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), Fatty acids, C8-18 and C18-unsatd., esters with trimethylolpropane (CAS No. 85186-89-6), 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8), and Fatty acids, C16-18 (even numbered), esters with pentaerythritol (CAS No. 85116-93-4)

Inhalation: LC50 > 5 mg/L air

Read-across from structural analogue source substances Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7) and Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2)

Dermal (OECD 402, GLP): > 2000 mg/kg bw

Read-across from structural analogue source substance Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9) and 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No.

62125-22-8)

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
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:
17 Sep - 01 Oct 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Study period:
04 Jan - 01 Feb 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
limited data on test material given
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Hsd/Cpb:WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Weight at study initiation: males: 212 - 220 g; females: 165 - 205 g
- Housing: 5 animals per Makrolon type III cage
- Fasting period before study: 16 h before treatment until 3 - 4 h after dosing
- Diet: Ssniff-R Alleindiät, Ssniff Spezialdiäten GmbH, Soest, Germany, ad libitum
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- 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: 2.15 mL/kg
Doses:
2000 mg/kg bw (taking into account the specific gravity of 0.93 g/mL)
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: observations: 10 min, 1 h, 6 h, 24 h, and thereafter once daily up to 14 days; weighing: Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology
Preliminary study:
Single application of 2000 mg/kg bw in 2 female rats.
No deaths occurred.
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 sings of toxicity were observed up to the end of the 14-day observation period.
Body weight:
Body weight gain was normal up to Day 7. At Day 14, body weight gain was reduced in 1 male and 2 female rats reaching statistical significance in females.
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:
supporting study
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:
supporting study
Study period:
30 Aug - 13 Sep 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: Altromin-Haltungsdiät 1324, ad libitum
- Water: 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; weighing 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
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No significant signs of toxicity except for transient rough fur and reduced activity direct after dosing were observed.
Body weight:
Normal weight gain after dosing was noted.
Gross pathology:
No macroscopic findings were found at necropsy.
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

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
24 Jul - 8 Dec 1988
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 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
no analytical purity reported
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Kingston, NY, USA
- Age at study initiation: 8 weeks
- Housing: individually in stainless wire mesh cages.
- Diet: certified Purina rodent chow #5002, ad libitum (except during exposures)
- Water: tap water (delivered via automatic system except during exposures)
- Acclimation period: minimum of 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel exposure chamber
- Exposure chamber volume: 400 L
- Method of holding animals in test chamber: Animals were housed in a nearby room and loaded into cages designed for the inhalation chamber for exposure
- Source and rate of air: Pressurized air passed through the hollow stream of nebulizer and exited at high velocity through holes in its side. This high velocity air stream passed over the top of the hollow feed barrels and caused the aspiration of the liquid test material up into the feed barrel. The liquid was aerosolized as it was drawn into the airstream by the relative negative pressure there.
- System of generating particulates/aerosols: Laskin nebulizers
- Method of particle size determination: The mass median aerodynamic diameter of the aerosol was determined once during exposure by use of a cascade impactor
- Temperature, humidity, pressure in air chamber: 24.4 °C (control group) and 23.8 °C (0.48 and 4.06 mg/L groups); 60% (control and 4.06 mg/L group), 64% (0.48 mg/L)

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of aerosol in the exposure chamber was determined gravimetrically by drawing known volumes of air from the chamber through glass fibre filters and measuring the increase in weight of the filters. The weight increase was divided by volume of air sampled to give aerosol concentration.
- Samples taken from breathing zone: no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.9/1.9 (0.48 mg/L) and 1.1/1.7 (4.06 mg/L)

Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
ca. 4 h
Concentrations:
0.48 or 4.06 mg/L (analytical concentration)
0.60 or 4.07 mg/L (nominal concentration)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weight were recorded on days 1 (day of first exposure), 2, 9, and 17. Clinical signs were recorded daily except of weekends.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
Data on body weights were analyzed by ANOVA and Tukey´s multiple range test for comparison of control and exposed groups.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.06 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: 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 examination revealed no substance-related findings.
Other findings:
- Organ weights: No treatment-related changes were observed in the weights of the liver or kidneys. Both wet and dry weight of the right middle lung lobe tended to be higher in the exposed males at 2 weeks post-exposure. Dry weight was significantly greater in group 3 relative to group 1, but only in males at 2 weeks.
- Histopathology: Histopathological examination revealed no substance-related findings. Since no treatment-related morphologic changes were found at macroscopic post mortem examination of the animals, without this morphologic confirmation, the small changes in lung weight were considered not to be biologically relevant.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: inhalation
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 (no analytical purity reported)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted in 1996
Deviations:
yes
Remarks:
analytical purity not reported
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sprague-Dawley CD®
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Klingston, NY, USA
- Age at study initiation: approximately 9 weeks (control group); approximately 10 weeks (test group)
- Weight at study initiation: 332 g (control group, males only); 358 g (test group, male) and 247 (test group, female)
- Fasting: feed was not provided during the exposure
- Housing: animals were group-housed in suspended, stainless steel, wire mesh cages during the acclimation period and individually-housed during all other non-exposure period.
- Diet: certified Rodent Diet, # 5002 meal, ad libitum
- Water: ad libitum
- Acclimation period: The control group animals were acclimated for 12 days. The test group animals were acclimated for 19 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 18-30
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cast aluminium and alloy exposure chamber with polycarbonate nose-only tubes housed within 10 m³ Harford glass and stainless steel exposure chamber.
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: animals were placed in polycarbonate tubes attached to the chambers.
- Source and rate of air: 20 L/min
- System of generating particulates/aerosols: Approximately 110 mL of test material were placed into a nebulizer. House-supply air was delivered from a regulator and backpressure gauge, via ¼” tubing, to a plastic Y tube which split the airflow into the generation and dilution systems. The generation air (7.0 Lpm) was directed, via ¼” tubing, through a flowmeter regulated by a metering valve, and a backpressure gauge, to the nebulizer. The test material-laden airstream was directed through a flowmeter regulated by a metering valve, into the dilution port at the top of the nose-only exposure chamber.
- Method of particle size determination: In the control group the particle size distribution measurements were performed each hour of exposure for the chamber and room air using a TSI Aerodynamic Particle Sizer. The samples were drawn for 20 seconds at a rate of 5.0 Lpm. The mass median aerodynamic diameter, geometric standard deviation and in the test group samples for particle size distribution assessment were drawn each hour of exposure using a cascade impactor. The samples were drawn for one minute at a flowrate of 1.00 Lpm. The mass median aerodynamic diameter, geometric standard deviation and percent of particles ≤ 1.0, ≤ 4.0 and ≤ 10 microns were calculated based on the amount of material collected on the seven impactor stages and a final filter stage using a graphical analysis of an assumed lognormal distribution.
- Temperature, humidity, pressure in air chamber: 21°C (average), 23% (average)

TEST ATMOSPHERE
- Brief description of analytical method used: Sample concentration (mg/L) was determined gravimetrically on a total formulation basis. A drop of the test material was placed on a weighed filter, weighed immediately and again after drying overnight. This was done in triplicate. The resultant data were used to determine the fraction of solids in the test material. During the exposure, the filter was weighed before and immediately after sampling (wet weight). The exposure concentration (mg/L) was calculated on both a “wet” and “dry” basis by dividing the appropriate net weight (mg) by the volume of air sampled (liters). For the test group, only exposure levels were calculated on a formulation by dividing the exposure concentration on a “dry” basis (mg/L) by the fraction of solids.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.18/2.03
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
5.50 mg/L (analytical concentration)
6.6 mg/L (nominal concentration)
No. of animals per sex per dose:
10 (air control)
10 (males, test group)
5 (females, test group)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (5 males were sacrificed on Day 3)
- Frequency of observations and weighing: on day 1 all animals were observed individually immediately prior to the exposures, as a group at approximately 15 minute intervals during the first hour of each exposure, and hourly for the reminder exposure periods. All surviving animals were observed individually upon removal from the chambers (30 min after each exposure termination) and every hour for two hours post-exposure. Detailed physical observations (general condition, skin and fur, eyes, nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration and palpation for tissue masses) were recorded at each interval. From day 2 to 15 detailed observations were recorded once daily. Individual body weights were recorded on day 1 (just prior to exposure), on Day 3 (just before sacrifice). Animal sacrificed on Day 15 were weighed on day 8 and 15 (just prior sacrifice)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, gross pathology.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.

Clinical signs:
other: Test group: nasal discharge was noted as only sign of toxicity. Wet fur was noted as well but was considered an artefact of the nose-only exposure regimen. A few incidences of chromodacryorrhea were also noted to a comparable degree to the Group II animal
Body weight:
The test group females lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In all other animals no effect on body weight was noted.
Gross pathology:
Necropsy examination revealed no substance-related findings.

