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EC number: 203-166-4 | CAS number: 104-01-8
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
The reproductive toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with respect to the descriptor log Kow; to evaluate the toxic effects of administration of 4-methoxyphenylacetic acid (CAS No. 104-01-8) in rat by the oral route. No significant effects was observed. Therefore, the no observed adverse effect level (NOAEL) of 4-methoxyphenylacetic acid for reproductive toxicity study was considered to be 1480.5 mg/kg bw/day.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Prediction is done using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Prediction is done using OECD QSAR Toolbox version 3.3 with respect to the descriptor log Kow.
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material (as cited in study report):(4-methoxyphenyl)acetic acid
- Molecular formula:C9H10O3
- Molecular weight:166.175 g/mole
- Substance type:Organic - Species:
- rat
- Strain:
- Fischer 344
- Sex:
- female
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Duration of the test: approx. 54 days
- Frequency of treatment:
- Daily
- Dose / conc.:
- 1 480.5 mg/kg bw/day
- Control animals:
- not specified
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. Mortality was observed.
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- 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: yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data - Postmortem examinations (parental animals):
- GROSS NECROPSY: Yes
HISTOPATHOLOGY / ORGAN WEIGHTS: Yes - Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- 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 specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 1 480.5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food consumption and compound intake
- gross pathology
- histopathology: non-neoplastic
- other: No effects observed.
- Critical effects observed:
- no
- Remarks on result:
- not measured/tested
- Critical effects observed:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Remarks on result:
- not measured/tested
- Critical effects observed:
- not specified
- Remarks on result:
- not measured/tested
- Critical effects observed:
- not specified
- Reproductive effects observed:
- no
- Conclusions:
- The reproductive toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with respect to the descriptor log Kow; to evaluate the toxic effects of administration of 4-methoxyphenylacetic acid (CAS No. 104-01-8) in rat by the oral route. No significant effects was observed. Therefore, the no observed adverse effect level (NOAEL) of 4-methoxyphenylacetic acid for reproductive toxicity study was considered to be 1480.5 mg/kg bw/day.
- Executive summary:
The reproductive toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with respect to the descriptor log Kow; to evaluate the toxic effects of administration of 4-methoxyphenylacetic acid (CAS No. 104-01-8) in rat by the oral route. No significant effects was observed. Therefore, the no observed adverse effect level (NOAEL) of 4-methoxyphenylacetic acid for reproductive toxicity study was considered to be 1480.5 mg/kg bw/day.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
(((((((((((("a"
or "b" or "c" or "d" or "e" )
and ("f"
and (
not "g")
)
)
and ("h"
and (
not "i")
)
)
and "j" )
and ("k"
and (
not "l")
)
)
and "m" )
and "n" )
and "o" )
and ("p"
and (
not "q")
)
)
and ("r"
and (
not "s")
)
)
and ("t"
and (
not "u")
)
)
and ("v"
and "w" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Class 1 (narcosis or baseline
toxicity) by Acute aquatic toxicity classification by Verhaar (Modified)
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Aryl OR Carboxylic acid OR Ether
by Organic Functional groups ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Aryl OR Carboxylic acid OR Ether
OR Overlapping groups by Organic Functional groups (nested) ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Acid, aliphatic attach [-COOH]
OR Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic
Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR
Carbonyl, aliphatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or
oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic
attach [-O-] by Organic functional groups (US EPA) ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Alkylarylether OR Aromatic
compound OR Carbonic acid derivative OR Carboxylic acid OR Carboxylic
acid derivative OR Ether by Organic functional groups, Norbert Haider
(checkmol) ONLY
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Thioacylation via
nucleophilic addition after cysteine-mediated thioketene formation OR
AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated
thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR
Michael addition OR Michael addition >> Quinone type compounds OR
Michael addition >> Quinone type compounds >> Quinone methides OR
Radical OR Radical >> Radical mechanism by ROS formation (indirect) or
direct radical attack on DNA OR Radical >> Radical mechanism by ROS
formation (indirect) or direct radical attack on DNA >> Organic Peroxy
Compounds OR Radical >> ROS formation after GSH depletion OR Radical >>
ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >>
Alkylation after metabolically formed carbenium ion species OR SN1 >>
Alkylation after metabolically formed carbenium ion species >>
Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation,
direct acting epoxides and related after P450-mediated metabolic
activation OR SN2 >> Alkylation, direct acting epoxides and related
after P450-mediated metabolic activation >> Haloalkenes with
Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides
and related after P450-mediated metabolic activation >> Polycyclic
