Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol]

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 5000 mg/kg bw (OECD 401, GLP, analogue approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP, analogue approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 5.0 mg/L air (OECD 403, analogue approach)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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. Lack of data on test substance.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Lack of data on test substance.

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

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: Winkelmann, Borchen, Germany
- Weight at study initiation: about 168 g (males) and 150 g (females)
- Fasting period before study: 16 h
- Housing: the animals were housed in groups of 5 in Makrolon 3 cages with a bedding of softwood granules.
- Diet: Altromin 1324, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 60
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 15 Mar 1988
To: 29 Mar 1988

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

5000 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: there was a repeated observation of the animals on the application day. During the 14 d observation period, the animals were observed twice daily. Individual body weights were recorded the day prior to application, the day of application and on Days 2, 7 and 14 of the observation period.
- Necropsy of survivors performed: yes

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:

other: No clinical signs of toxicity were observed up to the end of the 14 d 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

Quality of whole database:

The available information comprises an adequate, reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to 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 (EC) No 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 adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to 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 (EC) No 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 dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to 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 (EC) No 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.

Additional information

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5). In order 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, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substance listed below are selected as reference substances for hazard assessment.

Overview of acute toxicity

CAS	Acute toxicity oral	Acute toxicity inhalation	Acute toxicity dermal
CAS 91050-80-5 (a) Target substance	RA: CAS 63705-03-3	RA: CAS 68424-31-7 RA: CAS 85536-35-2 RA: CAS 73398-61-5	RA: CAS 63705-03-3 RA: CAS 555-43-1
CAS 68424-31-7(b)	LD50 > 2000 mg/kg bw	LC50 > 5.1 mg/L	--
CAS 85536-35-2	--	LC50 > 5.0 mg/L	--
CAS 73398-61-5	LD50 > 34020 mg/kg bw	LC50 > 1.86 mg/L	--
CAS 63705-03-3	LD50 > 5000 mg/kg bw	--	LD50 > 5000 mg/kg bw
CAS 555-43-1	LD50 > 20000 mg/kg bw	--	LD50 > 2000 mg/kg bw

(a) Substances subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

 (b) Substances that are either already registered under REACh or not subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Acute toxicology: oral

Since no studies investigating the acute oral toxicity Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS 91050-80-5) are available,in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) was conducted.

CAS 63705-03-3

For 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3), an acute oral toxicity study (limit test) according to OECD TG 401 (Potokar, 1988) and GLP compliant is available. Groups of 5 female Wistar rats received doses of 5000 mg /kg bw of test substance by gavage. The animals were observed for 14 days. No mortality, signs of systemic toxicity and no abnormalities during necropsy were observed. No effect on body weight was noted. Thus, the acute oral LD 50 in rats was determined to be greater than 5000 mg/kg bw.

Acute toxicology: inhalation

Since no studies investigating the acute inhalation toxicity of oleic acid, toxicity Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5) are available,in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from structurally related category members Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) and Glycerides, mixed decanoyl and octanoyl (CAS#73398-61-5) was conducted.

CAS 68424-31-7

An acute inhalation toxicity study (limit test) was performed withFatty acids, C5-10, mixed esters with pentaerythritol (CAS# 68424-31-7)according to OECD guideline 403 (Parr-Dobrzanski, 1994). Five rats per sex wereexposed(nose only) to an aerosol of the test material with an analytical concentration of 5.10 mg/L air (nominal concentration was 5.0 mg/L) for an exposure duration of four hours. No mortality occurred during the 14 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.No effect on body weight was noted. Finally necropsy and histopathological examination revealed no substance-related findings. Thus, the LC 50 after acute inhalation ofFatty acids, C5-10 mixed esters with pentaerythritolin male and female rats was found to be greater than 5.1 mg/L air.

CAS 85536-35-2

An acute inhalation toxicity study (limit test) was performed with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) according to OECD guideline 403 (Parr-Dobrzanski, 1994). Five rats per sex were exposed(nose only) to an aerosol of the test material with an analytical concentration of 5. 0 mg/L air for an exposure duration of four hours. No mortality occurred during the 14 day study period. Clinical signs were 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. No effect on body weight was noted. Finally necropsy and histopathological examination revealed no substance-related findings. Thus, the LC 50 after acute inhalation offatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritolin male and female rats was found to be greater than 5.0 mg/L air.

