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EC number: 211-776-7 | CAS number: 694-83-7
- 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:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- From 17 MAY 1990 to 1 DEC 1993
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Basic data given, comparable to current standards
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1993
Materials and methods
- Principles of method if other than guideline:
- standard subacute method
- GLP compliance:
- yes
- Remarks:
- according to EPA GLP Regulations (40 CFR 792)
- Limit test:
- no
Test material
- Reference substance name:
- Cyclohex-1,2-ylenediamine
- EC Number:
- 211-776-7
- EC Name:
- Cyclohex-1,2-ylenediamine
- Cas Number:
- 694-83-7
- Molecular formula:
- C6H14N2
- IUPAC Name:
- cyclohexane-1,2-diamine
- Details on test material:
- - Name of test material (as cited in study report): 1,2-Diaminocyclohexane, DCH
- Physical state: liquid
- Analytical purity: 93.3%
- Composition of test material, percentage of components:
93.3% DCH
5.87% 2-Methylpentamethylenediamine
0.22% Hexamethylenediamine
0.08% Water
- Stability under test conditions: test material was expected to be stable under the conditions of the study
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD*BR
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Source: Charles River Breeding Laboratories, Inc. Raleigh, North Carolina, USA
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: approximately ranging from 207 to 243 grams
- Housing: individually housed in stainless steel, wire mesh cages
- Diet: ground Purinae Certified Rodent Chow #5002, ad libiitum
- Water: tap water, ad libitum
- Acclimation period: one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C) targeted: 23 +/-2
- Humidity (%): targeted: 50 +/-10
IN-LIFE DATES: From: 8 JUN 1990 To: 6 JUL 1990
Administration / exposure
- Route of administration:
- other: inhalation of an aerosol/vapour mixture
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Remarks on MMAD:
- MMAD / GSD: Aerosol size (MMDA): ranging from 2.6 to 5.8 micrometres
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 29 litre exposure chambers (made of glass)
- Method of holding animals in test chamber: restrainers (perforated stainless steel or polycarbonate cylinders with conical nose pieces, which were inserted into face plates to yield nose-only exposure conditions)
- System of generating particulates/aerosols: Atmospheres containing aerosol and vapour test material were generated by pumping the test material with a Harvard compact infusion pump to a glass J-tube containing 6 nm glass beads. A Goodburn Model T2 electronic torch heated the air entering the J-tube to about 60 to 70°C. The torch temperature was controlled by an Omega Model CS-6001-J temperature controller. The control chamber also had a torch at similar temperatures controlled by an Omega temperature controller. The aerosol/vapour mixture entered the chamber and was dispersed by a glass baffle to promote uniform distribution of the test material throughout the exposure chamber.
- Method of particle size determination: determined weekly for each exposure concentration with a Sierra Series 210 Cascade Impactor
- Treatment of exhaust air: Chamber atmospheres were exhausted through an emissions-abatement train consisting of a water scrubber (240 cg/ms chambers only), a cold trap, and an HSA cartridge filter prior to discharge into a fume hood.
TEST ATMOSPHERE
- Brief description of analytical method used:
The exposure chambers were monitored approximately hourly for the test material during the animal exposures. A minimum of 4 samples were
taken per exposure. For test material analysis, a measured volume of the chamber atmosphere was drawn through a glass-fiber filter in tandem with the methanol impinger. The filter trapped the test material aerosol particles, the methanol-filled impinger trapped the vapour.
The atmospheric concentration of test material aerosol was calculated from the pre- and post-sampling filter weights which were determined with a Cahn Model 26 Automatic Electrobalance. For the GC analysis, methanol trapped samples were analysed using a Hewlett-Packard Model 5890A GC equipped with a flame-ionization detector. Samples were chromatographed isothermally at 160°C on a 30 meter X 0.53 mm I.D. fused-silica column lined with polyphenylmethylsiloxane. Improved test material detection was obtained in the last 4 exposures using a Hewlett-Packard Model 5890A GC equipped with a nitrogenn-phosphorous detector. Samples were chromatographed isothermally at 160°C on a 10 meter X 0.53 mm I.D. fused-silica column lined with crosslinked 50% phenylmethylsilicone. Test material chamber concentrations were determined by comparing the GC response of the chamber samples with those of standard samples which were prepared by quantitatively diluting the test material in methanol.
