Registration Dossier

Administrative data

Description of key information

There are 10 skin irritation and 6 eye irritation studies for the hydrotrope category substances.
      
The studies consistently demonstrate that the hydrotrope substances are not irritating or only slightly irritating to the skin and slightly to moderately irritating to the eye.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: As described in the U.S. Federal Register Vol. 38, No. 187, Section 1500:41, 1973
Deviations:
not specified
Principles of method if other than guideline:
Shaved skin; abraded and non-abraded; two sites per animal; exposed area covered; oedema and erythema assessed at 24 and 72 hours; primary irritation index evaluated following Draize scoring procedure.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: "recognized breeders"- Age at study initiation: 14-16 weeks- Weight at study initiation: 2.3 Kg average- Housing: caged singularly- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period:ENVIRONMENTAL CONDITIONS- Temperature (°C): 17 °C +/- 2 °C- Humidity (%): 50-70%- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): natural lighting conditionsIN-LIFE DATES: From: To: no data
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL- Concentration (if solution): undilutedVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
single application; patch removed at 24 hours but no indication of excess material wiped off
Observation period:
24 and 72 hours
Number of animals:
6 females
Details on study design:
TEST SITE- Area of exposure: Two 2.5 cm sites, one abraded and one not abraded- % coverage: no data- Type of wrap if used: Smith & Nephew Elastic bandage covered entire trunk of animal- 24 hours prior to dermal application, the backs of the rabbits were shaved over an area of at least 10% of the trunk. Two test sites lateral to the mid line of the back were used on each animal. Immediately before teh application of the test substance, the right hand site was abraded witht he point of a sterile hypodermic needle. The abrasions were sufficiently deep to penetrate the stratum corneum but not to damage the dermis. The left hand site remained intact. REMOVAL OF TEST SUBSTANCE- Washing (if done): not indicatedSCORING SYSTEM: J.H. Draize (1959) - primary irritation score (average for erythema and oedema for all six animals)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
>= 0.1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
other: 3 of 6 animals
Time point:
24 h
Score:
ca. 1
Irritant / corrosive response data:
No irritation on intact skin. Slight erythema (score = 1) in 3 of 6 animals at 24 hours with abraded skin. No oedema observed in any animals.
Other effects:
None reported.
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: primary irritation score of 0.1
Conclusions:
Sodium toluene sulfonate is a mild irritant
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline not specified, but with detailed documentation
Principles of method if other than guideline:
6 female animals exposed on shaved intact and abraded skin of back; one half of the shaved test site abraded in the manner described by J.H. Draize; single dose initially followed by repeated doses (up to 5 times); occluded; scored for erythema and edema using each rabbit's untreated area of skin as its own control; followed procedures described in 1964 US Federal Register
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: no data- Age at study initiation: no data- Weight at study initiation: 2.5 to 3.5 kg- Housing: caged individually - Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: no dataENVIRONMENTAL CONDITIONS- Temperature (°C): thermostatically controlled- Humidity (%): no data- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): no dataIN-LIFE DATES: From: To:no data
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
other: first test: distilled water; repeat test: no vehicle (undiluted)
Controls:
other: compared with the corresponding control for each rabbit
Amount / concentration applied:
First test:TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL in 1 cm square gauze patch- Concentration (if solution): dilution of test samples with distilled water to 25%VEHICLE- Amount(s) applied (volume or weight with unit): no dataRepeat test:TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL in 1 cm square gauze patch- Concentration (if solution): 40% active ingredient
Duration of treatment / exposure:
24 hours for each of 5 repeated single dose applications in both tests
Observation period:
At 24, 48, 72, 96 and 120 hours (each observation was 24 hours following a subsequent repeat dosing)
Number of animals:
6 females
Details on study design:
TEST SITE- Area of exposure: shaved half of back (one half intact skin, the other abraded)- % coverage: 1 cm square on half of back- Type of wrap if used: gauze patches secured in place with adhesive tape, occluded with polythene sheetREMOVAL OF TEST SUBSTANCE- Washing (if done): no dataSCORING SYSTEM: separate 0 to 4 scores for erythema and edema:No erythema = 0; very slight erythema = 1; well defined erythema = 2; moderate-severe erythema = 3; severe erythema = 4No oedema = 0; very slight oedema = 1; slight oedema = 2; moderate oedema = 3; severe oedema = 4
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours (including 4 repeated doses)
Score:
>= 0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
All the scores were 0 for erythema and oedema on intact and abraded skin
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance (Sodium toluenesulphonate, 40% active ingredient) was not irritating to the skin in repeated application.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline not specified, but with detailed documentation
Principles of method if other than guideline:
6 female animals exposed on shaved intact and abraded skin of back; one half of the shaved test site abraded in the manner described by J.H. Draize; single dose initially followed by repeated doses (up to 5 times); occluded; scored for erythema and edema using each rabbit's untreated area of skin as its own control; followed procedures described in 1964 US Federal Register
