Registration Dossier

Administrative data

Description of key information

Diethylamine is considered corrosive to skin and eyes and irritant to the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
28 July 2015
Qualifier:
according to
Guideline:
other: International Maritime Organization (I.M.O.) criteria
GLP compliance:
yes
Remarks:
additionally Quality assurance statement available
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry, Loudonville, Ohio
- Age at study initiation: young adult
- Weight at study initiation: 1.9- 2.2 kg
- Housing: individually housed in suspended stainless steel cages
- Diet: Agway Prolab Rabbit Ration, ad libitum
- Water: ad libitum
- Acclimation period: minimum of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 - 26.5 °C
- Humidity (%): 35-70 %
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 4/12/89 - 4/19/89
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml
Duration of treatment / exposure:
3 min
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: one and one-half inch square gauze patch
- Type of wrap if used: double layer of plastic wrap


REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test article wiped from the site with gauze soaked in distilled water
- Time after start of exposure: 3 min

SCORING SYSTEM: Draize system
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h - 48 - 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
2.2
Max. score:
3
Reversibility:
fully reversible
Remarks:
7 days
Remarks on result:
positive indication of irritation

Table 1. Erythema score (animal1/animal2/animal3):

 Exposure time 3 min  1 h  24 h  48 h  72 h  7 days
 3 min 4/4/4 4/4/4 4/4/4 4/4/4 4/4/4 4/4/4


Table 2. Edema score (animal1/animal2/animal3):

 Exposure time 3 min  1 h  24 h  48 h  72 h  7 days
 3 min 1/1/1 2/2/2 2/3/3 2/2/2 2/2/1 0/0/0

The test substance produced dermal corrosion at all sites exposed to the test article. The dermal response was initially characterized by necrosis at the three minute scoring interval and progressed to eschar at one hour (2/3 rabbits) and 24 hours (3/3 rabbits). The eschar persisted throughout the remainder of the seven day study. A very slight edema was noted during the test period and diminished by test termination.

Interpretation of results:
Category 1A (corrosive) based on GHS criteria
Conclusions:
The test substance caused corossion of the rabbit skin under the tested conditions.
Executive summary:

In a GLP compliant study the potential of the test item to cause skin corrosion/irritation was investigated with 3 New Zealand White rabbits. According to the International Maritime Organization (I.M.O.) criteria, 0.5 mL of the test substance was applied at the dorsal area of the trunk at a single site on the right flank after clipping. The exposure site was wrapped with a double layer of plastic wrap over the soaked gauze patch. After 3 min of exposure the plastic wrap and gauze patch were removed and washing of the residual test article was performed. Dermal reactions were observed at 3 min, 1 h, 24 h, 48 h, 72 h and 7 d after exposure initiation.

The test substance produced dermal corrosion at all sites exposed to the test article. The dermal response was initially characterized by necrosis at the three minute scoring interval and progressed to eschar at one hour (2/3 rabbits) and 24 hours (3/3 rabbits). The eschar persisted throughout the remainder of the seven day study. A very slight edema was noted during the test period and diminished by test termination.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
21 Mar 1955 - 15 Apr 1955
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
- Principle of test:
Two animals were treated for 1, 5 and 15 minutes using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance (1 animal concentrated test substance, the other animal 20% solution and 20% solution pH 7.5). After the application time, the skin was washed with Lutrol (25%) which contained acetic acid (5%).
GLP compliance:
no
Remarks:
predating GLP
Species:
rabbit
Strain:
Vienna White
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
water
Remarks:
unless used undiluted
Controls:
other: untreated skin site of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): undiluted, 20% in water; 20% in water (pH 7.5)
Duration of treatment / exposure:
1 minute, 3 minutes, 15 minutes
Observation period:
up to 4 weeks
Number of animals:
1 rabbit undiluted test substance; 1 rabbit each 20% dilutions
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing with Lutrol (25%) containing 5% acetic acid
- Time after start of exposure: after the exposure (1 min, 5 min or 15 min).


Irritation parameter:
other: Necrosis score, 1, 5 or 15 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Full thickness necrosis

- Immediately after application of the concentrated test substance severe leathery necrosis and erythema were noted. After 4 weeks deep crusts were detected. The 1 minute exposure caused red-brown necrosis. After 4 weeks scurfy sites were detected. The observed effects were considered as full thickness necrosis.

