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EC number: 202-492-4 | CAS number: 96-24-2
- 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

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- In or before 2006
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- No information on whether female mice are nulliparous and non-pregnant, no data on opthalmoscopic, neurobehavorial and detailed clinical observations, limited blood chemistry analysis performed.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 3-chloropropane-1,2-diol
- EC Number:
- 202-492-4
- EC Name:
- 3-chloropropane-1,2-diol
- Cas Number:
- 96-24-2
- Molecular formula:
- C3H7ClO2
- IUPAC Name:
- 3-chloropropane-1,2-diol
- Details on test material:
- - Name of test material (as cited in study report): 3-MCPD
- Analytical purity: 98%
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: stability in drinking water and the dose formulations of animal room samples were analyzed and the analytical results for all dose formulations were within 10% of the theoretical concentrations.
- Storage condition of test material: at 4°C protected from light
- Other: purchased from Sigma Aldrich Inc. (St. Louis, MO, USA)
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: 6 weeks
- Weight at study initiation: no data
- Fasting period before study: not applicable
- Housing: female mice: 5 per cage; male mice individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1
- Humidity (%): 55 +/- 5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: drinking water solutions were prepared using deionized water. The dose formulations were prepared every 2 weeks and stored at 4°C in glass vessels that were protected from light.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test substance in drinking water and the dose formulations of animal room samples were analyzed by LabFrontier Co. Ltd., Korea. The analytical results for all dose formulations were within 10% of the theoretical concentrations.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- continuous via the drinking water
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
5, 25, 100, 200 and 400 ppm
Basis:
nominal in water
- Remarks:
- Doses / Concentrations:
0.94, 4.59, 18.05, 36.97 and 76.79 mg/kg bw/d
Basis:
other: average daily intake in males
- Remarks:
- Doses / Concentrations:
0.79, 3.94, 15.02, 30.23 and 61.34 mg/kg bw/d
Basis:
other: average daily intake in females
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: not applicable
- Section schedule rationale (if not random): no data - Positive control:
- not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: mortality, any clinical signs
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: weekly
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to scheduled sacrifice
- Anaesthetic used for blood collection: Yes, ether
- Animals fasted: Yes
- How many animals: all
- Parameters examined: erythrocyte count, hemoglobin concentration, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count, differential leukocytes counts
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to scheduled sacrifice
- Animals fasted: Yes
- How many animals: all
- Parameters examined: alkaline phosphatase, total protein, albumin, blood urea nitrogen, creatinine
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER:
Females: estrus cycle: for 12 consecutive days prior to the scheduled sacrifice, samples of vaginal fluid were taken and stained. The relative leukocytes, nucleated epithelial cells and large squamous epithelial cells were determined and used to determine estrus cycle stage.
Males: sperm motility: the left testis and left epididymis were isolated and weighed. The cauda epididymis was then removed and weighed. Sperm effluxing from the cauda epididymus was analysed. - Sacrifice and pathology:
- A complete necropsy was performed on all animals.
Organ weights: liver, kidneys, testes, ovaries, heart, spleen
Microscopic examination: liver, kidneys, testes, ovaries, spleen, brain, clitoral gland, esophagus, eyes, femur with marrow, gallbladder, harderian glands, heart and aorta, small and large intestine, lungs and mainstem bronchi, mandibular and mesenteric lymph nodes, mammary gland with adjacent skin, muscle, nasal cavity and nasal turbinate, pancreas, parathyroid glands, pituitary gland, preputial glands, prostate, salivary glands, seminal vesicle, skin, spinal cord and sciatic nerve, stomach, epididymis, thymus, thyroid gland, trachea, urinary bladder, uterus and vagina. - Other examinations:
- Not applicable.
- Statistics:
- Variance in the data was checked for homogeneity using Bartlett's procedure. If homogeneous the data were assessed by one-way analysis of variance. If not, the Kruskal-Wallis test was applied. When statistically significant differences were indicated, a Dunnett's multiple test was used to compare the control and treatment groups. Data comparisons were considered significant if P<0.05.
