Registration Dossier

Administrative data

Description of key information

Oral
Key, LD50 oral > 2000 mg/kg bw (test item), Sanders, 2013
Supporting, LD 50 oral > 2000 mg/kg bw (EC 234-392-1), Clouzeau, 1990
Supporting, LD50 oral >2000 mg/kg bw (CAS 85116-93-4), Potokar, 1983
Supporting, LD50 oral >2000 mg/kg bw (CAS 68424-31-7), Robinson, 1991
Supporting, LD50 oral >2000 mg/kg bw CAS 131459-39-7, Allen, 1999


Dermal
Key, LD50 dermal > 2000 mg/kg bw (test item), Sanders, 2013
Supporting, LD50 dermal: >2000 mg/kg bw (EC 234-392-1), Blanset, 1997
Supporting, LD50 dermal: >2000 mg/kg bw (CAS 131459-39-7), Allen, 1999


Inhalation
Supporting, LD50 inhalation: > 5100 mg/m3 air (aerosol) (CAS 68424-31-7), Parr-Dobrzanski, 1994


Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-06-06 to 2013-06-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 152-163 g
- Fasting period during the study: Animals were fasted for overnight period before test item administration and for approximately 3-4 h after dosing.
- Housing: Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2013-06-06 To: 2013-06-27
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
SPECIFIC GRAVITY OF TEST ITEM: 0.932

MAXIMUM DOSE VOLUME APPLIED: 2.15 mL/kg bw

Doses:
- Sighting test: 2000 mg/kg bw
- Main test: 2000 mg/kg bw
No. of animals per sex per dose:
- Sighting test: 1 female/dose
- Main test: 4 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations were made 0.5, 1, 2, and 4 h after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
- Frequency of weighing: Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes; at the end of the observation period the animals were killed by cervical dislocation and were subjected to a macroscopic examination.
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.
Preliminary study:
- No mortality or signs of systemic toxicity were noted during the observation period.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed.
Mortality:
No mortality was observed.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were observed at necropsy.
Other findings:
None

Individual body weights and body weight changes:

Dose level mg/kg

Animal number and sex

Body weight (g) at Day

Body weight gain (g) during week

0

7

14

1

2

2000

1-0

156

168

187

12

19

2-1

152

166

182

14

16

2-2

163

171

208

8

37

2-3

158

168

190

10

22

2-4

153

166

183

13

17

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the oral LD50 for test item is higher than 2000 mg/kg bw in female rats therefore it is not classified according to CLP Regulation (EC) No. 1272/2008.
Executive summary:

Test Guidance

OECD Guideline 420 and EC Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

 

Method and materials

Groups (4 females/dose) of Wistar rats (RccHan™:WIST) were given a single oral (gavage) dose of the test material at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. A sighting test was conducted with one female at the dose level of 2000 mg/kg bw to determine the dose for main study.

 

Results

No mortality was observed. No signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight over the observation period. No abnormalities were observed at necropsy. In this study, the oral LD50 of the test item was considered to be higher than 2000 mg/kg bw in female rats.

 

Conclusion

Under the test conditions, the oral LD50 is higher than 2000 mg/kg bw in female rats, therefore the substance is not classified according to CLP Regulation (EC) No. 1272 /2008.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
December 07th, 1998 - December 23rd, 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance CAS 68424-31-7. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
: Limited data on test substance
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
: Limited data on test substance
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 207 to 221 g (males) and 218 to 226 g (females)
- Fasting period before study: ON until 3 h after dosing
- Housing: groups of three separated by sex
- Diet (e.g. ad libitum): ad libitum (Rat and mouse expanded diet No.1, Special Diets Services Limited, UK)
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 37 - 67
- Air changes (per hr): minimum 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.03 ml/kg

