Registration Dossier

Administrative data

Description of key information

Two GLP studies are available assessing the skin sensitising potential of VAM. These include an OECD guideline Local Lymph Node Assay in mice (OECD 429) and a non-guideline Bueler assay in guinea pigs (similar to OECD 406). Limited data is also available assessing the potential for skin sensitisation in workers to VAM, although this data is considered of limited value.

There is no data available to assess the potential for respiratory sensitisation of VAM.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands, B.V. Postbus 6174, NL 5960 AD Horst, The Netherlands
- Age at study initiation: 9-13 weeks
- Weight: 16.4-21.4 g (at the beginning of the acclimatisation period)
- Housing: 5 per cage in Makrolon type-3 cages
- Diet: Pelleted standard Kliba 3433, batch #75/02 mouse maintenance diet ad libitum
- Water: Community tap water ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C
- Humidity: 30-70%
- Air changes (per hr): 10-15
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 29 January 2003 To: 5 February 2003
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
5 %, 10 %, 25 %, 50 % (w/v) of vinyl acetate
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS:
- To determine the highest non-irritant and technically applicable test item concentration, a non-GLP pretest was performed in 2 mice with concentrations of 10 %, 25 %, 50 % (w/v) in acetone:olive oil, 4:1 (v/v) and 100 % (undiluted). No irritation effects were observed in the concentrations applied.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 5 %, 10 %, 25 %, 50 % (w/v) in acetone:olive oil, 4:1 (v/v) and 100 % (undiluted). The application volume, 25 µL, was spread over the entire dorsal surface (0-8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
- The ear swelling (ear thickness) of both ears (left and right) of mice at application area was measured using calipers prior to the first application, daily 24 (± 2) hours after each dosing and prior to necropsy.
- Five days after the first topical application, all mice were administered with 250 µL of 79.4 µCi/mL 3HTdR (equal to 19.8 µCi 3HTdR) by intravenous injection via a tail vein.
- Approximately five hours after treatment with 3HTdR all mice were euthanized by intraperitoneal injection of VETANARCOL (Veterinaria AG, Zurich). Both ears (left and right) of mice at apical area were punched using a biopsy punch (Stietel, 0 8 mm). Both punches of each animal were pooled and immediately weighed using an analytical balance.
- The draining lymph nodes were rapidly excised and pooled for each individual animal (2 nodes per mouse). Single cell suspensions (phosphate buffered saline) of pooled lymph node cells were prepared by gentle mechanical disaggregation through stainless steel gauze (200 µm mesh size). After washing two times with phosphate buffered saline (approx. 10 mL) the lymph node cells were resuspended in 5% trichloroacetic acid (approx. 3 mL) and incubated at approximately +4°C for at least 18 hours for precipitation of macromolecules. The precipitates were then resuspended in 5% trichloroacetic acid (1 mL) and transferred to glass scintillation vials with 10 mL of 'Ultima Gold' scintillation liquid and thoroughly mixed.
- The level of 3HTdR incorporation was then measured on a ß-scintillation counter. Similarly, background 3HTdR levels were also measured in two 1 mL aliquots of 5% trichloroacetic acid. The ß-scintillation counter expresses 3HTdR incorporation as the number of radioactive disintegrations per minute (DPM).

