Registration Dossier

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,1,1,2,2,3,3,4,4,5,5,6,6-Tridecafluorooctane
- Physical state: colourless liquid
- Batch number: #060616
- Purity: 99.9%
- Storage condition of test material: ambient temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, OX25 1TP, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: Males 243–297 g, Females 172–193 g
- Fasting period before study: during exposure
- Housing: 5 per cage, sexes separately, in multiple rat racks suitable for animals of this strain and the weight range expected during the course of the study. Additional animals for trial exposures were housed 2 per cage, sexes separately.
- Diet: Diet (RM1) supplied by Special Diets Services Limited, Witham, Essex, UK (ad libitum)
- Water: mains water, supplied by an automatic system (ad libitum)
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test atmosphere was generated using a large glass condenser column and large roundbottomed flask. The test substance was delivered to the heated glass column using a Watson Marlow pump (pump speed 4%). The pump tubing size was 817743. The glass condenser column was heated to approximately 50°C using a Techne water bath.
- Exposure chamber volume: Approximately 9.2 L. The chamber located on to a base-plate, fitted with castors for manoeuvrability. A conical aluminium lid ensured good distribution of the atmosphere across the chamber, the atmosphere having being generated from above. The conical lid and the base together had a volume of approximately 9.2 L. In this study two sections were connected, giving a total chamber volume of approximately 27.6 L.
- Method of holding animals in test chamber: Animals were restrained in polycarbonate tubes supplied by Battelle, Geneva, Switzerland
- Source and rate of air: Clean, dry air (dried and filtered using equipment supplied by Atlas-Copco, Sweden), at a flow rate of 20 l/min
- Temperature, humidity, pressure in air chamber: 21.2-21.5ºC and 15-30%. Pressure has not been measured.

TEST ATMOSPHERE
- Brief description of analytical method used: The test atmospheres were sampled manually using gas tight syringes and analysed using gas chromatography. Each test atmosphere was analysed regularly during each exposure period. The analysis system was calibrated using an appropriate range of freshly prepared standards prior to the study and at intervals thereafter. The peaks obtained were used to calculate the atmosphere concentrations. Control atmospheres and room air were also sampled and analysed.
- Samples taken from breathing zone: yes

SELECTION OF TEST CONCENTRATIONS
- Rationale for the selection of the starting concentration: An atmospheric concentration of 1400 ppm (20 mg/L), a limit test concentration as recommended by a number of national and international guidelines on toxicity testing was selected as the initial target exposure level. A higher dose level was requested by the sponsor to generate safety data relevant to human exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target concentration: 1400 and 10000 ppm
Analytical concentration: 1443 and 9631 ppm (20.9 and 139.7 mg/l)
Nominal concentration: 1576 and 10594 ppm (22.85 and 153.7 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: observations during exposure, immediately after exposure and at the end of the observation period; weighing on day -1, 1, 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 10 000 other: ppm (target)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 139.7 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 153.7 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no deaths during the exposure or observation periods.
Clinical signs:
other: Observations during exposure Abnormalities generally associated with restraint (wet fur) were observed in all animals during exposure. Most animals had stains around the snout. Changes indicative of mild irritation of the upper respiratory tract (irregula
Body weight:
All animals had gained weight by day 15 of the study. The majority of animals had gained weight by day 8 and continued to gain weight to the end of the study, except for 2 females that did not increase in weight between day 1 - 8 and also 1 male that lost weight between day 1 – 8.
Gross pathology:
There were no treatment related macroscopic abnormalities.
Only one finding was noted at necropsy – one male animal had 50% reduced left testis and epididymis.

Applicant's summary and conclusion