2,2-bis(hydroxymethyl)propane-1,3-diyl didocosanoate

Endpoint summary

Description of key information

Oral (WoE): LD50>2000 mg/kg bw
Dermal (RA-A CAS 62125-22-8, OECD 402): LD50>2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
Taken together the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation 1907/2006. Therefore, the available information as a whole is 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

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (no data on test substance purity).

Qualifier:

according to guideline

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 or test system 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:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate, reliable (Klimisch score 2 due to read-across) study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
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.

Additional information

Justification for read-across

Data on the acute oral, inhalation and dermal toxicity of 2,2-bis(hydroxymethyl)propane-1,3-diyl didocosanoate (CAS 68258-72-0) are not available. The assessment of acute toxicity was therefore based on studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

Acute toxicity: oral

CAS 85116-93-4

An acute oral toxicity study (limit test) was conducted with fatty acids, C16-18 (even numbered), esters with pentaerythritol according to a protocol similar to OECD guideline 401 (Potokar, 1983). The study report contained very limited data. The test substance was administered by gavage at a concentration of 2000 mg/kg bw to 2 Wistar rats/sex. No mortality occurred during the 14-day observation period. Rough fur and reduced activity was observed directly after dosing. No effects on body weight were noted and no macroscopic findings were reported at necropsy. The acute oral LD50 was determined to be > 2000 mg/kg bw.

CAS 62125-22-8

In an acute oral toxicity study performed according to OECD guideline 401 and under GLP conditions, 5 rats/sex were administered 5000 mg 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) /kg bw by gavage (Debets, 1984). No mortality occurred during the 14-day observation period. There were no clinical signs of toxicity and no significant changes in body weight were reported. The macroscopic examination did not show treatment-related effects. The acute oral LD50 was found to be > 5000 mg/kg bw.

CAS 19321-40-5

An acute oral toxicity study was performed with pentaerythritol tetraoleate according to OECD guideline 423 and under GLP conditions (Pels Rijcken, 1997). Pentaerythritol tetraoleate was administered by oral gavage to three Wistar rats at 2000 mg/kg bw. No mortality occurred during the 15-day observation period. No clinical signs were observed in the animals during the study period. The increase in body weight was within the normal range reported for animals of this strain. No substance-related findings were noted during the gross pathology examination. The acute oral LD50 value in rats was considered to be > 2000 mg/kg bw.

Acute toxicity: inhalation:

2,2-bis(hydroxymethyl)propane-1,3-diyl didocosanoate (CAS 68258-72-0) is waxy solid with a predicted very low vapour pressure (<0.001 Pa at 20⁰C), which indicates a low inhalation potential. In addition test substance is marketed or used in a non-granular form. Therefore, during normal handling and use of the test substance, it can be assumed that no acute toxic effects due to inhalation of the test substance are likely to occur and inhalation of the substance is not considered to be a significant route of exposure.

 

Acute toxicity: dermal

CAS 62125-22-8

 

An acute dermal toxicity study (limit test) was performed on 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) according to OECD guideline 402 and under GLP conditions (Debets, 1984). 5 Wistar rats/sex were exposed to 2000 mg test substance/kg bw for 24 hours under occlusive conditions. No signs of systemic toxicity were noted in any animal during the 14-day observation period. The increase in body weight was within the normal range reported for animals of this strain. Gross pathology did not reveal any substance-related findings in the treated animals. The local effects on the skin at the application site were not reported. The acute dermal LD50 value in rats was found to be > 2000 mg/kg bw.

 

Conclusion for acute toxicity

The reliable data available for the source substances indicate a very low level of acute toxicity following the oral, and dermal route, as LD50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, 2,2-bis(hydroxymethyl)propane-1,3-diyl didocosanoate is not expected to be hazardous following acute exposure.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
No study required since exposure of humans via inhalation is unlikely taking into account the physico-chemical properties of the substances and the lack of exposure to aerosols, particles or droplets of inhalable size under normal conditions of use.

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

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 analogue concept is applied to 2,2-bis(hydroxymethyl)propane-1,3-diyl didocosanoate (CAS 68258-72-0), data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.