Reaction mass of 2,6-dimethylheptan-4-ol and 4,6-dimethylheptan-2-ol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948-06

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:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

Single dermal dose
4 or 5/dose level, male albino Rabbits
14-day observation period
Deaths recorded, used to calculate LD50
Procedures detailed in original bound volumes and replicated in publications

GLP compliance:

no

Remarks:

Conducted pior to the advent of GLP.

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Age at study initiation: Not identified.
- Weight at study initiation: See Table 1 Below

Type of coverage:

other: Dermal

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The application of undiluted diisobutyl carbinol to the truck of rabbits under an imprevious sheeting "Vinylite" for 24 hours.

Duration of exposure:

24 Hours

Doses:

2.52, 5.0, 10.0, 20.0 mL/Kg.

No. of animals per sex per dose:

4 animals @ 2.5mL/Kg
5 animals @ all other doses

Control animals:

no

Details on study design:

Single dermal dose
4/low dose levle, 5/all other dose levels, male albino rabbits
24 hour exposure
14-day observation period
Deaths recorded, used to calculate LD50
Procedures detailed in original bound volumes and replicated in publications.
The application of undiluted diisobutyl carbinol to the trunk of rabbits under an imprevious sheeting for 24 hours also produced erratic mortalities
at dosage levels differing by 100?%. Four of 5 rabbits diedat levels of 10 and 20 ml./kg. The R.F. LD50 is 5.66 (2.51 to 12.8) ml./kg. Marked erythema and in
some instances necrosis of the skin were noted. Livers showed varying degrees of congestion and the kidneys were usually pale. There appears to be a wide
variation in individual susceptibility to the action of this compound both by oral dose and skin penetration.

Statistics:

probit method used to calcluate LD50.

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 5.66 mL/kg bw

Based on:

test mat.

95% CL:

ca. 2.51 - ca. 12.8

Mortality:

1/4 @ 2.52 mL/Kg
2/5 @ 5.0 mL/Kg
4/5 @ 10.0 mL/Kg
4/5 @ 20 mL/Kg

Clinical signs:

other: marked erythema necrosis

Gross pathology:

Liver showed varying degrees of congestion and the kidneys were usually pale.

Other findings:

not applicable

No additional informations or results.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 is 5.66 (2.51 to 12.8) mL./Kg. Marked erythema and in some instances necrosis of the skin were noted. Livers showed varying degrees
of congestion and the kidneys were usually pale. There appears to be a wide variation in individual susceptibility to the action of this compound both by oral dose and skin penetration.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Single oral dose
5/dose level, male Wistar
14-day observation period
Deaths recorded, used to calculate LD50
Procedures detailed in original bound volumes and replicated in publications
The R.F. LD50 of diisobutyl carbinol for male albino rats fed a 20%
dispersion in 1.0% "Tergitol" 7 is 3.56 (1.43 to 3.86) gm./kg. The compound
formed an unstable dispersion with "Tergitol" and the broad range for the LD50
may reflect, in part at least, inaccuracies in the individual doses. Death
followed in each instance when prostration or narcosis occurred after dosing. On
the basis of these results, the compound is of the same order of oral toxicity as
undecanol and 2,6-dimethyl heptanol. Ethanol has an LD50 of 13.66gm./kg. and
isopropanol 5.84 gm./kg. by way of comparison.

GLP compliance:

no

Remarks:

Conducted prior to the advent of GLP.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

No additional details available.

Route of administration:

oral: gavage

Vehicle:

other: 20% dispersion in 1.0% Tergitol in water

Details on oral exposure:

Single oral dose vial stomach tube.

Doses:

1000, 2000, 3980 and 7950 mg/Kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Single oral dose
5/dose level, male Wistar
14-day observation period
Deaths recorded, used to calculate LD50
Procedures detailed in original bound volumes and replicated in publications
The R.F. LD50 of diisobutyl carbinol for male albino rats fed a 20%
dispersion in 1.0% "Tergitol" 7 is 3.56 (1.43 to 3.86) ua./kg. The compound
formed an unstable dispersion with "Tergitol" and the broad range for the LD50
may reflect, in part at least, inaccuracies in the individual doses?. Death
followed in each instance when prostration or narcosia occurred after dosing. On
the basis of these results, the compound is of the same order of oral toxicity as
undecanol and 2,6-dimethyl heptanol.Ethanol has an LD50 of 13.66 gm./Kg and
isopropanol 5.84 gm./kg. by way of comparison.

