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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 204-506-4 | CAS number: 121-91-5
- 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:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1988-03-30 to 1988-05-19
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Isophthalic acid
- EC Number:
- 204-506-4
- EC Name:
- Isophthalic acid
- Cas Number:
- 121-91-5
- Molecular formula:
- C8H6O4
- IUPAC Name:
- isophthalic acid
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): isophthalic acid
- Physical state: white powder
- Storage condition of test material: stored at room temperature
- Lot/batch No.: 10820-59-A
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): isophthalic acid
- Physical state: white powder
- Storage condition of test material: stored at room temperature
- Lot/batch No.: 10820-59-A
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratoreies, Inc., Portage, Michigan, USA
- Age at study initiation: 6 weeks
- Weight at study initiation: ~ 277 ± 42 g
- Fasting period before study: No data
- Housing: The rats were housed individually in stainless steel cages measuring 15.5 x 17.0 x 15.8 com dueint the 3 week quarintine and recovery period.s. The rats were confined in inhalation cages measuring 13.0 x 20.0 x 27.5 cm during the exposure phase. The cages were suspended over excrement pans fitted with deotised cage boards except during exposures.
- Diet (e.g. ad libitum): Purina Rodent Chow 5001 ad libitum (except during inhalation exposures)
- Water (e.g. ad libitum): water supplied from a reverse osmosis purifier, ad libitum (except during inhalation exposures)
- Acclimation period: 3 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): 40 %
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours darkness
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: Average particle size was 5.04, 5.59 and 5.74 microns for the low, medium and high exposure groups, respectively. The proportion of respirable size particles (10 microns or less) averaged 87.9% overall and 91.6%, 87.4% and 84.6% in the low, medium and high exposure chambers, respectively.
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test article aerosol entered the exposure chamber through the top via a venturi tube and was discharged through a pipe located near the bottom of the chamber. Exposures were conducted in 2-m3 stainless steel and glass chambers.
- Method of holding animals in test chamber: No data
- Source and rate of air: a Transvector Jet blew the test article aerosol from the mixing chamber into the exposure chamber. The chamber airflw was between 305 and 315 l/min depending on the exposure concentration.
- Method of conditioning air: The chamber air was filtered by high efficieny particle absorbing filters and controlled for temperature and humidity.
- System of generating particulates/aerosols: The generator was a dry materials feeder. The feeder consisted of a reservoir into which the test article was placed. The tapered walls of the feeder were flexible and moved the test article to the bottom of the feeder by slow peristalic action. The test article was picked up by a rotating helix and carried to the generator exhaust. At the end of the line, a Transvector Jet blew the test article into mixing chamber. Another Transvector Jet drew the test article aerosol from the mixing chamber through a tygon line and blew it into the tubing leading to the exposure chamber.
- Temperature, humidity, pressure in air chamber: chamber temperatures, humidity and airflow were measured hourly during each exposure period: 22 °C, 40 % humidity
- Air flow rate: ranged between 305 and 315 l/min depending on the exposure concentration
- Air change rate: no data
- Method of particle size determination: The particle size of the aerosol in each expsoure chamber was determined weekly using an Anderson Cascade Impactor.
- Treatment of exhaust air: The chamber exhaust air was passed through a filtering system before being discharged to the outside environment.
TEST ATMOSPHERE
- Brief description of analytical method used: The test article aerosol concentrations were determined both gravimetrically and spectophotometrically. Samples were collected by drawing a given volume of test atmosphere (i.e. approximately 200, 300 and 1000 liters for the high, medium and low exposure chambers, respectively, and 1000 liters for the filtered air control chamber) across an open-faced filter. Test article concentration was determined gravimetrically by dividing the weight of the test article collected by the volume of the sample taken. During each exposure day, two samples were taken from the filtered air control and low exposure chambers and four samples were taken from each of the medium and high exposure chambers.
