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Description of key information

Acute oral on registered substance.

The purpose of the study was to evaluate the potential toxic effect of the test item 2,2-bis[[(2-hexyl-1-oxodecyl)oxy]methyl]-1,3-propanediyl bis(2-hexyldecanoate) when administered as a single oral dose to Wistar rats. The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. Available information indicated that the test item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg was used as a starting dose. Two groups of 3 females were dosed. All 6 females survived the limit dose. The limit dose of 2000 mg/kg did not cause death, evident signs of toxicity or body weight loss during the 14-day long observation period. Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the LD50 of the test item 2,2-bis[[(2-hexyl-1-oxodecyl)oxy]methyl]-1,3 - propanediyl bis(2-hexyldecanoate) is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

An acute dermal toxicity test (OECD 402) was conducted on CAS 62125 -22 -8, a polyol ester member of the category. Test material with no vehicle was placed on clipped skin and occluded. The single dose was 2000 mg/kg bw. Exposure for 24 hours was allowed and then the test material was removed. Daily observations were made for 14 days, with post-dose body weight determinations at 7 and 14 days. No mortality, clinical signs, gross pathology, or body weight effects were noted. Therefore the effect level was > 2000 mg/kg bw.

Thus no hazard for acute oral, inhalation, and dermal toxicity was identified.


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:
March 10, 2016 - March 30, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
performed in compliance with GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted: 17th December 2001
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 04549/MA
- Expiration date of the lot/batch: 15.05.2018
- Purity test date: not given

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Velaz Prague, Czech Republic
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 180 - 190 g
- Fasting period before study: yes, overnight
- Housing: in plastic cages suspended on stainless steel racks, up to 3 animals per cage
- Diet: laboratory food Altromin (Altromin Spezialfutter GmbH, Germany), offered in recommended doses each day approximately at the same time
- Water: tap water for human consumption ad libitum, quality of drinking water is periodical analysed (including microbiological control) and recorded
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): not mentioned, room equipped with central air conditioning
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: March 15, 2016 To: March, 30, 2016
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Oil is a standard vehicle according to OECD TG 423
- Lot/batch no. (if required): OC14019842, Galvex
- Purity: not stated

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: available information on similar tested compound indicated that the test item is likely to be nontoxic considering to acute toxicity, therefore a limit dose of 2000 mg/kg was used as a starting dose
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days. Individual weights of animals were determined shortly before the test item was administered and weekly thereafter.
- Necropsy of survivors performed: All test animals were subjected to gross necropsy.
- Other examinations performed: clinical signs (observations included changes in skin and fur, eyes and mucous membranes, respiratory,circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern, observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma), body weights (weight differences after first and second weeks after administration were calculated and recorded), gross pathological changes (full, detailed gross necropsy included careful examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents)
Statistics:
not performed
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
other: Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered.
Gross pathology:
During necropsy, no macroscopically changes were noticed.
Other findings:
none
Table: Body Weight           
Sex Dose ID Body weight (g) Body weight difference (g)
initial week 1 week 2 week 1 - initial week 2 - initial week 2 - week 1
2000 mg/kg 1 190 220 230 30 40 10
2 180 210 220 30 40 10
3 190 210 210 20 20 0
4 190 220 230 30 40 10
5 180 200 220 20 40 20
6 190 220 230 30 40 10
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item 2,2-bis[[(2-hexyl-1-oxodecyl)oxy]methyl]-1,3-propanediyl bis(2-hexyldecanoate) is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.
Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item 2,2-bis[[(2-hexyl-1-oxodecyl)oxy]methyl]-1,3-propanediyl bis(2-hexyldecanoate) when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. Available information indicated that the test item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg was used as a starting dose. Two groups of 3 females were dosed. All 6 females survived the limit dose. The limit dose of 2000 mg/kg did not cause death, evident signs of toxicity or body weight loss during the 14-day long observation period. Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the LD50 of the test item 2,2-bis[[(2-hexyl-1-oxodecyl)oxy]methyl]-1,3 - propanediyl bis(2-hexyldecanoate) is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
29 Apr - 13 May 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. 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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
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 or test system 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:
other: No clinical signs of toxicity were observed during the study period.
Gross pathology:
No abnormatlities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
04 Jan - 01 Feb 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. 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
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 or test system 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:
other: No clinical sings of toxicity were observed up to the end of the 14-day observation period.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
see chapter 13 read-across justification
Reason / purpose for cross-reference:
read-across source
Key result
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:
other: No symptoms of systemic toxicity were observed during the study period.
Gross pathology:
No treatment related gross alterations were found at macroscopic examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Several studies are available investigating the acute oral toxicity of polyol esters category members resulting in oral LD50 values greater than 2000 mg/kg bw. Five reliable studies investigating the acute inhalation toxicity within the polyol esters category are available resulting in LC50 values > 5.0 mg/L. Seven reliable acute dermal toxicity studies consistently showed no effects at the limit dose of 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the category members and thus, no hazard for acute oral, inhalation and dermal toxicity was identified. 

The category justification is found in IUCLID section 13. 

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” 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 category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis. Therefore, based on the group concept, all available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.