DOSAGE PREPARATION (if unusual): The volume administered was calculated for each animal according to the fasted bodyweight and the specivic gravity of the test compound (0.988)
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Four times on the day of dosing and once a day subsequently until day 14 on the day. Body weight was recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality
Clinical signs:
No symptoms observed
Body weight:
Normal body weight gain
Gross pathology:
No abnormalities
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Insufficient for assessment due to reduced animal number. Only 2 male and 2 female rats were used, details on test substance not documented.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: Only two male and two female animals used
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Alderley Park SPF albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 215 g - 237 g for males and 145 g - 163 g for females
- Fasting period before study: 24 h
Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Frequency of observations and weighing:daily
- Necropsy of survivors performed: yes
- Duration of observation period following administration: Not stated
- Other examinations performed: body weight, macroscopic abnormalities (post mortem)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
No significant signs of toxicity in females but males showed slight toxicity following a 2000 mg/kg dose.
Body weight:
Initial loss of weight (due to predose fasting) with normal weight gain after dosing.
Gross pathology:
No macroscopic findings

The limit dose of 2000 mg/kg showed no mortality in male and female rats. Although only 2 animals per sex were tested, the observations do not indicate a severe toxic effect.

Interpretation of results:
not classified
Remarks:
Migrated information The acute oral lethal dose was greater than 2000 mg/kg in male and female rats. Criteria used for interpretation of results: EU
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
August 30th, 1983 - September 13th, 1983
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Insufficient for assessment due to reduced animal number. Only 2 male and 2 female animals were used, details on test substance not documented.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: Only two male and two female animals used, details on test substance not documented
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: >6 weeks
- Weight at study initiation: males: 282.5 g; females: 166.0 g
- Fasting period before study: 15 h
- Housing: Makrolon Type III cages
- Diet (e.g. ad libitum): Altromin-Haltungsdiät 1324 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: > 6 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 1.62 ml - 2.95 ml depending on body weight


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:
2000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Frequency of observations and weighing: evaluation of mortality: twice daily; weighting on days 0, 2, 7 and 14
- Necropsy of survivors performed: yes
- Duration of observation period following administration: 14 d
- Other examinations performed: body weight, macroscopic abnormalities (post mortem)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
No significant signs of toxicity except for transient rough fur and reduced activity direct after dosing
Body weight:
Normal weight gain after dosing.
Gross pathology:
No macroscopic findings

The limit dose of 2000 mg/kg showed no mortality in male and female rats. Although only 2 animals per sex were tested, the observations do not indicate a toxic effect.

Interpretation of results:
not classified
Remarks:
Migrated information The acute oral lethal dose was greater than 2000 mg/kg in male and female rats. Criteria used for interpretation of results: EU
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
November 06th, 1990 - November 20th, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study Limited details on test compound
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: Limited details on test compound
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: ICO: OFA-SD (IOPS Caw)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédo, France
- Age at study initiation: 6 weeks
- Weight at study initiation: 173 +/- 3 g for males and 144 +/- 7 g for females
- Housing: 5 animals per polycarbonate cage (48x27x20 cm)
- Fasting period before study: 18 h before until 4 h after dosing
- Diet (e.g. ad libitum): ad libitum (Rats - Mice substance ref. A04 C)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.13 ml taking into account the specific gravity of 0.94
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily, weighing on days 1, 5, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology
Statistics:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality
Clinical signs:
Hypokinesia was observed 2 and 4 h after treatment. From day 2 to the end of the study, no clinical signs were observed.
Body weight:
Normal body weight gain
Gross pathology:
No apparent abnormalities
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: analogue substance
Justification for type of information:
Acute oral toxicity does not need to be investigated because available data indicate that structural variation does not influence test results or adverse effect profile (see read-across and category justifications attached in Section 13).
Reason / purpose:
read-across source
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
March 22nd, 1994 - April 05th, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
: No details on test material
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Alpk:APfSD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Alderly Park, Cheshire, UK
- Age at study initiation: approx. 7 weeks
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Source and rate of air: dried and filtered air
- System of generating aerosols: glass concentric jet atomiser
- Method of particle size determination: Marple Cascade Impactor
- Temperature, humidity, pressure in air chamber: 20 l/min


TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrically
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.51 µm/2.51


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: maximum concentration of 5 mg/l (OECD limit test)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
particulate concentrations of the test atmospheres close to the animals breathing zone were measured gravimetrically
Duration of exposure:
4 h
Concentrations:
5.0 mg/l (nominal)
5.10 mg/l (analytical)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily, recording of body weight on days 1, 2, 3, 8 and 15
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
None
Clinical signs:
other: Reversible and consistent with the use of restraint for exposure to the test atmosphere. Hunched position, chromodacryorrhea, piloerection, stains around the nose and wet fur.
Body weight:
Body weight gain was within normal limits.
Gross pathology:
No treatment related gross pathological findings.
Other findings:
- Organ weights: Lung weight was within normal limits.