For histopathological data analysis, the incidences were compared using a Fischer's exact probability test. A P<0.05 was considered significant.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No mortality or deterioration in the general conditions
BODY WEIGHT AND WEIGHT GAIN
Body weights were significantly suppressed (p<0.05) in the 400 ppm groups from week 12 in males and week 8 in females. Final body weights were significantly decreased at 400 ppm in both males (92.7%, p<0.05) and females (85.7%, p<0.01), and a decrease of the final body weights (but not statistically significant) was also oberserved in females at 100 ppm (95.9%) and 200 ppm (96.9%).
The body weight suppression can be explained by the sweetish taste of the test substance.
HAEMATOLOGY
No definite dose-related changes observed. There was a slight decrease (p<0.05) in MCV observed in 400 ppm males and in females given 100 and 200 ppm. Furthermore, a minimal increase in the MCHC was observed in the males given 100 and 400 ppm and in the 25 ppm females, but there was no corresponding decrease in the erythrocyte counts. The leukocyte, lymphocyte and monocyte counts were higher in 100 ppm males.
The changes are mainly within the limits of the normal biological ranges and not accompanied by other toxicological or histopathological findings.
ORGAN WEIGHTS
In the 400 ppm males, a decrease in the absolute liver weights was observed (92.2%, p<0.05) and an increase in relative kidney weights in males given 200 ppm (112.3%, p<0.01) and 400 ppm (115.1%, p<0.01).
In the 400 ppm females, an increase in the relative liver weights was observed (116.1%, p<0.05) and an increase in relative kidney weights in females given 200 ppm (118.3%, p<0.05) and 400 ppm (122.6%; p<0.01).
Liver weights changes are not considered toxicologically relevant as the changes are not consistent and in the absence of histopathological changes.
Kidney weight changes, although no significant histopathological changes occurred, are thought to be toxicologically relevant. The nephrotoxic mechanisms are thought to be due to the inhibition of glycolysis by metabolites associated with beta-chlorolactate pathway.
HISTOPATHOLOGY: NON-NEOPLASTIC
In the testes, there was an increase in the incidence and severity of degeneration of the germinal epithelium in males given 200 ppm (4 minimal , 1 mild) and 400 ppm (4 minimal, 4 mild). Microgranulomas in the liver, interstitial nephritis, basophilic tubules and mineralization in the kidneys were detected as spontaneously occurring lesions in the males, so not related to the test substance treatment.
In females, microgranulomas in the liver, interstitial nephritis, basophilic tubules, hyaline cast, and cystic tubules in the kidneys, and pigmentation and cystic dilatation in the ovaries were also observed. Other lesions were also detected sporadically but there were no significant changes in the incidence between the control and treatment groups.
OTHER FINDINGS
The percentage of motile sperm in the 400 ppm males was significantly lower (60.2%) than those of the controls (73%).
The length of the estrus cycle in the 400 ppm females was significantly longer (6.30 days) than those of the controls (4.90 days), because the 400 ppm females spent more time in diestrus (36.5% of the cycle) than the control females (30.6% of the cycle). There were however no treatment-related histopathological changes in the female reproductive organs. Luteolytic and antiestrogenic effects may have influenced the totalestrus cycle length.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 100 ppm
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Average daily test substance intake at 5, 25, 100, 200 and 400 ppm in the drinking water:
Males: 0.94, 4.59, 18.05, 36.97 and 76.79 mg/kg bw/day, respectively
Females: 0.79, 3.94, 15.02, 30.23 and 61.34 mg/kg bw/day, respectively
Applicant's summary and conclusion
- Conclusions:
- A 13-week study in B6C3F1 mice showed that the test substance suppressed the body weight gains in the 400 ppm group and increased the relative kidney weights in the 200 and 400 ppm groups in both males and females. The nephrotoxic effects are thought to be due to the inhibition of glycolysis by metabolites associated with beta-chlorolactate pathway. In addition, decreased sperm motility and degeneration of the germinal epithelium was seen in male mice, which may be caused by alkylation of spermatozoa cysteine and by metabolites which have an inhibitory activity on enzymes in the spermatozoa glycolysis. In females, a delayed total estrus cycle was observed, which may be caused by luteolytic and antiestrogenic effects.
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