1-propoxypropan-2-ol

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01/2009-03/2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-study according to OECD guideline 429

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan (Indianapolis, Indiana)
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 24 g (mean)
- Housing: Animals were housed up to six per cage in filter tubs containing corncob bedding, food pellets and a water bottle. On the day the animals were euthanized and following the injection of 3H-thymidine, each treatment group of mice was housed in shoebox cages containing corncob bedding, food pellets, and a crock filled with water. The mice were euthanized five hours later.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 40-70%
- Air changes (per hr): 12-15 times/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark (on at 6:00 a.m. and off at 6:00 p.m.)

Vehicle:

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

Concentration:

Screening study: 1%, 5%, 25%, 50%, 75% and 100%
Final study: 5%, 25% and 100%

No. of animals per dose:

6

Details on study design:

Irritation screen:

Prior to the LLNA study, several concentrations of the test material were evaluated for irritation potential as measured by erythema of the ears. Mice (one female/concentration) received one application of PnP (1%, 5%, 25%, 50%, 75%, or 100%), on the dorsal surface of each ear (25 µl) on three consecutive days. The test solutions (25 µl/ear) were spread over the dorsal surface of each ear in a manner to prevent material loss. Ears were inspected prior to application of the test material solutions, and erythema was evaluated on days 2, 3, and 6. All mice were weighed on days 1 and 6. Erythema scores and body weight data following test material applications were compared to the response of the animals treated with vehicle alone.

Main study:

The application of the test material (25 μl/ear) was made on the dorsal surface of both ears as described above. Six female mice/group received one of three concentrations of PnP (5%, 25%, or 100%) or vehicle (4:1 AOO) once daily for three consecutive days. HCA at 30% (v/v) in vehicle was run concurrently as a positive dermal sensitization control. Ears were inspected prior to application of the test material solutions, and erythema was evaluated on days 2, 3, and 6. All mice were weighed on days 1 and 6. On day 6, all mice received a 250 μl intravenous injection (i.v.) via the lateral tail vein containing 20 μCi of 3H-thymidine (specific activity 2Ci/mmol; Amersham code TRA310, Buckinghamshire, United Kingdom) diluted in phosphate-buffered saline (PBS). Approximately five hours post administration, the mice were euthanized via CO2 asphyxiation and both auricular lymph nodes located at the bifurcation of the jugular veins were excised and placed in PBS. A single cell suspension of the auricular lymph nodes from each mouse was prepared and the cells were washed and suspended in 5% trichloroacetic acid (TCA) for approximately 18-70 hours. The suspended precipitates were centrifuged and the supernatant removed. The pellet from each mouse was reconstituted in 5% TCA and subsequently transferred to a scintillation vial containing Aquasol-2 scintillation cocktail. The radioactivity in each precipitate was measured using a beta-scintillation counter and reported as disintegrations per minute (dpm) per mouse.

Positive control substance(s):

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

Statistics:

Mean dpm values + SD (standard deviation) were calculated for each experimental group. The SI was calculated using the absolute dpm value for each mouse as the numerator and the mean dpm value from the vehicle control mice as the denominator; the mean SI + SD was calculated for each experimental group. Any test material that produces a SI of > 3 in the LLNA should be considered “positive” for contact sensitization.

Positive control results:

Proper conduct of the LLNA was demonstrated via the positive response from the positive control, 30% HCA which elicited a stimulation index (SI) that was 6.4 in comparison to vehicle-treated mice.

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

Mice dosed with 5%, 25%, and 100% PnP elicited proliferative responses with stimulation indices (SI) that were respectively 1.6, 1.2, and 1.1 in comparison to vehicle-treated mice. PnP did not demonstrate dermal sensitization potential in the mouse LLNA as the lymph nodes draining the area of topical application did not demonstrate a 3-fold increase in proliferation when compared to vehicle-treated mice.

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see attachment below

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

PnP did not elicit a stimulation index (SI) that met the 3-fold increase, thus indicating a lack of dermal sensitization potential in the mouse LLNA.

Executive summary:

The Local Lymph Node Assay (LLNA) was conducted to assess the potential of PnP to cause contact sensitization by measuring lymphocyte proliferative responses from auricular lymph nodes following topical application of the test material to the mouse ear. Screening Study: Three daily topical applications of 1%, 5%, 25%, 50%, 75% or 100% PnP were given to one animal at each dose level. Erythema was absent and body weights were unaffected in all dose groups. Results from this study were used to determine the dosing concentrations for PnP in the LLNA. LLNA: Six female mice/group received 5%, 25%, or 100% of PnP, or vehicle (4:1 AOO) or 30% α-hexylcinnamaldehyde (HCA; positive control) on days 1-3. On day 6, uptake of 3H-thymidine into the auricular lymph nodes draining the site of chemical application was measured five hours post administration. Proper conduct of the LLNA was confirmed via a positive response using 30% α-hexylcinnamaldehyde (HCA), a moderate contact sensitizer, which elicited proliferation that was 6.4 in comparison to vehicle-treated mice. Erythema was absent and body weights were unaffected in all dose groups Mice dosed with 5%, 25%, and 100% PnP elicited proliferative responses with stimulation indices (SI) that were 1.6, 1.2, and 1.1, respectively, in comparison to vehicle-treated mice. PnP did not demonstrate dermal sensitization potential in the mouse LLNA as the lymph nodes draining the area of topical application did not demonstrate a 3-fold increase in proliferation when compared to vehicle-treated mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

PnP did not elicit a stimulation index (SI) that met the 3-fold increase, thus indicating a lack of dermal sensitization potential in the mouse LLNA.

Migrated from Short description of key information:
A GLP-study according to OECD guideline 429 is available for propylene glycol n-propyl ether.

Justification for selection of skin sensitisation endpoint:
A GLP-study according to OECD guideline 429

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Given the absence of skin sensitising potential and the absence of reactivity in other assays such as genotoxicity and clastogenicity assays, it is considered highly unlikely that this substance would be a respiratory sensitiser.

Migrated from Short description of key information:
no data available

Justification for classification or non-classification

No skin sensitization potential was observed with propylene glycol n-propyl ether in mice. Hence, propylene glycol n-propyl ether should not be classified as skin sensitizer.