- The diluted test substance (20%) caused after 15 minutes grey-brown necrosis, after 5 minutes severe irritation (superficial necrosis, reversible within 3 weeks), and the 1 minute application showed no symptoms. The diluted and neutralised (pH 7.5) substance caused no iriitation.

Interpretation of results:
Category 1A (corrosive) based on GHS criteria
Conclusions:
The test substance caused necrosis of rabbit skin under the tested conditions (1 min exposure).
Executive summary:

Two animals were treated for 1, 5 and 15 minutes with the test substance using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance (1 animal concentrated test substance, the other animal 20% solution and 20% solution pH 7.5). After the application time, the skin was washed with Lutrol (25%) which contained acetic acid (5%). Immediately after application of the concentrated test substance severe leathery necrosis and erythema were noted. After 4 weeks deep crusts were detected. The 1 minute exposure caused red-brown necrosis. After 4 weeks scurfy sites were detected. The observed effects were considered as full thickness necrosis. The diluted test substance (20%) caused grey-brown necrosis after 15 minutes, after 5 minutes severe irritation and the 1 minute application showed no symptoms. The diluted and neutralised (pH 7.5) substance caused no irritation.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Short study summary with basic data.
Principles of method if other than guideline:
- Principle of test:
0.5 mL of the sample was applied to one intact and one abraded skin site under standard gauze patches on each of three albino rabbits. The entire hair-clipped trunk of each animal was then covered with an impervious sleeve for a skin contact period of 24 h. The animals were observed for 7 days.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
7 days.
Number of animals:
3

The sample spread beyond the intended sites of contact and caused pain on abraded skin only. The skin turned brown within 15 min. 24 h after initial contact, all treated sites consisted of large (3 cm) necrotic lesion. These became dry, hard, and concave within 48 h.

 

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The test substance caused necrotic skin reactions of intact and abraded rabbit skin.
Executive summary:

In this study 0.5 mL of the sample was applied to one intact and one abraded skin site under standard gauze patches on each of three albino rabbits. The entire hair-clipped trunk of each animal was then covered with an impervious sleeve for a skin contact period of 24 h. The animals were observed for 7 days. The sample spread beyond the intended sites of contact and caused pain on abraded skin only. The skin turned brown within 15 min. 24 h after initial contact, all treated sites consisted of large (3 cm) necrotic lesion. These became dry, hard, and concave within 48 h.

 

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
The chemical was applied in 0.01 mL amounts to clipped, uncovered intact skin of 5 rabbit bellies either undiluted or in progressive dilutions of 10, 1, 0.1, or 0.01% in solvent. One of 10 grade are, assigned based on appearance of moderate or marked capillary injection, erythema, edema or necrosis within 24 hours.
GLP compliance:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Charge No.of test material: 01067
- Identification: TK 2527
- Source: Chemicals and Plastics, South Charleston
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
open
Preparation of test site:
clipped
Vehicle:
water
Remarks:
additional testing of the undiluted substance
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.01 mL

Duration of treatment / exposure:
30 min
Observation period:
no data
Number of animals:
5 males
Details on study design:
TEST SITE
- Area of exposure: Ventral skin

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Moist gauze
- Time after start of exposure: 30 min

OBSERVATION TIME POINTS: 18- 24h after application




Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
6
Max. score:
10
Reversibility:
no data

Moderate erythema on 2 rabbits, marked erythema on one, moderate necrosis on two from the undiluted material. No irritation on 5 rabbits from a 10% dilution in distilled water.

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The test substance caused moderate to marked erythema and marked necrosis under the tested conditions.
Executive summary:

The test substance was applied in 0.01 mL amounts to clipped, uncovered intact skin of 5 male rabbit ventral skin sites either undiluted or in progressive dilutions of 10, 1, 0.1, or 0.01% in distilled water.

