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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
read-across
Justification for type of information:
Refer to the section 13 of IUCLID dataset for details on the read across justification. The acute oral toxicity study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Atsugi breeding center
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 191-214 g
- Fasting period before study: yes
- Housing: 1-3 animals/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 9-16 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.5-24.2°C
- Humidity (%): 48-81%
- Air changes (per h): 8/h
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6.40%w/v
- Amount of vehicle (if gavage): 0.5 mL/100 g weight
- Justification for choice of vehicle: Stability and uniformity of concentration
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6 animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: everyday for observation and Days 0, 7, 14 for weighting
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No motarity
Clinical signs:
other: One animal at 300 mg/kg bw suffered from diarrhea after 1 h of dosing. But it recovered after 4 h of dosing. There were no abnormality in other animals.
Gross pathology:
There were not any abnormalities for gross pathology at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median dose (LD50) of the substance in the female Crj:CD(SD) IGS rats was determined to be >2000 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of the read-across substance CAS 7299 -99 -2 in Crj:CD(SD) IGS rats according to OECD Guideline 423. Groups of rats were orally administered the test substance at dose levels of 300 and 2000 mg/kg bw as a solution in corn oil. Clinical signs and bodyweight development were monitored during the study period of 14 d. All animals were subjected to gross necropsy. No mortality was observed in either test group. No clinical signs were observed and there were no treatment-related effects on the body weight. No abnormalities were observed at necropsy. Under the study conditions, the acute oral LD50 of the substance in Crj:CD(SD)IGS rats was determined to be >2000 mg/kg bw (MHLW, 2005).

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
From June 1994 to August 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Read-across
Justification for type of information:
The supporting skin irritation study is considered sufficient to fulfil the information requirement.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 4924 - 5154 g
- Sex: Female
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of the test sample
Duration of treatment / exposure:
4 hours
Observation period:
Observation time points: 30 - 60 min, 24, 48, 72 and 96 h
Number of animals:
Three females
Details on study design:
The test sample was applied to a 2.5 cm square area on the shaved left flank of the dorso-lumbar area.

REMOVAL OF TEST SUBSTANCE
- Washing: cleansing with clean warm water
- Time after start of exposure: 4 h (upon removal of the dressing)

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1.3
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.7
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1.3
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the substance was not considered to be irritating to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation potential of the read-across substance CAS 68424 -31 -7 according to a method similar to OECD Guideline 404. Three female New Zealand White albino rabbits were used in the study. Approximately 0.5 mL of the test substance was applied to a 2.5 cm square area on the shaved left flank of the dorso-lumbar region of each animal under a semi-occlusive dressing for 4 h. Upon removal of the dressing, the skin was cleansed with clean warm water. The application sites were assessed for signs of erythema and oedema and scored according to the Draize scale at approximately 30 -60 min, 24, 48, 72 and 96 h after removal of the dressings. Very slight to well-defined erythema and very slight oedema were observed up to 72 h after application and the signs were resolved 96 h after application. Under the study conditions, the substance was not considered to be irritating to rabbit skin (Robinson, 1991).

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From June 1994 to August 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
read-across
Justification for type of information:
Refer to the section 13 for details on the read across justification. The skin irritation study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
limited documentation but relevant data given
GLP compliance:
yes
Species:
rabbit
Strain:
not specified
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
yes
Duration of treatment / exposure:
4 h
Observation period:
Time points: 30 - 60 min, 24, 48 and 72 h
Number of animals:
3 females
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
The only sign of irritation was a slight transient erythema observed in all three rabbits 30-60 min after patch removal.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the substance was non-irritating to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation potential of the read-across substance CAS 7299 -99 -2 in rabbits according to a method similar to OECD Guideline 404. The test substance was applied to the shaved skin of 3 female rabbits under a semi-occlusive patch for 4 h. Upon patch removal, the exposed skin was observed for signs of skin irritation at 30 -60 min, 24, 48 and 72 h. The only sign of irritation was a slight transient erythema observed in all three rabbits 30 -60 min after patch removal. Under the study conditions, the test substance was non-irritating to rabbit skin (Zeneca, 1994).

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 7th April 2004 to 13rd May 2014
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed in 2004, before the requirement for LLNA method was mandated as per the amendment to Annex VII.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SLC Japan Co., Ltd (3371-8 Koto-cho, Hamamatsu-shi, Shizuoka, Japan)
- Age at study initiation: four weeks old
- Weight at study initiation: 339 g at the time of induction and 486 g at challenge
- Housing:at the time of acquisition 5 per cage in aluminum cages which were installed in an automatically washable rack.
- Diet (e.g. ad libitum): Pellet feed (RC4, Oriental Yeast Co., Ltd)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2ºC
- Humidity (%): 50±10%
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
30%
Route:
intradermal
Vehicle:
other: FCA and physiological saline (1:1 v/v)
Concentration / amount:
0%
Route:
intradermal
Vehicle:
other: FCA and physiological saline (1:1 v/v)
Concentration / amount:
60%
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
0%
Route:
other: percutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Route:
other: percutaneous
Vehicle:
paraffin oil
Concentration / amount:
0%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
50%
No.:
#3
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
30%
No.:
#4
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
10%
No.:
#5
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
5%
No.:
#6
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
0%
No. of animals per dose:
Total 23 animals were allocated as follows: 8 animals to the preliminary study group, 10 to the sensitization group, and 5 to the control group.
Details on study design:
1) Preliminary study:
Formulations for intradermal injection (%): 40, 30, 25, 10, 5, 3, 1, 0.5, 0.3, 0.1, 0.05, 0.03
Formulations for closed application (%): 100, 50, 30, 10, 5, 3

