1,2,4-Benzenetricarboxylic acid, mixed lauryl and octyl triesters

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 08, 2015 - July 22, 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009

Deviations:

yes

Remarks:

ange of humidity deviation was 71 to 72 % (instead of 30-70 %), no abnormality, therefore study results not affected. Airflow 3.4 m³/h (instead of 0-2.4 m³/h), but particle size distribution and concentration were met, has no impact on reliability

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octy triesters

IUPAC Name:

1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octy triesters

Constituent 2

Reference substance name:

tris(mixed dodecyl and octyl)benzene-1,2,4-tricarboxylate

EC Number:

700-342-7

Cas Number:

1163775-81-2

Molecular formula:

C14H47O6 to C18H55O6

IUPAC Name:

tris(mixed dodecyl and octyl)benzene-1,2,4-tricarboxylate

Constituent 3

Reference substance name:

Linplast 812 TM

IUPAC Name:

Linplast 812 TM

Specific details on test material used for the study:

N/A

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Liaoning Changsheng Biology Technology Co., Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 235 -347 g
- Housing: Animals were raised in suspended, stainless steel cages (32x28x20cm) on cage racks (16 7x70x171 cm). There were 10 cages per layer, and 4 layers per rack. Animals were housed individually during the test.
- Diet (e.g. ad libitum): sterilized diet with complete nutrition supplied by Beijing keaoxieli Feed Co., Ltd.
- Water (e.g. ad libitum): was purified by HT-R01000 purity system, ad libitum
- Acclimation period: not mentioned

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-23.4 °C
- Humidity (%): 47-72 %
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: July 08, 2015 To: July 22, 2015

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

ca. 2.5 µm

Geometric standard deviation (GSD):

1.98

Remark on MMAD/GSD:

inhalable fraction (% < 4 µm: 99.77-99.85 %)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The test item was aerosolized using a stainless steel aerosol generation system. There were many nebulizers at bottom of generation system, through which compressed air was supplied. Test item was infused into generation system through peristaltic pump, which provided a continuous supply of test item. Aerosol of test item was generated when test item met with compressed air through nebulizers. Target concentration was achieved by adjusting air flow rate and peristaltic pump infusion velocity.
Exposure Method:
Before exposure, the test animals were restrained in a tube. The exposure tubes were installed in the portholes of the inhalation chamber and the chamber was sealed up. HOPE-MED 8052 dynamic snout-only aerosol inhalation instrument was used. Filtered and compressed air (0.06 m³) was mixed with quantitative test item in exposure chamber. The moving speed of exposure airflow rate was adjusted as appropriate. The aerosol was continuously generated from generation system on the top of the chamber with an aerosol producer. The exhausted air was removed from the outlet at the bottom of the chamber to absorption unit. The content of CO2 was less than and equal to 1%.
Concentration trial:
Test item concentrations were determined prior to test animal exposure. The 4 hours exposures of the rats began once to successive concentrations measurements fell within 20 % of target concentration.
Monitoring Parameters of Exposure Chamber:
Airflow, chamber temperature, chamber, relatitive humidity, oxygen concentration (air flow rate: 3.4 m³/h), temperature: 19.6-19.8 °C, humidity 45.8-50.3 %, oxygen concentration: 21 %.
Actual concentration:
Actual concentration at the animals breathing zone was determined by using filter gravimetric analysis. Samples were collected by using fiber filter fixed in filter holder attached to ESA-3Z auto-sampling device, on which airflow time and volume were set.
- Method of particle size determination: Aerodynamic Particle Sizer (APS) 3321
Frequency of determination was 4 time and mean values of particle size was calculated as final results. Determination data was collected and analyzed by Aerosol Instrument Manager. Frequency of determination was about 1 time per hour.
- Exposure apparatus: nose-only inhalation chamber

Duration of exposure:

4 h

Remarks on duration:

N/A

Concentrations:

2.24 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual weights of animals were determined at grouping, before dosing (day 0), on day 1, 3, 7 and 14.
observations during exposure: only once during the exposure, at immediately and 1 hour after dosing and then once daily for up to 14 days.
Observations of moribund and death was conducted daily at morning and afternoon, on weekends, holiday and necropsy only at the morning.
Observation included changes in fur, eyes and mucous membranes, and also respiratory system, circulating system, rhythm of breathing, changes patterns of inspiration and exhalation. Particular attention had been directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observation times were determined by the nature and time of onset of clinical signs and length of the recovery period. Any evidence of overt toxicity observed at each observation time was recorded.
- Necropsy of survivors performed: yes, all surviving animals were dissected at the end of the study by anesthetizing with aether inhalation and killed by exsanguination. Special attention was taken on the irritation of nose, pharynx and larynx, trachea, lung and eyes. The necropsy included following examinations such as the external features of the carcass, external body orifices, the abdominal, thoracic and their contents of all animals, and the location, size, hardness and the color. The necropsy examination findings were recorded. Histopathology examination was not conducted unless abnormal gross necropsy findings were observed.

Statistics:

N/A

Results and discussion

Preliminary study:

N/A

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

>= 2.24 mg/L air (analytical)

Based on:

test mat.

95% CL:

0.033

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

>= 2.24 mg/L air (analytical)

Based on:

test mat.

95% CL:

0.033

Exp. duration:

4 h

Mortality:

none

Body weight:

were decreased at day 1, began to increase at day 3

Gross pathology:

No abnormalities were found at necropsy for all test animals. Histopathological examiniation was not conducted.

Other findings:

N/A

Any other information on results incl. tables

N/A

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the condition of this study, the single exposure acute inhalation LC50 of the test substance is greater than 2.240 mg/L in male and female rats.

Executive summary:

The study was performed to assess the acute inhalation toxicity of 1,2,4 -Benzenetricarboxylic acid, mixed dodecyl and octyl triesters in Sprague Dawley rats according to OECD 403. The study was conducted at the single maximum generated concentration of 2000 mg/m3. A group of 10 animals (5 males and 5 females) were exposed for 4 hours using a snout-only exposure system. Concentration and particle size distribution were measured. Clinical observations were performed daily throughout the exposure period of 14 days. Body weights were periodically collected. At the end of the test, a gross necropsy was performed for all surviving animals.

Actual mean concentration was 2240 +-33 mg/m3. MMAD and GSC for four determinations were 2.50 µm and 1.98, respectively. The inhalable fraction (% < 4 µm) was more than 99 %. There were no deaths during the test. No abnormalities were noted for all test animals during exposure. Mean bodyweights showed to be decreased at day 1. Mean bodyweights began to increase beginning at day 3. No abnormality was found at necropsy.

The acute inhalation median lethal concentration (LC50, 4 h) of the test item in Sprague Dawley rat was as follows: Male rats: > 2240 +- 33 mg/m³. Female rats > 2240 +- 33 mg/m³.