CAS 73398-61-5

Another acute inhalation toxicity study was performed with Glycerides, mixed decanoyl and octanoyl (CAS# 73398-61-5) according to OECD guideline 403 (Reninghaus, 1976). Ten male rats were exposed (nose only) to an aerosol of the test material with an analytical concentration of 1.86 mg/L air for an exposure duration of six hours. No mortality occurred during the 14 day study period. No clinical signs of toxicity were observed in any of the animals during the 14-day observation period. No effect on body weight was noted. Finally necropsy and histopathological examination revealed no abnormal findings in lungs or tracheae. Macroscopically no deposits of oily test substance could be detected in the respiratory tissues. Thus, the LC50 after acute inhalation oftriglycerides, mixed decanoyl and octanoylin male rats was found to be greater than 1.86 mg/L air.

Acute toxicology: dermal

Since no studies investigating the acute dermal toxicity of Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5) are available,in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related category members 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) and Glycerol tristearate (CAS #555-43-1) was conducted.

CAS 555-43-1

The acute inhalation toxicity potential Glycerol tristearate (CAS# 555-43-1) was investigated in limit testperformed according to OECD guideline 402 (Krueger, 1988) and under GLP conditions. The dorsolumbar region of five male and female rats was treated semiocclusively with 2000 mg/kg bw test material. 24 hours after the dosing the treated area of skin was cleaned with corn oil and absorbent paper. No mortality occurred and no clinical signs of toxicity were observed in any of the animals during the 14-day observation period. With regard to the body weight male rats and achieved satisfactory body weight gains throughout the study.

Four female rats showed minimal body weight gain after the first week. One female showed little body weight loss after the first week. At the end of the study, minimal body weight gain was recorded in two female animals and one animal showed no body weight gain while two female rats achieved satisfactory body weight gains throughout the study. Finally the macroscopical examination of day 14 after treatment revealed no abnormalities. Thus, the dermal LC50 after treatment withglycerol tristearatein male and rats was found to be greater than 2000 mg/kg bw.

CAS 63705-03-3

The acute dermal toxicity potential of 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS #63705-03-3) was investigated in limit test performed according to OECD guideline 402 (Cords, 2012) and under GLP conditions. The dorsal and dorsolateral parts of the trunk of five male and female rats weretreated semiocclusively with 5000 mg/kg bw test material. 24 hours after application the treated area of skin was rinsed with warm water. No mortality occurred and no systemic clinical signs of toxicity were observed in any of the animals during the 14-day observation period. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. Finally the no macroscopic pathologic abnormalities were noted at necropsy. Thus, the dermal LC50 after treatment with1,2,3-Propanetriol, homopolymer, diisooctadecanoatein male and rats was found to be greater than 5000 mg/kg bw.

Conclusion for acute toxicity

In summary, acute oral toxicity study with1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) is available and resulted in oral LD50 values greater than 5000 mg/kg bw.

For acute inhalation toxicity, studies with Fatty acids, C5-10 esters with pentaerythritol (CAS# 68424-31-7), Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) and Glycerides, mixed decanoyl and octanoyl (CAS# 73398-61-5) are available. The studies conducted with Fatty acids, C5-10 esters with pentaerythritol (CAS# 68424-31-7) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS# 85536-35-2) resulted in no mortality and some clinical signs includinghunched position, chromodacryorrhoea, piloerection, staining around nose and wet fur. The LC 50 value in these studies was > 5.0 mg/mL air. In addition, the highest attainable concentration of Glycerides, mixed decanoyl and octanoyl (CAS# 73398-61-5) resulted in the LC50 value of > 1.86 mg/L air.

Acute dermal toxicity studies conducted 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) and Glycerol tristearate (CAS# 555-43-1) showed no treatment related effects at the limit dose of the current valid guideline. Therefore, the dermal LD50 is considered to be greater than 5000 and 2000 mg/kg bw respectively

Thus, the available data indicate a very low level of acute toxicity for the target and source substances and thus no hazard for acute oral, inhalative and dermal toxicity was identified.

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

Justification for selection of acute toxicity – inhalation 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 source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

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

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on oral, inhalation and dermal 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.