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: no data- Age at study initiation: no data- Weight at study initiation: 2.5 to 3.5 kg- Housing: caged individually - Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: no dataENVIRONMENTAL CONDITIONS- Temperature (°C): thermostatically controlled- Humidity (%): no data- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): no dataIN-LIFE DATES: From: To:no data
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
other: first test: distilled water; repeat test: no vehicle (undiluted)
Controls:
other: compared with the corresponding control for each rabbit
Amount / concentration applied:
First test:TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL in 1 cm square gauze patch- Concentration (if solution): dilution of test samples with distilled water to 33%VEHICLE- Amount(s) applied (volume or weight with unit): no dataRepeat test:TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL in 1 cm square gauze patch- Concentration (if solution): 30% active ingredient
Duration of treatment / exposure:
24 hours for each of 5 repeated single dose applications in both tests
Observation period:
At 24, 48, 72, 96 and 120 hours (each observation was 24 hours following a subsequent repeat dosing)
Number of animals:
6 females
Details on study design:
TEST SITE- Area of exposure: shaved half of back (one half intact skin, the other abraded)- % coverage: 1 cm square on half of back- Type of wrap if used: gauze patches secured in place with adhesive tape, occluded with polythene sheetREMOVAL OF TEST SUBSTANCE- Washing (if done): no dataSCORING SYSTEM: separate 0 to 4 scores for erythema and edema:No erythema = 0; very slight erythema = 1; well defined erythema = 2; moderate-severe erythema = 3; severe erythema = 4No oedema = 0; very slight oedema = 1; slight oedema = 2; moderate oedema = 3; severe oedema = 4
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours (including 4 repeated doses)
Score:
>= 0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
All the scores were 0 for erythema and oedema on intact and abraded skin
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance (Sodium xylenesulphonate, 30% active ingredient) was not irritating to the skin in repeated application.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD test guideline 404 (Acute Dermal Irritation / Corrosion) and in complaince with Good Laboratory Practice Regulations as described by the OECD annex 2 C(81)30.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Room temperature is 21°C to 25°C, Humidity is 54%to 89%, Dose is (0.20 g) 200mg
Principles of method if other than guideline:
None
GLP compliance:
yes
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: na- Weight at study initiation: 2.1 to 2.5 grams- Housing: Individually housed in stainless steel cages - Diet (e.g. ad libitum): Purina Certified Rabbit chow # 5322 - Water (e.g. ad libitum):Water purified by reverse osmosis -ad libitum - Acclimation period: 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 21°C to 25°C- Humidity (%): 54% to 89%- Air changes (per hr): na- Photoperiod (hrs dark / hrs light): 12 hour dark and 12 hour light IN-LIFE DATES: From: 1993-06-22 To: 1993-06-25
Type of coverage:
occlusive
Preparation of test site:
other: Intact
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 200mg of test article - Concentration (if solution): naVEHICLE- Amount(s) applied (volume or weight with unit):na- Concentration (if solution):na- Lot/batch no. (if required): na- Purity:na
Duration of treatment / exposure:
Three adult New Zealand white rabbits were treated with 200 mg of the test substance on to the intact skin sites with 25 mm Hilltop chamber with cotton pad.After 4 hours exposure period, the expendover tape were removeed and the treated sites were observed for erythema and edema at 4hr, 24 hour 48 hour and 72 hours.
Observation period:
41/2 hour,24 hour, 48 hour and 72 hours.
Number of animals:
Three New Zealand white rabbits.
Details on study design:
TEST SITE- Area of exposure: Dorsal area of the trunk of each animal - % coverage: na- Type of wrap if used: Wrappings of Expandover and Athletic tape was used. REMOVAL OF TEST SUBSTANCE- Washing (if done): na- Time after start of exposure: 4 hoursSCORING SYSTEM:Erythema and Eschar formation:0=no erythema, 1= very slight erythema, 2= slight erythema, 3=moderate to severe erythema, 4=severe erytheama, 4/4 highest possible erythema scoreEdema formation:0=no edema, 1=very slight edema, 2=slight edema, 3=moderate to severe edema, 4=severe edema,4/4 =highest possible edema
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 4 hr
Score:
1.33
Max. score:
1.33
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
erythema score
Basis:
mean
Remarks:
2 rabbits with grade 1 & 1 with grade 1
Time point:
other: 4 hr
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin iste
Irritation parameter:
edema score
Basis:
mean
Remarks:
all 3 rabbits with grade 1
Time point:
other: 4 hr
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24
Score:
1.66
Max. score:
1.66
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
erythema score
Basis:
mean
Remarks:
1 rabbit with grade 1 & 2 with grade 2
Time point:
other: 24 hr
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
edema score
Basis:
mean
Remarks:
all 3 rabbits with grade 0
Time point:
other: 24 hr
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 48 hr
Score:
0.66
Max. score:
0.66
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
erythema score
Basis:
mean
Remarks:
1 rabbit with grade 0 & 2 with grade 1
Time point:
other: 48 hr
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
edema score
Basis:
mean
Remarks:
all 3 rabbits with grade 0
Time point:
other: 48 hr
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin site
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin site
Irritant / corrosive response data:
PII 1.33 at 4 hours at erythema and 1.0 at edema intact skin site PII 1.66 at 24 hours at erythema and 0.0 at edema intact skin site PII 0.66 at 48 hours at erythema and 0.0 at edema intact skin site PII 0.0 at 72 hours at erythema and 0.0 at edema intact skin site
Other effects:
None

