3,5,5-trimethylhexanoic acid

Acute Toxicity: inhalation

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-reference

Cross-reference 1

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.

Cross-reference 2

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.

Cross-reference 3

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:

other: Dyspnoea, apathy, atonia, lacking reflexes, ruffled fur

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

Test material information

Constituent 1

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.