Other findings:
- Histopathology: There were no test material related microscopic findings. At the end of each of the post-exposure observation periods, incidental findings occurred with comparable incidence and severity in rats from the control and test groups or they occurred sporadically. The have been seen of this strain and age used in similar studies conducted in the study facility.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
22 Mar - 05 Apr 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (only few data on test item and animal husbandry were given)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
(No details on test material and limited data on animal husbandry)
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
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: animals were observed for gross clinical abnormalities during exposure and were checked daily thereafter. A detailed examination was conducted after exposure on day 1 and on consecutive days, up to and including day 15. Individual body weights were recorded on Day 1 and Days 2, 3, 8 and day 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for
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 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 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:
key study
Study period:
05 Jan - 19 Jan 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom, UK
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sprague-Dawley CD (Crl : CD® BR)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd, Margate, Kent, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 211 – 225 g (males) and 208 – 232 g (females)
- Housing: animals were housed individually during the 24-h exposure and in groups of five of the same sex, for the remainder of the study, in polypropylene cages furnished with woodflakes.
- Diet: Rat and Mouse SQC Expanded Diet No. 1 (Special Diets Services Limited, Witham, Essex, UK), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Example: 18-21
- Humidity (%): 47-67
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

OTHER
- On one occasion the temperature was below the limit specified in the protocol (19 °C). This deviation was considered not to affect the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks were clipped
- % coverage: 10%
- Type of wrap if used: The test substance was held in contact with the skin with surgical gauze and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed with cotton wool moistened with distilled water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):2.06 mL/kg bw
- Concentration (if solution): 100%
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: animals were observed 30 min, 1, 2 and 4 h after dosing and subsequently daily for 14 days and individual body weights were determined prior to dosing and 7 and 14 days after treatment.
- 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 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 (see Table 1).
Gross pathology:
Necropsy revealed no substance-related findings.
Other findings:
Dermal reactions:
No signs of skin irritation were noted during the study period in any animal.

Table 1. Individual body weights and weekly body weight changes.

Dose level mg/kg bw

Animal number and sex

Bodyweight (g) at Day

Body weight gain (g)

during week

0

7

14

1

2

2000

1-0 Male

225

267

319

42

52

1-1 Male

215

259

307

44

48

1-2 Male

217

255

291

38

36

1-3 Male

211

253

300

42

47

1-4 Male

221

248

286

27

38

1-0 Female

208

219

226

11

7

1-1 Female

210

210

231

0

21

1-2 Female

232

246

257

14

11

1-3 Female

208

210

217

2

7

1-4 Female

213

216

220

3

4

 

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:
supporting study
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 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 VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

The read-across from analogue source substances approach comprises aliphatic esters of poly-functional alcohols containing two to six reactive hydroxyl groups and one to six fatty acid chains. The analogue approach contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C22, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18, branched C5 and C9, branched C14 - C22 building mono-, di-, tri-, tetra- and hexa esters with an alcohol (i.e. the polyol).

The available data allows for an accurate hazard and risk assessment of the target substance 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 group by interpolation to the target substance applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006. In particular, for each specific endpoint the source substance(s) 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 and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 7.1 and 13).

Acute oral toxicity

There are several reliable acute oral toxicity studies available for structural analogue source substances. The most adequate studies are taken into account by means of a Weight-of-Evidence approach. They are further supported by additional studies.

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). The substance 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 thus found to exceed 2000 mg/kg bw.

An acute oral toxicity study (limit test) with Fatty acids, C8-18 and C18-unsatd., esters with trimethylolpropane (CAS No. 85186-89-6) was performed according to OECD Guideline 401 and GLP (WoE, RA-A, 85186-89-6, 1996). The test substance was administered by gavage at a concentration of 2000 mg/kg bw to groups of five male and female Hsd/Cpb:WU rats. The animals were observed for 14 days following administration. No mortalities occurred during the study period. No clinical signs of toxicity, only slight changes in body weights for some animals and no differences at macroscopic examination were reported. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

The acute toxicity via the oral route of 2 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS No. 62125-22-8) has been investigated in rats in two studies. A reliable and adequate acute oral toxicity study (limit test) was performed according to OECD Guideline 401 and following GLP provisions (WoE, RA-A, 62125-22-8, 1984a). The test substance was administered by gavage at a dose of 5000 mg/kg bw 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 was therefore found to be greater than 5000 mg/kg bw.

