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EC number: 213-361-6 | CAS number: 939-48-0
- 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
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- Remarks:
- other: 4 generation study
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 1960-2001
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- This is a summary of studies reviewed by the expert groups of the OECD High Production Volume (HPV) Chemicals Programme (SIDS Review Committee), JECFA and the U.S. Cosmetic Ingredient Review Expert Panel (CIR), which accepted the data as scientifically valid.. Documentation details may be missing as the studies were carried out some years ago and did not always fulfill present-day guidelines.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD guideline 416
- GLP compliance:
- not specified
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Route of administration:
- oral: feed
- Details on exposure:
- 0.5 or 1 % in diet (approx. 375 or 750 mg/kg/day)
- Analytical verification of doses or concentrations:
- not specified
- Remarks:
- Doses / Concentrations:
375 and 750 mg/kg/day
Basis:
nominal in diet
20 rats were fed contineuously with 375 or 750 mg/kg bw - No. of animals per sex per dose:
- 20 Rats per sex/ group
- Control animals:
- yes, plain diet
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- 750
- Effect level:
- >= 750 - <= 800 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 750 - ca. 800 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- >= 750 - 800 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Reproductive effects observed:
- not specified
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- Benzoic acid was administered in the diet to rats for 4 consecutive generations. In all 4 generations, no effects on fertility and lactation were found. The substance is not a reproductive toxicant. This study is informative for evaluation of the toxicity of members of the Alkyl Benzoates category, and is adequate for filling the data requirement for the registration of this substance. It is valid for hazard classification and risk assessment.
Reference
In all 4 generations no influence on growth (weight, weight gain and food efficiency and organ weights was found. In all 4 generations no effects on fertility (Forzplanzung) and lactation (Aufzugtder Jungen) was found.In addition aso-called "Alters Paarung" after 48 weeks gave no influence on start of menopause.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- adequate
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
(discussed below).
Short description of key information:
No reproductive toxicity was observed in a 4-generation chronic study on benzoic acid.
Justification for selection of Effect on fertility via oral route:
experimental data
Effects on developmental toxicity
Description of key information
No developmental toxicity was observed in a 4-generation chronic study on benzoic acid.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 1960-2000
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data reviewed by an expert panel of the OECD HPV Programme and considered "valid with restrictions." "Meets generally accepted scientific standards, well documented and acceptable for assessment. Flagged as a critical study for SIDS endpoint."
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD 416 Two-Generation Reproduction Toxicity
- Deviations:
- yes
- Remarks:
- Two doses (plus control) only, extends to 4 generations
- GLP compliance:
- not specified
- Limit test:
- yes
- Species:
- rat
- Route of administration:
- oral: feed
- Details on exposure:
- First 8 weeks: paired feed technique; afterwards, ad libitum.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No details provided. The mean compound consumption was calculated according to Lehman AJ, Food Drug Official Q. Bull., 66 (1954).
- Duration of treatment / exposure:
- Generations 1 & 2: lifelong.
Generation 3: 16 weeks
Generation 4: until breeding. - Frequency of treatment:
- continuously in diet
- Duration of test:
- 4 generations (48 weeks)
- No. of animals per sex per dose:
- 20 per sex per dose group. Initial body weight: 40-50 g.
- Control animals:
- yes
- Details on study design:
- Group I was dosed with 375 mg/kg.
Group II was dosed with 750 mg/kg;
An additional control group was used. - Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation after 21 days 3rd generation
- Organs examined: Live fetuses were removed, examined for gross malformations, weighed, and prepared for histological examination. Skeletal examination was carried out under low magnification. - Fetal examinations:
- - External examinations: Yes:
- Head examinations: No data - Statistics:
- No abnormalities survivors rates as comparable to the control animals.
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
In all 4 generations, no influence on growth (weight, weight gain and food efficiency (measured by protein efficiency)) and organ weights was found. In all 4 generations, no effects on fertility and lactation were found. No remarkable histopathological findings were found in the 3rd generation animals. In the paper no information is given on the organs investigated, however the robustness of the total study, the reputation of the investigators, as well as the reputation of the Professor who did the histopathologic investigation, a high quality has to be assumed. In addition after 48 weeks, there was no influence on start of menopause. Feeding of 375 mg/kg bw/d led to prolongation of survival compared to controls.