 Animal number       Degreeof erythema after (Observation ime)      Degreeof edema after (Observation ime)       Mean >=1.5 <2.3 ?   
   24 hr  48 hr  72 hr  24 hr  48 hr  72 hr  Erythema Edema  

 7803

  1  2  2  0  0  0 YES  NO
         Mean= 1.66         Mean= 0.00       
 7788  0  1  1  0  0  0  NO NO    
         Mean=0.66         Mean= 0.00       
 7789  0  0  0  0  0  0 NO  NO    
         Mean= 0.00         Mean= 0.00       
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test substance is a mild skin irritant.
Executive summary:

Three New Zealand white rabbits were treated with 200 mg of test substance occlusively, produced slight erythema of all 3 three animals at 4.5 hours reading. Similar observations were made at 24hr, 48 hr and 72 hours. The skin responses completely resolved by 72 hours reading. Based on the observations, the test substance is a mildly irritating to the dermal tissue of the rabbit.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
April 5-8, 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline test; GLP complince; full documentation
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Hazelton Research Products, Michigan- Age at study initiation: 7 months- Weight at study initiation: males 3457-3644g, females 3333-3598g- Housing: individually in hanging stainless steel wire mesh cages- Diet: up to 125g per day- Water: ad libitum- Acclimation period: minimum of 12 weeksENVIRONMENTAL CONDITIONS- Temperature (°C): controlled- Humidity (%): controlled- Air changes (per hr): controlled- Photoperiod (hrs dark / hrs light): 12/12- other: Animals were maintained in accordance with the recommendations contained in the D.H.H.S. Publication "Guide for the Care and Use of Laboratory Animals".IN-LIFE DATES: From: April 5 To: April 8
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL- Concentration (if solution): 31.2% active ingredientVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle usedOTHER:Test substance was applied to the site under a 1-inch square gauze secured with strips of Dermiform tape over a gauze bandage. A collar was attached to the rabbit
Duration of treatment / exposure:
4 hours followed by bandage removal and the site wiped with dry disposable toweling.
Observation period:
72 hours
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE- Area of exposure: 1 inch square- % coverage: - Type of wrap if used: gauze bandage with Dermiform tapeREMOVAL OF TEST SUBSTANCE- Washing (if done): wiped with dry toweling- Time after start of exposure: 4 hoursSCORING SYSTEM: Draize method
Irritation parameter:
other: erythema and edema
Basis:
mean
Time point:
other: 1-72 hours
Score:
0
Max. score:
0
Reversibility:
other: no irritation observed
Irritant / corrosive response data:
no dermal irritation was observed in any animal during the study period
Other effects:
no other effects observed
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance is not a dermal irritant
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: Guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Fa. Dr. Karl Thomae GmbH, Biberach, Germany- Age at study initiation: not mentioned- Weight at study initiation: 2.2 - 2.4 kg- Housing: single housing in stainless steel cages- Diet (e.g. ad libitum): Ssniff K4 complete feed for rabbits, ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany- Water (e.g. ad libitum): Drinking water ad libitum- Acclimation period: 14 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 ± 1- Humidity (%): 60 ± 5- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: 1982-09-07 To: 1982-09-20
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 cm³- Concentration (if solution): 60% in water
Duration of treatment / exposure:
4 hours
Observation period:
72 hours after patch removal
Number of animals:
6 (3 male, 3 female)
Details on study design:
TEST SITE- Area of exposure: 6 cm² of shaved skin of the dorsal and lateral parts of the trunk of the animals- % coverage: not mentioned- Type of wrap if used: on the application area a mull patch (2,5 x 2,5 cm) was placed, which was covered with a polyethylen film (6 x 6 cm). The application area was then immobilised with an elastic dressingREMOVAL OF TEST SUBSTANCE- Washing (if done): with distilled water- Time after start of exposure: 4 hoursSCORING SYSTEM: according to OECD guideline 404
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Irritant / corrosive response data:
AVERAGE SCORE- Erythema: 0- Edema: 0