Moderate erythema on 2 rabbits, marked erythema on one, moderate necrosis on two from the undiluted material were observed after 24 h. No irritation on 5 rabbits from a 10% dilution in distilled water was detected.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Remarks:
Date: 14 Jan 1986
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: TF-4-012482 5210 RN
- Purity: 100 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, dark

OTHER SPECIFICS:
pH: 10.8
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Maple Lane Rabbits Clifford, Ontario
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 2.2 to 2.6 kg
- Housing: individually housed in stainless steel cages
- Identification: Permanent individual number on the ventral surface of the pinnae
- Diet: Purina Certified Rabbit Chow 5322, ad libitum
- Water: water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.7 ± 0.92°C
- Humidity (%): 43.0 ± 5.66%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Remarks:
at least 24h before treatment
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin site of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
3 min
Observation period:
the animal was killed after the 3 minute exposure time, since necrosis was already observed.
Number of animals:
1 male
Details on study design:
TEST SITE
- Area of exposure: 2x2 cm
- Type of wrap if used: gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was wiped off with a dry gauze pad
- Time after start of exposure: 3 min

OBSERVATIONS
- Observations were performed at 3 minutes
- Scoring was performed according to the Draize scale
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 3 min
Score:
4
Max. score:
4
Reversibility:
not reversible

The test substance produced severe erythema (with sloughing of skin) 3 minutes post-application. The animal was euthanized 3 minutes post-application because of corrosivity.

Interpretation of results:
Category 1A (corrosive) based on GHS criteria
Remarks:
According to the Transport of Dangerous Goods Code of Canada, the substance is classified as Packing Group I compound
Conclusions:
In the present study the score for erythema and edema is reported for 1 animal after 3 min of treatment. The test substance was corrosive after 3 min of treatment based on severe erythema formation (with sloughing of skin) indicating the corrosive potential of the test substance.
Executive summary:

The study was performed to determine the realtive dermal irritancy and corrosivity of the test article after topical application to the intact skin of albino rabbits. One male animal was treated for 3 min with 0.5 mL undiluted test substance under a gauze patch on the dorsum. The animal was anesthetized before test substance appliaction. A severe erythema (with sloughing of skin) was observed 3 minutes post-exposure. The animal was euthanized 3 minutes post-application because of corrosivity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 Mar 1955 - 22 Apr 1955
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2017
Deviations:
yes
Remarks:
Immediate eye washing, 2 animals tested, observation after 48 h is missing
Principles of method if other than guideline:
Principle of the test:
50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals (2 animals concentrated test substance, 2 other animals 20% solution and a third group of 2 animals with 20% solution pH 7.5).The eyes were washed out immediately after the application.The animals were observed after 10 min, 1 h and 3 h on the day of treatment and up to 2 weeks afterwards.
GLP compliance:
no
Remarks:
predating GLP
Species:
rabbit
Strain:
Vienna White
Vehicle:
water
Controls:
other: the adjacent eye served as control treated with 0.9 % NaCl (saline).
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL
- Concentration (if solution): concentrated, 20%; 20% pH 7.5

Duration of treatment / exposure:
single application and immediate washing
Observation period (in vivo):
up to 2 weeks (undiluted); up to 4 weeks (20% dilution)
Number of animals or in vitro replicates:
2 per dose
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tap water
- Time after start of exposure: immediately

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Undiluted substance, 48 h reading is missing.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24/72 h
Score:
0.3
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: Undiluted substance, 48 h reading is missing
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Undiluted substance, 48 h reading is missing
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Undiluted substance, 48 h reading is missing.

Table 1. Findings animal 1/2 (undiluted test substance)

 Time   Opacity Iritis   Conjunctival  Erythema  Conjunctival Chemosis                  
1 h 2/2 0/0 3/3 2/2                  
24 h 2/2 0/0 3/3 2/2                  
48 h

-/-

-/- -/- -/-                  
72 h 2/2 0/2 3/3 2/2                  
 8 d 2/x 0/x 3/x 0/x                  
 Mean: 24h - 48h - 72h 2/2 0.3 3/3 2/2                  

-/-: 48 h reading is missing.

x: the animal died on day 7.

The original BASF grading was converted into the numerical grading according to the OECD Draize system

The application of the test substance caused corrosion to the exposed eyes predominantly expressed by severe erythema, chemosis and misty-like corneal opacity with bloody discharge. In one animal occured severe iritis after 72 h. Severe corneal opacity is considered to be an irreversible effect to ophthalmic tissue.

