Registration Dossier

Administrative data

Description of key information

Acute toxicity:

Oral: LD50 > 2000 mg/kg bw

Inhalation: LC50 > 5.0 mg/L

Dermal: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study predates Good Laborary Practices
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
Report predates GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Visual description of substance was "Clear yellow, slightly viscous liquid with a faint odor."
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Described in study report as "Adult male albino rats of the Holtzman (Sprague-Dawley-derived) strain."
Sex:
male
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
A single dose was administered by oral gavage as either the neat substance (5000 and 10000 mg/kg) or as a 3% weight per volume solution (419 and 1450 mg/kg) in corn oil. All animals were fasted three to four hours prior to dosing.
Doses:
417, 1450, 5000, and 10000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Rats were observed for mortality and toxic effects immediately after dosing; at one, four, and 24 hours; and once dally thereafter for a total of 14 days.
Body weights were measured initially and terminally.
Statistics:
Statistical analysis was described as "Litchfield, J. T., and Wilcoxon, F., J. Pharmacol. Exptl. Therap. 96, 99, 1949"
Key result
Sex:
male
Dose descriptor:
LD0
Effect level:
>= 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred at any of the tested doses.
Clinical signs:
At doses of 5000 or 10000 mg/kg animals showed slight depression by one hour and excessive urination and/or diarrhea. Complete recovery occurred by 48 hours (5000 mg/kg level) or Day 5 (10,000 mg/kg level)
Body weight:
No effects on body weight were reported.
Gross pathology:
No observable gross pathology was found
Interpretation of results:
GHS criteria not met
Conclusions:
Acute oral exposure to the test substance at doses up to 10,000 mg/kg did not result in any mortality in a 14-day post-exposure observation period. The results indicate negligible potential for acute oral toxicity.
Executive summary:

Groups of five male Sprague-Dawley rats were administered 419, 1450, 5000, or 10000 mg/kg triisononyl trimellitate by oral gavage and observed 14 days following exposure. No mortality occurred. At 5,000 and 10,000 mg/kg activity was slightly depressed one hour following exposure, with observation of excessive urination and/or diarrhea. Complete recovery was reported by 48 hours (5,000 mg/kg) or five days (10,000 mg/kg). The results indicate negligible potential for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Study predates development of OECD Test Guidelines
GLP compliance:
no
Remarks:
Study predates the establishment of GLP guidelines
Test type:
fixed concentration procedure
Limit test:
yes
Specific details on test material used for the study:
One large bottle of the test substance was received from Esso Research and Engineering Company on March 7, 1969. The test substance was described as a light gold liquid.
Species:
rat
Strain:
not specified
Sex:
male
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
The exposure was conducted in a 1000-liter stainless steel and plexiglas chamber under dynamic conditions. The experimental atmosphere was generated by metering the compound with a Precision dual syringe feeder into a positive pressure spray nozzle situated within the chamber. The chamber airflow was maintained by a positive pressure rotary pump located on the exhaust side of the chamber and was monitored by a rotameter. The nominal concentration of test material in the experimental atmosphere was calculated from the ratio of the weight of compound aerosolized to the total chamber airflow (volume of air ejected from the spray nozzle plus the volume of makeup air) per unit time. During exposure, the animals were housed individually in stainless steel exposure baskets, centered in the chamber on a rack. They were observed for signs of irritation, toxicity, or death.

