Branched hexatriacontane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-01-23 to 1995-03-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified reliable without restriction. The study was conducted according to OECD 403 Guidelines and followed GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-dodecene dimer, hydrogenated

IUPAC Name:

1-dodecene dimer, hydrogenated

Details on test material:

- Substance type: 1-dodecne dimer, hydrogenated
- Physical state: liquid, clear colourless
- Lot/batch No.: C1527-04-2
- Storage condition of test material: room temperature

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 (UK) Ltd., Kent, U.K.
- Age at study initiation: 10-12 weeks
- Weight at study initiation: Male: 285-294 grams; Females: 214-251 grams
- Fasting period before study: Only during exposure of 4 hours
- Housing: In groups of 5 by sex in polypropylene cages
- Diet (e.g. ad libitum): Rat and Mouse Expanded Pelleted Diet No. 1, Special Diets Services Ltd., Essex, U.K.) ad libitum
- Water (e.g. ad libitum): Mains drinking water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23˚C
- Humidity (%): 45% - 56%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hts light

IN-LIFE DATES: From: 1995-01-23 To: 1995-03-06

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: cylindrical exposure chamber connected to glass concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK) located at the top of the exposure chamber
- Exposure chamber volume: 30 liters
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring. Only the nose of each animal was exposed to the test atmosphere
- Source and rate of air: Compressed air was supplied by means of a 'Gast' oil free compressor and was passed through a water trap and respiratoryquality filters which removed particulate material above 0.005 pm before it was introduced to the nebuliser.
- System of generating particulates/aerosols: The test material was aerosolised using a glass concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK) located at the top of the exposure chamber
- Method of particle size determination: The particle size of the generated atmosphere of the test material inside the exposure chamber was determined three or four times during each exposure period using a Cascade Impactor
- Treatment of exhaust air: The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Kane-May Ltd., Welwyn Garden City, Hertfordshire, UK) located in a vacant port in the animals breathing zone of the chamber and recorded every thirty minutes throughout each exposure period

TEST ATMOSPHERE
- Brief description of analytical method used: Homogeneity of the test atmosphere within the chamber was not specifically determined during this study, but, chambers of the same design (ADG Developments Ltd., Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animals' breathing zone with a wide variety of test materials
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Remarks on duration:

Nose only

Concentrations:

1.19, 2.57, and 5.06 mg/L

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed, for clinical signs, at hourly intervals during the exposure, immediately on removal from the restraining tubes at the end of the exposure, one hour after termination of the exposure and subsequently once daily for 14 days. Body weights determined on Days 0, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology: The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity. The lungs, larynx, pharynx, trachea, kidneys, liver, nasal cavities and sinuses were retained from all animals together with tissues showing macroscopic abnormalities and preserved in buffered 10% formalin.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 1.71 mg/L air

Based on:

test mat.

95% CL:

> 0.49 - < 5.99

Exp. duration:

4 h

Remarks on result:

other: Based on mortality and adverse clinical toxicity observed in female rats post 4 hour nose only exposure. LC50 for male rats is considered to be >5.06 mg/L.

Mortality:

Mortality was observed at every dose tested as follows: 1 male and 4 females at the 5.06 mg/L concentration; 3 females at the 2,57 mg/L concentration; and 2 females at the 1.19 mg/L concentration. All animals that died were found dead on day 1 of exposure.

Clinical signs:

other: During exposure wet fur and increased respiratory rate were commonly noted. On removal from the chamber hunched posture, pilo-erection and incidents of ptosis were also noted in all dose groups and in the females exposed to 1.19 mg/L there were signs of l

Body weight:

Surviving animals showed normal bodyweight gain during the study.

Gross pathology:

At necropsy animals that died during the study commonly showed swollen and abnormally dark lungs and dark liver whilst several showed reddening of the small intestine. Dark kidneys were noted in one male exposed to 5.06 mg/L and pale kidneys were noted in one of the females exposed to 2.57 mg/L. No abnormalities were detected in surviving animals at necropsy.

Any other information on results incl. tables

Group No.	Conc (mg/L): Mean	Sex	Deaths during Exposure	Deaths Post Exposure (1 hr)	Deaths During Observation Period (Days)								Total Deaths
					1	2	3	4	5	6	7	8-14
1	5.06	Male	0	0	1	0	0	0	0	0	0	0	5/10
		Female	0	0	4	0	0	0	0	0	0	0
2	2.57	Female	0	0	3	0	0	0	0	0	0	0	3/10
3	1.19	Female	0	0	2	0	0	0	0	0	0	0	2/10

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the results observed in female Sprague-Dawley rats, the acute inhalation LC50 of 1-dodecene dimer, hydrogenated (aerosol) was considered to be 1.71 mg/L (0.49 – 5.99 95% C.I.). The test material is considered Harmful (Category 4) under the current CLP regulation.

Executive summary:

In an acute inhalation toxicity study (Blagden, S. M., 1995; Klimisch score =1), Sprague-Dawley rats (5/sex/dose) were exposed for 4 hours to aerosols (nose only) of test material 1-dodecene dimer, hydrogenated using standard exposure apparatus. The animals observed over a 14 day period for signs of mortality and clinical toxicity. Body weights were determined on Days 0, 7, and 14 and the respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity. 

 

Mortality was observed at every dose tested as follows: 1 male and 4 females at the 5.06 mg/L concentration; 3 females at the 2.57 mg/L concentration; and 2 females at the 1.19 mg/L concentration. All animals that died were found dead on day 1 of exposure. During exposure wet fur and increased respiratory rate were commonly noted. On removal from the chamber hunched posture, pilo-erection and incidents of ptosis were also noted in all dose groups and in the females exposed to 1.19 mg/L there were signs of lethargy, ataxia and pallor of the extremities. One male exposed to 5.06 mg/L showed decreased respiratory rate. One hour after completion of exposure signs of wet fur had diminished whilst incidents of ptosis were increased in animals exposed to 5.06 mg/1. Ataxia and pallor of the extremities were no longer evident in females exposed to 1.19 mg/1 but one animal in this group showed tiptoe gait. On day one following exposure hunched posture, p110-erection and increased respiratory rate were still common in surviving animals. Several animals exposed to 5.06 mg/L showed lethargy and four continued to show decreased respiratory rate or ptosis. Ptosis was also noted in one female exposed to 1.19 mg/L. Surviving animals in all dose groups recovered slowly with signs of hunched posture and p110-erection diminishing from around day 3, dependent on concentration, but signs of increased respiratory rate continued for seven to nine days after exposure. Surviving animals appeared normal around days 8 to 10 and for the rest of the study. Body weight of surviving animals appeared unaffected through the study period. Necroscopy of animals that died during the study showed swollen and abnormally dark lungs and dark liver whilst several showed reddening of the small intestine. Dark kidneys were noted in one male exposed to 5.06 mg/L and pale kidneys were noted in one of the females exposed to 2.57 mg/L. No abnormalities were detected in surviving animals at necropsy.

 

Based on the results of this study the acute inhalation LC₅₀ of 1-dodecene dimer, hydrogenated (aerosol) was considered to be 1.71 mg/L (0.49 – 5.99 95% C.I.). The test material is considered Harmful (Category 4) under the current CLP regulation.