The exposure concentrations of the test article were also monitored using a UV/VIS Spectrophotometer operated at 287.3 nm. This filter was extracted with approximately 6 ml of HPLC/Spectro Grade Methanol and the optical density of the extract was determined.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The exposure concentrations of the test article were also monitored using a UV/VIS Spectrophotometer operated at 287.3 nm. This filter was extracted with approximately 6 ml of HPLC/Spectro Grade Methanol and the optical density of the extract was determined. The absorbance of the extracted samples was compared to a previously prepared standard curve and the exposure concentration was determined from the amount of test article extracted.
- Duration of treatment / exposure:
- Three groups of 10 male and 10 female rats were exposed for 6 hours per day.
In addition, 5 rats/sex designated for pre-exposure, single exposure and weekly serum analysis for IPA were included in the control and high exposure groups. These rats were retained for 3 weeks after the last exposure to monitor diminishing serum levels of IPA and to evaluate recovery from IPA-induced effects. - Frequency of treatment:
- 5 days per week for four weeks
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
1.0, 5.0, 10.0 mg/m3
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0.96, 4.59 and 9.59 mg/m3
Basis:
analytical conc.
- Dose / conc.:
- 1 mg/m³ air (nominal)
- Remarks:
- 0.96 mg/cubic metre air (analytical)
- Dose / conc.:
- 5 mg/m³ air (nominal)
- Remarks:
- 4.59 mg/cubic metre air (analytical)
- Dose / conc.:
- 10 mg/m³ air (nominal)
- Remarks:
- 9.59 mg/cubic metre air (analytical)
- No. of animals per sex per dose:
- Three groups of 10 male and 10 female rats per test concentration. A fourth group of equal size was exposed to filtered air only and served as a control group.
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: No data
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: no data
- Post-exposure recovery period in satellite groups: 5 rats/sex designated for pre-exposure, sinlge exposure and weekly serum analysis for IPA were included in the control and high exposure groups. - Positive control:
- A positive control was not included.
Examinations
- Observations and examinations performed and frequency:
- The rats were observed once daily for morbidity and mortality during the quarantine period. Following treatment initiation, all rats were observed at least once daily, 7 days/week. Recovery rats were continued to be observed daily after the final exposure. Bodyweights and food consumption were measured weekly.
Haematology
- Time schedule for collection of blood: blood samples were taken after the 18 hours of fasting
- Anaesthetic used for blood collection: Yes - sodium pentobarbital
- Animals fasted: Yes, for 18 hours following the last exposure
- How many animals: 30 rats
WBC, RBC, Hb, HCT, MCV, MCH, MCHC, differential count
CLINICAL CHEMISTRY:
- Time schedule for collection of blood: blood samples were taken after the 18 hours of fasting
- Animals fasted: Yes, for 18 hours following the last exposure
- How many animals: 30 rats
Glucose, BUN, ALT, AST, ALP, albumin, globulin, total protein, CK, Na+, Cl-, K+
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
ORGAN WEIGHTS: brain, heart, lung, liver, spleen, kidneys, adrenals. gonads, lungs
LUNG VOLUMES: - Sacrifice and pathology:
- All animals were subjected to gross and microscopic investigation at necropsy
- Other examinations:
- Blood samples were investigated for the presence of the test material.
- Statistics:
- Mean and standard deviations were calculated for all quantitative parameters. The data were log-transformed and statistically analysed using both multivariate and univariate two-factor fixed effects analyses of variance (ANOVA). The body weights were evaluated using a multivariate repeated-measures analysis of variance to determine the shape of the dose-response relationship over time. These analytical methods were applied using SYSTAT software. A minimum significance level of P =< 0.05 was used in all comparsions.
There were no statistically significant effects of treatment on any body weight or organ weight parameter in the exposed rats. There were no significant differences between exposed and control rats with regards to haematology or clinical chemistry parameters.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- : redness round the nose
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- : redness round the nose
- 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:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No deaths occurred during the study, other than four serum analysis rats which succumbed during anaesthesia or were sacrificed due to trauma of the eye. The incidence of redness around the nose was increased in all exposed groups compared to the filtered air controls.
