4-oxovaleric acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from September 25th to October 10th, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: EPA OPPTS 870.1000 (Acute Toxicity Testing - Background)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-oxovaleric acid

EC Number:

204-649-2

EC Name:

4-oxovaleric acid

Cas Number:

123-76-2

Molecular formula:

C5H8O3

IUPAC Name:

4-oxopentanoic acid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS s.r.l., San Pietro al Natisone (UD), Italy.
- Breeder: Envigo RMS B.V., Kreuzelweg 53, 5961 NM Horst, Netherlands.
- Females nulliparous and non-pregnant: yes.
- Age: 6 to 8 weeks old.
- Weight range at arrival: 198.3 to 202.6 grams (males); 189.7 to 189.9 grams (females).
- Housing: clear polysulfone H-Temp solid bottomed cages (Tecniplast Gazzada S.a.r.l., Buguggiate, VA, Italy) measuring 59.5×38×20 cm during acclimatisation period and 42.5×26.6×18.5 cm during the study with nesting material provided into suitable bedding bags. At allocation animals were individually caged.
- Diet: ad libitum throughout the study, 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
- Water: ad libitum, drinking water supplied to each cage via a water bottle.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 2 °C.
- Humidity: 55 % ± 15 %.
- Air changes: approximately 15 to 20 air changes per hour.
- Photoperiod: artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back (clipped with an electric clipper)
- % coverage: 10 % of the total body surface.
- Type of wrap if used: On test day 1, the test article was applied evenly on the skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The treated skin was washed with lukewarm tap water, dried with disposable paper towels Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied: 4 ml at 2000 mg/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Cage control: daily inspected and changed as necessary (at least 3 times/week)
- Mortality and morbidity observations: throughout the study, all animals were checked twice daily.
- Clinical signs: the animals were observed on the day of dosing; session 1: on dosing- session 2: approximately 1 hour after dosing- session 3: approximately 2 hours after dosing- session 4: approximately 4 hours after dosing and daily thereafter for a total of 14 days.
- Body weighing: all animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 8 and 15. Body weight change calculated for Days 8 and 15 of the dosing phase was relevant to Day 1 of the phase.
- Termination: all animals were sacrificed on Day 15 by carbon dioxide narcosis.
- Necropsy of survivors performed: yes. Necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the treatment site).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred in male or female animals after treatment during the observation period.

Clinical signs:

other: No clinical signs were observed in male or female animals after treatment during the observation period.

Gross pathology:

No abnormalities were found at necropsy examination performed on all animals at termination of the study

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful/toxic according to the CLP Regulation (EC) No.1272/2008

Conclusions:

LD50 > 2000 mg/kg

Executive summary:

The acute toxicity of the test material was investigated following dermal administration of a single dose to the rat, according to the OECD Guideline 402. A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours, under semi-occlusive dressing. Animals were observed for mortality and clinical signs and were weighed on the day of allocation, on the day of dosing and on days 8 and 15. After 14 days, all animals were killed and subjected to necropsy examination.

No mortality occurred and no signs of toxicity were observed in male or female animals during the observation period. The body weight changes observed during the study were within the expected range for this species and age of animals. No significant abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site.

LD50 > 2000 mg/kg