Statistics:

probit method used to calcluate LD50.

Preliminary study:

No additional information.

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 3 560 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 430 - ca. 8 860

Mortality:

1000 0/5
2000 2/5
3980 3/5
7950 3/5

Clinical signs:

other: prostration narcosis

Gross pathology:

Not available.

Other findings:

No additional details.

Table 11-129

Disobutyl Carbinol

Single Dose to Male Albino Rats by Mouth

Fed by Stomach Tube as a Dispersion in 1% “Tg” 7, 1ml. – 0.020 gm.

Rat Number	1948 Date Dosed	Grams Wt.	Weight Change in 14 Days	Dosage: Grams per Kilo	Dose in Grams	Dose in ml. of Disper- sion	Days to Death
70259	4-6	90	-	7.95	0.715	3.6	1
70236	“	108	-	7.95	0.860	4.3	1
70397	“	106	-	7.95	0.844	4.2	8
70396	“	90	+ 60	7.95	0.715	3.6	-
70403	“	106	+ 52	7.95	0.844	4.2	-
71219	4-13	92	-	3.98	0.366	1.8	1
71223	“	106	-	3.98	0.422	2.1	4
71231	“	90	-	3.98	0.358	1.8	3
71229	“	100	+ 46	3.98	0.398	2.0	-
71230	“	110	+ 32	3.98	0.438	2.2	-
72712	5-4	106	-	2.00	0.212	1.1	1
72714	“	100	-	2.00	0.200	1.0	1
72710	“	92	+ 18	2.00	0.184	0.92	-
72795	“	96	+ 50	2.00	0.192	0.96	-
72798	“	90	+ 40	2.00	0.180	0.90	-
70408	4-6	106	+ 54	1.00	0.106	0.53	-
70407	“	90	+ 40	1.00	0.090	0.45	-
70409	“	98	+ 62	1.00	0.098	0.49	-
70379	“	94	+ 58	1.00	0.094	0.47	-
70376	“	100	+ 70	1.00	0.100	0.50	-

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 is 3.56 (1.43 to 8.86) gm./kg.

Executive summary:

Diisobutyl carbinol is of a low order of toxicity when administered by stomach tube to rats. The LD₅₀ is 3.56 mg/Kg (1.43 to 8.86 gm/Kg).

Cross-reference 3

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

eye irritation: in vivo

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

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

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Measured volumes of undiluted fluid chemicals are placed on the center of the cornea of an ablino rabbit which has just previously been shown to have uninjured eyes, and 24-hours later observe the eye for gross evidence of injury and for corneal necrosis revealed by fluorescein stain. The
volumes used are 0.001, 0.005, 0.02. 0.1 and 0.5 mL.

GLP compliance:

no

Remarks:

Conducted prior to the advent of GLP.

Species:

rabbit

Strain:

other: Albino

Details on test animals or tissues and environmental conditions:

No additional details on animals and environmental conditions.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

An excess of undiluted material.

Duration of treatment / exposure:

24-hour.

Observation period (in vivo):

After 24-hours.

Number of animals or in vitro replicates:

5 eyes.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Remarks on result:

not measured/tested

Remarks:

Only minor damage to the cornea was reported - observed after 24 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Remarks on result:

not measured/tested

Remarks:

Only minor damage to the cornea was reported - observed after 24 hours

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Remarks on result:

not measured/tested

Remarks:

Only minor damage to the cornea was reported - observed after 24 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

ca. 2

Max. score:

10

Reversibility:

not specified

Remarks on result:

other: Only minor damage to the cornea was reported - observed after 24 hours

Irritant / corrosive response data:

Minor damage to the cornea resulted from the instillation of an excess of undiluted material. This result regulates the compound to Grade 2 in our
10-grade rating series comparable in activity to "Carbitol".

No additional information on results or tables are available.