Bodiweight, bodyweight gain and lung weights for all treated animals were within normal limits and there were no gross pathological findings. In general, animals showed rapid recovery from effects seen.

The medium lethal concentration in the rat is considered to be in exess of 5.1 mg/l

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-06-12 to 2013-06-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8-12 Weeks
- Weight at study initiation: 200 g
- Fasting period before study: None
- Housing: Animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 h exposure period and in groups of five, by sex, for the remainder of the study.
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2013-06-12 To: 2013-06-26
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks
- % coverage: ca. 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Specific gravity of test item: 0.932
- Dose volume: 2.15 mL/kg bw
- Constant volume or concentration used: Yes
Duration of exposure:
24 h
Doses:
Single dose level of 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days.
- Frequency of weighing: Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes, at the end of the study the animals were killed by cervical dislocation and subjected for macroscopic examination.
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no mortality was observed.
Mortality:
- No mortality was observed.
Clinical signs:
- No signs of systemic toxicity were noted during the observation period.
- There were no signs of dermal irritation.
Body weight:
- All animals showed expected gains in body weight over the observation period.
Gross pathology:
- No abnormalities were noted at necropsy
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the acute dermal LD50 is higher than 2000 mg/kg bw in rats therefore the substance is not classified according to CLP Regulation (EC) No. 1272/2008.
Executive summary:

Test Guidance

OECD Guideline 402 and EC Method B.3 (Acute Toxicity Dermal)

Method and materials

A group of Wistar (RccHanTM:WIST) rats (5/sex/dose) were given a single dermal application of test item at 2000 mg/kg bw. The test item was placed directly on back and flanks of the skin representing approximately 10 % of the total body surface of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days.

Results

No mortality and no clinical signs were observed during the study. There were no signs of dermal irritation. All animals showed expected gains in body weight over the observation period. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 was considered to be higher than 2000 mg/kg bw in rats.

Conclusion

Under the test conditions, the acute dermal LD50 is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) No. 1272/2008.

 

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
January 05th, 1999 - January 19th, 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance CAS 131459-39-7. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
: Limited data on test substance
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
: Limited data on test substance
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: males: 202 - 217 g (male) and 202 - 212 g (female)
- Housing: Individually housed in suspended polypropylene cages for the time of exposure and in groups of five, by sex, for the reminder of the study.
- Diet (e.g. ad libitum): ad libitum, Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, UK
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 (18 at one ocasion, this was not considered relevant for the study)
- Humidity (%): 47-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks
- % coverage: approx. 10% of total body surface
- Type of wrap if used: Gauze secured with self adhesive bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiping with cotton wool moistened with distilled water
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5 h; 1 h; 2 h and 4 h after dosing and daily thereafter for 14 days. Weighting on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Skin reactions according to Draize (1977)
Statistics:
Not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No
Clinical signs:
No adverse effects observed
Body weight:
Treatment had no influence on body weight gain
Gross pathology:
No adverse effects observed
Other findings:
- Other observations: No sign of skin irritation

Results of dermal observations

Dose Level

mg/kg

Animal Number

and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0; Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1; Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2; Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3; Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4; Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
June 19th, 1996 - July 05th 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance CAS 11138-60-6. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HRP, Pennsylvania
- Age at study initiation: Young adults (at least 8 weeks)
- Weight at study initiation: males: 2.4-3.1 kg, females 2.5-2.7 kg
- Housing: Individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet (e.g. ad libitum): Lab Rabbit Diet HF, No 5326, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: males 58 d, females 60 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-21
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 12 cm x 14 cm, clipped area of the dorsal trunk surface
- % coverage: approx. 10% of body surface
- Type of wrap if used: Gauze secured with tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiping with distilled water
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality: twice daily; dermal observations: 1, 24, 48 and 72 h after bandage removal; observations of pharmacologic and toxicologic signs: 1, 2 and 4 h after dosing and daily thereafter for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: check of clinical signs and body weight
Statistics:
Not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No
Clinical signs:
No adverse effects observed
Body weight:
No or only slight body weight gain. One animal with weight loss by day 8 but gained weight between days 8 and 15.
Gross pathology:
No adverse effects observed
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: analogue substance
Justification for type of information:
Acute dermal toxicity does not need to be investigated because available data indicate that structural variation does not influence test results or adverse effect profile (see read-across and category justifications attached in Section 13).
Reason / purpose:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