Aromatic Hydrocarbon Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA
alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with
aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >>
Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion
formation (enzymatic) >> Vicinal Dihaloalkanes by DNA binding by OASIS
v.1.3
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OECD
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Michael addition OR Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals OR Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised
Alkenes-Michael addition OR Michael addition >> Polarised
Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael
addition >> Polarised Alkenes-Michael addition >> Alpha, beta-
unsaturated esters OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >>
Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Low (Class I) by Toxic hazard
classification by Cramer (original) ONLY
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as No alert found by in vitro
mutagenicity (Ames test) alerts by ISS
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as alpha,beta-unsaturated aliphatic
alkoxy group by in vitro mutagenicity (Ames test) alerts by ISS
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "n"
Similarity
boundary:Target:
COc1ccc(CC(O)=O)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "o"
Similarity
boundary:Target:
COc1ccc(CC(O)=O)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "p"
Referential
boundary: The
target chemical should be classified as Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Aliphatic/Alicyclic hydrocarbons
(Alpha 2u-globulin nephropathy) Rank C OR Tamoxifen (Hepatotoxicity)
Alert by Repeated dose (HESS)
Domain
logical expression index: "r"
Referential
boundary: The
target chemical should be classified as Inclusion rules not met by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Ethylenglycolethers by Skin
irritation/corrosion Inclusion rules by BfR
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as No alert found by Respiratory
sensitisation
Domain
logical expression index: "u"
Referential
boundary: The
target chemical should be classified as Pro-SN2 OR Pro-SN2 >> Pro-ring
opening SN2 OR Pro-SN2 >> Pro-ring opening SN2 >> Vinyl benzenes by
Respiratory sensitisation
Domain
logical expression index: "v"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.268
Domain
logical expression index: "w"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 2.13
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 480.5 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- The data is Klimicsh 2 and from OECD QSAR toolbox version 3.3 (2017).
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Toxicity to reproduction
Various studies including predicted results from the validated model and experimental study has been investigated for reproductive toxicity to a greater or lesser extent for the test chemical 4-methoxyph enylacetic acid (CAS No. 104-01-8) along with its structurally similar read across substance Hexan-1-ol (CAS No. 111-27-3). The predicted data for target chemical 4-methoxyphenylacetic acid (CAS No. 104-01-8) has been compared with experimental study for target and read across substance. The studies are summarized as below:
The reproductive toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with respect to the descriptor log Kow; to evaluate the toxic effects of administration of 4-methoxyphenylacetic acid (CAS No. 104-01-8) in rat by the oral route. No significant effects was observed. Therefore, the no observed adverse effect level (NOAEL) of 4-methoxyphenylacetic acid for reproductive toxicity study was considered to be 1480.5 mg/kg bw/day.
In addition, a reproductive toxicity study was conducted by National Cancer Institute (1968), B6C3F1 and B6AKF1 female mice were treated with 4-Methoxyphenylacetic acid in the concentration of 0 and 215 mg/kg bw/day in 0.5% gelatin for 7 to 28 day and after dose is administered through diet at 560 ppm for 18 months. Body weight gain was observed with the increase in duration of treatment. No gross pathological changes were observed in treated female mice. In addition, No fibroadenoma and carcinoma mammary gland were observed in treated female mice as compared to control. Therefore, NOAEL was considered to be > 215 mg/kg bw when B6C3F1 and B6AKF1 female mice by using 4-Methoxyphenyl-Acetic Acid for 18 months.
Moreover, in an oral gavage reproductive screening study by Bingham, E. et al (Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:440), CD rats were dosed with 0, 200, and 1000 mg/kg of 1-hexanol (in corn oil) on days 6 to 15 of gestation. Maternal toxicity occurred at the 1000 mg/kg level as indicated by clinical signs and decreased body weight gain. No embryotoxic or teratogenic effects were observed at either dose level. Thus, under the condition of this study, the no observed adverse effect level (NOAEL) for maternal toxicity study was considered to be 200.0 mg/kg whereas NOAEL for teratogenicity study was considered to be 1000.0 mg/kg.
Based on the above mentioned studies for target substance and to its read across substance by applying weight of evidence approach and also according to CLP criteria, it can be concluded that no adverse effects on sexual function and fertility was observed, therefore the substance 4-methoxyphenylacetic acid (CAS No.- 104-01-8) cannot be classified as reproductive toxicant.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the available data for the assessment of reproductive toxicity and following CLP Regulation EC No. 1272/2008 no classification of 4-methoxyphenyl acetic acid (CAS No.- 104-01-8) as reproductive toxicant is warranted.
Additional information
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