OTHER:
- The sensitivity and reliability of the experimental technique employed was assessed by use of a substance which is known to have skin sensitization properties in CBA/CaOlaHsd mice. The validation/positive control study was performed with ALPHA-HEXYLCINNAMALDEHYDE in acetone:olive oil, 4:1 (v/v) using CBA/CaOlaHsd mice (RCC Study Number 846871) between 8-22 January 2003.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations of body weights, ear thickness, ears punches weights and DPM values were calculated.
Positive control results:
Stimulation indices of 2.5, 3.7 and 9.7 were determined with alpha-hexylcinnamaldehyde at concentrations of 5 %, 10 % and 25 % (w/v) in acetone:olive oil, 4:1 (v/v). The test item alpha-hexylcinnamaldehyde was found to be a sensitizer and an EC3 value of 7.08% (w/v) was derived.
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
Stimulation indices of 2.0, 2.4, 1.9, 1.7 and 1.3 were determined with vinyl acetate at 5%, 10%, 25%, 50% (w/v) in acetone:olive oil, 4:1 (v/v) and 100% (undiluted). A Stimulation index of 16.6 was determined with the positive control substance 25% (w/v) in acetone:olive oil, 4:1 (v/v).
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
A significant difference of dpm/mouse was determined at concentration of 10% (w/v) comparing with the vehicle control group at p:=0.05 (Dunnett-test, two sides). A significant difference of dpm/mouse was determined between the positive control group and the vehicle control group at p:=0.05 (Dunnett-test, two sides).
Key result
Parameter:
SI
Value:
2
Test group / Remarks:
5% (w/v)
Key result
Parameter:
SI
Value:
2.4
Test group / Remarks:
10% (w/v)
Key result
Parameter:
SI
Value:
1.9
Test group / Remarks:
25% (w/v)
Key result
Parameter:
SI
Value:
1.7
Test group / Remarks:
50% (w/v)
Key result
Parameter:
SI
Value:
1.3
Test group / Remarks:
100%

No test item-related clinical signs were observed in any animals of the vehicle control group or Group 3 (5%). On the second application day a slight to moderate ear swelling was observed at both dosing sites in all mice of Group 2 (HCA, 25%) (moderate), Group 4 (10%) (slight, persisting for two days), Group 5 (25%) (slight), Group 6 (50%) (moderate) and Group 7 (100%, undiluted) (moderate), persisting for the remaining days. All treated animals survived the scheduled study period.

Summary of results

Group

Test substance

% (w/v)

Dpm/Ln M±SD

S.I. M±SD

T value

1 (-ve control)

-

-

161±58

-

-

2 (+ve control)

HCA

25

2677±871

16.6±5.4

6.44**

3

vinylacetate

5

318±74

2.0±0.5

2.24

4

vinylacetate

10

389±217

2.4±1.3

3.26**

5

vinylacetate

25

301±64

1.9±0.4

2.00

6

vinylacetate

50

279±99

1.7±0.6

1.69

7

vinylacetate

100 (undiluted)

208±60

1.3±0.4

0.67

**significant difference at p 5 0.05 (two sides)

The results obtained and reported in the above table, show a negative dose response potential at the concentrations of 25%, 50% and 100% (undiluted), demonstrated by decreasing S.I. values. As some test item related findings such as, slight to moderate ear swelling were observed at the local dosing sites, it might be considered that the effect obtained is based on local irritation rather than on local Langerhans cells as the immuno targets.

Interpretation of results:
GHS criteria not met
Conclusions:
Vinyl acetate was non-sensitising when tested up to 100% (undiluted) in the LLNA.
Executive summary:

Five groups each of five female mice were treated with vinyl acetate at concentrations of 5%, 10%, 25%, 50% (w/v) in acetone:olive oil, 4:1 (v/v) and 100 % (undiluted) by topical application to the dorsum of each ear lobe (left and right) on three consecutive days. A negative control group of five mice was treated with an equivalent volume of the vehicle (acetone:olive oil, 4:1 (v/v)) only. A positive control group of five mice was treated with alpha-hexylcinnamaldehyde at concentration of 25% (w/v) in acetone:olive oil, 4:1 (v/v). The ear swelling (ear thickness) of both ears (left and right) of mice at application area were measured prior to the first application, daily 24 (± 2) hours after each dosing and prior to necropsy. Five days after the first topical application the mice were intravenously injected into a tail vein with radio-labelled thymidine (H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed and both ears at apical area were punched and pooled per mouse. The pooled ear punches were immediately weighed. The draining auricular lymph nodes were excised and pooled per animal. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells were determined by the incorporation of 3H-methyl thymidine measured in a R-scintillation counter. No test item-related clinical signs were observed in any animals of the vehicle control group or Group 3 (5%). On the second application day a slight to moderate ear swelling was observed at both dosing sites in all mice of Group 2 (HCA, 25%) (moderate), Group 4 (10%) (slight, persisting for two days), Group 5 (25%) (slight), Group 6 (50%) (moderate) and Group 7 (100%, undiluted) (moderate), persisting for the remaining days. All treated animals survived the scheduled study period.

Vinyl acetate (CAS 108-05-4) was found to be a non-sensitizer when tested up to 100% (undiluted).