There is no specific data on the substance. Read-across to the properties of Hexanoic acid, 3,5,5-trimethyl-, 1,1'-[2-ethyl-2-[[(3,5,5-trimethyl-1-oxohexyl)oxy]methyl]-1,3-propanediyl] ester (EC 613-848-7, CAS 65870-94-2), Fatty acid polyols (Fatty acids, C5-9, esters with pentaerythritol (EC 270-290-3, CAS 68424-30-6) and Decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate (EC 234-392-1, CAS 11138-60-6)) and their analogues is applicable based on the similarity in structure and physico-chemical properties. The justification for read-across is presented in Section 13 Assessment reports- Read-across justification.

 

Acute Oral toxicity

One reliable study is available for an analogue substance (EC 613 -848 -7). In this study (Sanders, 2013) performed under GLP according to OECD TG 420 and EC Method B.1 bis, female Wistar rats (total of five animals) were dosed by gavage at 2000 mg/kg bw of the substance and observed for a period of 14 days. No mortality was observed. No signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight over the observation period. No abnormalities were observed at necropsy. In this study, the oral LD50 of the test item was considered to be higher than 2000 mg/kg bw in female rats.

 

Treatment of rats with 2000 mg/kg bw with EC 234 -392 -1 (Clouzeau, 1990) and CAS No. 85116-93-4 (Potokar 1983) revealed the oral LD50 to be higher than 2000 mg/kg bw.

 

The study conducted with CAS No. 68424-31-7 (Robinson, 1991) had the same limitations (reduced animal number), but revealed similar results. An initial weight loss was observed after treatment of rats with 2000 mg/kg bw, but this effect was completely reversible and the animals showed subsequently normal body weight gain.

 

Treatment of rats with 2000 mg/kg bw of CAS 131459-39-7 (Allen, 1999) did not cause adverse effects in a study conducted according to OECD Guideline 423.

 

Acute Dermal toxicity

One reliable study is available for an analogue substance (EC 613 -848 -7). In this study (Sanders, 2013) performed under GLP according to OECD TG 402 and EC Method B.3, Wistar rats (5/sex) were given a single dermal application of the substance at 2000 mg/kg bw under semi-occlusive conditions for 24 hours. Animals were then observed for 14 days. No mortality and no clinical signs were observed during the study. There were no signs of dermal irritation. All animals showed expected gains in body weight over the observation period. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 was considered to be higher than 2000 mg/kg bw in rats.

 

In supporting studies, the semi-occlusive application of 2000 mg/kg bw of EC 234 -392 -1 (Blanset, 1997) or CAS 131459-39-7 (Allen, 1999) for 24 h (according to OECD 402) did not cause any adverse effects in rats.

 

Acute Inhalation toxicity

In a supporting study, rats were exposed nose only for 4 hours to approx. 5.1 mg/L of an analogue substance, CAS 68424-31-7 (analytical concentration) of the aerosol of the test material (Parr-Dobrzanski, 1994). No mortality occurred and no signs of systemic toxicity were observed. Other effects observed (hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur) were reversible. Body weight gain and lung weight were within normal limits and there were no treatment related gross pathological findings.

Justification for classification or non-classification

The oral LD50 is higher than 2000 mg/kg bw in female rats, therefore the analogue substance is not classified according to CLP Regulation (EC) No. 1272 /2008 for acute oral toxicity.

 

The acute dermal LD50 is higher than 2000 mg/kg bw in rats therefore the analogue substance is not classified according to CLP Regulation (EC) No. 1272/2008 for acute dermal toxicity.

 

Based on data available for the analogue substance where the LC50 (4 h) was > 5.1 mg/L, the substance is not classified according to CLP Regulation (EC) No. 1272/2008 for acute inhalation toxicity.