3-sec-[C15-18-(branched and linear)-alk-2-enyl]pyrrolidine-2,5-dione

Endpoint summary

Description of key information

Oral: LD50 >2000 mg/kg bw in rats

Dermal: LD50 >5000 mg/kg bw in rabbits

Inhalation: No study available; endpoint waived due to exposure considerations

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:

7th November to 22nd November 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young, adult male and female Sprague-Dawley rats 10 weeks and weighing between 226-268 grams were obtained from Envigo RMS, Indianna. The females were nulliparous and nonpregnant. The rats were housed individually in stainless steel cages in a temperature , humidity and light controlled (12 hour/cycle) room. Each animal was assigned a test animal number which appeared on a cage card visible on the front of each cage. The rats were maintained according to the recommendations contained in teh National Academy Pres. Purina Laboratory Rat Chow and were were available ad libitum. The rats were acclimated at least five days prior to treatment.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg

No. of animals per sex per dose:

3/sex

Control animals:

no

Details on study design:

A 2000 mg/kg body weight limit test will be conducted. A limit test at one dose level of
2000 mg/kg body weight will be conducted on six rats (three rats per sex). If significant test
substance mortality is produced, further testing at the next dose level may be carried out. The
additional testing will be conducted starting at an appropriate dose levels (usually 300 mg/kg) to
determine the LD50. If greater than 50% of the rats survive at 2000 mg/kg, the LD50 will be
considered greater than the limit dose and the study will be terminated (i.e. carried out to 14 days
observation without dosing further rats).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities observed

Clinical signs:

other: No clinical signs of toxity observed

Gross pathology:

no gross changes observed

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 was determined to be greater than 2000 mg/kg body weight. Based on GHS and OECD 423 guidelines, as there were no deaths in the 6 rats tested the LD50 > 2000 mg/kg, and the substance does not need to be classified for acute oral toxicity.

Executive summary:

The test substance was administered by oral gavage at a 2000 mg/kg body weight limit dose level, according to the Acute

Toxic Class Method to male and female rats. The acute oral LD50 was determined to be greater than 2000 mg/kg body weight. Based on GHS and OECD 423 guidelines, as there were no deaths in the 6 rats tested, the LD50 > 2000 mg/kg, and the substance does not need to be classified for acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Available study is compliant with GLP and OECD Test Guidelines. The dataset meets the requirements of Regulation (EC) No. 1907/2006 and is considered to be sufficiently reliable for classification purposes.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

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:

8th November to 26th November 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Well documented, OECD and GLP compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young, adult male and female New Zealand Albino Rabbits2, at least 12 weeks of age and weighing
between 2.32 – 2.72 kilograms were obtained from Kuiper Rabbitry, Gary, Indiana. The females were
nulliparous and nonpregnant. Rabbits were housed individually in stainless steel cages in a temperature
(63-73 °F), humidity (30-70%), and light controlled room. The rabbits were maintained according to the
recommendations contained in the National Academy Press 2011: "Guide for the Care and Use of
Laboratory Animals". Purina Rabbit Chow and water were available ad libitum. The rabbits were
acclimated at least 5 days prior to treatment. The rabbits were individually identified by an ear tag.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The neat test substance was adminstered by dermal application at a dose of 5000 mg/kgbw to five male and 5 female rabbits. All animals were weighed on the day of dosing. Based upon the animals weight the test substance was applied uniformly over approximatley 10 percent of the total body surface area, covered with two layers of porous gauze dressing and a sleeve of plastic sheeting was fitted over the shaved trunk of the animal and secured in place with non-irritating surgival tape. The test animals were then returned to their cages for the 24 hour contact period. The test substance remained in contact with the skin for a 24 hour period afte which time the wrap was removed and any remaining test susbtance wiped off.

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occured

Clinical signs:

other: No signs of clinical toxicity were observed

Gross pathology:

No gross changes observed

Interpretation of results:

GHS criteria not met

Conclusions:

The administration of test substance by dermal application at a dose of 5000 mg/kg body weight to male and female rabbits produced no mortality,
indicating that the dermal LD50 of the sample is greater than 5000 mg/kg body weight

Executive summary:

The test substance was tested for acute dermal toxicity according to OPPTS, OECD Guidelines. The test substance described as a brown liquid, was administered by dermal application at a dose of 5000 mg/kg body weight to five male and five female rabbits. No mortality occurred during the 14 day observation period. The acute dermal LD50 was found to be greater than 5000 mg/kg body weight. Based on GHS and OECD 402 guidelines, the test substance is not classified for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Available study is compliant with GLP and OECD Test Guidelines. The dataset meets the requirements of Regulation (EC) No. 1907/2006 and is considered to be sufficiently reliable for classification purposes.

Additional information

The test substance was administered by oral gavage at a 2000 mg/kg body weight limit dose level, according to the Acute

Toxic Class Method to male and female rats. The acute oral LD50 was determined to be greater than 2000 mg/kg body weight. Based on GHS and OECD 423 guidelines, as there were no deaths in the 6 rats tested, the LD50 > 2000 mg/kg, and the substance does not need to be classified for acute oral toxicity.

The test substance was tested for acute dermal toxicity according to OPPTS, OECD Guidelines. The test substance described as a brown liquid, was administered by dermal application at a dose of 5000 mg/kg body weight to five male and five female rabbits. No mortality occurred during the 14 day observation period. The acute dermal LD50 was found to be greater than 5000 mg/kg body weight. Based on GHS and OECD 402 guidelines, the test substance is not classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity via the oral, dermal and inhalation routes, in accordance with Regulation (EC) No. 1272/2008.