Airborne particle size (reported as mass median aerodynamic diameter and percent of mass less than 10 micrometers aerodynamic diameter) was
determined weekly for each exposure concentration with a Sierra Series 210 Cascade Impactor. During each exposure, chamber temperatures were
measured continually with thermocouples during each exposure. Temperatures were averaged and recorded hourly by means of Grant 1200 Series Squirrel Meter/Logger Relative humidity was measured twice per exposure with a Belfort Instrument Co. Model 566 Electric Psychrometer, and chamber oxygen concentration was measured twice per exposure with a Biosystems Model 3100R Oxygen Monitor.
- Samples taken from breathing zone: no
VEHICLE (if applicable)
- Justification for use and choice of vehicle: due to substance characteristics and resulting aerosol/vapour mixture generation via heat-evaporation - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- see "Details on inhalation exposure"
- Duration of treatment / exposure:
- two weeks
- Frequency of treatment:
- 6 hours per day, 5 days a week, for two weeks (i.e. 10 exposures in total) followed by a 14-day recovery period
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 10, 49 and 240 mg per cubic metre
Basis:
analytical conc.
- Remarks:
- Doses / Concentrations:
0, 10, 50 and 250 mg per cubic metre
Basis:
nominal conc.
- No. of animals per sex per dose:
- 10 males per dose group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Exposure concentrations in the present study were selected based on results of rangefinding studies
- Post-exposure recovery period in satellite groups: 14 days (5 animals of each treatment group as well as control)
Examinations
- Statistics:
- Mean body weights and body weight gains for exposed rats were compared to control rats during the exposure and recovery periods.
Data were statistically analysed by one-way analysis of variance. Exposure group values were compared to controls by the least significant difference test when the ratio of variance (F) indicated a significant among-to-within group variation. Significant differences were declared at the 0.05 probabiility level. The statistical analyses used to evaluate the clinical pathology and the pathology data are described below:
A one-way analysis of variance (ANOVA) and Bartlett's test were calculated for each sampling time. When the F-test from ANOVA was
significant, the Dunnett test was used to compare means from the control group and each of the groups exposed to the test material. When the results of
the Bartlett test were significant (p < 0.005), the Kruskal-Wallis test was employed and the Mann-Whitney U test was used to compare means from the
control group and each of the groups exposed to the test material. Significance was judged at the 5% probability level.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- high dose group: 1 out of 10 rats showed black nasal discharge, 2 out of 10 rats showed alopecia
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- high dose group: 1 out of 10 rats showed black nasal discharge, 2 out of 10 rats showed alopecia
- Body weight and weight changes:
- no effects observed
- 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:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- dose related lesions confined to the upper respiratory tract; fully reversible (inflammation and necrosis in the nasal mucosa and the larynx/pharynx region, of only minimal to mild severity for low and mid dose group, but moderate in the high dose group)
- Details on results:
- CLINICAL SIGNS AND MORTALITY
all groups: clinical signs as commonly found in restrained animals (clear nasal and ocular discharge, discoloured and wet fur)
HISTOPATHOLOGY: NON-NEOPLASTIC
all dose groups: dose dependent nasal lesions consisted of inflammation and necrosis which occurred in the nasal mucosa immediately after the two week exposure
- low dose group:
# nasal lesions, which were considered to be of minimal severity.
# minimally inflammation and necrosis in the larynx/pharynx region in 1 out of 5 rats.
- mid dose group:
# nasal lesions, which were considered to be of mild severity;
# minimally inflammation and necrosis in the larynx/pharynx region in 1 out of 5 rats.
- high dose group:
# nasal lesions, which were considered to be of moderate severity.
# minimal to moderate inflammation and necrosis in the larynx/pharynx region in 2 out of 5 rats.
#minimal to mild inflammation of the tracheal muscle in 2 out of 5 rats
After the two week recovery period none of the above mentioned nasal lesions were observed in any test material exposed rats.