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Minor damage to the cornea resulted from the instillation of an excess of undiluted material. This result relegates the compound to Grade 2 in our
10-grade rating series comparable in activity to "Carbitol". Carbitol (Diethylene Glycol ethyl ether) is not classified as an eye irritant, therefore DIBC is not considered to be irritating

Executive summary:

Exposure to an excess of undiluted diisobutyl carbinol results in minor damage to the cornea. this result relegates the compound to Grade 2 in our 10 -grade rating series comparable in sensivity to "Carbitol".

Cross-reference 4

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Inhalation of saturated vapor by 6 rats for 8 hours.
Inhalation of a cooled mist generated by heating compound to 170°C while air was bubbled through it.
The vapor pressure is 0.3 mm at 20°C and air saturated at this temperature would contain on the order of 400 ppm.

GLP compliance:

no

Remarks:

Conducted before the advent of GLP.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Albino

Sex:

male

Details on test animals or test system and environmental conditions:

No additional details on test aminals and environmental conditions..

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

A group of six albino rats were exposed to of saturated vapor produced at room temperature for 8-hours. Similarly, a group of six albino rats were exposed to a a cooled mist produced by heating the compound to 170°C. while air was bubbled through for 8-hours..

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

ca. 8 h

Concentrations:

For the vapor dose, vapor pressure is 0.3 mm. at 20°C. and air saturated at this temperature would contain on the order of 400 ppm.
For the mist dose, cooled mist produced by heating the compound to 170°C. while air was bubbled through.

No. of animals per sex per dose:

6 rats per 8 hour vapor dose and
6 rats per 8 hour mist dose

Control animals:

no

Details on study design:

No additional details on the study design.

Statistics:

No additional details on statistics.

Preliminary study:

No preliminary study data.

Sex:

male

Dose descriptor:

LC0

Effect level:

ca. 400 ppm

Based on:

other: vapor pressure

Exp. duration:

8 h

Mortality:

No deaths after 8 hour exposure.

Clinical signs:

other: N/A

Body weight:

N/A

Gross pathology:

N/A

Other findings:

N/A

No additional results or table.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Neither air saturated at room temperature nor a mist produced by heating the compound to 170°C, while aerated, killed rates in an 8-hour
exposure. The Vapor hazard is therefore low.

Executive summary:

Neither air staurated at room temperature nor a mist produced by heating the compound to 170^oC while aerated, killed rats in an

8-hour exposure. Vapor hazard is therefore low.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1948

Report date:

1948

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Apply 0.01mL of undiluted sample to an area of the clipped belly of an albino rabbit and observe the area after 24-hours, recording necrosis, edema,erythema or congestion of capillaries.

GLP compliance:

no

Remarks:

Conducted prior to the advent of GLP.

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 2,6-dimethylheptan-4-ol and 4,6-dimethylheptan-2-ol

EC Number:

939-420-2

Molecular formula:

C9H20O

IUPAC Name:

Reaction mass of 2,6-dimethylheptan-4-ol and 4,6-dimethylheptan-2-ol

Details on test material:

No additional details on the test material.

Test animals

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No additional data available.

Test system

Type of coverage:

open

Preparation of test site:

other: Clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.01mL of undiluted sample.

Duration of treatment / exposure:

Single treatment.

Observation period:

Observed after 24-hours

Number of animals:

5 rabbits

Details on study design:

Apply 0.01mL of undiulted sample to an area of the clipped belly of an albino rabbit and observe the area after 24-hours, recording necrosis, edema,erythema or congestion of capillaries.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

0

Remarks on result:

other: assessment was for only 24 hours - no irritation was reported

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

0

Remarks on result:

other: assessment was for only 24 hours - no irritation was reported

Remarks:

no indication of irritation

Irritant / corrosive response data:

Diisobutyl carbinol produced minimum detectable capillary injection on 1 of 5 rabbits.

Other effects:

No additional effects noted.

Any other information on results incl. tables

No additional information or table available.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Conclusions:

The compound is non irritating to the rabbit skin.

Executive summary:

Apply 0.01mL of undiulted sample to an area of the clipped belly of an albino rabbit and observe the area after 24-hours, recording necrosis, edema, erythema or congestion of capillaries. Diisobutyl carbinol produced minimum detectable capillary injection on 1 of 5 rabbits.