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

Endpoint summary

Description of key information

Skin irritation:

In a rabbit skin irritation/corrosion test according to OECD Guideline 404, the test substance showed corrosive effects towards the skin (Lemoncelli, 2012).
Eye irritation:

No study on eye irritation/corrosion is available. However, in accordance with the specific rules for adaptation from column 1 (REACH Annex VII and VIII), no in vitro or in vivo eye irritation study needs to be conducted as the criteria are met for classification of the substance as corrosive to the skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-07-10 - 2012-07-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Millbrook
- Age at study initiation: 13 weeks at start of dosing
- Weight at study initiation: 2.7 kilograms at the outset (day 1) of the study
- Housing: Animals were individually housed. The room in which the animals were kept was documented in the study records. No other species was kept in the same room.
- 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): 18 to 22°C
- Humidity (%): 55 to 79%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

Frequency: once
4 hours

Observation period:

Mortality/morbidity: once daily and additionally as needed
Clinical observations: prior to dose administration, then daily, and additionally needed
Dermal observations: 3 minutes and 60 minutes sites: the animal was examined for signs of erythema and edema and the responses scored immediately after patch removal and at 30-60 minutes, then daily as needed; 4 hour sites, if applicable: The animal was examined for signs of erythema and edema and the responses scored 30-60 minutes, 24, 48, 72 hours (± 1 hour) after patch removal, and additionally as needed, daily. Since irritation persisted at the 72 hour scoring interval, daily scoring occurred for a maximum of 14 days.
Body weight: prior to dose administration and after the final skin grading.

Scheduled sacrifice:
The animal was euthanized by intravenous barbiturate overdose following final skin/dermal grading.
Gross necropsy:
No gross necropsy was performed at experimental completion.

Number of animals:

1

Details on study design:

TEST SITE
- Area of exposure: Three test sites were created and delineated on the back of a single animal. The test article was applied to one site (~ 5 cm x 5 cm) on the dorsal trunk of the animal (intact sites).
- Type of wrap if used: The test site was covered with a gauze patch. The patches were loosely held in contact with the skin.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure periods, residual test article was removed using water and gauze, without altering the existing response or integrity of the epidermis.
The first patch was removed after three minutes and the response was graded. If no serious skin reactions are observed, the second patch was removed after one hour and the responses graded. Since the observations at this stage indicated that four-hour exposure was necessary and could be humanely conducted, the third patch was removed four hours after application and the responses graded.

SCORING SYSTEM: Draize technique

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 30-60 minute, 24, 48 and 72 hour observations for the 4 hour site

Score:

8

Max. score:

8

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

after 4 hrs exposure

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

after 4 hrs exposure

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

after 60 min exposure

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

after 60 min exposure

Time point:

24/48/72 h

Score:

4

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

after 3 min exposure

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

after 3 min exposure

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

3 minutes exposure: severe erythema and severe edema (starting on day 8), necrosis of the skin (starting on day 8 through to day 10)
60 minutes exposure: severe erythema and edema (starting on day 2), necrosis of the skin (starting on day 2 through to day 14)
4 hour exposure: severe erythema and severe edema (starting at 30-60 minutes after unwrap), necrosis of the skin (starting on day 1 through to day 14)

Other effects:

Mortality/clinical observations:
No mortality was observed during the study. No clinical signs were recorded during the course of the study.
Body weights:
Initial: 2.7 kg, final: 3.1 kg

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

The test substance was found to be corrosive according to the criteria of the CLP Regulation. The test substance can be classified as category 1B as the exposure period was 1 hours (CLP: > 3 min - <= 1hr) and the observation period was 72 hrs (CLP: <= 14 days).
The primary irritation index was 8.0.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

Lemoncelli (2012) studied skin irritation/corrosion by applying the test substance on three test sites on the back of a single animal. The test article was applied to one site (~ 5 cm x 5 cm) on the dorsal trunk of one animal (intact sites) in semi-occlusive condition, according to OECD guideline 404 and EPA OPPTS 870.2500. Dermal observations were performed as follows: 3 minutes and 60 minutes sites: the animal was examined for signs of erythema and edema and the responses scored immediately after patch removal and at 30-60 minutes, then daily as needed; 4 hour sites, if applicable: The animal was examined for signs of erythema and edema and the responses scored 30-60 minutes, 24, 48, 72 hours (± 1 hour) after patch removal, and additionally as needed, daily. Since irritation persisted at the 72 hour scoring interval, daily scoring occurred for a maximum of 14 days. Lesions were scored according to the Draize system: erythema and edema scores of 4 were observed. Effects were not fully reversible within 14 days. Following responses were observed: 3 minutes exposure: severe erythema and severe edema (starting on day 8), necrosis of the skin (starting on day 8 through to day 10); 60 minutes exposure: severe erythema and edema (starting on day 2), necrosis of the skin (starting on day 2 through to day 14); 4 hour exposure: severe erythema and severe edema (starting at 30-60 minutes after unwrap), necrosis of the skin (starting on day 1 through to day 14). In conclusion, the substance was found to be corrosive according to the criteria of the CLP Regulation.

Eye irritation:

In accordance with the specific rules for adaptation from column 1 (REACH Annex VII and VIII), no in vitro or in vivo eye irritation study needs to be conducted as the criteria are met for classification of the substance as corrosive to the skin.

Justification for classification or non-classification

According to the criteria of the CLP Regulation the substance is classified as corrosive category 1B, H314 (causes severe skin burns and eye damage). As the substance is corrosive to the skin, it should also be classified for serious eye damage category 1, H318 (causes serious eye damage).