Body weight: Animals were weighed prior to dosing on Day 1 and on days 8 and 15 or upon death.
- Necropsy of survivors performed: yes: all surviving animals were euthanized by CO2 asphyxiation following final observation.
The terminal necropsy included examination of:
- the external body surface
- all orifices
- the thoracic, abdominal and pelvic cavities and their contents

Statistics:

Body weights were summarized using descriptive statistics (mean and standard deviation).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed at 50 or 200 mg/kg. Nine of ten animals were found dead at 2000 mg/kg and one of ten were found dead at 1000 mg/kg.

Clinical signs:

other: All animals at 50 mg/kg were observed to be clinically normal without signs of dermal irritation throughout the study. At 2000 mg/kg, all ten animals exhibited signs of irritation and necrosis at the application site by day 2 with clinical observations. T

Gross pathology:

No visible lesions were observed in the animals at terminal necropsy. Necropsy of found dead animals revealed: fluid filled stomachs in four of eight animals found dead in the 2000 mg/kg group on day 3 as well as dark red intestines in one animal found dead on day 4. Necropsy of the found dead animal in the 1000 mg/kg group on day 3 revealed dark red intestines.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based upon the results of the acute dermal toxicity study in rats with the test substance, the estimated LD50 was considered to be greater than 1000 mg/kg but less than 2000 mg/kg based on the results of the preliminary test (9 of 10 rats were found dead). Therefore, based on the criteria of the CLP Regulation, the substance is considered to be a category 4 acute dermal toxicant.