BODY WEIGHT AND WEIGHT GAIN
There were no staristically significant effects od treatment on body weight or body weight gain.
FOOD CONSUMPTION
No data
FOOD EFFICIENCY
No data
WATER CONSUMPTION
no data
OPHTHALMOSCOPIC EXAMINATION
no data
HAEMATOLOGY
There were no statistically significant effects of treamtment on haematological parameters
CLINICAL CHEMISTRY
There were no statistically significant effects of treamtment on clinical chemistry parameters
URINALYSIS
no data
NEUROBEHAVIOUR
no data
ORGAN WEIGHTS
There were no statistically significant effects of treamtment on absolute or relative organ weights or lung volumes.
GROSS PATHOLOGY
Prominent lesions observed at necropsy included lung foci and enlargd, reddened mandibular lymph nods. However, there was no difference in incidence of these lesions between the exposed and the control groups so thye were not considered to be treatment related. Other lesions were of a minor, incidental nature, unrelated to the treatment.
HISTOPATHOLOGY: NON-NEOPLASTIC
No microscopic lesions were observed in the nasal turbinates, trachea or lungs of any of the rats exposed to the test article. The most common microscpoic lesions seen included lymphoid and plasma cell hyperplasia in the mandibular lymph nodes, but these were of similar incidence among the exposed and control rats, so that the lesions were not considered to be treatment-related. Other lesions were of a minor, incidental nature, unrelated to the treatment.
OTHER FINDINGS
SERUM IPA ANALYSIS :
Four rats died or were sacrificed in extremis as a result of the blood sampling procedure. Numbers of rats in the two groups were minimally 9 controls and 12 high exposure rats. IPA was detected in the serum of male and female high exposure rats immediately after the first exposure and level remained elevated for the duration of the exposure period. Mean male concentrations ranged from 1.44 to 3.99 ug/ml; mean female concentrations were consistently higher, ranging from 5.33 to 9.26 ug/ml. All traces of serum IPA were gone from all exposed rats one week following the last exposure. No IPA was detected in the serum of any control rat at any time.
Effect levels
- Dose descriptor:
- NOAEC
- Effect level:
- 9.59 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Summary of mortality and clinical observations (10/sex/group)
Observation |
Study Group |
|||||||
Filtered Air Control |
Target Concentrations (mg/m3) |
|||||||
1.0 |
5.0 |
10.0 |
||||||
M |
F |
M |
F |
M |
F |
M |
F |
|
No signs observed |
5 |
10 |
- |
3 |
3 |
8 |