2)Formulations for intradermal induction:
a) Emulsion of FCA and physiological saline at a ration of 1:1 (v/v)
b) 30% test substance solution
c) Emulsion of 60% test substance solution and physiological saline at a ratio of 1:1 (v/v)
d) Liquid paraffin

3) Formulation for percutaneous induction: Sensitization group: 100% test substance solution
Control group: liquid paraffin

4) Formulations for challenge (%): 100, 50, 30, 10, 5, 0
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10

Sensitization group challenged on Day 21: Summary Table (24 hr closed application, 10 animals)

 Formulation  Concentration (%) Observation time after removal (hr)   Score of erythema  Score of edema  Mean reaction strength
0 1 2 3 4  0 1 2 3 4  
 1 100  3 10 0 0 0 0 10 0 0 0 0  0
 1 100   24 10 0 0 0 0 10 0 0 0 0  0
 1  100  48 10 0 0 0 0  10 0 0 0 0  0
 2  50  3 10 0 0 0 0 10 0 0 0 0  0
 2  50  24 10 0 0 0 0 10 0 0 0 0   0
 2  50  48 10 0 0 0 0 10 0 0 0 0   0
 3  30  3 10 0 0 0 0 10 0 0 0 0  0
 3  30  24 10 0 0 0 0 10 0 0 0 0   0
 3  30  48 10 0 0 0 0 10 0 0 0 0  0
 4  10  3 10 0 0 0 0 10 0 0 0 0  0
4   10  24 10 0 0 0 0 10 0 0 0 0  0
 4  10  48 10 0 0 0 0 10 0 0 0 0   0
5  5   3 10 0 0 0 0 10 0 0 0 0   0
 5  5  24 10 0 0 0 0 10 0 0 0 0   0
 5  5  48 10 0 0 0 0 10 0 0 0 0   0
 6  100  3 10 0 0 0 0 10 0 0 0 0   0
 6  100  24 10 0 0 0 0  10 0 0 0 0  0
 6 (LP)  100  48 10 0 0 0 0 10 0 0 0 0   0

Mean reaction strenght=Scores of erythema and eshar formation +Score of edema/Total number of animals (Vehicle: liquid paraffin (LP))

Control group challenged on Day 21: Summary Table (24 hr closed application, 5 animals)

 Formulation  Concentration (%) Observation time after removal (hr)   Score of erythema  Score of edema  Mean reaction strength
0 1 2 3 4  0 1 2 3 4  
 1 100  3 5 0 0 0 0 5 0 0 0 0  0
 1 100   24 5 0 0 0 0 5 0 0 0 0  0
 1  100  48 5 0 0 0 0  5 0 0 0 0  0
 2  50  3 5 0 0 0 0 5 0 0 0 0  0
 2  50  24 5 0 0 0 0 5 0 0 0 0   0
 2  50  48 5 0 0 0 0 5 0 0 0 0   0
 3  30  3 5 0 0 0 0 5 0 0 0 0  0
 3  30  24 5 0 0 0 0 5 0 0 0 0   0
 3  30  48 5 0 0 0 0 5 0 0 0 0  0
 4  10  3 5 0 0 0 0 5 0 0 0 0  0
4   10  24 5 0 0 0 0 5 0 0 0 0  0
 4  10  48 5 0 0 0 0 5 0 0 0 0   0
5  5   3 5 0 0 0 0 10 0 0 0 0   0
 5  5  24 5 0 0 0 0 10 0 0 0 0   0
 5  5  48 5 0 0 0 0 5 0 0 0 0   0
 6  100  3 5 0 0 0 0 5 0 0 0 0   0
 6  100  24 5 0 0 0 0  5 0 0 0 0  0
 6 (LP)  100  48 5 0 0 0 0 5 0 0 0 0   0

Mean reaction strenght=Scores of erythema and eshar formation +Score of edema/Total number of animals (Vehicle: liquid paraffin (LP))

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the substance did not show skin sensitization potential in guinea pigs.
Executive summary:

A study was conducted to determine the skin sensitisation potential of the substance according to a method similar to guinea pig maximisation test protocol. 23 animals were used for the study, i.e. 8 for the preliminary study, 10 for the sensitization group, and 5 for the control group. In the induction phase, animals received intradermal injections of (a) emulsion of Freund's Complete Adjuvant (FCA) and physiological saline at a ratio of 1:1, (b) 30% test substance solution (vehicle: liquid paraffin), and (c) emulsion of 60% test substance solution (vehicle: FCA) and physiological saline at a ratio of 1:1. On Day 8 of induction, undiluted test substance was applied under occlusive conditions into each of the treated sites for 48 h. Liquid paraffin was used in the control group in the same manner. The challenge was performed on Day 21 after induction by closed application for 24 h with the test substance at concentrations of 0, 5, 10, 30, 50 and 100%. The skin reactions were observed at 24 and 48 h after application and scores were evaluated. No skin reactions were observed at any of the time points at any concentration. Under the study conditions, the substance did not show skin sensitisation potential in guinea pigs (Hashiyada, 2004).

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion