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EC number: 202-461-5 | CAS number: 95-87-4
- 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:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 26 July 2004 - 17 Sept 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2,3-xylenol
- EC Number:
- 208-395-3
- EC Name:
- 2,3-xylenol
- Cas Number:
- 526-75-0
- Molecular formula:
- C8H10O
- IUPAC Name:
- 2,3-dimethylphenol
- Reference substance name:
- 2,4-xylenol
- EC Number:
- 203-321-6
- EC Name:
- 2,4-xylenol
- Cas Number:
- 105-67-9
- Molecular formula:
- C8H10O
- IUPAC Name:
- 2,4-dimethylphenol
- Reference substance name:
- 2,5-xylenol
- EC Number:
- 202-461-5
- EC Name:
- 2,5-xylenol
- Cas Number:
- 95-87-4
- Molecular formula:
- C8H10O
- IUPAC Name:
- 2,5-dimethylphenol
- Reference substance name:
- 2,6-xylenol
- EC Number:
- 209-400-1
- EC Name:
- 2,6-xylenol
- Cas Number:
- 576-26-1
- Molecular formula:
- C8H10O
- IUPAC Name:
- 2,6-dimethylphenol
- Reference substance name:
- 3,4-xylenol
- EC Number:
- 202-439-5
- EC Name:
- 3,4-xylenol
- Cas Number:
- 95-65-8
- Molecular formula:
- C8H10O
- IUPAC Name:
- 3,4-dimethylphenol
- Reference substance name:
- 3,5-xylenol
- EC Number:
- 203-606-5
- EC Name:
- 3,5-xylenol
- Cas Number:
- 108-68-9
- Molecular formula:
- C8H10O
- IUPAC Name:
- 3,5-dimethylphenol
Constituent 1
Constituent 2
Constituent 3
Constituent 4
Constituent 5
Constituent 6
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Test animals:
Age: 9 weeks (males and females)
Weight at dosing:333 - 365 g males; 205 - 237 g females
Source: Charles River Laboratory, Raleigh, North Carolina, USA
Acclimatisation: 5 days
Diet:Chow (#5002), ad libitum
Water: Tap water ,ad libitum
Housing: F0 generation rats were individually housed except during the cohabitation and postpartum periods. During cohabitation, each pair of rats were housed in the male rat's cage. Each dam and delivered litter was housed in a common nesting box during the postpartum period.
Environmental conditions:
Temperature: 18 - 26°C
Humidity: 30 - 70%
Photoperiod: Alternating 12-hour light/dark cycles
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on mating procedure:
- Male and female rats were pair 1:1 and cohabited for a maximum of 14 days. Female rats with spermatozoa observed in a smear of the vaginal contents and/or a copulatory plug in situ were considered to at GD 0 and then individually housed.
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- Minimum of 28 days (14 days of dosing prior to cohabitation).
- Frequency of treatment:
- Once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 30 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 245 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10 male and 10 females/group
Examinations
- Parental animals: Observations and examinations:
- Observations:
Observed twice daily for mortality and morbidity for all F0 animals. Clinical signs of toxicity were performed weekly. Functional observational battery evaluations were performed once on 5 male and 5 female F0 generation animals.
Body weight:
Recorded weekly.
Food consumption and compound intake:
Recorded every other day.
Haematology & clinical chemistry:
Collected from 5 male and 5 female F0 generation animals at necropsy. Blood samples were collected from the vena cava. The following haematology and clinical chemistry parameters were measured:
Haematology: total leukocyte count, differential leukocyte count (neutrophil, lymphocyte, monocyte, eosinophil, basophil, large unstained cell); RBC indices (mean corpuscular volume, mean corpuscular haemogloblin, mean corpuscular haemoglobin concentration), platelet count, prothombin time and activated partial thromboplastin time.
Clinical chemistry: blood urea nitrogen, alanine aminotransferase activity, aspartate transaminase activity, alkaline phosphatase, glucose, cholesterol, calcium, chloride, phosphorous, potassium, sodium, total protein, albumin, globulin, albumin/globulin ratio, total bilirubin, creatinine, triglycerides. - Litter observations:
- Observations:
Observed twice daily for mortality and morbidity for all F1 generation animals. - Postmortem examinations (parental animals):
- Sacrifice and pathology:
Gross pathological examination was performed on 5 male and 5 females/group of the F0 generation. An initial examination of external surfaces and all orifices, as well as the cranial, thoracic and abdominal cavities, including contents. The epidodymides, seminal vesicles with coagulating gland and prostate were retained.
