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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

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Diss Factsheets

Administrative data

Endpoint:
repeated dose toxicity: inhalation
Remarks:
other: Repeated Dose via inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP statement; However, is a well-conducted, well-documented study with Quality Assurance oversight.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
This was a repeated-dose study with daily exposure 6 hours/day, 5 days/week for 2 weeks.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
6-hydroxy-2-naphthoic acid
EC Number:
240-759-7
EC Name:
6-hydroxy-2-naphthoic acid
Cas Number:
16712-64-4
Molecular formula:
C11H8O3
IUPAC Name:
6-hydroxynaphthalene-2-carboxylic acid
Constituent 2
Reference substance name:
6-HNA
IUPAC Name:
6-HNA
Constituent 3
Reference substance name:
C-195
IUPAC Name:
C-195
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): C-195
- Substance type: Solid
- Physical state: White Powder
- Analytical purity: 100%
- Impurities (identity and concentrations): Not stated
- Composition of test material, percentage of components: Not stated
- Isomers composition: Not stated
- Purity test date: Not stated
- Lot/batch No.:
- Expiration date of the lot/batch: Test material received on 6 Mar 1981, with expiration of March, 1982.
- Stability under test conditions: Not stated
- Storage condition of test material: Not stated
- Other:

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 Laboratories, Kingston, NY
- Age at study initiation: Males, 42 days; Females, 58 days.
- Weight at study initiation: Males, 200 g mean (range 189-214g); Females, 187 g mean (178-197g)
- Fasting period before study: Not stated
- Housing: Individual in stainless steel, wire mesh cages, during both exposure and non-exposure periods.
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow ad libitum during non-exposure period, no food during exposure.
- Water (e.g. ad libitum): city tap water (Elizabethtown Water Co.) ad libitum during non-exposure period, no water during exposure.
- Acclimation period: 2 weeks.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not stated.
- Humidity (%): Not stated.
- Air changes (per hr): Chambers operated at an airflow rate between 155 - 257 liters per minute, giving one complete air change every 6.5 to 3.9 minutes.
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: 30 March 1981 To: 10 April 1981

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: MMAD for 20 mg/m^3 group was 4.29 micron, with GSD of 2.44.
MMAD for 60 mg/m^3 group was 4.34 micron, with GSD of 2.95.
MMAD for 200 mg/m^3 group was 3.80 micron, with GSD of 3.56.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chambers were stainless steel and glass construction, with a total volume of one cubic meter and an effective volume of 760 L.
- Method of holding animals in test chamber: Animals were placed in the exposure chamber in individual stainless steel, wire mesh cages.
- Source and rate of air: Dry air, at a back pressure between 3.0 and 6.0 psi was passed through the dust feed mechanism (Wright Dust Feed Cylinder).
- Method of conditioning air: Not stated.
- System of generating particulates/aerosols: Test material was first ground with a mortar and pestle, sieved through a 60-mesh screen, and vacuum dessicated. The test material was then press-packed into a Wright Dust Feed Cylinder using a Carver Hydraulic Press at a pressure of 2000 psi. The packed cylinders were placed on Wright Dust Feed mechanisms mounted on the horizontal portals of the exposure chamber.
- Temperature, humidity, pressure in air chamber: Not stated.
- Air flow rate: Between 155 and 257 liters per minute.
- Air change rate: One complete air change every 6.5 to 3.9 minutes.
- Method of particle size determination: Batelle Cascade Impactor.
- Treatment of exhaust air: Not stated.

TEST ATMOSPHERE
- Brief description of analytical method used: Airborne concentration determined by dividing the amount of material sampled by the total volume of air sampled.
- Samples taken from breathing zone: yes.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 hours per day.
Frequency of treatment:
5 days a week, for 2 weeks.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
Air Control
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
19.6 mg/m^3 (20 was target)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
58.9 mg/m^3 (60 was target)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
186 mg/m^3 (200 was target)
Basis:
analytical conc.
No. of animals per sex per dose:
5 males/5 females (10 animals total) per dose.
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily during exposure and non-exposure periods.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Full, recorded physical assessments were performed twice weekly.