The application of a 20% solution of the test substance caused similar effects then the undiluted test substance (erythema, chemosis and misty-like corneal opacity with bloody discharge). Irreversible corneal opacity.

The application of a neutralized 20% solution of the test substance caused only slight erythema and chemosis on the day of exposure.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test substance caused severe damage to rabbit eye under the tested conditions.
The application of the undiluted test substance caused corrosion to the exposed eyes predominantly expressed by severe erythema, chemosis and misty-like corneal opacity with bloody discharge. In one animal occured severe iritis after 72 h.
Executive summary:

In this eye irritation study, 50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals (2 animals concentrated test substance, 2 other animals 20% solution and a third group of 2 animals with 20% solution pH 7.5). The eyes were washed out immediately after the application.The animals were observed after 10 min, 1 h and 3 h on the day of treatment and up to 2 weeks afterwards (longer observation period after dilution application). The treatment of the undiluted test substance caused corrosion to the exposed eyes predominantly expressed by severe erythema, chemosis and misty-like corneal opacity with bloody discharge. In one animal occured severe iritis after 72 h. The application of a 20% solution of the test substance caused similar effects then the undiluted test substance (erythema, chemosis and misty-like corneal opacity with bloody discharge). Cornea opacity was observed until the end of the observation period (up to 4 weeks). The application of a neutralized 20% solution of the test substance caused only slight erythema and chemosis on the day of exposure.

Endpoint:
eye irritation: in vivo
Remarks:
2% dilution used
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Cited as Directive 84/449/EEC, B.5
GLP compliance:
not specified
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source of test material: Merck, Darmstadt, FRG

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
Species:
rabbit
Strain:
New Zealand White
Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µl
- Concentration (if solution): 2%
Observation period (in vivo):
7 days, but only mean values or 24, 48, 72h included in publication
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: Erythema, chemosis and corneal opacity were scored according to Draize
Corneal swelling was measured via an ultrasonic pachpmeter
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
2.44
Max. score:
4
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.96
Max. score:
3
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.44
Max. score:
4
Reversibility:
not specified
Irritation parameter:
other: corneal swelling
Basis:
mean
Remarks:
3 rabbits only
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
other: 103% compared to pre-treatment
Conclusions:
A 2% solution of diethylamine caused irritant effects on rabbit's eye.
Executive summary:

In an eye irritation study in 6 rabbits, 100 µL of the test substance (2% solution) were applied to the conjunctival sac of on eye. The untreated eye served as control. Mean ocular reactions after 24, 48, 72 are presented.

A 2% solution of diethylamine caused irritant effects on rabbit's eye.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Short study summary with basic data
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Principle of the test: 0.1 mL of the test substance was placed in the conjunctival sac of both eyes of each of three albino rabbits. One eye of each animal was washed with flowing water initiated 15 seconds after instillation and continued for a period of one minute. The contralateral eye remained unwashed. The irritant reactions were scored periodically for seven days.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
100 µL
Duration of treatment / exposure:
One eye was washed after 15 seconds, the other eye remained unwashed
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
performed for one eye, Second eye remained unwashed
- Washing (if done): flowing water
- Time after start of exposure: 15 seconds

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Remarks on result:
not determinable

Reactions in washed and unwashed eyes were identical. The cornea began to opacify immediately and opacification was virtually complete with ten minutes. Severe conjunctival inflammation also developed promptly. In addition, tissue necrosis appeared within minutes in portions of the conjunctivae and along the borders of the eyelids. The latter solidified within a day or two. The reactions persisted though the 7th day without change and appeared to be irreversible.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Severe, irreversible eye damage was observed after test substance application in washed and unwashed rabbit eyes.
Executive summary:

