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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979-06-11 to 1979-06-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
Method similar to FEDERAL REGISTER 38 NO. 187 PARA. 1500.41. S. 27029 (27.September 1973)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Type of coverage:
open
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
about 0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
8 days
Number of animals:
6
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/72 h
Score:
4.9
Max. score:
8
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: substance is corrosive
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.9
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Superficial but no deep skin necrosis was observed in one treated female, for further details see attached document.
For details on erythema and edema score see belowl.

Intact skin

(erythema)

animal no.0.357

animal no.0.366

animal no.0.474

animal no.0.473

animal no.0.476

animal no.0.329

24 hours

3

3

3

3

2

2

48 hours

3

3

3

4

3

2

72 hours

3

3

3

4

3

2

8 days

1

2

1

4

1

2

Intact skin

(edema)

 

 

 

 

 

 

24 hours

2

2

2

2

2

2

48 hours

2

2

2

2

2

1

72 hours

2

2

2

2

2

1

8 days

0

2

0

2

2

1

 

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the conditions of this study, the dermal effects were not reversible within 8 days. Therefore the test substance is considered to be irritant to skin.
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
Method similar to FEDERAL REGISTER 389 NO. 1879 PARA. 1500.42. S. 27029 (27.September 1973)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
8 days
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing : no
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
29
Max. score:
100
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
not determinable because of methodological limitations
Remarks:
observation period only 8 d instead of 21 d
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.22
Max. score:
3
Reversibility:
not fully reversible within: 8 d
Remarks on result:
not determinable because of methodological limitations
Remarks:
observation period only 8 d instead of 21 d
Irritant / corrosive response data:
for details see below

 

Time

Cornea

Iris

Conjunctiva - chemosis

Conjunctiva - redness

24 h

 

 

 

 

Animal 1

1

0

0

2

Animal 2

1

0

0

2

Animal 3

1

0

1

2

48 h

 

 

 

 

Animal 1

1

0

0

2

Animal 2

1

0

0

2

Animal 3

1

1

1

3

72 h

 

 

 

 

Animal 1

1

1

0

2

Animal 2

1

0

0

2

Animal 3

1

1

1

3

8 d

 

 

 

 

Animal 1

1

0

0

1

Animal 2

0

0

0

1

Animal 3

2

0

0

1

Mean all animals after 24, 48 and 72 h

1

0.33

0.33

2.22

Interpretation of results:
study cannot be used for classification
Remarks:
observation period only 8 d instead of 21 d
Conclusions:
Under the conditions of this study, the test substance caused irritant effects to the eyes of rabbits which diminished during the 8 day observation period but were not fully reversible within the observation time.
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
other: US-rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeder
- Weight at study initiation: 160-300 g (male), 160-230 g (female)

ENVIRONMENTAL CONDITIONS
not reported
Route of administration:
oral: gavage
Vehicle:
other: 0.5 % aqueous carboxymethylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10, 12.1, 14.7, 21.5, 31.6 %
- Amount of vehicle (if gavage): 10 mL/kg bw
Doses:
1000, 1210, 1470, 2150 and 3160 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 350 mg/kg bw
Based on:
test mat.
Mortality:
Mortality: 1000 mg/kg bw: 0; 1210 mg/kg bw: 6; 1470 mg/kg bw: 7; 2150 mg/kg bw: 8; 3160 mg/kg bw: 10
Clinical signs:
Dyspnoea, apathy, atonia, lacking reflexes, ruffled fur
Body weight:
mostly initial loss
Gross pathology:
deceased animals: dilatation and congestion of hearts, yellowish coloured livers, gray kidneys
no histopathological alterations in animals sacrifices at end of study
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study, the LD50 of male and female rats was 1350 mg/kg bw
Executive summary:

Each five male and female rats were gavaged with the test substance at doses of 1000, 1210, 1470, 2150 and 3160 mg/kg bw and observed for 14 days. The mean LD50 for male and female rats was 1350 mg/kg bw.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
Inhalation hazard test
Deviations:
no
GLP compliance:
no
Test type:
traditional method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3,5,5-trimethylhexanoic acid
EC Number:
221-975-0
EC Name:
3,5,5-trimethylhexanoic acid
Cas Number:
3302-10-1
Molecular formula:
C9H18O2
IUPAC Name:
3,5,5-trimethylhexanoic acid
Test material form:
liquid

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female

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
Rats exposed for 7 h, respectively, to a vapour saturated atmosphere. Vapour was generated by bubbling 200 l/h dry air (no CO2) through the liquid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder. The glas cylinder was heated in a water bath. Temperature in the exposure chamber was 20°C. Concentration was stated in the raw data to be 0.436 mg/L. This was calculated based on the substance loss. Based on a vapour pressure of 0.0044 hPa (see 4.6) and a molecular weight of 158.24 a saturated vapour concentration of 0.03 mg/L can be calculated. Due to this discrepancy, this latter value is assumed to be more reliable with respect to human exposure.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Concentrations:
0.03 mg/l (nominal)
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
not necessary

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.03 mg/L air (nominal)
Exp. duration:
7 h
Remarks on result:
other: inhalation hazard test
Mortality:
No Mortality was observed
Clinical signs:
other: Slight irritation of mucous membranes, nasal discharge, accelerated breathing, ruffled fur
Body weight:
no data
Gross pathology:
no substance related findings

Any other information on results incl. tables

The acute inhalation risk test demonstrates that no hazard has to be expected from exposure to saturated vapour of 3,5,5 -trimethylhexanoic acid at room temperature.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, a saturated atmosphere did not produce mortality, but only slight signs of toxicity
Executive summary:

6 rats (3 males, 3 females) were exposed to a saturated atmosphere (calculated to 0.03 mg/L) of the test substance for 7 h. Within the observation period of 14 days, there was no mortality, but only slight signs of toxicity during exposure. No organ damage was detected at necropsy.

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