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were determined pre-test, and before and after exposures 1, 5 and 10.

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Collected at terminal sacrifice.
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All animals.
- Parameters checked: Hemoglobin, Hematocrit, Leukocyte count (total and differential), clotting time, erythrocyte count.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Collected at terminal sacrifice.
- Animals fasted: No data
- How many animals: All animals.
- Parameters checked: Blood Urea Nitrogen (BUN), Serum Glutamic Pyruvic transaminase, glucose, total protein.

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
- Organ weights: Adrenal Glands, Heart, Kidneys (paired), Liver, Lungs, Spleen, Testes with epididymides (paired) and Ovaries (paired).
HISTOPATHOLOGY: Yes
- High Dose Group: Trachea, esophagus, lungs, liver, kidneys, eyes, nasal turbinates (3 sections).
- Low and Mid-Dose Groups: Liver.
Statistics:
METHOD FOR BODY WEIGHTS, ORGAN WEIGHTS, ORGAN/BODY WEIGHT RATIOS:
One way ANOVA, followed by a multiple comparison procedure if needed. First, Bartlett's test was performed to determine if groups had equal variance. If variance was equal, parametric procedures were used. If not, non-parametric were used. Parametric procedure was standard ANOVA. Non-Parametric was the Kruskal-Wallis test, and if differences were indicated, a summed rank (Dunn) test was used. A statistical test for trend in the dose level was also performed. For Parametric analyses, a standard regression techniques, with a test for trend, were used. In a Non-Parametric Case, Jonckheere's test was used. The Bartlett's test was performed at the 1%, 2-sided risk level, while all other tests were at the 5% and 1% two-sided risk levels.

METHOD FOR HEMATOLOGY AND CLINICAL CHEMISTRY:
Means were first tested for equal variance. If the variance was equal, a standard, independent, 2-sample t-test was utilized. If the variances differed, Welch's t-test was used. All tests were performed at the 5% and 1%, 2-sided risk levels.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
All animals survived to terminal sacrifice. Increase in dried material around face, and increase in lacrimation observed.
Mortality:
no mortality observed
Description (incidence):
All animals survived to terminal sacrifice. Increase in dried material around face, and increase in lacrimation observed.
Body weight and weight changes:
no effects observed
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:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Depressed SGPT values in the high-dose females when compared to control. However, values were within normal biological limits, and were therefore not of Toxicological significance.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Absolute and relative spleen weights were significantly lower in high-dose females, when compared to controls.
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Increased mitotic activity of parenchymal liver cells was found in all male rats of the high-dose group.
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEC
Effect level:
> 60 mg/m³ air
Based on:
other: Expert Opinion
Sex:
male/female
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
See Executive Summary.
Executive summary:

A two-week inhalation toxicity study was performed with a dust of the test article. Groups of five male and five female Sprague-Dawley derived CD® rats were exposed six hours per day, five days per week for two weeks. The cumulative mean exposure concentrations were 19.6, 58.9, and 186 mg/m3 for Groups II, III and IV, respectively. The aerodynamic mass median diameters were 4.29, 4.34, and 3.80 microns, with mean geometric standard deviations of 2.44, 2.95 and 3.56 for Groups II, III and IV, respectively.

All animals survived the duration of the study. Physical observations of the exposed animals revealed increased instances of dried material around the facial area and lacrimation in Groups III and IV. These observations suggest a treatment-related effect. Body weights, hematology, and clinical chemistry parameters were unremarkable for all exposed animals when compared to the control group.

Absolute and relative spleen weights for females at the high level were lower than control, and may associate with treatment. There were no macro-pathology findings that associated with treatment. Sections of selected tissues were examined microscopically from all rats. Increased mitotic activity of parenchymal liver cells was found in all male rats of the high-dose group. This increase was considered to be related to administration of the test substance.

Other pathomorphologic findings occurred sporadically in control rats as well as test-article exposed rats. They were not related to the administration of the test substance.