Table: Irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score:

Max. score:

60 min

0/0/0/0/0/0

0/0/0/0/0/0

24 h

0/0/0/0/0/0

 0/0/0/0/0/0

48 h

 0/0/0/0/0/0

 0/0/0/0/0/0

72 h

 0/0/0/0/0/0

 0/0/0/0/0/0

Average 24h, 48h, 72h

 0

 0

Reversibility*)

 -

 -

Average time (unit) for reversion

 -

 -

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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: Guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Fa. Dr. Karl Thomae GmbH, Biberach, Germany- Age at study initiation: not mentioned- Weight at study initiation: 1.8 - 2.6 kg- Housing: single housing in stainless steel cages- Diet (e.g. ad libitum): Ssniff K4 complete feed for rabbits, ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany- Water (e.g. ad libitum): Drinking water ad libitum- Acclimation period: 14 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 ± 1- Humidity (%): 60 ± 5- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 g- Concentration (if solution): 0.5 g of the test material was wetted with 0.5 cm³ deionised waterVEHICLE- Amount(s) applied (volume or weight with unit): 0.5 cm³
Duration of treatment / exposure:
4 hours
Observation period:
up to 6 days
Number of animals:
3
Details on study design:
TEST SITE- Area of exposure: 6 cm² of shaved skin of the dorsal and lateral parts of the trunk of the animals- % coverage: not mentioned- Type of wrap if used: on the application area a mull patch (2,5 x 2,5 cm) was placed, the application area was then immobilised with an elastic dressingREMOVAL OF TEST SUBSTANCE- Washing (if done): with warm water- Time after start of exposure: 4 hoursSCORING SYSTEM: according to OECD guideline 404
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.11
Max. score:
8
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
AVERAGE SCORE- Erythema: 0.11- Edema: 0

Table: Irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

0/0/1

0/0/1

24 h

0/0/1

 0/0/0

48 h

0/0/0

0/0/0

72 h

0/0/0 

 0/0/0

Average 24h, 48h, 72h

 0.11

 0

Reversibility*)

 c.

