Fatty acids, C5-9, hexaesters with dipentaerythritol

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, GLP)
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:

experimental study

Adequacy of study:

key study

Study period:

07 Dec - 26 Mar 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with acceptable restrictions (no data on analytical purity)

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted in 1992

Deviations:

yes

Remarks:

no data on analytical purity

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: Albino Rats (Outbred). Stock: Sprague-Dawley – derived (CD ®) [Crl: CD ® (SD) IGS BR]

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Kingston, New York, USA
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 279 – 318 g (males); 204 – 219 g (females)
- Fasting period before study: animals were fasted overnight prior to administration
- Housing: 2 – 6/ cage during acclimation. Individually housed in suspended and stainless steel cages with wire mesh bottoms during study.
- Diet: Certified Rodent Diet, No. 5002, ad libitum
- Water: automatic watering system, ad libitum.
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24
- 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: 2.0 mL/kg

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality was observed twice daily for 14 days. Clinical signs were observed several times on the day 1, and daily until day 14. Body weights were measured on day 0 (at time of fasting), 1 (just prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes (on day 15)
- Other examinations performed: clinical signs, body weight, food consumption, gross pathology and histopathology

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 up to the end of the 14-day observation period.

Gross pathology:

Necropsy examination revealed no substance-related findings.

Other findings:

- Histopathology: there were no treatment-related effects on histopathology.

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 adequate, reliable (Klimisch score 1) and consistent study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, 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

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

Study period:

05 Jan - 19 Jan 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD) (limited data on test substance).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

limited data on test substance

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

limited data on test substance

GLP compliance:

yes (incl. QA statement)

Remarks:

Safepharm laboratories ltd., Derby, UK

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: males: 202 - 217 g (male) and 202 - 212 g (female)
- Housing: individually housed in suspended polypropylene cages for the time of exposure and in groups of five, by sex, for the reminder of the study.
- Diet: ad libitum, Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, UK
- Water: ad libitum
- Acclimation period: minimum 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 (18 at one ocasion, this was not considered relevant for the study)
- Humidity (%): 47-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: approx. 10% of total body surface
- Type of wrap if used: gauze secured with self adhesive bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiping with cotton wool moistened with distilled water
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5 h; 1 h; 2 h and 4 h after dosing and daily thereafter for 14 days. Weighing on Days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Skin reactions according to Draize Scoring System (1977)

Statistics:

Not required

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 up to the end of the 14-day observation period.

Gross pathology:

Necropsy and histopathological examination 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 due to read-across) 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.

Additional information

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1). 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.

Overview for acute toxicity

CAS	Acute toxicity oral	Acute toxicity inhalation	Acute toxicity dermal
67762-52-1(a) Target substance	LD50 > 2000 mg/kg bw	RA: CAS 68424-31-7 RA: CAS 85536-35-2	RA: CAS 131459-39-7
68424-31-7 (b)	LD50 > 2000 mg/kg bw	LD50 > 5.1 mg/L air	--
131459-39-7	--	--	LD50 > 2000 mg/kg bw
85536-35-2	--	LD50 > 5 mg/L air	--

(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 the structural and similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1)

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

Discussion 

Acute toxicity: oral

For Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1), an acute oral toxicity study (limit test) according to OECD TG 420 (Bailey, 1999) is available. Groups of 5 male and female Sprague-Dawley received a dose of 2000 mg /kg bw of test substance by gavage. No treatment related mortality, signs of systemic toxicity and abnormalities during gross necropsy were observed. No effects on body weight, gross morphology and histopathology were observed in treated animals. Thus, the acute oral LD 50 in rats was determined to be greater than 2000 mg/kg bw.

Acute toxicity: inhalation

Since no studies investigating the acute inhalation toxicity of Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances 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) was conducted.

CAS 68424-31-7

An acute inhalation toxicity study (limit test) was performed with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) 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 5.10 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 LC50 after acute inhalation of Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) in 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) for four hours to an aerosol of the test material with an analytical concentration of 5.0 mg/L air. 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 LC50 after acute inhalation of Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol, in male and female rats, was found to be greater than 5.0 mg/L air.

Acute toxicity: dermal

Since no acute dermal toxicity studies with Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substance 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS# 131459-39-7) was conducted.

CAS 131459-39-7

The acute dermal toxicity potential 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS#131459-39-7) was investigated in limit test performed according to OECD guideline 402 (Allen, 1999) and under GLP conditions. The back and flanks regions of five male and female Sprague-Dawley rats was treated with 2000 mg/kg bw test material under semiocclusive conditions. 24 hours after the dosing the treated area of skin was cleaned with distilled water and cotton wool. No mortality occurred and no clinical signs of toxicity were observed in any of the animals during the 14-day observation period. The test substance had no effect on body weight. Necropsy and histopathological examination revealed no substance-related findings. The test substance had no effect on body weight.

Thus, the dermal LD50 after treatment with 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid in male and female rats was found to be greater than 2000 mg/kg bw.

Conclusion for acute toxicity

In summary, one acute oral toxicity study is available. The study conducted with Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) resulted in an oral LD50 value greater than 2000 mg/kg bw. For acute inhalation toxicity, two studies are available for structurally related substances 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). From these studies a LC50 value for male rats and female rat greater than 5.0 mg/L air was evaluated. An acute dermal toxicity study conducted with 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS# 131459-39-7) showed no effects at the limit dose 2000 mg/kg bw. Thus, the available data indicate a very low level of acute toxicity for fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) thus, no hazard for acute oral, inhalative and dermal toxicity was identified.

 

 

 

Justification for selection of acute toxicity – oral endpoint
There is only one study available.

Justification for selection of acute toxicity – inhalation 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 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 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 classification or non-classification

Based on data received on the substance and 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.