7 |
4 |
Salivation |
2 |
- |
2 |
1 |
- |
- |
1 |
1 |
Redness around eyes |
- |
- |
2 |
- |
1 |
- |
1 |
1 |
Redness around nose |
3 |
- |
8 |
6 |
7 |
2 |
2 |
5 |
Dicsoloured Inguinal Fur |
1 |
- |
- |
- |
- |
- |
- |
- |
Discoloured paws |
1 |
- |
- |
- |
- |
- |
- |
- |
Hair loss: Forepaws/shoulder/back |
2 |
- |
- |
3 |
2 |
- |
1 |
- |
Miscellaneous lesions: Neck/shoulder Broken teeth |
1 - |
- - |
- - |
- - |
1 - |
- - |
- 1 |
- - |
Mean combined male and female clinical chemistry values (mean and SD (10 rats/sex/group))
Parameter |
Filtered air control |
Isophthalic Acid |
||
1.0 (mg/m3) |
5.0 (mg/m3) |
10.0 (mg/m3) |
||
GLU |
128.6 ± 17.4 |
120.2 ± 13.5 |
123.9 ± 12.0 |
127.3 ± 13.6 |
BUN |
15.0 ± 1.9 |
15.6 ± 2.2 |
15.1 ± 2.5 |
15.9 ±2.0 |
ALT/SGPT |
26 ± 6 |
28 ± 10 |
27 ± 6 |
26 ± 7 |
AST/SGOT |
79 ± 16 |
81 ± 18 |
84 ± 18 |
79 ± 21 |
ALK P |
87 ± 18 |
85 ± 30 |
88 ± 25 |
79 ± 31 |
ALB |
3.5 ± 0.3 |
3.5 ± 0.2 |
3.4 ± 0.2 |
3.5 ± 0.3 |
T PRO |
5.5 ± 0.3 |
5.5 ± 0.3 |
5.4 ± 0.4 |
5.4 ± 0.3 |
GLOB |
2.0 ± 0.2 |
2.0± 0.2 |
1.9 ± 0.3 |
2.0 ± 0.2 |
ALB/GLOB |
1.8 ± 0.3 |
1.8 ± 0.2 |
1.8 ± 0.2 |
1.8 ± 0.2 |
CK |
379 ± 150 |
356 ± 176 |
477 ± 119 |
431 ± 228 |
K |
3.9 ± 0.3 |
4.0 ± 0.4 |
4.0 ± 0.3 |
3.8± 0.3 |
Cl |
108.1 ± 2.8 |
108.0 ± 3.1 |
108.5 ± 3.1 |
107.5 ± 2.6 |
Na |
143 ± 2.6 |
143 ± 2.1 |
142 ± 2.1 |
142 ± 2.7 |
Mean combined male and female haematology values
Parameter |
Filtered air control |
Isophthalic Acid |
||
1.0 (mg/m3) |
5.0 (mg/m3) |
10.0 (mg/m3) |
||
WBC |
7.2 ± 1.4 |
6.7 ± 2.6 |
6.6 ± 1.3 |
7.0 ± 1.8 |
RBC |
7.96 ± 0.48 |
7.78 ± 0.43 |
7.96 ± 0.44 |
7.84 ± 0.58 |
HGB |
15.5 ± 0.5 |
15.3 ± 0.6 |
15.3 ± 0.5 |
15.3 ± 0.7 |
HCT |
42.9 ± 1.7 |
42.2 ± 1.6 |
42.4 ± 1.7 |
42.1 ± 2.3 |
MCV |
54.0 ± 2.0 |
54.3 ± 1.7 |
53.4 ± 2.0 |
53.8 ± 1.9 |
MCH |
19.6 ± 0.8 |
19.7 ± 0.6 |
19.3 ± 0.8 |
19.6 ± 0.8 |
MCHC |
36.3 ± 0.6 |
36.3 ± 0.4 |
36.1 ± 0.4 |
36.4 ± 0.6 |
Mean combined differential white blood cells values
Parameter |
Filtered air control |
Isophthalic Acid |
||
1.0 (mg/m3) |
5.0 (mg/m3) |
10.0 (mg/m3) |
||
IM NEU |
0 ± 0 |
0 ± 0 |
0 ± 0 |
0 ± 0 |
MAT NEU |
15 ± 6 |
15 ± 5 |
15 ± 6 |
16± 7 |
LYM |
80 ± 7 |
80 ± 5 |
80 ± 7 |
78 ± 8 |
MONO |
4 ± 2 |
4 ± 1 |
4 ± 2 |
4 ± 3 |
EOS |
1 ± 1 |
1 ± 1 |
1 ± 1 |
1 ± 1 |
BASO |
0 ± 0 |
0 ± 0 |
0 ± 0 |
0 ± 0 |
NRBC |
0 ± 0 |
0 ± 0 |
0 ± 0 |
0 ± 0 |
Mean combined absolute organ weights (g)
Parameter |
Filtered air control |
Isophthalic Acid |
||
1.0 (mg/m3) |
5.0 (mg/m3) |
10.0 (mg/m3) |
||
Brain |
2.09 ± 0.11 |
2.06 ± 0..09 |
2.08 ± 0.11 |
2.12 ± 0.09 |
