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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Oct. 19, 1987 to Jan. 22, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
A mixture of: α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-hydroxypoly(oxyethylene); α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyloxypoly(oxyethylene)
EC Number:
400-830-7
EC Name:
A mixture of: α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-hydroxypoly(oxyethylene); α-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyl-ω-3-(3-(2H-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl)propionyloxypoly(oxyethylene)
Cas Number:
104810-48-2
IUPAC Name:
14-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)-3,6,9,12-tetraoxatetradecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 14-hydroxy-3,6,9,12-tetraoxatetradecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; tris(17-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)-3,6,9,12,15-pentaoxaheptadecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate); tris(17-hydroxy-3,6,9,12,15-pentaoxaheptadecan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate); 2-(2-hydroxyethoxy)ethan-1-ol; 2-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)ethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 2-[2-(2-hydroxyethoxy)ethoxy]ethan-1-ol; 2-[2-(2-hydroxyethoxy)ethoxy]ethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 2-hydroxyethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 2-methoxyethan-1-ol; 2-{2-[2-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)ethoxy]ethoxy}ethyl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 20-({3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoyl}oxy)-3,6,9,12,15,18-hexaoxaicosan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 20-hydroxy-3,6,9,12,15,18-hexaoxaicosan-1-yl 3-[3-(2H-1,2,3-benzotriazol-2-yl)-5-tert-butyl-4-hydroxyphenyl]propanoate; 3,6,9,12,15,18,21-heptaoxatricosane-1,23-diol; 3,6,9,12,15-pentaoxaheptadecane-1,17-diol; 3,6,9,12-tetraoxatetradecane-1,14-diol; bis(ethane-1,2-diol)
Details on test material:
- Purity: commercial grade
- Physical properties: liquid (oil)
- Lot/batch No.: EN 20419.72
- Expiration date: July 1992
- 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
- Strain as stated in the report: Tif:RAI f (SPF) hybrids of RII/1 x RII/2
- Source: CIBA-Geigy Ltd. Animal Production, 4332 Stein Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 195 to 234 g
- Housing: group housed (5 per cage) in Macrolon cages, type 4
- Diet ad libitum: rat chow (NAFAG 890 tox)
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: ethanol
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The exposure apparatus was a nose-only exposure system developed by Battelle Research Centres (Geneve/Switzerland). The internal chamber volume was less than 1 l. The flow in any individual aerosol delivery tube was 2 l/min (velocity 1.25 m/sec) and the total flow was 32 l/min. The aerosol was generated using 2 pneumatic nebulizers in parallel.

- Method of holding animals in test chamber:
The rats were placed in macrolon animal holders during exposure.

- Treatment of exhaust air:
The exhaust air was decontaminated by passage through a Pall HDC absolute filter.

TEST ATMOSPHERE
The aerosol concentration in the chamber was determined gravimetrically 5 times during the exposure period. In the same time interval temperature, relative humidity and oxygen content of the inhalation chamber were assessed. The particle size was analyzed with an aerodynamic particle sizer, equipped with appropriate dilution systems to avoid coincidence counts.

VEHICLE
The test article was too viscous to be directly aerosolized. Preliminary experiments showed that a dilution with absolute ethanol (End concentration 30%) was suitable to generate an appropriate concentration in the inhalation atmosphere.

Analytical verification of test atmosphere concentrations:
yes
Remarks:
determined gravimetrically 5 times during exposure period
Duration of exposure:
4 h
Concentrations:
nominal; 11672 mg/m3
measured; 5838 +/- 151 mg/m3
No. of animals per sex per dose:
5 males, 5 females
Control animals:
yes
Details on study design:
The control animals were treated with 61.8 g/h absolute ethanol (nominal concentration of 32.2 g/m3).
During exposure the animals were examined for clinical symptoms and mortalities at 1, 2, and 4 h, as well as 2 h after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period. Gross pathological examinations were performed on all animals at day 14.
Statistics:
Inhalation LC50 values and their 95% confidence limits were not calculated because there were no mortalities. The body weights of the treated animals and the controls were compared by analysis of variance.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: None of the animals died.
Mortality:
None of the animals died.
Clinical signs:
other: Ruffled fur, dyspnea, hunched posture and reduced spontaneous activity were seen in animals exposed to test material. They recovered within 6 days.
Body weight:
Males exposed to the test article showed a statistically significant higher body weight gain compared to controls during the first week after exposure.
Gross pathology:
No treatment related macroscopic findings were observed.
Other findings:
None

Any other information on results incl. tables

Table 1: Mean body weights in gram (Dose level: 5.8 mg/l)

Test day

0

7

14

 

 

 

 

Control males

223 +/- 8

258 +/- 9

301 +/- 10

Treated males

232 +/- 2

273 +/- 4 *

314 +/- 9

 

 

 

 

Control females

206 +/- 7

218 +/- 10

236 +/- 16

Treated females

208 +/- 9

222 +/- 18

239 +/- 22

Body weights on day 0 were assessed before application of test article.

* p<0.05 versus control

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU

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