Reaction mass of 2-hydroxyethyl oleate, oleic acid, and 2-hydroxyethyl palmitate

Endpoint summary

Description of key information

In a reliable acute toxicity study a structurally similar substance was administered to Sprague Dawley rats (5 animals/sex/dose) by oral gavage at a dose level of 5000 mg/kg bw (single administration). There were no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination. The oral LD50 is >5000 mg/kg bw.

In a reliable acute toxicity study a structurally similar substance was administered to Wistar rats (5 animals) by oral gavage at a dose level of 2000 mg/kg bw (single administration). There were no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination. The oral LD50 is greater than 2000 mg/kg bw.

In a reliable acute dermal toxicity study a structurally similar substance was administered to Wistar rats (5 animals/sex/dose) by semi occlusive dermal application at a dose level of 2000 mg/kg bw (single administration). There were no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination. The dermal LD50 is greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of 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:

Remarks:

Read-across to a K1 study therefore K2 is the maximum Klimisch score that can be assigned.

Justification for type of information:

A read-across justification is provided in section 13 of the IUCLID file.

Reason / purpose for cross-reference:

read-across source

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany.
- Fasting period before study: 16 h
- Housing: 5 animals of the same sex per cage in Makrolon 3 cages.
- Litter: soft wood granulate.
- Diet: Altromin-Haltungsdiät 1324 (Altromin GmbH, Lage, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 8 days
- Identification of the test animals: Group identification by cage labelling, individual identification by labelling with saturated picric acid solution.

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

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

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: At day of application, animals were observed several times, thereafter 2 times per day until Day 14. Weighing was performed one day before application, directly before application, 48 h after application and at Day 7 and Day 14 after application.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross necropsy and 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 clinical signs of toxicity were observed at the end of the 14-day observation period.

Gross pathology:

Males: tightly filled urinary bladder in 1/5 males 14 days after application. 4/5 males showed no clinical signs of toxicity at the end of the 14-day observation period.
Females: 4/5 females showed no clinical signs of toxicity. In 1/5 females a mild hydrometra was observed. According to the author the hydrometra was not due to the substance treatment.

Table 1. Mean body weights in g.

Doses	2000 mg/kg bw	2000 mg/kg bw
- 1 d	185	168
0 d	173	159
2 d	194	172
7 d	213	172
14 d	239	182
body weight gain	54	14

d = day of study

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 is greater than 2000 mg/kg bw.

Executive summary:

In an acute toxicity study the substance was administered to Wistar rats (5 animals) by oral gavage at a dose level of 2000 mg/kg bw (single administration). There were no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination.The oral LD50 is greater than 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of 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:

comparable to guideline study with acceptable restrictions

Remarks:

Read-across to K2 study therefore K2 is the maximum Klimisch value.

Justification for type of information:

Read-across approach - see read-across justification in section 13.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

White flaky solid.
Lot #12735

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Weight of animals 184 - 205g.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2.5%

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None.

Clinical signs:

other: None.

Gross pathology:

There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

Other findings:

All animals appeared active and healthy.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 is >5000 mg/kg bw.

Executive summary:

In an acute toxicity study the substance was administered to Sprague Dawley rats (5 animals/sex/dose) by oral gavage at a dose level of 5000 mg/kg bw (single administration). There were no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination. The LD50 is >5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Sufficient to address requirements.

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:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Read-across to K1 study therefore K2 is the maximum Klimisch value.

Justification for type of information:

Read-across approach - see read-across justification in section 13.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

yes

Test type:

standard acute method

Specific details on test material used for the study:

Batch number: 12430
General characteristics: Odourless oily liquid
Purity: Butanediol dioctanoate: 36.3 (% by area); Butanediol octanoate decanoate: 46.3 (% by area); Butanediol didecanoate: 15.1 (% by area)
Storage conditions: In a closed container in a laboratory hood
Stable until: 06/1993

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Body weight of animals at start of test: 200-300 g
Room temperature: 20±3°C
Rel humidity: 30-70%
Acclimitisation: At least 5 days

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The volume administered was 2.2 cm3/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals/sex

Control animals:

not specified

Details on study design:

The animals were examined for clinical signs 1/2, 1, 2, 3, 4, 5 and 6 hours after administration and once a day for the next two weeks. The relevant area was examined for dermal reactions related to the test substance. The time of occurrence and the nature of the signs were recorded separately for each animal. The animals were weighed on the day of administration (day 0), on day 7 and at the end of the test (day 14). After the observation period of 14 days, all the animals were sacrificed by inhalation of carbon dioxide, necropsied and inspected for macroscopic changes to organs. The necropsy results were recorded separately for each animal.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities during the study.

Clinical signs:

other: No signs of toxicity related to the substance were found with the dose of 2000 mg/kg bodyweight during the 14-day observation period.

Gross pathology:

The necropsies at the end of the study revealed no macroscopic changes to organs, nor were there any abnormalities in the skin and subcutaneous tissue in the application area.

Other findings:

The animals showed no dermal reactions 24 hours after administration and up to the end of the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 is greater than 2000 mg/kg bw.

Executive summary:

In an acute toxicity study the substance was administered to Wistar rats (5 animals/sex/dose) by semi occlusive dermal application at a dose level of 2000 mg/kg bw (single administration). There were no mortalities or signs of clinical toxicity, mean body weight gain was as expected and no abnormalities found at macroscopic post-mortem examination. The dermal LD50 is greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Sufficient to address requirements.

Justification for classification or non-classification

Based on the findings of a reliable acute oral toxicity study conducted on a structurally similar substance, classification of the substance is not justified.

Based on the findings of a reliable dermal toxicity study conducted on a structurally similar substance, classification of the substance is not justified.