Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw

Read-across from structural analogue source substances Pentaerythritol tetraoleate (CAS No. 19321-40-5), Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS No. 71010-76-9), Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2), Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7), Pentaerythritol ester of pentanoic acids , mixed esters with pentaerythritol, isopentanoic and isononanoic acid (CAS No. 146289-36-3) and 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8)

Inhalation: LC50 > 5 mg/L air

Read-across from structural analogue source substance Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS No. 85536-35-2)

Dermal: LD50 > 2000 mg/kg bw

Read-across from structural analogue source substances 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8) and Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS No. 71010-76-9)

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study similar to guideline with acceptable restrictions (limited information on test substance, applied volume (1.5 mL/100 g bw) exceeds the recommended value).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 24 February 1987
Deviations:
yes
Remarks:
limited information on test substance, applied volume (1.5 mL/100 g bw) exceeds the recommended value
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent
- Weight at study initiation: males: 247.2 g ± 3.4 g, females: 201.2 g ± 9.0 g
- Fasting period before study: overnight before dosing
- Housing: in single sex groups in polypropylene cages
- Diet: smodified 41B diet, Pilsbury´s Limited, Birmingham, UK, ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
controlled temperature and lighting conditions
Route of administration:
oral: gavage
Vehicle:
vegetable oil
Details on oral exposure:
VEHICLE
- Amount of vehicle: 15 mL/kg bw
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 15 mL/kg bw
Doses:
10.000 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: animals were examined immediately and 4 h after dosing and then daily.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
All the rats were hypoactive at the 4 h observation period. No further signs of toxicity were noted during the study period.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
17 Sep - 01 Oct 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no data on purity of test substance).
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 12 May 1981
Deviations:
yes
Remarks:
(no data on purity of test substance)
GLP compliance:
yes
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: Broekman Institute, Someren, The Netherlands
- Weight at study initiation: males: 283 g ± 4.2 g, females: 178.4 g ± 2.4 g
- Fasting period before study: overnight before until 4 h after dosing
- Housing: individually in Macrolon cages
- Diet: standard laboratory animal diet, RMH-B, Hope Farms, Woerden, The Netherlands, ad libitum
- Water: tap-water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 - 80
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.5 mL/kg bw
Doses:
5000 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: frequency of observations not given. Individual body weights were determined weekly (Days 0 (pre-administration), 7 and 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No symptoms of systemic toxicity were observed during the study period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No treatment related gross alterations were found at macroscopic examination of the animals.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given (comparable to standards) (limited documentation, test substance purity not specified).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
limited documentation
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
- Weight at study initiation: medium weight 250 g
Route of administration:
oral: gavage
Doses:
5 mL/kg (4.6 mg/kg; calculated using density of 0.92 g/mL (Chapter 4.4))
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 mL/kg bw
Based on:
test mat.
Mortality:
No animal died during the test period.
Clinical signs:
No toxicity occured during the test period.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
08. Jan. - 29. Jan. 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar TNO
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: mean 190 g (male), 160 g (female)
- Fasting period before study: 16 hours
- Housing: 5 animals per cage: Makrolon type-3 with standard soft wood bedding
- Diet: pelleted maintenance diet 1324 (Altromin GmbH), ad libitum
- Water: community tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: arachidis oil, DAB9
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

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: weighing one day before application, on day 2, 7 and 14 after application, animals were checked for mortality/viability two times daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: macroscopic examination of the cranial, thoracic and visceral cavities
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy and histopathological examination revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
29 Apr - 13 May 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain Crl:(WI) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: males: 275 g ± 20 g, females: 188 g ± 12 g
- Fasting period before study: overnight before until 3-4 h after dosing
- Housing: 3 animals/sex/cage in polycarbonate cages, containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands)
- Diet: standard laboratory animal diet, Carfil Quality BVBA, Oud-Turnhout, Belgium, ad libitum
- Water: tap-water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes: approx. 15 (air conditioned room)
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.17 mL/kg bw
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: animals were observed twice daily for mortality. Individual body weights were determined weekly (Days 1 (pre-administration), 8 and 15). Animals were observed for clinicals signs at periodic intervals on Day 1 and once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was performed (the method used is not intended to allow the calcuation of a precise LD50 value)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed during the study period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No abnormatlities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
7 Dec - 23 Dec 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no analytical purity reported)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
adopted in 1992
Deviations:
yes
Remarks:
no analytical purity reported
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: Albino Rats (Outbred). Stock: Sprague-Dawley-derived (CD) [Crl: CD (SD) IGS BR]
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston, New York, USA
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 279-318 g (males), 204-219 g (females)
- Fasting period before study: animals were fasted overnight prior administration
- Housing: 2 to 6 animals of the same sex per cage (during acclimation) und individual (during study) per cages. Cages were suspended, stainless cages with wire mesh bottoms.
- Diet: certified Rodent Diet, No. 5002 (PMI Nutrition International, Inc., St. Louis, MO), ad libitum
- Water: automatic watering system, Municipal water supply (Elizabethtown Water Company), ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 26
- 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 mL/kg



Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were checked for viability daily. Each animal was examined (general condition, skin and fur, eyes nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration and palpation for tissue masses) approximately 1, 2, and 4 hours after dosing and daily thereafter for 14 days. Individual body weights were determined on day 0 (at the time of fasting), day 1 (just prior to dosing; weights were used for calculation of doses), day 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption, macroscopic post-mortem examination.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity related to the administration of the test substance were observed up to the end of the 14-day observation period. However alopecia extremities on snout was seen in a single animal on day 9 through day 15 after the dose administration. This finding was not considered to be related to the administration of the test substance.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (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: males: 215 g - 237 g; females: 145 g - 163 g
- 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
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No significant signs of toxicity in females but males showed slight toxicity following a 2000 mg/kg bw dose.
Body weight:
Initial loss of weight (due to predose fasting) with normal weight gain after dosing.
Gross pathology:
Necropsy and histopathological examination revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions. (Lack of data on test material.)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
adopted in 2008
Deviations:
yes
Remarks:
lack of data on test material
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: 214 - 223 g
- Fasting period before study: animals were fasted over night prior to administration.
- Housing: animals were group housed upon receipt and individually housed upon assignment to study in compliance with the National Research Council "Guide for the Care and Use of Laboratory Animals".
- Diet: Harlan Teklad Rodent Diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 23 - 59
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 10 Jan 2006
To: 26 Jan 2006
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Up-and-Down Procedure: The first animal was dosed at an initial dose level of 2000 mg/kg bw. Since this animal survived, four additional females received the test substance at 2000 mg/kg bw.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed prior to dosing, approximately 30 min and 4 h post-dose as well as once daily on Days 2 to 15. Animals were weighed prior to dosing on Day 1 and on Day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Mortality/morbidity (once daily)
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 1 and 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on common precursors and hydrolysis products and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 Mar - 05 Apr 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions. (Limited data on study substance)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Limited data on study substance
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Alpk:APfSD
Sex:
male/female
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Not stated
- Source and rate of air: 20 L/min using a peristaltic pump
- Method of conditioning air: Clean dry air (dried and filtered, no further details)
- System of generating particulates/aerosols: Glass concentric jet atomiser
- Method of particle size determination: Marple Cascade Impactor

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

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: No Data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.76 µm / 2.35 µm
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gravimetrically measurement of particulate concentrations
Duration of exposure:
4 h
Concentrations:
5 mg/L
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: daily
- Frequency of weighing: on Days 1, 2, 3, 8 and 15
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
Clinical signs seen during and/or immediately after exposure were hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur. In general, animals showed a rapid recovery from these effects by Day 2, although, hunched posture and piloerection persisted in few animals to Days 4 and 8, respectively.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy and histopathological examination revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 2) study from a source substance with similar structures and intrinsic properties. Read-across is justified based on common precursors and hydrolysis products and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study wit acceptable restrictions (no data on test substance purity).
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Adopted 12 May 1981
Deviations:
yes
Remarks:
(no data on test substance purity)
GLP compliance:
yes
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: Broekman Institute, Someren, The Netherlands
- Weight at study initiation: males: 301.2 g ± 3.7 g, females: 196.8 g ± 5.4 g
- Housing: individually in Macrolon cages
- Diet: standard laboratory animal diet, RMH-B, Hope Farms, Woerden, The Netherlands, ad libitum
- Water: tap-water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 - 80
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the dorsal area of the trunk
- % coverage: approx. 10 % of the total body surface
- Type of wrap: The test material was held in contact with the skin with surgical gauze fixed on alumina foil with vaseline. This was fixed with successively tape and flexible bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: residual test material was removed with tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2.2 mL/kg bw
- Concentration: 100%
- Constant volume or concentration used: yes
Duration of exposure:
24 h
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 cage-side observations were done. Individual body weights were determined weekly (Days 0 (pre-administration), 7 and 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No symptoms of systemic toxicity were observed during the study period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No treatment related gross alterations were found at macroscopic examination of the animals.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions. (Lack of data on test material.)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
(no data on test substance purity)
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted in1992
Deviations:
yes
Remarks:
(no data on test substance purity)
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1998
Deviations:
yes
Remarks:
(no data on test substance purity)
GLP compliance:
yes
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: Harlan
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: 247 - 253 g (males), 217 - 239 g (females)
- Housing: animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council " Guide for the Care and Use of Laboratory Animals".
- Diet: Harlan Teklad Rodent Diet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 23 - 59
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 9 Jan 2006
To: 23 Jan 2006
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the dorsal area of the trunk
- Type of wrap if used: the treated skin site was covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed with 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:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were recorded immediately after dosing and at approximately 1, 2.5 and 4 h after dosing and daily thereafter through Day 15. Animals were weighed prior to dosing on Day 1 and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Mortality/morbidity (twice daily)
Statistics:
Body weights were summarized using descriptive statistics (mean and standard deviation).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
Body weight gains of all animals were withinthe normal ranges during the whole study period.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on common precursors and hydrolysis products and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

