Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 943-438-6 | CAS number: 90063-59-5
- 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: inhalation
Administrative data
- Endpoint:
- repeated dose toxicity: inhalation, other
- Remarks:
- inhalation during developmental toxicity study (GD 6-15)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Developmental toxicity study comparable to guideline study (OECD Guideline 414) with sufficient documentation, well documented
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Reference
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1993
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: See remarks:
- Remarks:
- Although this investigation has only been published as an abstract, additional data on the test conditions are available from a valid developmental toxicity study (Gaworski et al., 1992) from the same working group. The results on maternal toxicity in the developmental toxicity study confirm the test results of the repeated dose inhalation toxicity study. Acceptable restrictions in documentation are: number of exposed animals not given, no details on test results given; study acceptable for derivation of a NOAEL for local and systemic effects based on weight of evidence approach
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- F344/N rats were expo 6 hrs/day for either 21 consecutive days at concentrations of 10 & 34 ppm, or 68 ppm, or for 13 weeks at concentrations of 1, 3, or 10 ppm. No mortalities occurred during the 21 day study. Investigated endpoints were mortality, body weight, organ weigths (13 week study only), signs of ocular, nasal and oral irritation, and histological examination of nose tissues, larynx, trachea and lungs. Reversibility was investigated after a 5-week recovery period.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- not specified
- Route of administration:
- other: exposure to vapours for low concentrations; exposure to vapour/aerosol mixtures to achieve higher concentrations
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: nitrogen
- Remarks on MMAD:
- MMAD / GSD: no data
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION (Information taken from Gaworski et al., 1992)
- Exposure apparatus: Rochester-type stainless steel inhalation chambers of 1 cubic meter volume
- Method of conditioning air: filtered through coarse particulate and HEPA filters and an activated carbon cartridge
- System of generating particulates/aerosols: aerolization of liquid citral with a DeVilbiss Model 41 nebulizer using nitrogen as a carrier gas to prevent degradation, which had been observed during nebulization in the presence of air
- Temperature, humidity, pressure in air chamber: no data
- Air flow rate: not data
- Air change rate: 15 +- 3 changes/hr
- Method of particle size determination: cascade impactor; MMAD 4.2 µm, geometric standard deviation 1.9; about 90% of the aerosol with aerodynamic diameter < 10 µm
- Treatment of exhaust air: no data
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography with flame ion detection
- Samples taken from breathing zone: not specified
VEHICLE
- Justification for use and choice of vehicle: to prevent degradation of citral
- Composition of vehicle: nitrogen - Analytical verification of doses or concentrations:
- yes
- Remarks:
- (Information taken from Gaworski et al., 1992)
- Details on analytical verification of doses or concentrations:
- Analysis of vapour and aerosol samples indicated that citral purity degraded less than 5% with nitrogen nebulization, with only a slight entrichment of the neral isomer (< 3%) in the vapour phase
Chamber vapour atmospheres sampled by cryogenic trapping. Sampling was performed at a flow rate of 400 mL/min for 25 min through two all-glass and teflon traps immersed in a dry-ice methanol bath. The tubes were rinsed with 10 mL of isopropanol containing n-octanol as internal standard. Analysis performed by gas chromatography and flame ion detection. - Duration of treatment / exposure:
- 21 days or 13 weeks
- Frequency of treatment:
- Daily for 21 days, 6 h/d
13 w, 5 d/w, 6 h/d
additional group with 5 week recovery period after the 13 week treatment - Dose / conc.:
- 10 ppm
- Remarks:
- 63 mg/m3
21 Days exposure - Dose / conc.:
- 34 ppm
- Remarks:
- 215 mg/m3
21 Days exposure - Dose / conc.:
- 68 ppm
- Remarks:
- 430 mg/m3
21 Days exposure - Dose / conc.:
- 1 ppm
- Remarks:
- 6 mg/m3, 13 week exposure
- Dose / conc.:
- 3 ppm
- Remarks:
- 19 mg/m3, 13 week exposure
- Dose / conc.:
- 10 ppm
- Remarks:
- 63 mg/m3, 13 week exposure
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice a day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice a day
BODY WEIGHT: Yes
- Time schedule for examinations: not specified
FOOD CONSUMPTION: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Key result
- Dose descriptor:
- NOAEC
- Remarks:
- subchronic inhalation
- Effect level:
- 34 ppm
- Based on:
- test mat.