NOAEL (Parental) > 750 mg/kg/day - Dose descriptor:
- NOAEL
- Effect level:
- >= 500 - 750 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 500 - 750 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
NOAEL (F1 Offspring) > 750 mg/kg/day
NOAEL (F2 Offspring) > 750 mg/kg/day - Dose descriptor:
- NOAEL
- Effect level:
- > 750 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No fetal effects observed.
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- In a 4-generation study (48 weeks) reproductive toxicity study of 0.5 and 1% benzoic acid in rats by the dietary route, there were no observed adverse effects in growth, body weight, organ weights, reproductive parameters or developmental effects. The Parental and offspring NOAELs were greater than 500-750 mg/kg bw/d. This study is informative for evaluation of the toxicity of members of the Alkyl Benzoates category, and is adequate for filling the data requirement for the registration of this substance. It is valid for hazard classification and risk assessment.
Reference
There are differing estimates of the dose as expressed in mg/kg bw/d, which range from 500 to 750. See discussion in Kieckebush and Lang, 1960, endpoint study record under Repeated Dose Toxicity.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- adquate
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
There are several reproductive toxicity studies of benzoic acid (Kieckebush and Lang, 1960, Kimmel et al., 1971) and sodium benzoate (Mortgareidge (U.S. FDA), 1972) which indicate that oral administration of these substances does not result in reproductive toxicity to rats. The studies have been evaluated as valid and supportive of benzoic acid and salts as food additives (JECFA, beginning in 1961; U.S. FDA). There was no maternal toxicity nor adverse reproductive outcomes among rats in 4 generations of dietary exposure to 1% benzoic acid (Kieckebush and Lang, 1960), equivalent to approximately 500-750 mg/kg bw/d. The maternal and offspring NOAELs are established 500 mg/kg bw/d, supported by the findings of Kimmel, et al, 1971 at 510 mg/kg bw/d, and Mortgareidge, 1972, at 175 mg/kg bw/d. The Scientific Committee on Food (SCF) in 2002 reviewed the available data and concluded that the data were adequate and that no additional reproductive/developmental toxicity studies on benzoic acid were indicated. Many expert toxicology groups have made the same conclusion.
Isopropyl benzoate is part of a category of chemicals, the Alkyl Benzoates, which utilize this data on benzoic acid and sodium benzoate for safety evaluation. The establishment of a benzoates category has been accepted by numerous expert toxicology groups, including the Joint Expert Committee for Food Additives (JECFA), the Scientific Committee on Food (SCF), the European Food Safety Organization (EFSA), the U.S. Food and Drug Administration (FDA), the World Health Organization (WHO), and the OECD High Production Volume Chemicals Programme (OECD HPV). The basis of the large category for all these organizations (EFSA now has a category of 41 substances qualifying as Benzyl Derivative flavours) is a common breakdown product, benzoic acid, which forms rapidly by acidic hydrolysis as well as due to the action of esterase enzymes. Genetic and reproductive toxicity studies are also negative. In addition to this category, the U.S. Cosmetic Ingredient Review (CIR) Expert Panel evaluated the safety of 17 alkyl benzoate esters as a category (2012) based on a common functional group (benzoic acid ester) which is metabolized to benzoic acid.
For the alcohol metabolite, isopropanol, reproductive and developmental toxicity was investigated in rats in several guideline studies (one- and two-generation reproductive toxicity protocols) and also in a developmental neurotoxicity study (Bates et al., 1994). There were no significant findings specific to reproduction, and no evidence of adverse effects in offspring at doses which were not toxic to the dams. The alcohol, likely via central nervous system depression, resulted in decreased mating indices (Beyer et al., 1993). High doses resulted in death, increased liver and kidney weights and liver pathology. The parental NOAEL in the two-generation study was 500 mg/kg bw/d, and for offspring, 1000 mg/kg bw/d. The parental NOAEL in the developmental neurotoxicity was 700 mg/kg bw/d, and for offspring, 1000 mg/kg bw/d.
The NOAEL of 500 mg/kg bw/d is adequate to address the endpoints of reproductive and developmental toxicity.
Justification for selection of Effect on developmental toxicity: via oral route:
experimental data
Justification for classification or non-classification
As no reproductive and developmental toxicity was observed with metabolites of isopropyl benzoate, the criteria for classification and labelling according to Regulation EC No. 1272/2008 are not met.
Additional information
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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