Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited study summary, no guideline and no GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
The test was made to determine the acute inhalation toxicity of Dimethyl-2,6-Naphthalene Dicarboxylate when administered to rats by a single nose-only exposure. A single group of five male and five female rats were exposed to respirable concentration of 2.15 mg/L for 4 hours. Clinical signs observed, body weights and necropsy findings were made during the test.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethyl naphthalene-2,6-dicarboxylate
EC Number:
212-661-4
EC Name:
Dimethyl naphthalene-2,6-dicarboxylate
Cas Number:
840-65-3
Molecular formula:
C14H12O4
IUPAC Name:
2,6-dimethyl naphthalene-2,6-dicarboxylate
Test material form:
solid: flakes
Details on test material:
CAS number: 840-65-3

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, Inc., Portage, MI
- Weight at study initiation: 125-150 g
- Housing: The rats were housed individually in suspended stainless steel cages measuring 15.8 x 15.5 x 17.0 cm.
- Diet (e.g. ad libitum): Purina Rodent Chow 5001 was available ad libitum
- Water (e.g. ad libitum): Water supplied from a reverse-osmosis purifier by an automatic watering system was available ad libitum
-Acclimation period: Approximately four weeks.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): 40%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 2 October 1987 To: 16 October 1987

No additional information

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The chamber was made of glass and stainless steel.
- Exposure chamber volume: 0.5 m3
- Source and rate of air: 37 L/min.
- System of generating particulates/aerosols: The generator was a dry materials feeder (Model 310, AccuRate, Whitewater, WI) which contained a reservoir into which the ground Dimethyl-2,6-Naphthalene Dicarboxylate was placed.
- Method of particle size determination: The particle size of the aerosol was determined twice during the exposure using an Andersen cascade impactor (Andersen Samplers, Atlanta, GA).
- Treatment of exhaust air: The chamber air was exhausted into a waste collecting drum before being discharged to the outside environment.
- Temperature, humidity, pressure in air chamber: 21°C, relative humidity of 33%.

TEST ATMOSPHERE
- Brief description of analytical method used: The aerosol concentration was determined gravimetrically by drawing a known volume of the test atmosphere across an open-face filter and dividing the weight of Dimethyl-2,6-Naphthalene Dicarboxylate collected by the sample volume.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The average particle size was 10.74 microns with a geometric standard deviation of 2.20.

No additional information.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal concentrations: 273 mg/L
Test concentration: 2.15 mg/L
No. of animals per sex per dose:
A single group of five male and five female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The test rats were observed approximately 1/2 and 3 hours after the exposure, and at least once per day for the balance of the 14-day observation period. All test rats were weighed prior to the exposure, weekly thereafter, and immediately prior to necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: Chamber concentration and chamber condition monitoring.
Statistics:
None stated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.15 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No rats died during the study.
Clinical signs:
other: Salivation, redness around the nose and eyes, and discolored facial fur were observed immediately following exposure. The inguinal fur of all rats was also soiled due to confinement in the nose-only exposure tubes. A single incident of discolored paws, ab
Body weight:
The mean initial body weights of the male and female rats were 353 g and 242 g, respectively. Mean body weights increased during the study, although several rats lost weight during the first week following exposure.
Gross pathology:
Necropsy findings consisted of grey lungs in nine rats and distended large intestines in one rat. One rat had no gross lesions.
Other findings:
Chamber concentration:The Dimethyl-2,6-Naphthalene Dicarboxylate was generated as a particulate aerosol The nominal concentration based on the total amount of Dimethyl-2,6-Naphthalene Dicarboxylate consumed was 273 mg/L. The gravimetric time weighted average (TWA) concentration was calculated to be 4.03 mg/L with 53.3% of the particles measuring less than 10 microns, thus resulting in an actual respirable concentration of 2.15 mg/L The average particle size was 10.74 microns with a geometric standard deviation of 2.20.
Chamber Conditions: The average chamber temperature was 21°C with a relative humidity of 33%. Temperature and relative humidity could not be monitored during the entire exposure, due to the heavy dust concentration.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 4-hour acute inhalation median lethal concentration (LC50) of NDC in rats in a nose-only exposure ≥2.15 mg/L.