The specific gravity of the test substance was determined to be 0.96 g/mL. The test substance was metered into the chamber and aerosolized at the rate of 9.0 mL/minute (8.64 grams/minute). Airflow through the chamber was maintained at 154 L/min. Thus, the nominal concentration of MRD-69-31 in the chamber atmosphere was calculated to be 56 mg/L air.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 6 h
Concentrations:
56 mg/L
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
Six male animals of each species were exposed to filtered room air under experimental conditions to serve as controls. After exposure, the animals were removed from the chamber and group housed according to species. They were observed daily for 14 days for latent toxic effects. Necropsies were performed on all animals. The lungs, trachea, liver, and kidneys were removed, examined for gross pathological signs, and preserved in 10% buffered formalin for possible future histopathological examination.
Sex:
male
Dose descriptor:
LC0
Effect level:
>= 56 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
6 h
Mortality:
No mortality occured in rats
Clinical signs:
other: During exposure altered respiratory patterns consisting of slow and irregular breathing were observed. Restlessness, partial eye closure, and rapid respiration were noted in most of the animals within five minutes after initiation of exposure. After 15 mi
Body weight:
No significant effects were noted. Initial average rat body weight of 253 grams increased to 311 grams at termination.
Gross pathology:
Necropsy findings showed compound-related effects in the areas of discoloration in lungs and discoloration of the renal medullae.
Interpretation of results:
GHS criteria not met
Conclusions:
No test substance related mortality occurred under the study conditions.
Executive summary:

A group of 10 male rats (strain not specified) were exposed of a 56 mg/L aerosol of the test substance for six hours and subsequently observed for up to 14 days. No test substance-related mortality occured. Gross necropsy findings included some discoloration of the lung and kidney (renal medullae).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
56 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Study predates GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
Study predates GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Visual description of substance was "Clear yellow, slightly viscous liquid with a faint odor."
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Not described in study report
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test substance was applied to the closely clipped, abraded abdominal skin of each rabbit beneath a binder of rubber dam. The trunk of each animal was then wrapped in gauze and adhesive tape, and the animals were collared to prevent ingestion of the compound. After an exposure period of 24 hours, the binders and collars were removed, and the abdominal skin was cleansed with corn oil to remove any compound residue.
Duration of exposure:
24 hours
Doses:
50, 200, 794, and 3160 mg/kg
No. of animals per sex per dose:
Four
Control animals:
no
Details on study design:
Mortality and toxic effects were recorded immediately following application and at one, four, and 24 hours. Following the initial period observations were performed once daily thereafter for a total of 14 days. Dermal irritation recorded at 24 hours and once daily thereafter for a total of 14 days. Body weights were measured initially and terminally.
Statistics:
No details provided in the study report
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 3 160 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred at any of the dosage levels tested. The acute dermal LD50 was, therefore, assumed to be greater than 3160 mg/kg of body weight.
Clinical signs:
Depression, soft feces, and/or few feces were noted in two animals at the 3160 mg/kg level.
Body weight:
Two animals exposed to 3160 mg/kg exhibited terminal body weight loss.
Gross pathology:
Study report indicates "Gross organ alterations were limited to those associated with incidental disease." This is interpreted as no treatment related gross pathology findings.
Other findings:
Skin irritation was slight and consisted of erythema (moderate in two animals at 3160 mg/kg) in all animals at 24 hours which persisted for two to six days. Desquamation was observed in one low level animal on Days 5 and 6.
Interpretation of results:
GHS criteria not met
Conclusions:
Acute dermal exposure to the test substance at doses up to 3,160 mg/kg did not result in any mortality in a 14-day post-exposure observation period. The results indicate negligible potential for acute dermal toxicity.
Executive summary:

Groups of four male or female New Zealand White rabbits were exposed to 50, 200, 794, or 3160 mg/kg on abraded skin using occulsive dressing for 24 hours. Rabbits were observed for 14 days following exposure. No mortality occured. Effects were limited to rabbits exposed to 3160 mg/kg, where two rabbits were reported to show depression, soft feces, and/or few feces, and terminal body weight loss. There was some indication of slight skin irritation in all animals at the 24 hour time point, but completely resolved by the seventh day following exposure. The results indicate negligible potential for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 160 mg/kg bw

Additional information

Justification for classification or non-classification

According to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification and labelling is not indicated for acute toxicity, as no mortality/significant toxicity was apparent at limit dose levels.