Dams with no suriving pups were sacrificed after the last pup was found dead, missing or presumed cannibalised. A gross necropsy of the thoracic, abdominal and pelvic viscera was performed.
Organ weights:
The following organs were weighed from 5 male and 5 females/group of the F0 generation at necropsy:
liver, spleen, kidneys, brain, adrenals, heart, thymus. ovaries, testes, uterus (with cervix) and epidiymides. - Postmortem examinations (offspring):
- F1 generation pups that died before the initial examination of the litter for pup viability were evaluated for vital status at birth. The lungs were removed and immersed in water. Pups with lungs that sank were considered stillborn; pups with lungs that floated were considered liveborn and to have died shortly after birth. Pups with gross lesions found on days 2 to 4 postpartum were preserved for possible future evaluation. On day 5 postpartum, pups were sacrificed and examined for gross lesions. Necropsy included a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross sectioned brain.
- Statistics:
- Statistical analysis was limited to body weights and reproductive endpoints. Dunnett's test was used.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Food efficiency:
- not specified
Details on results (P0)
Relative weights of the kidney, liver and ovaries were observed to be increased in the 245 mg/kg/day treatment group,
Decreased mating and fertility indices were reported at the highest dose level (245 mg/kg bw) in the combined repeated dose toxicity and reproduction/developmental toxicity screening test. The number of female rats that mated was reduced from 100% in the control group (10/10) to 80% at 245 mg/kg bw (8/10) but the difference was not significantly different. The historical control value was reported as 97.6% over the period 1992-2002 but as no range was given this figure was of limited value. Following a request to Argus addition historical control data were provided on 19 April 2010. The information provided showed fertility data for individual years from 1992 to 1997 giving the range as well as the mean values and these are shown in Table 1.
It is clear from the historical control data that fertility in the mixed xylenols study was within the historical control range in several years during the period from 1992-1997 which corresponds to the time when the mixed xylenols study was conducted.
As the reduced fertility at 245 mg/kg bw was not statistically significant and was within the historical control range, this effect is considered not to be related to treatment and the NOAEL for reproductive effects in this study should be ≥ 245 mg/kg bw.
Effect levels (P0)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- general toxicity
- Effect level:
- ca. 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Due to clinical observations (urine-stained fur, increased kidney, liver and ovarian relative weight).
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- Reproductive
- Effect level:
- >= 245 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Whilst a reduced mating frequency was observed, this was within the laboratory's historical control range, therefore not considered biologically relevant.
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: F1 generation
Details on results (F1)
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 245 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed up to highest dose
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Any other information on results incl. tables
Table 1: Fertility index for studies conducted in Crl:CD(SD) Rats
Year |
Average |
Minimum |
Maximum |
No of studies |
1992 |
94.1 |
80.0 |
100.0 |
4 |
1993 |
89.5 |
80.0 |
100.0 |
9 |
1994 |
90.5 |
66.7 |
100.0 |
17 |
1995 |
93.8 |
89.7 |
100.0 |
5 |
1996 |
93.1 |
84.0 |
100.0 |
13 |
1997 |
91.7 |
71.4 |
100.0 |
23 |
1992 - 1997 |
91.7 |
66.7 |
100.0 |
71 |
Applicant's summary and conclusion
- Conclusions:
- The test substance mixed xylenol isomers was administered to rats by oral gavage at 0, 30, 100 and 245 mg/kg/day. The general toxicological No Observable Adverse Effect Level was shown to be 100 mg/kg bw/day.
The SD determined that the reproductive NOAEL was found to be 245 mg/kg bw/day due to reduced mating at 245 mg/kg/day, however following request of the historical control data from the laboratory, the reduction in mating frequency to 80% was within the laboratory's historical vehicle control data for this period.
Therefore the reproductive NOAEL is considered to be in excess of 245 mg/kg bw/day.
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