In this study, 0.1 mL of the test substance was placed in the conjunctival sac of both eyes of each of three albino rabbits. One eye of each animal was washed with flowing water initiated 15 seconds after instillation and continued for a period of one minute. The contralateral eye remained unwashed. The irritant reactions were scored periodically for seven days. the reactions in washed and unwashed eyes were identical. The cornea began to opacify immediately and opacification was virtually complete with ten minutes. Severe conjunctival inflammation also developed promptly. In addition, tissue necrosis appeared within minutes in portions of the conjunctivae and along the borders of the eyelids. The latter solidified within a day or two. The reactions persisted though the 7th day without change and appeared to be irreversible.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Principles of method if other than guideline:
Principle of the test:
Eye injury in rabbits is recorded in a 10-grade ordinal series and is based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical, as detailed by Carpenter and Smyth. Grade 1 in the Table indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.
GLP compliance:
no
Remarks:
predating GLP
Species:
rabbit
Strain:
not specified
Vehicle:
other: propylene glycol
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 1 %

Duration of treatment / exposure:
24 h
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
5
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: no data
Score:
10
Max. score:
10
Reversibility:
not reversible

A 1% dilution in propylene glycol applied in excess to the rabbit eye caused severe corneal damage.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test substance cause severe eye damage under the tested conditions.
Executive summary:

A 1% dilution in propylene glycol applied in excess to the rabbit eye caused severe corneal damage. This places it among the worst eye offenders in grade 10.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Principle of the test:
Eye injury in rabbits was recorded in a 10-grade ordinal series based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical.  Grade 1 indicates at most a very small area of necrosis resulting from 0.5 mL of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 mL, and Grade 10 indicates a severe burn from 0.5 mL of a 1% solution in propylene glycol.
GLP compliance:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Charge No.of test material: 01067
- Identification: TK 2527
- Source: Chemicals and Plastics, South Charleston
Species:
rabbit
Strain:
New Zealand White
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.005 mL undiluted; 0.5 mL 1% and 5% solution in water
- Concentration (if solution): 1% or 5 %

Duration of treatment / exposure:
24 h
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
5 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with water
- Time after start of exposure: 18-24 h

Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: no data
Score:
10
Max. score:
10
Reversibility:
not reversible

0.005 ml undiluted substance: severe corneal opacity; necrosed lids.

0.5 ml of a 5% solution in water: severe corneal opacity; necrosed lids.

0.5 ml of a 1% solution in water: moderate corneal opacity; iritis.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test substance caused severe, irreversible damage to rabbit's eye under the tested conditions.
Executive summary:

In this study the eyes of 5 male rabbits were treated with the test substance (undiluted, 5% dilution, 1% dilution). The vehicle was water. Exposure with 0.005 ml undiluted substance and 0.5 ml of a 5% solution caused severe corneal opacity and necrosed lids. Instillation of 0.5 ml of a 1% solution caused moderate corneal opacity and iritis. In can be concluded that the test substance is severely iritating (Grade 10).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

In a GLP compliant study (Hoechst, 1989) the potential of the test item to cause skin corrosion/irritation was investigated with 3 New Zealand White rabbits. 0.5 mL of the test substance were applied to the dorsal area of the trunk at a single site on the right flank after clipping. The exposure site was wrapped with a double layer of plastic wrap over the soaked gauze patch. After 3 min of exposure the plastic wrap and gauze patch were removed and washing of the residual test article was performed. Dermal reactions were observed at 3 min, 1 h, 24 h, 48 h, 72 h and 7 d after exposure initiation. The test substance produced dermal corrosion at all sites exposed to the test article. The dermal response was initially characterized by necrosis at the three minute scoring interval and progressed to eschar at one hour (2/3 rabbits) and 24 hours (3/3 rabbits). The eschar persisted throughout the remainder of the seven day study. A very slight edema was noted during the test period and diminished by test termination.

In a second study (BASF, 1955) two animals were treated for 1, 5 and 15 minutes with the test substance using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance (1 animal concentrated test substance, the other animal 20% solution and 20% solution pH 7.5). After the application time, the skin was washed with Lutrol (25%) which contained acetic acid (5%). Immediately after application of the concentrated test substance severe leathery necrosis and erythema were noted. After 4 weeks deep crusts were detected. The 1 min exposure caused red-brown necrosis. After 4 weeks scurfy sites were detected. The observed effects were considered as full thickness necrosis. The diluted test substance (20%) caused grey-brown necrosis after 15 min, after 5 min redness and superficial necrosis, and the 1 min application showed no symptoms. The diluted and neutralised (pH 7.5) substance caused no irritation.

