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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Acceptable, well-documented study report equivalent or similar to OECD guideline 403: pre-GLP. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Test type:
fixed concentration procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
Alcohols, C7-9-iso, C8-rich
IUPAC Name:
Alcohols, C7-9-iso, C8-rich
Constituent 2
Reference substance name:
Alcohols, C7-9-iso-, C8-rich
EC Number:
271-231-4
EC Name:
Alcohols, C7-9-iso-, C8-rich
Cas Number:
68526-83-0
IUPAC Name:
6-methylheptan-1-ol
Details on test material:
- Name of test material (as cited in study report): MRD-78-48
- Physical state: liquid

Test animals

Species:
other: mouse, rat and guinea pig were tested
Strain:
other: Swiss-Webster mice, Sprague Dawley rats, and Hartley guinea pigs
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Housing: 5 per cage
- Diet (e.g. ad libitum): Purina cubed diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: closed chamber
- Exposure chamber volume: 100 l
- Method of holding animals in test chamber: Plexiglass chamber
- Source and rate of air: 30 l/min
- Method of conditioning air: Dried, filtered and preheated
- System of generating particulates/aerosols: three-necked flask immersed in a heated water bath and bubbled with air
- Treatment of exhaust air: Fume hood
- Temperature, humidity, pressure in air chamber: room temp
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 6 h
Concentrations:
Exposure concentration was determined on a nominal basis only and was calculated by dividing the net weight of compound used during the 6 h experiment by the total air flow through the chamber during the exposure. The nominal concentration was computed to be 24 ug/l.
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Statistics:
No data was analyzed

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
> 0.024 mg/L air (nominal)
Exp. duration:
6 h
Remarks on result:
other: For mice, rats, and guinea pigs
Mortality:
0%
Body weight:
The exposed animals appeared to gain weight normally during the observation period.
Gross pathology:
Lungs were observed to be grayish or marked by gray and red foci. There were moderate incidences of mottled livers and kidneys.
Other findings:
As the experiment progressed, most mice became quiet, went to sleep or were mildly sedated. Respiration in some of the rats and guinea pigs appeared to be slightly labored. All signs of depressed physiological function were resolved upon moving the animals to fresh air.

Any other information on results incl. tables

Read-across justifications and data matrices are presented in IUCLID section 13.

Applicant's summary and conclusion

Interpretation of results:
other: not classifiable
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
This data can not be used for classification purposes.
Executive summary:

In this study, groups of male mice, rats and guinea pigs were subjected to a whole body exposure of a nominal concentration of 24 ug/l of isooctanol as a saturated vapor for 6 hours. All animals survived the study. There were indications of depressed physiological function in all animals; indicated by sedation and labored breathing. These observations were resolved once the animals were moved into fresh air. From this study, it is concluded that the LC50 is greater than 0.024 mg/l as a 6 hour exposure.

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