Heart |
1.07 ± 0.16 |
1.06 ± 0.17 |
1.10 ± 0.16 |
1.04 ± 0.13 |
Liver |
9.49 ± 1.68 |
9.52 ± 1.26 |
9.89 ± 1.41 |
9.63 ± 1.37 |
Spleen |
0.66 ± 0.10 |
0.62 ± 0.08 |
0.68 ± 0.08 |
0.67 ± 0.08 |
Kidneys |
2.47 ± 0.43 |
2.46 ± 0.37 |
2.56 ± 0.50 |
2.53 ± 0.46 |
Adrenals |
0.066 ± 0.016 |
0.068 ± 0.015 |
0.070 ± 0.016 |
0.068 ± 0.014 |
Gonads |
1.634 ± 1.587 |
1.606 ± 1.555 |
1.606 ± 1.563 |
1.578 ± 1.531 |
Lungs |
1.25 ± 0.10 |
1.28 ± 0.09 |
1.30 ± 0.17 |
1.30 ± 0.10 |
Mean lung volumes (ml)
Parameter |
Filtered air control |
Isophthalic Acid |
||
1.0 (mg/m3) |
5.0 (mg/m3) |
10.0 (mg/m3) |
||
Males |
1.7 ± 0.2 |
1.7 ± 0.2 |
1.9 ± 0.3 |
1.8 ± 0.2 |
Females |
1.6 ± 0.1 |
1.7 ± 0.1 |
1.7 ± 0.2 |
1.7 ± 0.2 |
Combined |
1.7 ± 0.1 |
1.7 ± 0.2 |
1.8 ± 0.2 |
1.7 ± 0.2 |
Summary of necropsy observations
Tissue and Observation |
Study Group |
|||||||
Filtered Air Control |
Target Concentrations (mg/m³) |
|||||||
1.0 |
5.0 |
10.0 |
||||||
M |
F |
M |
F |
M |
F |
M |
F |
|
No. gross lesions |
1 |
2 |
- |
2 |
1 |
3 |
1 |
4 |
Lungs |
||||||||
Foci |
5 |
5 |
9 |
6 |
9 |
3 |
8 |
2 |
Pale |
1 |
- |
1 |
- |
1 |
- |
1 |
- |
Puffy |
- |
- |
- |
- |
2 |
- |
1 |
- |
Total rats with lung lesions |
6 |
5 |
9 |
6 |
9 |
3 |
8 |
2 |
Liver |
||||||||
Lobular |
- |
- |
- |
- |
- |
1 |
1 |
- |
Pale |
- |
1 |
- |
- |
- |
1 |
- |
2 |
Mandibular Lymph Nodes |
||||||||
Red |
2 |
- |
2 |
1 |
1 |
- |
3 |
1 |
Red Foci |
1 |
- |
- |
- |
1 |
2 |
- |
1 |
Enlarged |
2 |
1 |
1 |
2 |
- |
3 |
1 |
1 |
Mesenteric Lymph Nodes |
||||||||
Red |
- |
- |
1 |
- |
- |
- |
- |
- |
Enlarged |
- |
- |
- |
- |
- |
2 |
- |
- |
Kidneys |
||||||||
Dilated Pelvis |
- |
1 |
1 |
- |
- |
1 |
- |
- |
Unusual Fluid Present |
- |
- |
- |
- |
- |
1 |
- |
- |
Urinary Bladder |
||||||||
Calculi |
5 |
- |
- |
- |
4 |
- |
- |
- |
Red, thickened, distended |
- |
- |
- |
- |
- |
- |
- |
1 |
Ovaries |
||||||||
Enlarged |
- |
2 |
- |
- |
- |
1 |
- |
- |
Cyst |
- |
1 |
- |
- |
- |
- |
- |
- |
Uterus |
||||||||
Enlarged |
- |
1 |
- |
- |
- |
- |
- |
- |
Summary of histopathological incidence data
Organ Lesion |
Filtered Air Control |
10 mg/m³ Isophthalic Acid |
||
Males |
Females |
Males |
Females |
|
Respiratory Lymph Node |
||||
Haemorrhage |
0/10* |
1/10 |
0/9 |
4/10 |
Reticuloendothelial cell hyperplasia |
0/10 |
0/10 |
1/9 |
1/10 |
Thymus |
||||
Haemmorrhage |
0/10 |
0/10 |
1/10 |
0/10 |
Liver |
||||
Focus of cellular alteration, clear cell |
0/10 |
0/10 |
0/10 |
1/10 |
Kidneys |
||||
Cyst, medulla |
1/10 |
0/10 |
0/10 |
0/10 |
Hydropelvis, bilateral |
0/10 |
1/10 |
0/10 |
0/10 |
