Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Modern GLP compliant guideline study, no restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TAEE, tert-amyl ethyl ether, CAS No. 919-94-8
- Lot/batch No.: 00931302
- Description: colourless liquid
- Purity: 99.4%
- Date received: 22 October 2008

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK, Margate, Kent, UK
- Age at study initiation: approx. 11-12 wk
- Weight at study initiation: males approx. 280 g, females approx. 210 g
- Fasting period before study: no
- Housing: group, 5/cage
- Diet (e.g. ad libitum): yes (except during exposure)
- Water (e.g. ad libitum): yes (except during exposure)
- Acclimation period: animals acclimated to holding tubes on study days -14, -13, -9, -8, -7 and -4

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 January 2009 To: 9 February 2009

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ADG flow-through chamber
- Exposure chamber volume: 40 l
- Method of holding animals in test chamber: restraining tubes
- System of generating vapour: J-tube generator
- Airflow: 12 changes/hr

TEST ATMOSPHERE
- Analytical method used: GC-FID
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Mean concentration over 4 hr = 23.2 mg/l
Concentration range over 4 hr = 21.9 to 25.8 mg/l
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
GENERAL
Male and female rats were exposed by nose-only inhalation for a single 4-hour inhalation exposure followed by an observation period of at least 14 days. The target concentration was 20 mg/l.

NOMINAL VAPOUR CONCENTRATION
The weight of the test article within the reservoir was recorded before and after the exposure and together with the volume of air passing through the chamber, and the nominal vapour concentration in the chamber calculated. This was found to be 34.0 mg/l.

ACHIEVED VAPOUR CONCENTRATION
Samples of chamber air were collected from the animals breathing zone at 30 min intervals into acetone (Dreschel tubes)and analysed by GC-FID (Varian CP-3380 with FID detection; J&W Scientific column with DB-1). The analytical procedures and method were subject to validation to international standards (Covance study 3042-007).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 23.2 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: One animal died during exposure; signs of mild CNS depression present in survivors
Mortality:
One male animal died suddenly in the first hour of exposure. No clinical signs preceded its death.
Clinical signs:
other: Treatment-related clinical signs included ataxia, bradypnoea, dyspnoea, hunched posture, prone and ptosis following exposure to the test article. One male exhibited decreased activity on Day 2. All animals appeared normal thereafter.
Body weight:
Both sexes exhibited a slight (approx. 3%) reduction in body weight during exposure and body weights remained depressed (at or just below pre-exposure values) to days 4-5. Weight gain thereafter appeared normal.
Gross pathology:
The decedent animal had red lungs, nasal cavity, adrenal, mandibular lymph node and dark thymus. The animal also had approximately 2 ml of red fluid in its thoracic cavity. Other animals had minor findings unrelated to treatment.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Not harmful by inhalation
Executive summary:

Acute inhalation toxicity was determined in GLP compliant guideline study (OECD 403) using young adult Wistar rats of both sexes (age approx. 11-12 wk, bwt 210-280 g). Animals were exposed nose-only to a single vapour concentration of the test substance, and the achieved concentration confirmed using GC-FID. One male died during exposure, and the survivors exhibited signs of mild CNS depression with a slight (3%) reduction in body weight. There were no deaths during the 14 day follow-up period and no gross abnormalities detected in survivors at necropsy. The results demonstrate that the acute inhalation LC50 of tert-amyl ethyl ether is greater than 23.2 mg/l.