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EC number: 203-738-3 | CAS number: 110-13-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- fertility, other
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2004
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 004
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The effect of 2,5-Hexanedione on the fertility of male rats is examined.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Hexane-2,5-dione
- EC Number:
- 203-738-3
- EC Name:
- Hexane-2,5-dione
- Cas Number:
- 110-13-4
- Molecular formula:
- C6H10O2
- IUPAC Name:
- hexane-2,5-dione
- Test material form:
- not specified
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- MALE WISTAR RATS, approximately 10 weeks old,
were used in the current study. The health status
of the rats were checked and then acclimated to the
laboratory environment for 2 weeks before the experiment.
The room temperature and relative humidity were
set at 24°C and 54%, respectively. The light was controlled
to provide a 12 h light cycle and a 12 h dark cycle. All
the animals were kept in stainless-steel cages and given
pelleted commercial laboratory animal food and water
throughout the study.
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Male rats were randomly allocated to three treatment
groups. Each group had six rats and each group was
given 2,5-HD subcutaneously at dose levels of 100, 200
and 400 mg/kg per day for 5 days per week (no
injection given on the other 2 days i.e., resting days) for
12 weeks. The control group had 10 rats which were
given only food and water throughout the experiment.
The concentration of the doses were based on the most
recent bodyweights. The dose levels and period were
selected as most likely to cause toxicity based on preliminary
studies on both testicular and nerve toxicity. - Details on mating procedure:
- not applicable
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 12 weeks
- Frequency of treatment:
- 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
100, 200, 400 mg/kg body weight
Basis:
nominal conc.
- No. of animals per sex per dose:
- 6 animals per group, 10 control animals
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Male rats were randomly allocated to three treatment
groups. Each group had six rats and each group was
given 2,5-HD subcutaneously at dose levels of 100, 200
and 400 mg/kg per day for 5 days per week (no
injection given on the other 2 days i.e., resting days) for
12 weeks. The control group had 10 rats which were
given only food and water throughout the experiment.
The concentration of the doses were based on the most
recent bodyweights. The dose levels and period were
selected as most likely to cause toxicity based on preliminary
studies on both testicular and nerve toxicity. - Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- On day 90 of 2,5-HD treatment, all the rats were anesthetized
with diethyl ether, weighed and killed. The
testis and epididymides were collected for analysis of
sperm motility and count. The right-sided epididymis
was excised and placed in a pre-warmed Petri dish
containing 1 mL of calcium and magnesium free Hank’s
solution at 37°C. The tissue was minced with scaples
for approximately 60 s and then placed in a 37°C incubator
for approximately 20 min prior to determining
the sperm motility. The suspension was stirred and one
drop was placed on to a pre-warmed slide and a coverslip
added. A minimum of 10 microscopic fields were
observed for each slide at 400× magnification using a
standard optical microscope and the percentage of motile
sperm were counted. For the morphological examination,
another drop of the sperm suspension was added
to another slide and then a thin smear was made and
stained with Papanicolau and the morphology of 200
sperm cells was assessed for each slide.
The left-sided epididymis and testis were frozen immediately
until evaluation. After thawing at room temperature,
the whole epididymis and the testis specimens
were homogenized separately in 1 mL of a solution of
0.9% NaCl containing 0.01 mL Triton X-100. The testis
and epididymis homogenates were each diluted with
1.5 mL of the same solution and spermatozoa and
spermatids were counted 400× in a Neubauer hemocytometer
(Erma, Tokyo, Japan) and three counts per sample
were averaged. - Sperm parameters (parental animals):
- Histologic examination of the testis was performed after
fixing the right-sided testis in a formalin solution. Sixmicron
thick paraffin sections were stained with hematoxylin
and eosin and examined by light microscopy. - Statistics:
- Data were analyzed using the Levene’s test for equality
of variances. If P > 0.05, the variances were considered
equal and the Student’s t-test was calculated and P < 0.05
was considered as significant. If P < 0.05, then the variances
were considered unequal and a Wilcoxon signed-ranked
test was also performed and P < 0.05 was considered
significant.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- testicles
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- adverse effects observed
- Reproductive performance:
- not examined
Effect levels (P0)
open allclose all
- Dose descriptor:
- other: reduced sperm motility
- Effect level:
- ca. 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Dose descriptor:
- other: no sperm motility, maturation arrest
- Effect level:
- ca. 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Dose descriptor:
- other: no sperm motility, reduced sperm concentration, testicular injury
- Effect level:
- ca. 400 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In conclusion, we have shown that 2,5-hexanedione
severely affected sperm motility even at low doses, whereas
high doses adversely affected all the sperm parameters as well
as causing testicular injury. - Executive summary:
No sperm motility was observed in the 200 mg and
400 mg/kg per day treatment groups and significantly reduced
motility was observed in the 100 mg/kg per day group. The
morphology were also significantly reduced in the 200 mg and
400 mg/kg per day groups compared to the control group,
but the sperm concentration was significantly reduced only in
the 400 mg/kg per day group. Histological examination of
the testes in the 400 mg/kg per day group revealed that twothirds
of the testes had Sertoli cell only syndrome, whereas in
the 200 mg/kg per day group half of the testes showed maturation
arrest and sperm as well as spermatids were observed in
83% of the testes.
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