Linseed oil, ester with pentaerythritol

Endpoint summary

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:

weight of evidence

Study period:

Not mentioned on study report

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

Secondary literature source (documentation insufficient for assessment)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

other: Acute oral toxicity

Limit test:

yes

Specific details on test material used for the study:

Test substance: Linseed oil, ester with pentaerythritol
CAS number: 68648-28-2
Purity: not indicated

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 49-74 d old
- Weight at study initiation: 222-235 g (males), 21l-229 g (females)
- Fasting period before study: Overnight
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg (dosing volume 2 ml/kg, undiluted)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Five male and 5 female Sprague-Dawley rats were fasted overnight and dosed by oral gavage with 2000 mglkg body weight of the test material. No controls; feeding and water ad libitum hour after dosing.

Statistics:

None required

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: No clinical signs of toxicity were observed in any of the female or male rats.

Gross pathology:

No abnormalities or gross lesions were observed at necropsy.

Other findings:

Clinical observations and necropsy observations were normal.

Interpretation of results:

other: CLP criteria not met

Conclusions:

Under the study conditions, the LD50 was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance according to OECD Guideline 401, in compliance with GLP. Five male and five female Sprague-Dawley rats were fasted overnight and dosed by oral gavage with 2000 mg/kg bw of the substance. No controls, feeding and water ad libitum hour after dosing. Observations for mortality and clinical manifestations were carried out daily for 14 d. Observations included changes in skin and fur, eyes and mucous membranes, and respiratory, circulatory, autonomic and central nervous system and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. No mortality or clinical signs of toxicity were observed in any of the female or male rats. There were no treatment-related body weight changes. No abnormalities or gross lesions were observed at necropsy. Clinical observations and necropsy observations were normal. Under the study conditions, the LD50 was determined to be >2000 mg/kg bw (US EPA HPV, 2004).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

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 d

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 substance
- 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 d
- 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

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:

other: CLP criteria not met

Conclusions:

Under the study conditions, the acute dermal LD50 of the test substance in rats was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance, 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate), according to OECD Guideline 402, in compliance with GLP. Male and femaleWistarrats were exposed 2000 mg/kg bw of the test substance to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by occlusive dressing for 24 h. The application area covered at least 10% of the total body surface area. The animals were observed for 14 d. No mortality occurred during the study. No signs of systemic toxicity were observed. No effect on body weight was noted.No treatment related gross alterations were found at macroscopic examination of the animals.Under the study conditions, the acute dermal LD50 of the substance in rats was determined to be >2000 mg/kg bw (Croda, 1984).

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity was assessed based on toxicity studies for the test substance itself, but also on substances representative of the main constituents, which can be categorised as pentaerythritol esters (PE) and glycerol esters (GE). The results are presented below:

Oral

Linseed oil, ester with pentaerythritol

A study was conducted to determine the acute oral toxicity of the test substance according to OECD Guideline 401, in compliance with GLP. Five male and five female Sprague-Dawley rats were fasted overnight and dosed by oral gavage with 2000 mg/kg bw of the substance. No controls, feeding and water ad libitum hour after dosing. Observations for mortality and clinical manifestations were carried out daily for 14 d. Observations included changes in skin and fur, eyes and mucous membranes, and respiratory, circulatory, autonomic and central nervous system and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. No mortality or clinical signs of toxicity were observed in any of the female or male rats. There were no treatment-related body weight changes. No abnormalities or gross lesions were observed at necropsy. Clinical observations and necropsy observations were normal. Under the study conditions, the LD50 was determined to be >2000 mg/kg bw (US EPA HPV, 2004).

Pentaerythritol esters (PE)

Study 1:

A study was conducted to determine the acute oral toxicity of pentaerythritol tetraoleate according to OECD Guideline 423 and EU Method B.1 tris, in compliance with GLP. Male and female Wistar strain Crl:(WI) BR rats were administered the substance by oral gavage at a dose of 2000 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. There were no mortality in this study. No evidence of systemic toxicity was noted during the study period. No toxicologically significant effects on bodyweight were recorded during the study period and no abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw (Croda, 1997).

Study 2:

A study was conducted to determine the acute oral toxicity of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) according to OECD Guideline 401, in compliance with GLP. Male and female Wistar rats were administered the substance by oral gavage at a dose of 5000 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. There were no mortality in this study. No evidence of systemic toxicity was noted during the study period. No toxicologically significant effects on bodyweight were recorded during the study period and no abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be >5000 mg/kg bw (Croda, 1984).

Glycerol esters (GE)

Study 1:

A study was conducted to determine the acute oral toxicity of glycerides, C16-18 and C18-unsatd. (in the form of alkali-refined linseed oil) according to OECD Guideline 401 and EG 84/449/EWG. Five male and female Wistar rats were administered the substance by oral gavage at a dose of 4763 mg/kg bw. Clinical signs, body weights and mortalities were recorded during the 14 d observation period. Immediately after death or at end of observation period, a complete necropsy was performed. No mortality or any other adverse effect was observed in any of the animals. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be > 4763 mg/kg bw (Chibanguza, 1988).

Overall, the test substance can be considered to have a low acute oral toxicity, with LD50 values for its main constituents >2000 mg/kg bw.

Dermal

As per Annex VIII (8.5.3), the acute dermal toxicity testing is not needed as the substance does not meet the criteria for classification for acute toxicity and STOT SE for the oral route. This is also supported by the absence of any systemic effects in the in vivo skin sensitisation study available with the constituent, fatty acids, C16-18 (even numbered) and C18 -unsatd., branched and linear, tri- and tetraesters with pentaerythritol. Moreover, given the physico-chemical properties of the test substance, the dermal LD50 value is less likely (due to lower absorption potential of dermal route) to be lower than oral LD50 or the oral doses showing clinical signs. Hence, testing via dermal route will less likely result in any additional hazard identification and testing is therefore considered unnecessary. This was supported by LD50 of acute dermal study on the read across substance, 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) in rats was determined to be >2000 mg/kg bw (Croda, 1984)

 

Inhalation

The substance is a highly viscous liquid with a low vapour pressure at room temperature. Due to its physical state and physical chemical properties it is unlikely that this substance will form inhalable dust, mist or fumes during normal processing and use conditions. In case inhalable forms of the substance are created under particular conditions (e.g. spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.

 

Justification for classification or non-classification

Based on the information available for its main constituents, the test substance is not considered to meet the requirements for acute toxicity classification according to the EU CLP (Regulation 1272/2008/EC) criteria.