Another GLP-compliant study (UCC, 1986) was performed to determine the realtive dermal irritancy and corrosivity of the test article after topical application to the intact skin of albino rabbits. One male animal was treated for 3 min with 0.5 mL undiluted test substance under a gauze patch on the dorsum. The animal was anesthetized before test substance appliaction. A severe erythema (with sloughing of skin) was observed 3 minutes post-exposure. The animal was euthanized 3 minutes post-application because of corrosivity.

Two other vaild study records report corrosive effects to rabbit skin (1976 and 1979). Only one study (UCC, 1950) showed no necrosis, but in this study, only 0.01ml were applied and left to freely evaporate.

Eye irritation

In an eye irritation study (BASF, 1955), 50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals (2 animals concentrated test substance, 2 other animals 20% solution and a third group of 2 animals with 20% solution pH 7.5). The eyes were washed out immediately after application. The animals were observed after 10 min, 1 h and 3 h on the day of treatment and up to 2 weeks afterwards (longer observation period after dilution application). The treatment of the undiluted test substance caused corrosion to the exposed eyes predominantly expressed by severe erythema, chemosis and misty-like corneal opacity with bloody discharge. In one animal severe iritis occured after 72 h. The application of a 20% solution of the test substance caused similar effects then the undiluted test substance (erythema, chemosis and misty-like corneal opacity with bloody discharge). Cornea opacity was observed until the end of the observation period (up to 4 weeks). The application of a neutralized 20% solution of the test substance caused only slight erythema and chemosis on the day of exposure.

Four other valid study records support the assumption that the substance causes severe eye damage after application into the rabbit eye.

In a study (Pennwalt, 1976), 0.1 mL of the test substance was placed in the conjunctival sac of both eyes of each of three albino rabbits. The reactions in washed and unwashed eyes were identical. The cornea began to opacify immediately and opacification was virtually complete after ten minutes. Severe conjunctival inflammation also developed promptly. In addition, tissue necrosis appeared within minutes in portions of the conjunctivae and along the borders of the eyelids. The latter solidified within a day or two. The reactions persisted though the 7th day without change and appeared to be irreversible.

A study (UCC, 1979) conducted with male rabbits revealed severe eye irritation after rabbit eye treatment with the test substance (undiluted, 5% dilution, 1% dilution). The vehicle was water. An exposure with 0.005 mL undiluted substance and 0.5 mL of a 5% solution caused severe corneal opacity and necrosed lids. Instillation of 0.5 mL of a 1% solution caused moderate corneal opacity and iritis.

In another eye irritation study (Jacobs, 1989), 100 µL of the test substance (2% solution) were applied to the conjunctival sac of 6 rabbit eyes. The untreated eye served as control. The ocular reactions were recorded at 4, 24, 48, 72, 96 and 168 h, though only the mean value for 24/48/72h was reported. The solution of the test substance caused irritant effects on rabbit's eye.

Severe corneal damage was detected with testing a 1% dilution in propylene glycol applied in excess to the rabbit eye (UCC, 1950). This places it among the worst eye offenders in grade 10.

Respiratory irritation

Limited information is available from several studies, which, in combination the data on skin and eye corrosion, is considered sufficient to classify the substance as an irritant to the respiratory tract. In two Alarie assays (Gagnaire, 1989 and Nielson, 1989 (see IUCLID section 7.2.2) RD50 values of 202ppm and 184ppm were reported, respectively. In humans, no or minimal effects would be expected at a 30 times lower concentration (0.03 x RD50), i.e., between 5.5 and 6ppm. This matches the observations by Lundquist et al. (1992, IUCLID section 7.10.5), in which 5 volunteers reported nose and/or eye irritation at an average exposure concentration of 10ppm (max. 12ppm) for 60 minutes, though responses varied greatly. No changes in nasal airflow of acoustic reflections were measured after exposure of 7 volunteers to 25ppm for 15min. Data are limited by the low number of volunteers and the non-blinded study design.


Justification for classification or non-classification

According to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance is classified as skin corrosive Cat. 1A (causes severe skin burns and eye damage) causing serious eye damage Cat. 1, and causing respiratory tract irritation (STOT SE Cat. 3)