Vinyl acetate showed a local irritation at 10%, 25%, 50% (w/v) in acetone:olive oil, 4:1 (v/v) and 100% (undiluted).

The positive control substance showed an allergenic potency when tested at concentration of 25% (w/v) in acetone:olive oil, 4:1 (v/v).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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
Justification for type of information:
Near EU guideline method (FIFRA, TOSCA, OECD), GLP compliant.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Changes in the number of induction exposures alongside the scale used to assess irritation
GLP compliance:
yes
Type of study:
Buehler test
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., PO. Box 29176, Indianapolis, Indiana 46229, USA
- Age at study initiation: Young adults
- Weight at study initiation: 313-458 g
- Housing: Individually in wire mesh suspended cages
- Diet: Teklad Guinea Pig Diet ad libitum
- Water: Tap water ad libitum
- Acclimation period: At least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 18 January 1995 To: 1 March 1995
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Undiluted VAM (100%)
Day(s)/duration:
3 times per week for 3 weeks
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
Hydroquinone in acetone (5 ppm) - Known sensitiser in concentrated form and used as a control on study
Day(s)/duration:
3 times per week for 3 weeks
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
VAM 25 % (w/v)
Day(s)/duration:
Approximately 2 weeks after last induction exposure
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
Hydroquinone in acetone (5 ppm) - Known sensitiser in concentrated form and used as a control on study
Day(s)/duration:
Approximately 2 weeks after last induction exposure
Adequacy of challenge:
not specified
No. of animals per dose:
20 test, 10 vehicle control and 10 naive control
Details on study design:
RANGE FINDING TESTS:
- The Irritation phase had the purpose of determining the proper level of test material to be used in the induction and challenge phase. The Irritation potential of vinyl acetate at levels of undiluted, 50%, 25%, 10%, 5%, 2.5%, and 1% and the vehicle, hydroquinone in acetone (5 ppm), was evaluated in two groups of four animate each. Four levels of test material were evaluated per animal such that each animal in a given pilot group was exposed to the same levels. Dilutions of the test material were formulated w/v in acetone.
- The day prior to test material exposure, the hair was removed from each of the animal's backs using a small animal clipper. The closed patches were applied to the animals in the following manner: A 0.3 mL amount of each test preparation was applied into a 25 mm Hill Top Chamber®. The animal was placed into the restrainer and the chamber(s) were applied to, the clipped surface as quickly as possible. The chamber(s) were occluded with rubber dental dam pulled taut and fastened to the bottom of the restrainer with clips. The restrainer was adjusted to minimize movement of the animal during exposure. Approximately six hours later the dental dam and chamber(s) were removed, the animal was taken from the restrainer, and placed in its cage. The day following the Irritation exposure all animals were depilated and scored using a 5-point scale.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 6 hours
- Test groups: 20 animals
- Control group: 10 animals. For the vehicle control animals, Hydroquinone in Acetone (5 ppm) was applied
- Site: the left shoulder
- Frequency of applications: 3 times per week for 3 weeks
- Concentrations: undiluted

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: approximately 2 weeks after the last induction exposure
- Exposure period: 6 hours
- Test groups: 20 animals
- Control group: ten naive animals, which had never been exposed to the test or vehicle materials, were concurrently treated with the same concentrations. For the vehicle control animals, Hydroquinone in Acetone (5 ppm) was applied.
- Site: the chambers were applied to a skin site that had not been exposed previously.
- Concentrations: 25% in acetone
- Evaluation (hr after challenge): 24 and 48 hours


OTHER:
Challenge controls:
Hydroquinone (a known sensitizer in concentrated form) is used in trace amounts as an inhibitor in vinyl acetate therefore was included as a control substance in the study.
Positive control substance(s):
yes
Remarks:
a-hexylcinnamaldehyde
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25% w/v in acetone
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25% w/v in acetone
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25% w/v in acetone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% w/v in acetone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
other: vehicle control, hydroquinone in acetone (5 ppm)
Dose level:
as received
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
other: vehicle control, hydroquinone in acetone (5 ppm)
Dose level:
as received
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none

The Buehler test conducted was not fully compliant with the OECD 406 Guideline and the test substance used was also of a commercial grade. Other methodological limitations of the available Buehler assay include the following:

Limitations relating to guideline deviations, concentration selection and local irritation

- The induction phase used a total of nine 6 hour exposures (3 per week for 3 weeks). The OECD 406 guideline requires seven exposure periods on Days 0, 6, 7, 8, 13, 14 and 15.

