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EC number: 205-109-9 | CAS number: 133-53-9
- 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:
- reproductive toxicity, other
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1991
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 83-4 (Reproduction and Fertility Effects)
- Version / remarks:
- GUIDELINE REFERENCE NO. 83-3
- Deviations:
- not specified
- GLP compliance:
- yes
- Justification for study design:
- This study was performed to detect and evaluate the potential
embryo toxic or teratogenic effects of the test article, 4 chloro 3, 5 xylenol
(PCMX.), when administered orally to pregnant rats during the period of major
organogenesis.
This report details experimental procedures and results of a teratology
study in rats treated with 4 chloro 3,5 xylenol (PCMX). This study was
performed to detect and evaluate the potential embryotoxic or teratogenic
effects of the test article when administered orally to pregnant rats during
the period of organogenesis. The Sprague-Dawley rat was selected as the
experimental model since it is recommended by the Environmental ProtectiQn
Agency (EPA) as a suitable species for teratology studies.
Test material
- Reference substance name:
- 4-chloro-3,5-xylenol
- EC Number:
- 201-793-8
- EC Name:
- 4-chloro-3,5-xylenol
- Cas Number:
- 88-04-0
- Molecular formula:
- C8H9ClO
- IUPAC Name:
- Phenol, 4-chloro-3,5-dimethyl-
- Test material form:
- solid: crystalline
- Details on test material:
- Sponsor's identification
Description
Batch number
Date received
Storage conditions
PCMX
cream coloured, crystalline solid
285/13847
27 September 2001
room temperature, in the dark
Constituent 1
- Specific details on test material used for the study:
- Test and Control Articles
l. Test Article
The test article was received at SLS and identified as follows:
Assigned
Sponsor's ID SLS ID
4 chloro 3,5 590.002.3227
xylenol (PCMX)
USP Grade
Lot No. Wl43-l
Physical
Description
Off-White
Crystalline
Powder
Receipt
Date
September 12, 1990
A reserve 5 g sample of the test article was taken and stored at
SLS. The reserve sample and bulk compound were stored at room temperature.
The Sponsor is responsible for any necessary evaluations related to chemical
identification, purity, strength and stability of the test article.
2. Test Control (Vehicle) Article
The vehicle control article for this study was corn oil. The corn
oil was supplied by Best Foods, Englewood Cliffs, NJ, as follows:
Assigned Receipt
Control Article Lot No. SLS ID Date
Mazola• Corn Oil JUL1691A V90.022 November 5, 1990
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- One hundred twenty-eight Sprague-Dawley Crl:CD~BR VAF/Plus~ rats
were received at SLS on December 27, 1990 from Charles River Laboratories,
Inc., Portage, MI, for use in this study. At the time ~f receipt, each rat
was identified with a metal ear tag displaying an unique number. ~nirnals
were housed individually during acclimation and while on study (except
during cohabitation for mating) in suspended stainless steel cages. - Sex:
- female
- Details on test animals or test system and environmental conditions:
- At the conclusion of acclimation, the animals were weighed and
examined. Females determined to be suitable test subjects based on age:
healthy appearance, and body weight, were cohabitated with proven resident
Sprague-Dawley Crl: CD®BR VAF /Plus® male rats. At the initiation of
breeding, all females were approximately 90 days of age with body weights
ranging from 222 to 283 g. Evidence of mating was determined by the
presence of a copulatory plug in the vagina or a sperm positive vaginal
smear. The day evidence of copulation was confirmed was designated as day
0 of gestation. At that time, the female rats were assigned consecutively,
in a block design, to study groups. Gestation day 0 body weights ranged
from 220-291 g.
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- corn oil
- Details on exposure:
- Dosage solutions were administered orally by gavage as a single dose
daily from gestation day 6 through gestation day 15. Oral administration
of the test article was selected since this is a potential route of human
exposure. Individual doses were adjusted based on the most recent body
weight data. - Details on mating procedure:
- At the conclusion of acclimation, the animals were weighed and
examined. Females determined to be suitable test subjects based on age:
healthy appearance, and body weight, were cohabitated with proven resident
Sprague-Dawley Crl: CD®BR VAF /Plus® male rats. At the initiation of
breeding, all females were approximately 90 days of age with body weights
ranging from 222 to 283 g. Evidence of mating was determined by the
presence of a copulatory plug in the vagina or a sperm positive vaginal
smear. The day evidence of copulation was confirmed was designated as day
0 of gestation. At that time, the female rats were assigned consecutively,
in a block design, to study groups. Gestation day 0 body weights ranged
from 220-291 g. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Prestudy analytical chemistry evaluations indicated that 4 chloro 3,5
xylenol (PCMX) was homogeneous and stable in corn oil for up to eight days
when stored at room temperature. Analysis of dosage preparations resulted
in average test article recoveries ranging from 9S.S to 103.0% indicating
that the preparations were accurately prepared. - Duration of treatment / exposure:
- The in-life phase of the study was initiated with the assignment of mated
female rats to study groups on January 8, 1991 (gestation day 0) and
concluded with terminal sacrifice on February 4, 1991 (gestation day 20). - Frequency of treatment:
- Dosage solutions were administered orally by gavage as a single dose
daily from gestation day 6 through gestation day 15. Oral administration
of the test article was selected since this is a potential route of human
exposure. Individual doses were adjusted based on the most recent body
weight data. - Details on study schedule:
- At the initiation of
breeding, all females were approximately 90 days of age with body weights
ranging from 222 to 283 g.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Remarks:
- Dosage solutions were administered orally by gavage as a single dose daily from gestation day 6 through gestation day 15. Oral administration of the test article was selected since this is a potential route of human exposure. Individual doses were adjusted based on the most recent body weight data.