Mandibular lymph node |
||||
Lymphoid hyperplasia |
2/10 |
6/10 |
4/10 |
8/10 |
Plasma cell hyperplasia |
4/10 |
4/10 |
3/10 |
6/10 |
Haemorrhage |
2/10 |
0/10 |
3/10 |
1/10 |
Jejunum |
||||
Lymphoid hyperplasia |
0/9 |
0/10 |
1/10 |
0/10 |
Cecum |
||||
Lymphoid hyperplasia |
1/10 |
0/10 |
2/10 |
2/10 |
Ileum |
||||
Lymphoid hyperplasia |
1/9 |
0/10 |
0/10 |
1/10 |
Colon |
||||
Lymphoid hyperplasia |
0/10 |
0/10 |
2/10 |
0/10 |
Mesenteric lymph node |
||||
Lymphoid hyperplasia |
2/10 |
2/10 |
0/10 |
1/10 |
Reticuloendothelial cell hyperplasia |
1/10 |
1/10 |
0/10 |
0/10 |
Plasma cell hyperplasia |
1/10 |
0/10 |
0/10 |
0/10 |
Uterus |
||||
Luminal distension |
-- |
3/10 |
-- |
3/10 |
Prostate |
||||
Chronic inflammation, interstitial |
2/10 |
-- |
3/10 |
-- |
Acute inflammation, intraglandular |
2/10 |
-- |
0/10 |
-- |
* incidence of lesion/total number of tissues examined
-- = tissue not examined
Mean concentrations of IPA in male and female (results combined) rat serum (µg/ml)
No. of Exposures |
Filtered Air Control |
IPA (10 mg/m3) |
0 |
0 ± 0 (5) |
0 ± 0 (15) |
1 |
0 ± 0 (9) |
4.32 ± 1.89 (15) |
6 |
0 ± 0 (10) |
4.22 ± 2.15 (13) |
11 |
0 ± 0 (10) |
6.55 ± 4.90 (13) |
16 |
0 ± 0 (10) |
5.09 ± 4.98 (12) |
20 |
0 ± 0 (9) |
4.38 ± 3.87 (12) |
Recovered 1 week |
0 ± 0 (9) |
0 ± 0 (12) |
Applicant's summary and conclusion
- Conclusions:
- No clearly treatment-related effects of toxicological significance were seen in this study.
- Executive summary:
Isophthalic acid (IPA) was administered as a particulate aerosol by inhalation at target concentrations of 1.0, 5.0 and 10.0 mg/m³ to three groups of 10 male and 10 female rats each. A fourth group of an equal size, was exposed to filtered air only and served as a control. The rats were exposed for 6 hours/day, 5 days per week for four weeks. In addition, 5 rats/sex designated for pre-exposure, single exposure and weekly serum analysis for IPA were included in the control and high exposure groups. These rats were retained for 3 weeks after the last exposure to monitor diminishing levels of IPA and to evaluate recovery from IPA-induced effects. IPA was detected in the serum of high exposure rats immediately after the first exposure and remained elevated for the duration of the exposure. One week after the last exposure, no IPA was detected in the serum of any exposed rat. No clearly treatment-related effects of toxicological significance were seen in this study; a NOAEC of 9.59 mg/m³ is therefore derived.
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.