3,6-dioxaoctamethylenediamine

Endpoint summary

Description of key information

Under the study conditions, the test article was found to be irritating to the eyes. As the test substance is classified as corrosive to the skin, it is classified as category 1 serious eye damage , according to CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

February 28, 1985 - March 14,1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor; 5601-49-1

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: There was no apparent changes in the physical state of the test article during administration

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None; used as received

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sgarlat's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2-3 kg
- Housing: Standard individual cages, sized in accordance with the 'Guide for the Care and Use of Laboratory animals' of the Institute of Laboratory resources, national Research council.
- Diet (e.g. ad libitum): ad libitum, Wayne Rabbit Ration
- Water (e.g. ad libitum): ad libitum, fresh tap water, fit for human consumption
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site; applied directly on the intact and abraded skin sites
- Concentration (if solution): As received

Duration of treatment / exposure:

24 hrs

Observation period:

14 days

Number of animals:

3 males, 3 females

Details on study design:

TEST SITE
- Area of exposure: 1 abraded and 1 intact site per animal, clipped free of hair. The skin was abraded using a 21 gauge burred needle; the abrasion penetrated the stratum corneum but not the derma. following the application of the test material, one inch square gauze patches were applied to each of the two sites.
- Type of wrap if used: Gauze patch, wrapped with a rubber dam, followed by an Ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure, the wrappings were removed and the test item removed in a suitable manner
- Time after start of exposure: 24 hrs

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) At 24 and 72 hrs, then on days 4-14.

SCORING SYSTEM:
- Method of calculation: Draize scoring
1) Draize Evaluation of Dermal Irritation

I. Dermal observations.
Erythema and Eschar Formation (most severely affected area graded):
- No erythema: 0
- Veyr slight erythema (barely peceptible): 1
- Well-defined erythema: 2
- Moderate to severe erythema: 3
- Severa erythema (beet redness) to slight eschar formation (injuries in depth): 4

Edema Formation (most severly affected area graded):
- No edema: 0
- Very slight edema (edges of area well perceptible): 1
- Slight edema (edges of area well-defined by definite raising): 2
- Moderate edema (raised approximately 1 mm):
- Severe edema (raised more than 1 mm and extending beyond area of exposure): 4

II: Primary Irritation Index.
Mean values (6 animals are calculated and summed as follows):
* Erythema and Eschar formation
Intact skin - 24 and 72 hours - 2 values
Abraded skin - 24 and 72 hours - 2 values

* Edema formation
Intact skin - 24 and 72 hours - 2 values
Abraded skin - 24 and 72 hours - 2 values

Total: 8 values
Sum of mean values divided by 4 = Primary Irritation Index

1) Draize, J. H. 1959. The Appraisal of Chemicals n Foods, Drigs and Cosmetics, pp. 36-45. Association of food and drug officials of the united states, Austin, Texay
Federal Hazardous Substances Act Regulations. 16 CFR 1500.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other: Average of 6 animals

Time point:

14 d

Score:

3.5

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

probability of severe irritation

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

abraded and intact skin

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: value for 48h post treatment is not available

Remarks:

value is 0 for abraded and intact skin at day 14.

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean for intact skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

not fully reversible within: 14 days

Remarks:

value of 1 at day 14.

Remarks on result:

other: value for 48h post treatment is not available

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean for abraded skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks:

value of 4 at day 14

Remarks on result:

other: value for 48h post treatment is not available

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean for intact skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks:

value of 4 at day 14.

Remarks on result:

other:

Remarks:

value for 48h post treatment is not available

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean for intact skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: value for 48h post treatment is not available

Remarks:

value of 4 at days 14.

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

mean for abraded skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: value is 0 for abraded and intact skin at day 14.

Remarks:

value for 48h post treatment is not available

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

mean for abraded skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: value is 0 for abraded and intact skin at day 14.

Remarks:

value for 48h post treatment is not available

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

mean for abraded skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: value is 0 for abraded and intact skin at day 14.

Remarks:

value for 48h post treatment is not available

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean for abraded and intact skin (24 + 72 hours)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: value for 48h post treatment is not available

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean for abraded and intact skin

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

other: abraded skin provide a score of one at day 14 and a score of 0 for the intact skin.

Remarks on result:

other: value for 48h post treatment is not available.

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean for abraded and intact skin

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Remarks:

score value is 1 at days 14

Remarks on result:

other: value for 48h post treatment is not available.

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

intact skin

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: value for 48h post treatment is not available.

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

abraded skin

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: value for 48h post treatment is not available

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

mean for abraded and intact skin.