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Remarks:
- Dosage solutions were administered orally by gavage as a single dose daily from gestation day 6 through gestation day 15. Oral administration of the test article was selected since this is a potential route of human exposure. Individual doses were adjusted based on the most recent body weight data.
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Remarks:
- Dosage solutions were administered orally by gavage as a single dose daily from gestation day 6 through gestation day 15. Oral administration of the test article was selected since this is a potential route of human exposure. Individual doses were adjusted based on the most recent body weight data.
- No. of animals per sex per dose:
- 25f
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- This report details experimental procedures and results of a teratology
study in rats treated with 4 chloro 3,5 xylenol (PCMX). This study was
performed to detect and evaluate the potential embryotoxic or teratogenic
effects of the test article when administered orally to pregnant rats during
the period of organogenesis. The Sprague-Dawley rat was selected as the
experimental model since it is recommended by the Environmental ProtectiQn
Agency (EPA) as a suitable species for teratology studies. - Positive control:
- n/a
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical signs were generally unremarkable at the 100 mg/kg/day level,
although a slightly higher incidence of mucoid stools, soft stools and few
feces was observed. Similar signs of gastrointestinal disturbance occurred
at a higher incidence and in a dose-related pattern at the SOO and 1000
mg/kg/day levels. Additional signs of toxicity at the 1000 mg/kg/day level
included decreased activity, shallow breathing, cool to the touch, no feces,
diarrhea, and dark material around the nose and/or mouth. These more severe
clinical signs occurred primarily in females that subsequently died. In
contrast to these changes, clinical observations in control females were
limited to occasional signs of gastrointestinal disturbance which were
attributable to the vehicle, corn oil. - Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Additional signs of toxicity at the 1000 mg/kg/day level
included decreased activity, shallow breathing, cool to the touch, no feces,
diarrhea, and dark material around the nose and/or mouth. These more severe
clinical signs occurred primarily in females that subsequently died. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean maternal body weight gain at the 500 mg/kg/day level was
statistically lower than the control group during gestation days 12-16. At
the 1000 mg/kg/day level, statistically significant body weight loss
occurred during gestation days 6-9 and statistically reduced weight gain was
noted during gestation days 12-16, 6-16 and 0-20. In addition, net maternal
body weight gain was statistically reduced at the 1000 mg/kg/day group when
compared to the control group. No adverse body weight effects were noted
at the 100 mg/kg/day level. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption calculated as grams/animal/day was statistically
reduced at the 500 mg/kg/day level during gestation days 6-9, 12-16 and 6-
16. At the 1000 mg/kg/day level, food consumption was statistically reduced
during gestation days 6-9, 9-12, 12-16, 6-16 and 0-20. Food consumption at
the 100 mg/kg/day level was similar to the control group throughout the
study. - Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
Effect levels (P0)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- clinical signs
- mortality
- reproductive performance
- Remarks on result:
- other: not toxic
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- 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
- Other effects:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- other: not examned
- Generation:
- F1
- Effect level:
- 0 other:
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other:
- Remarks on result:
- not measured/tested
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
- Lowest effective dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Treatment related:
- yes
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Any other information on results incl. tables
Maternal toxicity was produced by 4 chloro 3,5 xylenol (PCMX) at the
500 and 1000 mg/kg/day levels. At the 1000 mg/kg/day level, treatrnentrelated
effects consisted of mortality in 5 of 25 females, adverse clinical
signs, and decreased weight gain and food consumption. Similar but less
pronounced effects were observed at the 500 mg/kg/day level where no
maternal mortality occurred. At the 100 mg/kg/day level, there were no body
weight or food consumption effects. An apparent slight increase in the
occurrence of clinical signs, which were similar to controls, was noted at
the 100 mg/kg/day level. It was not clear whether these signs were
influenced by 4 chloro 3,5 xylenol (PCMX) or due to the corn oil vehicle.
Evaluation of cesarean section parameters revealed no differences among the
groups concerning the mean number of corpora lutea, implantation sites,
viable fetuses, fetal sex ratios, gravid uterus weights and fetal body
weights. A marginal increase in mean post-implantation loss was observed
at the 1000 mg/kg/day level where excessive maternal mortality occurred.
This difference was not statistically significant and remained within the
SLS historical control range. · No treatment-related malformations or
developmental variations were noted in the study.
Applicant's summary and conclusion
- Conclusions:
- Based on the results of this study, a dosage level of 100 mg/kg/day was
considered a no-adverse-effect level for maternal toxicity. A dosage level
of 1000 mg/kg/day was considered a no-observed-effect level for fetal
toxicity and teratogenicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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