- The pilot phase showed slight, patchy erythema in 3/4 and 2/4 animals at 24 or 48 hours respectively post exposure when treated at 25% w/v. The OECD 406 guideline requires that the challenge dose is the highest that is non-irritant. In this case minor irritation was observed at the challenge dose assessed in the pilot phase.

- In the induction phase excessive irritation was noted at several of the induction sites following the fourth induction exposure. In the guideline the induction concentration is one that is meant to cause mild skin irritation only, whilst here it is detailed as excessive. Observations observed (those detailed) mainly related to blanching of the skin and discolouration.

- In general, the vehicle and naïve control animals had a high incidence of slight patchy erythema. These reactions lead to a degree of uncertainty in the results and the possible confounding effects of local irritation rather than delayed hypersensitivity.

General methodological limitations

- It is not clear in the available report whether the animals were observed ‘blind’. If this is not the case then observer bias could have occurred.

- The formal Magnusson and Kligman grading scale included in the OECD 406 guideline has not been used in the available OECD 406 study (includes an additional grade band). As such there is some potential for misalignment with the grading used on the study and that intended in the guideline. Grade 2 or 3 in the OECD 406 guideline (moderate and confluent erythema/intense erythema and swelling) are in general used to indicate that skin sensitisation has occurred (ECETOC Monograph 29). However, grade 1 in the available study (on which designation as a skin sensitiser is based observed in 6/20 test animals) is scaled as slight but confluent or moderate patchy erythema. It is not clear whether the reactions in the 6/20 animals were slight but confluent or moderate and patchy erythema, the former not being designated in the OECD 406 guideline scale.

- For water soluble substances, the OECD 406 guideline prefers the use of water or a dilute-non irritating solution of surfactant as the vehicle. However, for the challenge exposure acetone was instead used even though the substance is highly soluble in water (ca. 20 g/L).

The general conclusions on the observations noted are that there is a degree of uncertainty and that under the specific circumstances the test may have warranted a re-challenge exposure (possibly at a lower test concentration) to assist in better interpreting the results. This re-challenge exposure was not performed.  

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the test, commercial grade vinyl acetate indicated a weak skin sensitising potential in the guinea pig. However, there were limitations to this study such as guideline deviations, issues with concentration selection, general methodological limitations etc.
Executive summary:

The potential of the test material, undiluted vinyl acetate (commercial grade), and the vehicle control material hydroquinone in acetone (5 ppm), to produce delayed contact hypersensitivity in guinea pigs was separately evaluated using an adaptation of the method of Ritz and Buehler. Hydroquinone (a known sensitizer in concentrated form) is used in trace amounts as an inhibitor in vinyl acetate and it was important to control for its possible contribution here. Following primary challenge using the test material, vinyl acetate as a 25% w/v formulation in acetone, the incidence of grade 1 responses in the test group (6 of 20) was compared to that of the naive control group (0 of 10). The incidence and severity of these responses in the test group were greater than those produced by the naive control group indicating that sensitization had been induced. Following primary challenge using the vehicle material, hydroquinone in acetone (5 ppm), there were no grades of 1 produced. The incidence of grade 1 responses in the vehicle control group (7 of 10) was compared to that of the naive control group (7 of 10). The incidence and severity of these responses in the vehicle control group were essentially comparable to those produced by the naive control group indicating that sensitization had not been induced. However, there were limitations to this study such as guideline deviations, issues with concentration selection, general methodological limitations etc.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Non-human information

The key study is a guideline and GLP compliant Local Lymph Node Assay (LLNA) using vinyl acetate of 99.9% purity (RCC, 2003c). No biologically significant positive stimulation responses were detected at concentrations of 5% to 100%. Increased ear thickness (indicative of local inflammatory reaction) after treatment with concentrations >5% correlate with the irritative properties reported following prolonged dermal exposure. The stimulation responses may have been reduced at higher concentrations of vinyl acetate (>10%)due to the physico-chemical properties of the substance; the LLNA may not have been able to adequately determine the stimulation responses as the decreased proportions of acetone/olive oil present may have resulted in increased volatility and evaporation from the application site. Nevertheless, the study incorporates the full range of vinyl acetate concentrations and whilst a weak sensitising effect of vinyl acetate was observed, the positive threshold level was not exceeded and no sensitisation classification was warranted. Some sensitising activity was also seen in an earlier Buehler test conducted by Hill Top Biolabs (1995).