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 dyas

Remarks on result:

other: value for 48h post treatment is not available

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

mean for abraded and intact skin

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 5 days

Remarks on result:

other: value for 48h post treatment is not available

Irritant / corrosive response data:

- Primary Irritation Index is calculated using the sums of the mean edema and erythema values from both sites at 24 and 72 hrs, and dividing by 4. The Primary Irritation Index for this study was calculated to be 3.5.
- very slight to severe erythema and edema were observed at every observation period
- necrosis was also observed during the course of the study

pH of the test article was 13.8

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the conditions of this study, the test article was found to be an irritant, with a Primary Irritation Index of 3.5. According to these data, the test substance should be considered classified as category 2 according to the CLP regulation. However, in a weight of evidence approach with an in vivo skin corrosion test, the substance is classified as category 1 corrosive to the skin.

Executive summary:

The purpose of the study was to evaluate the dermal irritation produced in rabbits by the administration of the test article on intact and abraded skin.

The test article was applied to one intact and one abraded skin site on each of six rabbits (three males and three females).

Observations were recorded at 24 and 72 hours and on days 4 through 14.

Very slight to severe erythema were observed ar every observation period.

Necropsis was also observed during the course of the study.

The study was terminated on day 14.

Primary Irritation Index = 3.5

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

April 9, 1985-April 19, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline followed

Principles of method if other than guideline:

DOT corrosivity test, with procedure in accordance with generally accepted scientific standards and described in sufficient detail

GLP compliance:

not specified

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:- 5601-49-1
- Standard handling and storage, normal precautions
- Test item applied as received

- Stability under test conditions: There was no apparent change in the physical state of the test article during administration

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sqarlet's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2-3 kg
- Housing: Standard size individual cages
- Diet (e.g. ad libitum): ad libitum, Wayne Rabbit Ration
- Water (e.g. ad libitum):ad libitum, fresh tap water
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C, +/- 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):12 h dark/12 h light

Type of coverage:

occlusive

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/site
- Concentration (if solution): Applied as recieved

Duration of treatment / exposure:

4 hours

Observation period:

Observations recorded at 4 and 48 hours

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: 1 inch square patch on trunk
- Type of wrap if used: Rubber dam wrapped with ace bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wiped only
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 4 and 48 hours

SCORING SYSTEM:
- Method of calculation: Corrosion was considered to have resulted if destruction or irreversible alteration of the tissue ocurred.

Irritation parameter:

other: necrosis

Basis:

animal #1

Time point:

other: 4 hours

Reversibility:

not specified

Remarks:

necrosis at 100% at site of application.

Remarks on result:

other: necrosis observed

Remarks:

necrosis observed

Irritation parameter:

other: necrosis

Basis:

animal #1

Time point:

48 h

Reversibility:

not specified

Remarks:

necrosis

Remarks on result:

other: necrosis (100%) of application site + moderate erythema of skin surrounding application site

Remarks:

necrosis (100%) of application site + moderate erythema of skin surrounding application site

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Reversibility:

not specified

Remarks:

erythema and herdening

Remarks on result:

other: slight erythema and hardening of the skin (10%) at application site

Remarks:

slight erythema and hardening of the skin (10%) at application site

Irritation parameter:

other: necrosis

Basis:

animal #3

Time point:

other: 4 hours

Reversibility:

not reversible

Remarks:

necrosis

Remarks on result:

other: animals unwrapped and necrosis (100%) at site of application.

Remarks:

animals unwrapped and necrosis (100%) at site of application.

Irritation parameter:

other: necrosis

Basis:

animal #4

Time point:

other: 4 hours

Reversibility:

not reversible

Remarks:

necrosis

Remarks on result:

other: animals unwrapped and necrosis (100%) at site of application.

Remarks:

animals unwrapped and necrosis (100%) at site of application.

Irritation parameter:

erythema score

Basis:

animal: animal 1 to 4

Time point:

24/48/72 h

Reversibility:

other: not appliacble

Remarks:

observation made at 4 and 48 hours after exposure

Remarks on result:

not measured/tested

Remarks:

no observation made at 24/48 and 72 hours.

Irritation parameter:

edema score

Basis:

animal: animal 1 to 4

Time point:

24/48/72 h

Reversibility:

other: not applicable

Remarks:

observation made at 4 and 48 hours after exposure

Remarks on result:

not measured/tested

Remarks:

no observation made at 24/48 and 72 hours.

Irritant / corrosive response data:

3 of 4 rabbits exhibited skin necrosis at 4 and 48 hrs after application of test article.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

Based upon the results of this study, the test article was considered to be corrosive. Therefore the test substance is considered classified as category 1C corrosive to the skin, according to CLP regulation.

Executive summary:

The test article was applied to an intact skin site on each of four rabbits (two males and two females). The test substance remained in contact with the skin for four hours.

Animals were observed at 4 and 48 hours after treatement. Skin necrosis was visible in three of the four rabbits at the 4 hour and 48 hour observation period.

Based upaon the results of the DOT Corrosivity study in, the test item was considered to be corrosive.

Reference 3

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes

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:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Justification for classification or non-classification

Based on the above mentioned results the substance does need to be classified as corrosive sub-categories 1C ( H314: Causes severe skin burns and eye damage) according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).