 -

Average time (unit) for reversion

 48 h

 -

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
late 1974 or January 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline not specified, but with detailed documentation
Justification for type of information:
Please see attached Category Approach
Qualifier:
no guideline available
Principles of method if other than guideline:
6 animals; clipped backs with minor incisions through the stratum corneum; single dose; occluded; 24 hour exposure followed by removal of any remaining test material; reactions scored using the Draize method.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: no data- Age at study initiation: no data- Weight at study initiation: no data- Housing: individually housed in metal cages elevated above the droppings- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: no dataENVIRONMENTAL CONDITIONS- Temperature (°C): no data- Humidity (%): no data- Air changes (per hr): no data - Photoperiod (hrs dark / hrs light): no dataIN-LIFE DATES: From: To: no data
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded through the stratum corneum but not disturbing the derma
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL- Concentration (if solution): undilutedVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE- Area of exposure: back- % coverage: 2 one-inch square patches per animal- Type of wrap if used: plastic binder and adhesive tapeREMOVAL OF TEST SUBSTANCE- Washing (if done): yes- Time after start of exposure: 24 hoursSCORING SYSTEM: Draize, Woodward and Calvery (J. Pharmacol, Exptl. Therap., 82:377, 1944)
Irritation parameter:
other: erythema and eschar plus edema
Basis:
mean
Time point:
other: 24 hours
Score:
>= 1.3
Max. score:
1.3
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
erythema and eschar average value at 24 hours = 1.3 (intact and abraded skin identical); = 1.2 at 48 hours (intact and abraded identical); = 0.3 at 72 hours (intact and abraded identical);average edema formation value at 24 hr = 1.2 (intact and abraded skin identical); = 0.3 at 48 hours (intact and abraded identical); = 0.0 at 72 hoursPrimary Irritation Index = 1.4
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Federal Hazardous Substances Act (FHSA)
Conclusions:
With a Primary Skin Irritation Index of 1.4 the test substance is found not to be a Primary Irritant
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
October 9 - 16, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline not specified, but with detailed documentation
Principles of method if other than guideline:
No guideline specified.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Boswell, S-K & Lomax- Age at study initiation: young adult- Weight at study initiation: no data- Housing:individually in metal cages elevated above the droppings- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: no dataENVIRONMENTAL CONDITIONS- Temperature (°C): no data- Humidity (%): no data- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): no dataIN-LIFE DATES: From: October 9, 1979 To: October 16, 1979
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit):0.5 mL of undiluted test material- Concentration (if solution): no dataVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
24 hours after which the plastic binder and patches were removed and any remaining material was wiped off the treated areas
Observation period:
At 24, 48, 72 and 96 hours and at 7 days following exposure
Number of animals:
6 of random sex
Details on study design:
The backs of the animals were clipped free of hair. Two sets of abrasions (minor incisions through the stratum corneum, but not deep enough to disturbe the derma) were made approximately ten centimeters apart on the right side of the back of each animal, while the skin of the left side remained intact. The animals were immobilized in a restrainer rack and 0.5 mL of the undiluted test substance applied to 2 intact and 2 abraded areas on each rabbit. Patches were first taped in place and then the entire trunk of the animal was enclosed in a plastic binder for 24 hours.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1 - 96 hr
Score:
>= 1.05
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Within 24 hours in all animals there was a barely perceptible to slight erythema and edema. This condition continued in all six animals at 48 hours and in five of six animals at 72 hours and 96 hours. The skin of all animals were reaction free at 7 days.
Other effects:
None reported
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Scoring method of Draize, Woodard and Calvery (J. Pharmacol. Exptl. Therap. 82:377, 1944)
Conclusions:
Ammonium xylene sulfonate is not a primary irritant in dermal exposure
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 2007 GLP Guideline Study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Kuiper Rabbitry, Gary, Indiana- Age at study initiation: 8 - 10 weeks- Weight at study initiation: 2.40 - 2.77 Kg- Housing: individually housed in steel cages- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: Conditioned for at least 5 days prior to study initiation. Maintained according to the recommendations contained in the "Guide for the Care and Use of Laboratory Animals", National Academy Press, 1996.ENVIRONMENTAL CONDITIONS- Temperature (°C): 16 - 22- Humidity (%): 30-70- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): "light controlled"IN-LIFE DATES: From: August 7, 2007 To: August 10, 2007
