Reaction products of furan-2,5-dione and octadec-1-ene

Endpoint summary

Description of key information

The LD50's for n-ODSA EC 701-338-8 for acute oral and dermal toxicity testing are greater than 2000 mg/kg bw.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

guideline study under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Specific details on test material used for the study:

As a result of increasingly rigorous criteria being applied to the analysis of commercial material used in physical property/toxicity testing, the identity of the material has been modified to reveal a more accurate and precise depiction of the commercial substance. This enhancement is reflected in changes in chemical identifiers such as EC and/or CAS numbers from those noted in earlier versions of data records or in study reports.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories, Inc.
- Age at study initiation: 8-12 weeks
- Weight at study initiation:
- Fasting period before study: no
- Housing: nimals will be housed singly in suspended stainless steel perforated bottom cages or plastic solid bottom cages. Litter paper placed beneath the cage will be changed at least three times/week or Corncob bedding (1/4 inch bed-o'-cobs®, or equivalent) will be changed at least once per week.
- Diet (e.g. ad libitum): Harlan Teklad Global 16% Protein Rodent Diet® #2016, ad libitum.
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 3C
- Humidity (%): 30-70%,
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Several trials were undertaken to solubilize this waxy solid test material in a suitable vehicle for oral gavage administration to rats. Care needed to be taken to avoid aqueous solvents, as the material hydrolyses in water. The substance was gently warmed to 80 degrees C and solubilized in corn oil, which, when cool, was administered to the animals.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Limit Test at 2000 mg/kg: If the initial animal survives following dosing, the test substance will be administered sequentially to four additional females so that a total of five animals are dosed; however, if at any time three animals die, the limit test will be terminated and the main test will be conducted. If an animal dies late in the observation period, all dosing should be stopped and the animals already on test should be observed for a similar period prior to proceeding. The LD50 of the test substance will be considered greater than the limit dose if three or more animals out of five survive.

Statistics:

Dose progression and stopping criteria will be calculated using a dedicated software program (Acute Oral Toxicity (Guideline 425) Statistical Program) provided by the U.S. Environmental Protection Agency (EPA).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths; LD0 > 2000 mg/kg bw.

Mortality:

No deaths occurred at 2000 mg/kg bw. The LD50 is greater than 2000 mg/kg bw.

Clinical signs:

other: No signs of toxicity

Gross pathology:

No findings on gross pathology

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information: The LD50 is greater than 2000 mg/kg bw, and so is not classified according to Regulation EC No. 1272/2008.

Conclusions:

n-ODSA was tested in an OECD 425 Up-and-down protocol according to GLP, and the LD50 was found to be 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:

adequate

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:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

experimental study

Adequacy of study:

key study

Study period:

October 2013-November 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

guideline study under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

As a result of increasingly rigorous criteria being applied to the analysis of commercial material used in physical property/toxicity testing, the identity of the material has been modified to reveal a more accurate and precise depiction of the commercial substance. This enhancement is reflected in changes in chemical identifiers such as EC and/or CAS numbers from those noted in earlier versions of data records or in study reports.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number of Animals: 10
Sex: 5 females and 5 males. Females tested were nulliparous and nonpregnant.
Age/Body weight: Young adult (8-9 weeks)/males 269-280 grams and females 178-196 grams at experimental start.
Source: Received from SAGE Labs on Octoer 21, 2015.

Housing: The animals were singly housed in suspended stainless steel caging, and conformed to size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011).
An enrichment toy was placed into each cage. Little paper was placed beneath the cage and was changed at least three times per week.

Animal Room Temperature and Relative Humidity Ranges: 19-23 degrees C and 40-61%, respectively.
Animal Room Air Changes/Hour: 12 or 13. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 8 days
Food: Envigo Teklad Global 16% Protein Rodent Diet #2016. The diet was available ad libitum.
Water: Filtered tap water was supplied ad libitum.
Contaminants: There were no known contaminants reasonably expected to be found in the water or food at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Product Safety Labs.

Cage: Each cage was identified with a cage card indicating at least the study number and identification and sex of the animal.
Animal: A number was allocated to each rat on receipt and a stainless steel ear tag bearing this number to the animal. This number, together with a sequential animal number assigned to study 41876, constituted unique identification.

Type of coverage:

occlusive

Vehicle:

other: 75% w/w mixture in mineral oil

Details on dermal exposure:

On the day prior to application, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial), and the skin checked for any abnormalities.
The test substance, as received, was a solid In order to ensure adequate contact with the skin, the test substance was applied as a dry paste (75% w/w mixture in mineral oil).
2000 mg/kg bw of test material was applied to a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface). The gauze pad and entire trunk of each animal were then wrapped with 3-inch Duropore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered day 0 of the study.

Duration of exposure:

Each test animal was exposed for 24 hours. After the 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove any residual test substance.

Doses:

All test animals received a similar dose of 2000 mg/kg bw. It was applied to a 2-inch x 3-inch area of the body.

No. of animals per sex per dose:

5 female rats and 5 male rats were used in the study. All animals received a similar dose of 2000 mg/kg of the test substance.

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths

Mortality:

The test substance caused no mortality in any of the animals tested.

Clinical signs:

other: There were no adverse clinical findings recorded for any animal over the course of the study.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day study.

Animal No.	Sex	Body Weight (g)			Dose
		Initial	Day 7	Day 14	g
3201	M	269	310	345	0.72
3202	M	275	322	360	0.73
3203	M	280	356	399	0.75
3204	M	279	340	375	0.74
3205	M	280	317	348	0.75
3206	F	196	209	223	0.52
3207	F	187	199	224	0.50
3208	F	179	195	217	0.48
3209	F	190	202	234	0.51
3210	F	178	194	210	0.48

Animal Number	Findings	Day of Occurance
Males
3201	Active and Healthy Erythema at dose site	0(1-4.5 hrs), 7-14 1-6
3202	Active and Healthy Erythema at dose site	0(1-4.5 hrs), 2-14 1
3203	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 11-14 1-6 5-10
3204	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 9-14 1 2-8
3205	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 3-14 1 2-8
Females
3206	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 11-14 1 2-10
3207	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 11-14 1-2 3-10
3208	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 9-14 1-6 3-8
3209	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 10-14 1-6 3-9
3210	Active and healthy Erythema at dose site Desquamation at dose site	0(1-4.5 hrs), 12-14 1-2 3-11

Animal Number	Tissue	Findings
Males
3201-3205	All tissues and organs	No gross abnormalities
Females
3206-3210	All tissues and organs	No gross abnormalities

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Under the conditions of an OECD 402 guideline study, the single dose acute dermal LD50 of n-ODSA is greater than 2000 mg/kg bw in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

adequate

Additional information

In guideline GLP in vivo studies on acute toxicity of n-ODSA EC 701-338-8 by the oral and dermal routes of administration, no deaths or toxicity were observed. The LD50 values are greater than 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
experimental data on registered substance

Justification for selection of acute toxicity – dermal endpoint
experimental result on the registered substance

Justification for classification or non-classification

As the oral and dermal LD50 values of n-ODSA EC 701-338-8 exceed 2000 mg/kg bw, the substance is not classified for acute toxicity, according to Regulation EC No. 1272/2008.