Results of an animal skin sensitization study (Buehler Test) showed a mild to moderate skin sensitising potential of vinyl acetate (commercial grade) of unknown purity (Hill Top Biolabs, 1995).The potential to produce delayed contact hypersensitivity in guinea pigs was evaluated for undiluted vinyl acetate (commercial grade of unknown purity) and the results indicated that vinyl acetate was a moderate skin sensitiser. The Buehler test conducted was not fully compliant with the OECD 406 Guideline. The test substance used was also of a commercial grade whilst the substance used for the LLNA was highly pure. Other methodological limitations of the available Buehler assay include the following:

Limitations relating to guideline deviations, concentration selection and local irritation

- The induction phase used a total of nine 6 hour exposures (3 per week for 3 weeks). The OECD 406 guideline requires seven exposure periods on Days 0, 6, 7, 8, 13, 14 and 15.

- The pilot phase showed slight, patchy erythema in 3/4 and 2/4 animals at 24 or 48 hours respectively post exposure when treated at 25% w/v. The OECD 406 guideline requires that the challenge dose is the highest that is non-irritant. In this case minor irritation was observed at the challenge dose assessed in the pilot phase.

- In the induction phase excessive irritation was noted at several of the induction sites following the fourth induction exposure. In the guideline the induction concentration is one that is meant to cause mild skin irritation only, whilst here it is detailed as excessive. Observations observed (those detailed) mainly related to blanching of the skin and discolouration.

- In general, the vehicle and naïve control animals had a high incidence of slight patchy erythema. These reactions lead to a degree of uncertainty in the results and the possible confounding effects of local irritation rather than delayed hypersensitivity.

- For water soluble substances, the OECD 406 guideline prefers the use of water or a dilute-non irritating solution of surfactant as the vehicle. However, for the challenge exposure acetone was instead used even though the substance is highly soluble in water (ca. 20 g/L).

General methodological limitations

- It is not clear in the available report whether the animals were observed ‘blind’. If this is not the case then observer bias could have occurred.

- The formal Magnusson and Kligman grading scale included in the OECD 406 guideline has not been used in the available OECD 406 study (includes an additional grade band). As such there is some potential for misalignment with the grading used on the study and that intended in the guideline. Grade 2 or 3 in the OECD 406 guideline (moderate and confluent erythema/intense erythema and swelling) are in general used to indicate that skin sensitisation has occurred (ECETOC Monograph 29). However, grade 1 in the available study (on which designation as a skin sensitiser is based observed in 6/20 test animals) is scaled as slight but confluent or moderate patchy erythema. It is not clear whether the reactions in the 6/20 animals were slight but confluent or moderate and patchy erythema, the former not being designated in the OECD 406 guideline scale.

The general conclusions on the observations noted are that there is a degree of uncertainty and that under the specific circumstances the test may have warranted a re-challenge exposure (possibly at a lower test concentration) to assist in better interpreting the results. This re-challenge exposure was not performed.  

Human information

There are some limited data regarding sensitising potential of vinyl acetate in workers (for example, Deese & Joyner, 1969) but these data are of rather limited value (EU RAR, 2008).No cases of skin sensitisation from the handling of vinyl acetate in the workplace have been reported. However, there are no data on negative patch tests to substantiate the conclusion that the substance has no skin sensitising potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No direct information is available from studies in humans on respiratory sensitization. In view of the widespread use, the absence of any reports suggests that vinyl acetate may not be a respiratory sensitiser.

Justification for classification or non-classification

The outcomes of two animal studies, using different methodologies, indicate some weak potential for sensitising activity of vinyl acetate. However, the LLNA was given a higher reliability for the reasons discussed and since the positive threshold level was not exceeded in the LLNA, vinyl acetate was considered not to be a skin sensitiser.