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit):0.5 gram- Concentration (if solution): undiluted; test substance is 40% active ingredient VEHICLE- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
4 hours; after which excess test material was removed from the site
Observation period:
30 minutes and 24, 48 and 72 hours after patches were removed
Number of animals:
3 (females)
Details on study design:
TEST SITE- Area of exposure: 6 sq cm- % coverage: - Type of wrap if used: 2 layer gauze patch covered with semiocclusive plastic overwrop held in place with Kendall Curity Standard Porous TapeREMOVAL OF TEST SUBSTANCE- Washing (if done): excess removed- Time after start of exposure: 4 hoursSCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hours
Score:
>= 0.25
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
The maximum skin irritation score was 1.0 at the 4.5 hour observation.
Other effects:
Final body weights were within expected values.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Not irritating
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Hazelton Research Products, Michigan- Age at study initiation: 4 months- Weight at study initiation: males 2722-2783g; females 2600-2779g- Housing: individually in hanging stainless steel wire mesh cages- Diet: up to 125 g/day - Water: ad libitum- Acclimation period: minimum of 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): controlled - Humidity (%): controlled- Air changes (per hr): controlled- Photoperiod (hrs dark / hrs light): 12/12- other: animals were maintained in accordance with the recommendations contained in the D.H.H.S. Publication "Guide for Care and Use of Laboratory Animals IN-LIFE DATES: From: April 13 To: April 18
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye of animal served as control
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 mL- Concentration (if solution): 31.2% active ingredientVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle used
Duration of treatment / exposure:
The test substance was instilled into the cupped conjunctival sac of the right (test) eye and the eyelids were then gently held together for one second before release.
Observation period (in vivo):
72 hours total
Number of animals or in vitro replicates:
4 male and 4 female
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): not doneSCORING SYSTEM: Draize methodTOOL USED TO ASSESS SCORE: fluoresceinLeft eye of each test animal served as control. Manipulated in an identical manner as right (test) eye except no test substance administered
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 hour
Score:
>= 0 - <= 18.6
Max. score:
18.6
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
hour 1 = 18.6; hour 24 = 6.2; hour 48 = 0.8; hour 72 = 0.0
Other effects:
The score for redness of the conjunctivae ranged from 3-2 at 1 hour but cleard by 48 hour in 3 animals and by 72 hour in all animals.The score for chemosis of the lids and /or nictitating membranes ranged from 3-2 at 1 hour but cleared by 48 hour in all animals.The score for conjuntival discharge ranged from 2-1 at 1 hour but none noted by 24 hours. Discharge was clear at 1 hour.
Interpretation of results:
other: mildly irritating
Remarks:
Criteria used for interpretation of results: not specified
Conclusions:
The test substance is mildly irritating to the eye
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Dr. Karl Thomae GmbH, Biberach, Germany- Age at study initiation: not mentioned- Weight at study initiation: 2.2 - 2.6 kg- Housing: conventional, singly in stainless steel cages- Diet (e.g. ad libitum): K4 complete feed for rabbits ad libitum, supplied by Ssniff Spezialfutter GembH, Soest, Germany- Water (e.g. ad libitum): Drinking water ad libitum- Acclimation period: 14 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 ± 1- Humidity (%): 60 ± 5- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: 1989-10-10 To: 1989-10-31
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours, and 6, 8, 10, 13, 17 and 21 days after application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): with warm physiological saline- Time after start of exposure: 24 hoursSCORING SYSTEM: according to guidelineTOOL USED TO ASSESS SCORE: ophthalmic lamp, fluorescein 72 hours after administration
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
31.2
Max. score:
110
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
AVERAGE SCORE (24, 48 and 72 h)- Cornea: 2.0- Iris: 1.0- Conjunctivae (Redness): 3.0- Conjunctivae (Chemosis): 2.11
Other effects:
Dark red erythema, strong swelling and necrotic variations of mucosa and nictitating membrane, all animals. Opacity and hemorrhage on iris, up to 6 days on two animals; strong opacity and strong circumcorneal injection of iris on day 21 still on one animal.