- Sex:
- not specified
- Remarks on result:
- other: 215 mg/m3
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 68 ppm
- Based on:
- act. ingr.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- clinical signs
- Remarks on result:
- other: 430 mg/m3
- Critical effects observed:
- not specified
- Conclusions:
- Based on the results of the present study the NOAEC for Citral is set to 34 ppm or 215 mg/m3 based on evident local irritation and systemic effects, i.e. body weight changes, observed at 68 ppm or 430 mg/m3.
- Executive summary:
To evaluate the potential toxic effects of inhaled citral, F344/N rats were expo 6 hrs/day for either 21 consecutive days at concentrations of 10 & 34 ppm, or 68 ppm, or for 13 weeks at concentrations of 1, 3, or 10 ppm. No mortalities occurred during the 21 day study. Rats exposed to 68 ppm citral displayed signs of severe ocular, oral & nasal irritation and had significantly reduced body weight gains compared to controls. Treatment related lesions consisted of dose-related chronic-active inflammation, hyperplasia, squamous metaplasia & goblet cell atrophy of the nasal respiratory epithelium. Animals exposed to 68 ppm citral also developed changes indicative of irritation in the tracheas and lungs, as well as corneal inflammation & ulceration. Exposure to citral for 13 wk at concentrations up to 10 ppm did not produce mortality or treatment related signs of tox. Body weight gains, clinical pathology indices and organ weight were not adversely affected by exposure. Rats exposed to 10 ppm citral developed minimal hyperplasia and squamous metaplasia of the laryngeal epithelium; however, these changes were completely reversed during a 5-wk recovery period. No significant lesions were observed in the rats exposed to 1 or 3 ppm citral.
Table: Overview on findings in a subacute and a subchronic inhalation study
Exposure time |
Concen- tration (ppm) |
Mortality |
Body weight gain |
Organ weights |
Signs of irritation |
Histological findings |
|
Nasal respiratory epithelium |
Other |
||||||
21 d |
10a |
no |
No effect |
No data |
No effect |
Dose related increase of chronic active inflammation, hyperplasia, squamous metaplasia and goblet cell atrophyc |
No data |
34a |
no |
No effect |
No data |
No effect |
No data |
||
68b |
no |
Significant reduction |
No data |
Severe nasal, oral and ocular irritation; corneal inflammation and ulceration |
Signs of irritation in trachea and lungs |
||
13 w |
1a |
no |
No effect |
No effect |
No effect |
No effect |
No effect |
3a |
no |
No effect |
No effect |
No effect |
No effect |
No effect |
|
10a |
no |
No effect |
No effect |
No effect |
No effect |
Minimal hyperplasia and squamous metaplasia of the laryngeal epithelium |
|
13 w + 5 w recovery |
10 |
Effect in laryngeal epithelium fully reversible |
avapour concentration
bconcentration of vapour/aerosol mixture
cno information given from which concentration up effects have to be considered as significant and biologically relevant
Data source
Reference
- Reference Type:
- publication
- Title:
- Developmental toxicity evaluation of inhaled citral in Spraque-Dawley rats.
- Author:
- Gaworksi C.L., Vollmuth T.A., York R.G., Heck J.D., Aranyi C.