The analogue approach comprises aliphatic esters of poly-functional alcohols containing four to six reactive hydroxyl groups and one to six fatty acid chains. The read-across analogue approach contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C20, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18 and branched C5, C7 and C9, building mono-, di-, tri-, and tetra esters with the polyol. The available data allow for an accurate hazard and risk assessment of the target substance and the source substances and the read-across concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substances within the read-across analogue approach by interpolation to the target substances in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006 (REACH). In particular, for each specific endpoint the source substance or substances structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source substance and target substances are the basis of read-across.

A detailed justification for the read-across applied is provided in the technical dossier (see IUCLID Section 7.1 and 13) and within Chapter 5.1 of the CSR.

Acute oral toxicity

There are several reliable acute oral toxicity studies available performed with structural analogue source substances. All studies are accounted for in a Weight-of-Evidence approach.

An acute oral toxicity study (limit test) was performed with Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in two studies with rats (CAS No. 67762-53-2) according to OECD Guideline 420 (fixed dose procedure) (Exxon, 1999a). Groups of 5 males and females fasted CD Sprague-Dawley rats received single oral gavage doses of 2000 mg/kg bw. The animals were observed for 14 days following administration. No mortalities occurred. One animal showed alopecia extremities on snout which was not considered treatment related. No further clinical signs of toxicity were reported. No effect on body weight was noted. Terminal necropsy revealed no substance-related findings. Thus, the acute oral LD50 value was found to be greater than 2000 mg/kg bw.

An acute oral toxicity study with Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS No. 71010-76-9) was performed according to OECD Guideline 425 (up and down procedure, limit test) and GLP (Exxon, 2006a). The test substance was administered by gavage to one female Sprague-Dawley rat at the starting dose of 2000 mg/kg bw. Since no mortality and no other toxic effects have been detected during the 14-day study period, 4 further female animals were equally dosed with 2000 mg/kg bw. No clinical signs of toxicity were observed up to the end of the 14-day observation period. No effect on body weight was noted. Terminal necropsy revealed no substance-related findings. The oral LD50 value in female rats was found to exceed 2000 mg/kg bw.

An acute oral toxicity study with Pentaerythritol tetraoleate (CAS No. 19321-40-5) was performed according to OECD Guideline 423 (acute toxic class method, limit test) and GLP (WoE, RA-A, 19321-40-5, 1997). Pentaerythritol tetraoleate was administered by oral gavage to three Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities were observed. The oral LD50 value in rats was found to exceed 2000 mg/kg bw.

The study conducted with Fatty acids, C5-10, esters with pentraerythritol (CAS No. 68424-31-7) (WoE, RA-A, 68424-31-7, 1991a) with limitations (reduced animal number), revealed no mortality and no other toxic effects, but an initial weight loss after treatment of rats with 2000 mg/kg bw. However this effect was completely reversible and the animals showed subsequently normal body weight gain. The oral LD50 value was therefore determined to exceed 2000 mg/kg bw.