Table: Irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

1/2/2

 1/0/0

 2/3/2

 3/2/2

24 h

2/2/2

 1/1/1

 3/3/3

 2/3/2

48 h

 2/2/2

 1/1/1

 3/3/3

 2/2/2

72 h

 2/2/2

 1/1/1

 3/3/3

 2/2/2

Average 24h, 48h, 72h

 2.00

 1.00

 3.00

 2.11

Area effected

1.44

 -

 -

 -

Reversibility*)

 n.

 n.

 n.

 n.

Average time (unit) for reversion

-

 -

 -

 -

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
moderately irritating
Remarks:
Migrated information Risk of serious damage to eyes Criteria used for interpretation of results: EU
Conclusions:
The test item had a moderately irritating effect on the eyes. 1 of 3 animals showed irreversible damages at cornea, iris and conjunctivae.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Principles of method if other than guideline:
6 animals; eyes examined with Fluorescein 72 hours before testind; test substance instilled into the conjuntival sac of one eye in each animal; washedout at 24 hours; evaluated at 1, 24, 48 and 72hours
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: no data- Age at study initiation: no data- Weight at study initiation: no data- Housing: individually housed in metal cages elevated above the droppings- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: at least 72 hoursENVIRONMENTAL CONDITIONS- Temperature (°C): no data- Humidity (%): no data- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): no dataIN-LIFE DATES: From: To: no data
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 mL- Concentration (if solution): undilutedVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
single application, washed out after 24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): washing at 24 hoursSCORING SYSTEM: scale for scoring ocular lesions as outlined by Lehman et al (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics Assoc, Food and Drug Officials of the US, 2nd printing, Topeka, Kansas, 1965. In accordance with Section 1500.42 Chapter 2, Title 16 Code of Federal Regulations under the Federal Hazardous Substances ActTOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 hour
Score:
>= 13
Max. score:
12
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: slight erythema at 72 hours
Irritant / corrosive response data:
Maximum mean total score at 1 hr = 13.0, at 24 hr = 12.2, at 48 hr = 5.0 and at 72 hr = 2.0
Other effects:
slight eye damage in the form of moderate erythema of the palpebral and bulbar conjunctivae, a slight chemosis of the lids, a slight acccumulation of mucoid discharge and a slight to moderate corneal opacity involving one-fourth or less of the corneal surface (4 test eyes only).
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: term defined in Federal Hazardous Substances Act
Conclusions:
The test material was found to be an eye irritant
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Principles of method if other than guideline:
Test material instilled undiluted into the conjunctival sac of six rabbits. The eyes of some treated animals were not washed following exposure and other animals had their eyes washed after 20 seconds of exposure. Exposure was followed by 14 days of observation and the grade of occular reaction, based on the scoring scale of Lehman et al 1965 (US FDA), recorded at prescribed intervals. A maximum average score for washed and unwashed eyes was calculated.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: SLK, Per-DOT, Issac's- Age at study initiation: young adult- Weight at study initiation: no data- Housing: individually in metal cages elevated above the droppings- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: no dataENVIRONMENTAL CONDITIONS- Temperature (°C): no data- Humidity (%): no data- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light):no dataIN-LIFE DATES: From:April 23, 1979 To: May 7, 1979
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 mL in one eye of each animal (the other eye was not treated and served as a control)- Concentration (if solution): undilutedVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
6 of the 9 animals were treated and their eyes were not washed. The remaining 3 animals had their eyes washed for one minute following 20 seconds of exposure.
Observation period (in vivo):
All animals (both eyes) at 1, 24, 48, 72 and 96 hours; and at 7, 10 and 14 days
Number of animals or in vitro replicates:
9 total; six with eyes not washed and 3 with eyes washed
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): 3 of 9 animals. One minute washing.- Time after start of exposure: 20 seconds - All animals were immobilized in a suitable restrainer rack for one hour following treatmentSCORING SYSTEM: scale for scoring as outlined by Lehman, A.J. et al. in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, 1965.TOOL USED TO ASSESS SCORE: fluorescein sodium 2% on the cornea
Irritation parameter:
other: maximum average score
Basis:
other: for the unwashed eyes and for the washed eyes
Time point:
other: 24 hours for unwashed; 48 hours for washed
Score:
ca. 13.7 - ca. 17.3
Max. score:
17.3
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: total possible maximum score is 110
Irritant / corrosive response data:
Rabbits with treated eyes that were not washed produced within 24 hours conjunctival lesions in the form of a moderate erythema of the palpebral and bulbar conjunctivae, a slight to moderate chemosis of the lids, a slight to moderate watery-mucoid discharge and a slight corneal opacity (4 of the 6 animals) involving one-fourth of less of the corneal surface. The test eyes showed steady improvement with the cornea of all test eyes being reaction free at 72 hours. A maximum average score of 13.7 was recorded at 24 hours.The rabbits with washed eyes following treatment produced within 24 hours conjunctival lesions in the form of a slight erythema of the palpebral and bulbar conjunctivae, a moderate chemosis of the lids, a slight watery-mucoid discharge and a slight corneal opacity involving one-fourth to one-half of the corneal surface. Little change was noted at 48 hours and some deduction of the reaction was noted at 72 hours. The corneal reaction was not present at 96 hours and all test eyes were reaction free by 10 days. A maximum average score of 17.3 was recorded at 48 hours.
Other effects:
None reported
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: maximum average score of 17.3 versus possible total maximum average score of 110
Conclusions:
Ammonium xylene sulfonate is slightly irritating to the eye
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Dr. Karl Thomae GmbH, Biberach, Germany- Age at study initiation: not mentioned- Weight at study initiation: 2.0 - 2.4 kg- Housing: conventional, singly in stainless steel cages- Diet (e.g. ad libitum): K4 complete feed for rabbits ad libitum, supplied by Ssniff Spezialfutter GembH, Soest, Germany- Water (e.g. ad libitum): Drinking water ad libitum- Acclimation period: 14 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 ± 1- Humidity (%): 60 ± 5- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: 1982-08-31 To: 1982-09-20
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 50 mg
Duration of treatment / exposure:
The test substance was not washed out of the eyes of the treated animals and remained until the test was terminated.
Observation period (in vivo):
1, 24, 48 and 72 hours, and 6, 8 and 14 days after application
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCETest substance was not washed outSCORING SYSTEM: according to guidelineTOOL USED TO ASSESS SCORE: ophthalmic lamp, the disappearance of corneal findings was checked by adding Sodium-Fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.44
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.94
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
see table below