Effect levels
- Dose descriptor:
- LOAEC
- Effect level:
- 10 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: dose dependent effects seen on the upper respiratory tract (e.g. nasal lesions) which were from minimal to moderate severity and were fully reversible within the 14-day recovery period
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Chamber atmosphere analysis summary
Conc. [mg/cubic metre] Mean (SD) (a) | [%] Aerosol / [%] Vapour (b) | Particle size - MMD [micrometre] (c) | Particle size - [%] < 10 micrometres (d) |
Control chamber | |||
10 (2) | 33/67 (e) | 4.8 | 79 |
49 (8.7) | 3/97 | 3.6 | 82 |
240 (66) | 36/64 | 5.1 | 80 |
a. Total test material chamber atmospheric concentration (combined aerosol and vapour). Mean and standard deviation of 10 exposures based on a minimum of 4 samples per exposure. b. Mean % of test material in the chamber atmosphere which was in the aerosol or vapour form. c. Mass median aerodynamic diameter, one measurement per week. (mean of two samples) d. Percent by weight of particles with aerodynamic diameter less than 10 micrometres. From cascade impactor determinations (mean of two samples). e. Percent aerosol for the 10 mg/m3 chamber increased dramatically during the second veek of exposures. See chamber atmosphere discussion below for further interpretation of this finding. |
Chamber atmosphere discussion
As expected from the low vapour pressure of the test material, the proportion of test material which was in the aerosol form was highest (36%) at the highest concentration tested (240 mg/m3 ). Low aerosol/vapour ratios were measured in the first week of exposure in the 10 and 49 mg/m3 chambers; the 10 mg/m3 chamber averaged 4.4% aerosol, and the 49 mg/m3 chamber averaged 3.2%. However, the average percent aerosol in the 10 mg/m3 chamber increased from 4.4% in the first week to 61% in the second week. The reason for the increase in the aerosol percentage for the 10 mg/m3 chamber in the second week of exposure is not known. There were no changes reported in the atmosphere generation system, however unobserved pressure or temperature changes in the system could have affected the vapour formation rate. A possible related change was a significant increase in the relative humidity (RH) in this chamber of about 20% in the second week. This was about twice the increase observed in the other chambers during this period. Changes in RE have been observed to change condensation aerosol formation rates. To determine whether the increase in aerosol/vapor ratio in the 10 mg/m3 group affected the biological outcome of the study would require further investigation. However, the effects observed in the rats at 10 mg/m3 were only minimal and completely reversible.
Applicant's summary and conclusion
- Conclusions:
- In this subacute inhalation toxicity study male rats were exposed for 6 hours per day and overall 10times within two weeks to a aerosol/vapour mixture of the test material. Concentrations used were 0, 10, 49 and 240 mg/m³ (analytical). Due to the fact that effects on the respiratory tract were seen in all concentration groups tested and these effects were clearly dose related a no observed adverse effect level could not be determined. The LOAEC of this study was established to be 10 mg/m³.
- Executive summary:
10 male rats were exposed via inhalation for 6 hours per day, 5 times a week for two weeks to an aerosol/vapour mixture containing test material in concentrations of 0, 10, 49 and 240 mg/m3 (analytical concentration). There were no adverse effects observed in any of the test groups with respect to the haematologic, clinical chemical, urinalysis, and body weight parameters measured. As expected from its chemical basicity, inhaled test material produced respiratory tract irritation in exposed rats. However, the lesions (inflammation/necrosis) observed occurred only in the upper respiratory tract (mainly the nose, larynx, and pharynx), were moderate at the highest concentration tested, and were decreased in severity at the lower test concentrations. Effects observed in the 49 mg/m3 group were mainly mild and those in the 10 mg/m3 group were minimal. The observed effects were completely reversible after a two-week recovery period even at the 240 mg/m3 concentration. Although a no-adverse-effect concentration was not determined in this study, the respiratory tract effects observed at the lowest tested concentration (10 mg/m3 ) were considered minimal and reversible.
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