Butyl propionate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD TG 406 and the report contains sufficient information to permit a meaningful evaluation of study results

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not specified

Principles of method if other than guideline:

not applicable

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed prior to the date that LLNA was selected as the preferred method

Test material

Test material information

Constituent 1

Reference substance name:

Butyl propionate

EC Number:

209-669-5

EC Name:

Butyl propionate

Cas Number:

590-01-2

Molecular formula:

C7H14O2

IUPAC Name:

butyl propanoate

Details on test material:

- Name of test material (as cited in study report): n-butyl propionate
- Physical state: colourless clear liquid
- Analytical purity: 99,825%
Impurities (identity and concentrations): n-Butyl alcohol 0.077%, i-Butyl propionate 0.031%, di-n-Butyl ether 0.021%, unknown 0.019%, unknown 0.008% and unknown 0.020%
- Lot/batch No.: PRP/139/88
- Stability under test conditions: yes
- Storage condition of test material: in the dark at room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Porcellus ltd.
- Age at study initiation: 5-9 weeks at receipt
- Weight at study initiation: 300-400 grams at receipt
- Housing: group housed initially and after acclimation, housed in groups of 2-3 animals/cage
- Diet and water (e.g. ad libitum): Pelleted diet (SG1 with vitamin C supplement, Grain Harvesters Ltd.) and water from the public supply were provided ad libitum.
- Acclimation period: at least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Induction 2

Concentration / amount:

Intradermal Induction - 0.1 ml of n-butyl propionate in vehicle and one week later, 0.3 ml of appropriately diluted test material applied topically on the same area of dorsal skin
Challenge - 0.1 ml of appropriately diluted test material applied topically

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Challenge 2

Concentration / amount:

Intradermal Induction - 0.1 ml of n-butyl propionate in vehicle and one week later, 0.3 ml of appropriately diluted test material applied topically on the same area of dorsal skin
Challenge - 0.1 ml of appropriately diluted test material applied topically

No. of animals per dose:

Range finding - 2 male + 2 female guinea pigs
Main study - 10 male + 10 female (treated group); 5 male + 5 female (control group)

Details on study design:

RANGE FINDING TESTS: Two male and two female guinea-pigs were closely shorn in the shoulder region using electric clippers followed by an electric razor. 0.1 ml doses of several dilutions of the test material were injected intradermally on each side of the mid-line. The animals were examined on the following day to determine the maximum concentration that could be used in the main test without causing untoward toxicity.

The flank of each animal in further groups of two male and two female guinea-pigs, was closely shorn. 0.3 ml doses of several dilutions of the test material were absorbed onto 16 cm2 Whatman No. 3 filter paper patches. The patches were applied to skin on the shorn flanks, covered by occlusive tape and retained by an elastic adhesive bandage for 24 hours. After removal of the patches and bandages the dermal test sites were examined for signs of irritation which were scored using a four point scale. The concentration selected for topical induction in the main test was that which just caused irritation and the concentration chosen for topical challenge was that which was just non-irritant

MAIN STUDY
A. INDUCTION EXPOSURE
- The animals were closely shorn in the shoulder region using electric clippers followed by an electric razor; two rows of intradermal injections were made, one on either side of the mid-line, as follows:

Test animals –
- Anterior sites - 0.1 ml of Freunds Complete Adjuvant (FCA)
- Middle sites - 0.1 ml of test material in vehicle
- Posterior sites - 0.1 ml of test material in 50:50 FCA/vehicle
Control animals –
- Anterior sites - 0.1 ml of FCA
- Middle sites - 0.1 ml of vehicle
- Posterior sites - 0.1 ml of 50:50 FCA/vehicle

One week after induction by intradermal injection, the same area of dorsal skin was shaven using electric clippers only. A 16 cm2 patch of Whatman No. 3 filter paper was moistened with 0.3 ml of the appropriately diluted test material and placed over the sites of intradermal injections. The patches were covered with occlusive tape and held in place by elastic adhesive bandage for 48 hours. Similar patches of filter paper moistened with the vehicle alone were applied to the control group guinea-pigs. Any abnormal reactions to the induction procedure were recorded.

B. CHALLENGE EXPOSURE
- Challenge was carried out three weeks after the intradermal phase of induction. Hair was removed from one flank of all test and control animals by clipping and shaving. A 4 cm2 patch of Whatman No. 3 filter paper, moistened with 0.1 ml of the appropriate dilution of test material, was placed on the shaven area, covered by occlusive tape and held in position by elastic adhesive bandage. Control group animals were treated with the same formulation of test material that was applied to test group animals. After 24 hours the patches and bandages were removed and the challenge sites examined for any response. The response was scored using a four point scale system.

Challenge controls:

not applicable

Positive control substance(s):

no

Study design: in vivo (LLNA)

Concentration:

not applicable

No. of animals per dose:

not applicable

Details on study design:

not applicable

Statistics:

no information available

Results and discussion

Positive control results:

not applicable

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: not applicable

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: not applicable

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, as no positive response was noted in any of the animals exposed to n-butyl propionate (50% in corn oil), hence based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-butyl propionate will not be classified for skin sensitization.

Executive summary:

In this skin sensitization study, groups of 10 male and 10 female guinea pigs were exposed to n-butyl propionate following an intradermal induction (injection) of 0.1 ml of n-butyl propionate in corn oil and a topical induction (occlusive) with 0.3 ml of n-butyl propionate. The topical induction was done one week after the intradermal induction by injection. A concurrent group of 5 male and 5 female guinea pigs served as negative control.

The test group was challenged with 0.1 ml of diluted n-butyl propionate 3 weeks after the intradermal phase of induction. The test sites were evaluated for any signs of sensitization 24 and 48 hours after the challenge exposure.

None of the twenty test animals showed any positive response at either 24 or 48 hours after removal of the challenge patches. Under the conditions of the study, as no positive response was noted in any of the animals exposed to n-butyl propionate (50% in corn oil), hence based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-butyl propionate will not be classified for skin sensitization.