- Year:
- 1 992
- Bibliographic source:
- Fd Chem. Toxic. 30, 269-275
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD414
- Deviations:
- yes
- Remarks:
- Mortalities, clinical signs of intoxication, body weight gains and gross lesions were investigated as signs of maternal toxicity during a developmental toxicity study.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- (Z)-3,7-dimethylocta-2,6-dienal
- EC Number:
- 203-379-2
- EC Name:
- (Z)-3,7-dimethylocta-2,6-dienal
- Cas Number:
- 106-26-3
- Molecular formula:
- C10H16O
- IUPAC Name:
- (Z)-3,7-dimethylocta-2,6-dienal
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratory, Inc. (Raleigh, NC, USA)
- Age at study initiation: 9-11 w
- Weight at study initiation: females ca. 230 g
- Fasting period before study: no
- Housing: individually
- Diet: ad libitum during non-exposure periods
- Water: ad libitum during non-exposure periods
- Acclimation period: 2 w
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 1
- Humidity (%): 31 +- 8
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: nitrogen
- Remarks on MMAD:
- no data
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rochester-type stainless steel inhalation chambers of 1 cubic meter volume
- Method of conditioning air: filtered through coarse particulate and HEPA filters and an activated carbon cartridge
- System of generating particulates/aerosols: aerolization of liquid citral with a DeVilbiss Model 41 nebulizer using nitrogen as a carrier gas to prevent degradation, which had been observed during nebulization in the presence of air
- Temperature, humidity, pressure in air chamber: no data
- Air flow rate: not data
- Air change rate: 15 +- 3 changes/hr
- Method of particle size determination: cascade impactor; MMAD 4.2 µm, geometric standard deviation 1.9; about 90% of the aerosol with aerodynamic diameter < 10 µm
- Treatment of exhaust air: no data
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography with flame ion detection
- Samples taken from breathing zone: not specified
VEHICLE
- Justification for use and choice of vehicle: to prevent degradation of citral
- Composition of vehicle: nitrogen - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis of vapour and aerosol samples indicated that citral purity degraded less than 5% with nitrogen nebulization, with only a slight entrichment of the neral isomer (< 3%) in the vapour phase Chamber vapour atmospheres sampled by cryogenic trapping. Sampling was performed at a flow rate of 400 mL/min for 25 min through two all-glass and teflon traps immersed in a dry-ice methanol bath. The tubes were rinsed with 10 mL of isopropanol containing n-octanol as internal standard. Analysis performed by gas chromatography and flame ion detection.
- Duration of treatment / exposure:
- 6 h/d, gestation day 6-15
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 10 ppm
- Remarks:
- nominal conc. corresponding to 63 mg/m3 (=MW*ppm/24.1*1000); MW=152,2 g/mol
- Dose / conc.:
- 34 ppm
- Remarks:
- nominal conc. corresponding to 215 mg/m3 (=MW*ppm/24.1*1000); MW=152,2 g/mol
- Dose / conc.:
- 68 ppm
- Remarks:
- nominal conc. corresponding to 430 mg/m3 (=MW*ppm/24.1*1000); MW=152,2 g/mol
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: highest selected to produce maternally toxic effects
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 2 4, 6, 8 (exposure), 12, 16, 20 (post-exposure)
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
FOOD CONSUMPTION: No data
WATER CONSUMPTION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No data - Statistics:
- Maternal body weights and body-weight gains were analysed by a one-way analysis of variance (ANOVA), followed by a Dunnett's when applicable ( Steel and Torrie, 1960).
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Ocular opacity, difficulty in breathing during the exposure phase of the study indicating stress of severe respiratory tract irritation; normal breathing returned in most of affected animals by gestation day 20; other frequently observed clinical signs: nasal discharge, salivation, redness around eyes, discolored facial fur, scrubby hair coat
However, after completion of the exposure period recovery clinical signs of toxicity occurred. - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 68 ppm: moribund condition of 1/25 animals (killed on gestation day 17);
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 68 ppm:
- Body weight loss during exposure period from gestation day (GD) 6 to 15; after exposure period body weight gain was comparable to other groups;
- Overall mean body weight (GD 20) significantly decreased
- Body weight gain (GD0-20) decreased by 39% compared to controls.
However, after completion of the exposure period recovery of body weight occurred. - 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
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 34 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: corresponds to 215 mg/m3
- Dose descriptor:
- LOAEC
- Effect level:
- 68 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: severe respiratory tract irritation with reduced body weight gain and clinical signs as secondary effects in pregant rats; corresponds to 430 mg/m3
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The results of the present study revealed no significant maternal toxicity or adverse developmental effects in rats exposed to citral vapour at concentrations up to 34 ppm (NOAEL: 215 mg/m3).
- Executive summary:
- The repeated dose inhalation toxicity of citral was evaluated based on maternal toxicity data from a OECD TG 414 developmental toxicity inhalation study in rats. Exposure atmospheres contained citral concentrations of 1, 3, 10 and 34 ppm (both as vapour), or 68 ppm (aerosol/vapour mixture) corresponding to 6, 19, 63, 215, 430 mg/m3. The exposure condition at 68 ppm comprised an aerosol/vapour mixture with the intention to produce signs of toxicity. Maternal toxicity was indicated at 68 ppm (430 mg/m3) by decreased body weights and by clinical signs as ocular opacity, breathing difficulty, nasal discharge and salivation. These signs of maternal toxicity were secondary to the stress produced by severe respiratory tract irritation, as recovery of body weight and clinical signs of toxicity occurred after completion of the exposure period. At 10 and 34 ppm, findings were incidental and not siginficantly different from control animals.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.