Bis(pentane-2,4-dionato-O,O')magnesium

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

2,4-Pentanedione. CAS N°: 123-54-6

Author:

OECD Organisation for Economic Co-operation and Development

Year:

2001

Bibliographic source:

SIDS Initial Assessment Report for SIAM 13 (Paris, France, in June) United Nations Environment Programme (UNEP) Publications, Nairobi, Kenya. 82 p. URL https://hpvchemicals.oecd.org/ui/handler.axd?id=AF8877C9-8DFB-45E0-8188-492EBA68CDAE

Reference 2

Reference Type:

publication

Title:

2,4- Pentanedione: 9-Day and 14-Week Vapor Inhalation Studies in Fischer-344 Rats.

Author:

Dodd DE, Garman RH, Pritts IM, Troup CM, Snellings WM, Ballantyne B

Year:

1986

Bibliographic source:

Fundamental and Applied Toxicology 7: 329-339

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Principles of method if other than guideline:

-Subchronic Inhalation Study in Fischer 344 Male and Female Rats
-Concentrations tested: 0, 100, 300 and 650 ppm
-Pathological observations: testicles, epididymis in males and uteri, cervix and ovaries in females

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pentane-2,4-dione

EC Number:

204-634-0

EC Name:

Pentane-2,4-dione

Cas Number:

123-54-6

Molecular formula:

C5H8O2

IUPAC Name:

pentane-2,4-dione

Test material form:

liquid

Test animals

Species:

rat

Strain:

Fischer 344

Details on species / strain selection:

TEST ANIMALS
- Source:
Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation:
34 days
- Housing:
2 animals per cage
- Diet :
ad libitum
- Water :
ad libitum
- Acclimation period:
18 days

DETAILS OF FOOD AND WATER QUALITY:

ENVIRONMENTAL CONDITIONS
- Temperature :
65-80 °F
- Humidity (%):
13-84%
- Air changes (per hr):
approx. 14
- Photoperiod (hrs dark / hrs light):
12/12

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Remarks on MMAD:

MMAD and GSD not available

Vehicle:

air

Details on exposure:

Liquid 2,4-pentanedione was assayed from a piston pump in a heated glass evaporator. The temperature in the evaporator was kept at the lowest level sufficient to vaporize the liquid. The resulting vapor was transported into the chamber by a countercurrent stream of air which entered the bottom of the evaporator.

Details on mating procedure:

not available

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The 2,4-pentanedione concentrations in the test chambers were analyzed approximately 2 times per hour (every 33 minutes during the 6 hours of daily exposure) during the 68 days of gas chromatographic testing. Concentration averages were 650 (± 19.3), 307 (± 10.3) and 101 (± 3.5) ppm for target concentrations.

Duration of treatment / exposure:

14 weeks of exposure, followed by a 4 weeks recovery time.

Frequency of treatment:

Treatment for 6 hours, 5 hours a day.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm (nominal)

Doses / concentrations 2

Dose / conc.:

100 ppm (nominal)

Remarks:

Corresponding to 417mg/m3 of 2,4-Pentanedione vapour.

Doses / concentrations 3

Dose / conc.:

300 ppm (nominal)

Remarks:

Corresponding to 1217mg/m3 of 2,4-Pentanedione vapour.

Doses / concentrations 4

Dose / conc.:

650 ppm (nominal)

Remarks:

Corresponding to 2711 mg/m3 of 2,4-Pentanedione vapour.

No. of animals per sex per dose:

20 males and 20 females

Control animals:

yes, concurrent vehicle

Details on study design:

20 male and 20 female rats per group, half sacrificed at the end of the exposure period and the remainder after a 4-week recovery period for determining the reversibility of observable effects, exposed to nominal concentrations of 0 , 100, 300 and 650 ppm of test substance, respectively. Ten male rats were added to control and high dose groups for glutaraldehyde infusion and subsequent ultrastructural examination of sciatic nerves.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality:

not examined

Body weight and weight changes:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Effect levels (P0)

1

Key result

Dose descriptor:

NOAEC

Effect level:

ca. 417 mg/m³ air (analytical)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: general effects

2

Dose descriptor:

LOAEC

Effect level:

ca. 2 711 mg/m³ air (analytical)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: general effects

3

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 144 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: general effects

4

Dose descriptor:

LOAEL

Effect level:

ca. 936.7 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: general effects

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: F1 generation

Effect levels (F1)

Remarks on result:

not measured/tested

Results: F2 generation

Effect levels (F2)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

The organic part of the substance to be registered does not show any negative effects on the reproductive organs of male and female rats.

Executive summary:

In a subchronic inhalation study in male and female F344 rats exposed to 0, 100, 300 and 650 ppm (nominal concentrations, corresponding to 0, 417, 1217 and 2711 mg / m3), no evidence of pathological effects were observed in the testes and epididymis of males as well as in the uterus, cervix and ovaries of females compared with untreated control animals immediately after the end of the study and after a period 4-week recovery, respectively, thus revealing no negative effects on the reproductive organs of male and female rats. A NOAEC of 417mg/m3 air was established for the test substance. A NOAEL of 144.1 mg/kg bw/day was then calculated.