A study performed according to OECD Guideline 401 investigated the acute oral toxicity of Pentaerythritol ester of pentanoic acids, mixed esters with pentaerythritol, isopentanoic and isononanoic acid (CAS No. 146289-36-3) (Emery, 1991). 5 male and 5 female Wistar rats were administered a single dose of 2000 mg/kg bw of the test substance by gavage. No mortality occurred during the study period. No clinical signs of toxicity were observed up to the end of the 14-day observation period and no effect on body weights was noted. Necropsy and histopathological examination revealed no substance-related findings. Therefore, the oral LD50 value in male and female rats was found to exceed 2000 mg/kg bw.

The acute toxicity via the oral route of exposure of the source substance 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8) has been investigated in rats in three studies. Two acute oral toxicity studies (limit tests) were performed according to OECD Guideline 401 (WoE, RA-A, 62125-22-8, 1984a, GLP-compliant; Stearinerie, 1997a). The test substance was administered by gavage at a concentration of 5000 mg/kg bw and 5 mL/kg (corresponding to 4600 mg/kg bw, based on density of 0.92 g/mL), respectively, to groups of five male and female Wistar rats. The animals were observed for 14 days following administration. No mortalities occurred. No clinical signs of toxicity, no changes in body weights and no differences at macroscopic examination were reported. The acute oral LD50 value was found to be greater than 5000 mg/kg bw and 4600 mg/kg bw, respectively.

Another acute oral toxicity study (limit test) was performed comparable to OECD Guideline 401 (WoE, RA-A, 62125-22-8, 1981). The test substance was administered by gavage at a concentration of 10000 mg/kg bw (1.5 mL/100 g bw) to groups of five male and female CD rats. The animals were observed for 14 days following administration. No mortalities occurred. All the rats were hypoactive at the 4 h observation time point. No further signs of toxicity were noted during the study period. The acute oral LD50 value was found to be greater than 10000 mg/kg bw.

Acute inhalation toxicity

There is a reliable and adequate key study available performed with a structural analogue source substance.

An acute inhalation toxicity study was performed with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS No. 85536-35-2) comparable to OECD Guideline 403. 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.0 mg/L air test substance aerosol by nose only inhalation (Key, RA-A, 85536-35-2, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Clinical signs during and immediately after exposure included hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur. In general, animals showed a rapid recovery from these effects by Day 2, although, hunched posture and piloerection persisted in few animals to Days 4 and 8, respectively. No effect on body weight was noted. Necropsy and histopathological examination revealed non substance-findings. The LC50 value was therefore found to be greater than 5.0 mg/L air.

Acute dermal toxicity

Acute dermal toxicity has been studied using two structural analogue source substances.

An acute dermal toxicity study (limit test) was performed on Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS No. 71010-76-9) comparable to OECD Guideline 402 and GLP (Exxon, 2006b). 5 male and female Sprague-Dawley rats were exposed to 2000 mg test substance/kg bodyweight for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 value in rats for was found to exceed 2000 mg/kg bw.

An acute dermal toxicity test (limit test) was performed on 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8) according to OECD Guideline 402 and GLP (WoE, RA-A, 62125-22-8, 1984b). 5 male and female Wistar rats each were exposed to 2000 mg test substance / kg bw for 24 hours on the back skin under occlusive conditions. The observation period was 14 days. No mortality and clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 value in rats was found to exceed 2000 mg/kg bw.

Conclusion on acute toxicity

Several reliable and adequate studies performed with analogue source substances are available investigating the acute oral, inhalation and dermal toxicity of polyol esters resulting in oral and dermal LD50 values greater than 2000 mg/kg bw and an inhalation LC50 value of > 5.0 mg/L. The available data indicate a very low level of acute toxicity for the source substances and thus, no hazard for acute oral, inhalation and dermal toxicity is identified for the target substance Fatty acids lanolin, di-, tri- and tetraesters with pentaerythritol and rape fatty acid.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 (REACH) information on intrinsic properties of substances may be generated by means other than tests, e.g. using information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI states that “substances whose physico-chemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the read-across concept is applied to the target substance Fatty acids lanolin, di-, tri- and tetraesters with pentaerythritol and rape fatty acid, data gaps can be filled by interpolation from representative structural analogue source substances to avoid unnecessary animal testing.

The read-across concept is also used to derive the classification of the target substance taking the properties of the source substances into account. Based on the read-across concept, all available data on acute toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.