Table: Irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

1/1/1/1/1/1

 0/0/0/0/0/0

 1/1/1/1/1/1

 1/1/1/3/1/2

24 h

 1/1/1/1/1/1

 1/1/1/1/1/1

 2/1/1/1/2/1

 1/1/0/2/1/0

48 h

 1/1/1/1/1/1

 0/1/0/1/0/0

 1/1/1/1/1/1

 0/0/0/1/0/0

72 h

 1/1/1/1/1/1

 0/0/0/0/0/0

 0/1/0/1/1/0

 0/0/0/0/0/0

Average 24h, 48h, 72h

 1.00

 0.44

 0.94

 0.33

Reversibility*)

 c.

 c.

 c.

 c.

Average time (unit) for reversion

 14 days

 72 hours

 6 days

 72 hours

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Animals #1 -3: male; #4 -6: female

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Kuiper RAbbitry, Gary, Indiana- Age at study initiation: 8-10 weeks- Weight at study initiation: 2.59-2.66 kg- Housing: individually in steel cages- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum):ad libitum- Acclimation period: conditioned for at least 5 days prior to study. Animals were maintained according to "Guide for the Carre and Use of Laboratory Animals", National Academy Press, 1996. ENVIRONMENTAL CONDITIONS- Temperature (°C): 16 - 22- Humidity (%): 30-70- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): "light controlled room"IN-LIFE DATES: From: August 7, 2007 To: August 14, 2007
Vehicle:
unchanged (no vehicle)
Controls:
other: unexposed eye of each animal served as its own control
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit):0.1 gram- Concentration (if solution): undiluted is 40% active ingredientVEHICLE- Amount(s) applied (volume or weight with unit): no vehicle
Duration of treatment / exposure:
single dose (no washing)
Observation period (in vivo):
at 1, 24, 48 and 72 hours and at 7 days
Number of animals or in vitro replicates:
3 (males)
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): no washingSCORING SYSTEM: DraizeTOOL USED TO ASSESS SCORE: fluorescein (2%) and ultraviolet light
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 hours
Score:
>= 23.33
Max. score:
27
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: total maximum score possible is 110
Irritant / corrosive response data:
The maximum irritation (noted as "moderate") occurred at 24 hours, with effects observed in the cornea, iris and conjunctiva of all three animals. The scores were noticeably lower at 48 hours and again at 72 hours. No irritation was detected at 7 days.
Other effects:
Final body weights were within expected range.
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test material would be classified as Toxicity Category III in accordance with OPPTS/OECD Guidelines. The test material is moderately irritating to the eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are a total of 10 skin irritation and 6 eye irritation studies on the hydrotrope category substances.

- All skin irritation studies show results which ranged from non-irritating to slightly irritating.

- The eye irritation studies show results which ranged from slightly to moderately irritating.

The in vivo skin/eye irritation data were obtained in studies performed before any in vitro skin irritation tests had been validated and accepted for regulatory purposes. 


Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Based on the available skin irritation studies no classification for skin effects is warranted.

The effects observed in the six eye irritation studies vary from slightly to moderately irritating. In only one of the available studies were the effects shown not to be reversible (in one single animal after 21 days). In all other studies the effects were observed to be reversible in all animals. Therefore based on the weight of evidence of data across the category members, a classification as "Eye irritant, category 2" is justified.