Reaction product of propylene and synthesis gas in a hydroformylation being a sidestream during purification

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

EC Number:

920-427-4

Details on test material:

- Name of test material (as cited in study report): Zorgol 48
- Analytical purity: not applicable
- Lot/batch No.: 20100223161335
- Expiration date of the lot/batch: 2011-02-09
- Stability under test conditions: not indicated by the sponsor
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/CaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratiories B.V., Postbus 6174, 5960 AD Horst, The Netherlands
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 20.8 ± 1.2 g (range 19.0 - 23.5 g)
- Housing: single housing in makrolon Type II cages with wire mesh top containing granulated soft wood bedding
- Diet (e.g. ad libitum): pelleted standard diet (Harlan Laboratories B.V., 5960 AD Horst, Netherlands), ad libitum
- Water (e.g. ad libitum): municipal tap water, ad libitum
- Acclimation period: at least 5 days prior to the start of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 45 - 65
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12 (artifical light from 6.00 a.m. to 6.00 p.m.)

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

25, 50, and 100% (in vehicle)

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: in a pretest, test substance was found soluble in vehicle up to 100%.
- Irritation: in a pretest, no irritation or systemic toxicity at all were observed when mice were treated at both ears for three consecutive days with test substance concentrations of 50 and 100% (one mouse per concentratio). Tested animals were observed for 7 days.
- Lymph node proliferation response: not examined

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: local lymph node test
- Criteria used to consider a positive response:
A test substance is regarded as a sensitizer
- if exposure to at least one concentration results in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index and
- if the data are compatible with a conventional dose response, although allowance must be made for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION:
- Test substance was placed into a volumetric flask on a tared balance and acetone/olive oil (4 : 1) was quantitatively added. The different test item concentrations were prepared serially. The preparations were made freshly before each dosing occasion. 25 µL of test substance/test substance solution in vehicle were administered epidermally to the dorsal surface of each ear (left and right).

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

The mean values and standard deviations were calculated for body weights.
A statistical analysis was conducted for assessment of the dose-response relationship, and the EC3 value was calculated using the co-ordinates of the two pair of data lying immediately above and below the S.I. value of 3 on the local lymph node assay dose response plot.

Results and discussion

Positive control results:

With α-hexylcinnamic aldehyde as positive control substance, the concentration for a stimulation index of 3 (EC3) was determined to be 12.9%. Respons was as expected.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: controls 25% test substance 50% test substance 100% test substance 1 2.02 4.83 5.75 EC3 was determined to be 33.7%

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: controls 25% test substance 50% test substance 100% test substance 3500 7060 16918 20108

Any other information on results incl. tables

No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

 

Body weights and body weight development were within the range common for animals of this strain and age.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

In a local lymph node assay, the test substance Zorgol 48 was demonstrated to exert a skin sensitising effect. Indicated by a EC3 of ca. 34%, Zorgol 48 is not a strong sensitizer.

Executive summary:

In a local lymph node assay with Zorgol 48 (1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues) as test substance, adult female CBA/CaOlaHsd mice (4 animals per group) were tested using concentrations of 25, 50, and 100% test substance in vehicle (4:1 acetone/olive oil).α-Hexyl cinnamic aldehyde was used as positive control material.

 

The positive control substance displayed the appropriate response. With the test substance Zorgol 48, neither effects on body weight development nor any systemic toxicity were seen. No skin irritation was observed at the application site for any test concentration.

 

Incorporation of radioactivity in lymph nodes was increased for all test concentrations over controls (SI 2.02, 4.83, and 5.75 respectively). EC3 was determined to be 33.7%. In this study, Zorgol 48 is a weak dermal sensitizer (Vogel/Laus, 2010).

 

This study is classified as acceptable and satisfies the guideline requirements of a local lymph node test (OECD TG 429, EU Method B.42) without restrictions.