Pentane-2,4-dione

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: 14 week repeated dose toxicity by inhalation route

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Conduction and documentation of study acceptable. Literature reference and study report available.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Materials and methods

GLP compliance:

yes

Test material

Test material information

Constituent 1

Details on test material:

Purity: 99%

Test animals

Species:

rat

Strain:

other: COBS, CDF (F-344/CrlBR)

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Vehicle:

not specified

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

2,4-pentanedione concentration in the exposure chamber measured every 33 min during the exposure.

Duration of treatment / exposure:

6 h/d; 7d/week

Frequency of treatment:

14 weeks

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 100, 300, 650 ppm
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0.409, 1.226, 2.656 mg/L
Basis:
nominal conc.

No. of animals per sex per dose:

20 Male and 20 female rats per group, with half being sacrificed at the end of exposure period and the remaining after a 4 week recovery period for the determination of the reversibility of observable effects.
Additionally 10 male rats were added to control and high dose groups for glutaraldehyde perfusion and subsequent ultrastructural examination of sciatic nerves.

Examinations

Parental animals: Observations and examinations:

Clinical signs of toxicity: daily
Ophtalmoscopy of the eye: prior to the first exposure and at sacrifice
Neurobehavioral screening: modified Irwin screen ; monthly before, during and after exposure
Body weight: weekly during the study and before sacrifice
Food and water consumption for 15 h in metabolic cages during the last exposure week (urin collection)
Organ weights (liver, kidneys, lungs, brain, heart, thymus and testes), urine chemistry (n=10 each group), serum chemistry and haematology of blood samples collected at the end of exposure or the 4-week recovery.

Postmortem examinations (parental animals):

Gross pathology at termination in all groups.
Histopathology (nasal turbinates, larynx, trachea, lungs, epididymides, testes, spleen, thymus, urinary bladder, adrenal glands, brain (5 sections), thyroides, parathyroides, heart, kidneys, pituitary, skeletal muscle (gastronemius), stemal bone, spinal cord (lumbosacral region) and liver) in high dose, mid dose females and control group as well as brains of the mid dose group were processed for histopathology.

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Analytical monitoring: No decomposition or chamber loss of the metered 2,4-pentanedione. Mean measured chamber concentrations were 0, 101, 307 and 650 ppm.
Toxicity results:
In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group . The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermediate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the intermediate dose group had size changes in the cervix ("luminal ectasia").

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

2.656 mg/L air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no histopathological effects on testes, epididymitis, uterus, cervix and ovaries were observed.

Overall reproductive toxicity

Reproductive effects observed:

not specified