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
Study period:
1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study for which full study report available. Only a single exposure concentration was used but this was effectively the saturated vapour concentration. Exposure time was only 1 hour

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994
Reference Type:
publication
Title:
Acute toxicity of ethylene glycol mono-n-butyl ether in the guinea pig
Author:
Gingell R
Year:
1998
Bibliographic source:
Food Chem Toxicol 36 (9-10) 825-9

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: CFR title 49, section 173.132
Deviations:
no
Principles of method if other than guideline:
Shorter test duration than OECD guideline
GLP compliance:
yes (incl. QA statement)
Test type:
traditional method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-butoxyethanol
EC Number:
203-905-0
EC Name:
2-butoxyethanol
Cas Number:
111-76-2
Molecular formula:
C6H14O2
IUPAC Name:
2-butoxyethanol
Details on test material:
- Name of test material (as cited in study report): ethylene glycol butyl ether
- Physical state: liquid
- Analytical purity: 99.87% (by GC/MS and NMR)
- Purity test date: 3-July-1994
- Lot/batch No.: 14MSH123
- Storage condition of test material: ambient
- Other: Source: Union Carbide, South Charleston

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HRP Inc, Denver
- Age at study initiation: 36 days
- Weight at study initiation: Males 400-472g, females 401-446g
- Housing: individual stainless steel mesh cages
- Diet ad libitum: AGWAY PROLAB animal diet guinea pig, except during exposure.
- Water ad libitum: tap, except during exposure
- Acclimation period: 8 days
- Other: animals prescreened for parasite infection.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-9-25C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12hr


IN-LIFE DATES: From: 9/3/94 To: 23/3/94

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: plexiglass and stainless steel construction
- Exposure chamber volume: 120 litres
- Method of holding animals in test chamber: in a stainless steel wire mesh sliding drawer cage (individual)
- Source and rate of air: filtered compressed air, 24 litres/min
- System of generating particulates/aerosols: sparging through two wash bottles in series maintained at 26C containing butoxyethanol. Prior to entering chamber, vapour passed through an empty 2 litre mixing flask.
- Temperature, humidity, pressure in air chamber: 24C, 29% RH. Mean O2 level 20.8%


TEST ATMOSPHERE
- Brief description of analytical method used: Sampling using charcoal tubes, subsequently analysed with GC/FID. Atmosphere also checked to ensure absence of aerosol particles.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see above
Duration of exposure:
1 h
Concentrations:
Calculated nominal: 1097ppm based on material consumed in vaporiser. This is the practical achievable vapour concentration.
Measured concentrations: 633 +/-14ppm for females, 691 +/-38ppm for males.
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: during exposure every 13mins. At 1-2 hours after exposure then daily.
- Necropsy of survivors performed: yes, after sacrifice using halothane.
- Other examinations performed: clinical signs, body weight,organ weights, complete necropsy.
Statistics:
Results not amenable to statistical analysis.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC0
Effect level:
> 691 ppm
95% CL:
> 653 - < 729
Exp. duration:
1 h
Sex:
female
Dose descriptor:
LC0
Effect level:
633 ppm
95% CL:
> 619 - < 647
Exp. duration:
1 h
Mortality:
no
Clinical signs:
other: No adverse observations recorded.
Body weight:
Weights measured at days 0, 7, 14. Whilst there was no control as a reference point, weight changes appeared to be normal and proportionate.
Gross pathology:
Findings in majority of both sexes but not all: Hyperinflation of lungs (3 males), dark red discoloration (punctate foci) of all lung lobes (1 male), dark red discolouration of the liver (1 female), abnormal pink fluid in gall bladder (1 female). Also a traumatized liver (median lobe appeared torn) and evidence of haemorrhage in the peritoneal cavity (1 female.) All findings regarded as incidental. Hyperinflation common in guinea pigs due to holding of breath when in contact with anaesthetic gas.
Other findings:
none other than reported above.

Any other information on results incl. tables

Difference between nominal and measured concentrations thought to be due to adsorption in test chamber and associated equipment.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Since there were no deaths up to the maximum achievable vapour concentration, the substance would not be classified for acute toxicity by the inhalation route. Lethal concentrations cannot be reached under ambient conditions. However, the guinea pig is not a species normally used for such a study although it is believed to be a more representative species for modelling toxicity to 2-butoxyethanol in humans.
Executive summary:

In a GLP study, a single group of male and female guinea pigs was exposed to the maximum pratically achievable vapour concentration of 2 -butoxyethanol by whole body exposure for a period of 1 hour. This concentration was nominally 1097ppm but the concentrations measured were 633ppm (3.1mg/l) for females and 691ppm (3.4mg/l) for males. The calculated saturated vapour pressure under ambient conditions is 791ppm. During exposure and the subsequent 14 day observation period, there were no deaths and no clinical signs of toxicity. Progressive body weight gain was observed. No pathological findings attributed to exposure were seen.

Synopsis:

LC0 (1 hour, guinea pig): >3.1mg/l for females, >3.4mg/l for males. Saturated vapour pressure = 3.9mg/l