In another supporting study, the acute oral toxicity was investigated in a limit test comparable to OECD Guideline 401 (Supporting, 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 was found to be greater than 10000 mg/kg bw.

An acute oral toxicity study (limit test) was conducted with Fatty acids, C16-18 (even numbered), esters with pentaerythritol (CAS No. 85116-93-4) comparable to OECD Guideline 401 (BASF, 1983). Reporting of test conditions and results was limited, only 2 male and 2 female animals were used and details on the test substance were not documented. The reliability of the study is therefore not assignable. However, the study can still be used to further support findings of other reliable investigations. The test substance was administered by gavage at a concentration of 2000 mg/kg bw to 2 male and female Wistar rats each. The animals were observed for 14 days following administration. No mortalities occurred during the study period. No significant signs of toxicity except for transient rough fur and reduced activity direct after dosing were observed. Normal weight gain was observed after dosing. Finally, no macroscopic findings were found at necropsy. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

Acute inhalation toxicity

Several reliable and adequate studies are available regarding the acute inhalation toxicity of structural analogue source substances. The studies are accounted for in a Weight-of-Evidence approach.

An acute inhalation toxicity study was performed with Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7) 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 (WoE, RA-A, 68424-31-7, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for exposure. The LC50 was therefore found to be greater than 5.1 mg/L.

Two studies investigating the acute toxicity via the inhalation route of exposure are available for the source substance Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2). The first study was conducted comparable to OECD Guideline 403 and according to GLP. 10 male and female Sprague-Dawley rats were exposed for 4 hours to 0.48 or 4.06 mg/L test substance aerosol by whole body inhalation exposure (Exxon, 1990). No mortality, clinical signs, body weight changes or abnormalities in necropsy were observed during the 15 day study period in any group. The LC50 was therefore found to be greater than 4.06 mg/L.

In the second study 10 male and 5 female CD Sprague-Dawley rats were exposed for 4 hours to 5.5 mg/L test substance aerosol by nose/head only inhalation (Exxon, 1999a). No mortalities occurred during the study period. Nasal discharge was noted as the only sign of clinical toxicity. The test group females lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In all other animals no effect on body weight was noted. Necropsy examination revealed no substance-related findings. The LC50 was therefore found to be greater than 5.50 mg/L.

Acute dermal toxicity

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

Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9) has been investigated for its acute dermal toxicity in a study according to OECD Guideline 402 and observing GLP provisions (Key, RA-A, 647028-25-9, 1999a). The unchanged test substance was applied to the clipped backs and flanks of 5 male and 5 female Crl:CD (SD) rats under semiocclulsive conditions. The exposure period was 24 h before residual test material was removed with cotton wool moistened with distilled water. After removal of the dressings and subsequently once daily during the 14-day observation period, the test sites were examined for evidence of primary irritation and scored according to the Draize scoring system. No mortality occurred during the study period. No clinical signs of toxicity and no effects on body weights were observed until the end of the observation period. Terminal necropsy revealed no substance-related findings. Moreover, no signs of skin irritation were noted during the study period in any animal. The acute dermal LD50 value was therefore determined to be > 2000 mg/kg bw.

To further support the result of the first study, a study with another structural analogue is used. 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 (Supporting, 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 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 different structural analogue polyol esters resulting in oral LD50 values of > 2000 mg/kg bw, inhalation LC50 values of > 5.0 mg/L air and a dermal LD50 value of > 2000 mg/kg bw. The available data indicate a very low level of acute toxicity for the analogue source substances and thus, no hazard for acute oral, inhalation and dermal toxicity is identified for the target substance Octadecanoic acid, 1,1'-[2-[[3-[(1-oxooctadecyl)oxy]-2,2-bis[[(1-oxooctadecyl)oxy]methyl]propoxy]methyl]-2-[[(1-oxooctadecyl)oxy]methyl]-1,3-propanediyl] ester (CAS No. 70967-57-2).

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 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 physicochemical, 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 Octadecanoic acid, 1,1'-[2-[[3-[(1-oxooctadecyl)oxy]-2,2-bis[[(1-oxooctadecyl)oxy]methyl]propoxy]methyl]-2-[[(1-oxooctadecyl)oxy]methyl]-1,3-propanediyl] ester, 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.