Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed prior to the implementation of GLP and OECD Guidelines, but is in general in compliance with the principles described in OECD Guideline 404.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not applicable
GLP compliance:
no
Remarks:
test predated GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Name of test material:
Methoxyacetic acid

Expiry date: May 1982

Impurities (identity and concentrations):
appr. 0.2 % formic acid
max. 0.5 % water
max. 0.1 % formaldehyde
< 0.1 % glycolic acid
< 0.1 % oxalic acid
< 0.5 % varied ester
< 0.001 % N

Test animals

Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler (Offenbach, Germany)
- Body Weight: 2.25 - 3.05 kg (average weight males: 2.63 kg, average weight females 2.58 kg)
- Housing: one animal per cage
- Diet: Ca. 130 g/d per animal
- Water: Ca. 250 mL/d per animal
- Acclimation period: Ca. 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 50 - 80
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: undiluted

Duration of treatment / exposure:
4 females were treated for 3 minutes and 1 hour using occlusive conditions.
2 males were treated for 4 hours using occlusive conditions.
Observation period:
Surviving animals were observed for 8 days.
Number of animals:
6 animals were treated.
Details on study design:
A cotton patch (edge length 2.5 cm) was loaded with appr. 0.5 mL of methoxyacetic acid and applied occlusively on clipped dorsal skin (application site 2.5 x 2.5 cm). Two patches were applied per animal (four animals in total) and removed after 3 min or 1 hour of exposure. 2 animals recieved one patch for an incubation period of 4 hours before removal of the patch. Remaining test substance was washed off with Lutrol (PEG400) and Lutrol/Water (1:1). Exposed skin was evaluated 15 - 30 minutes after removal of the patch and at 24 hours, 48 hours and 8 days after beginning test substance application. Untreated dorsal skin served as a negative control.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
(incubation period: 3 min)
Basis:
mean
Remarks:
of four animals
Time point:
other: 24 hours
Score:
1.75
Max. score:
4
Remarks on result:
other: slight to intense reddening
Irritation parameter:
erythema score
Remarks:
(incubation period: 3 min)
Basis:
animal #1
Time point:
other: 48 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 3 animals were sacrificed after 24 hrs.
Irritation parameter:
edema score
Remarks:
(incubation period 3 min)
Basis:
mean
Remarks:
of four animals
Time point:
other: 24 hours
Score:
1
Max. score:
4
Remarks on result:
other: marked oedema in 2 out of 4 animals
Irritation parameter:
edema score
Remarks:
(incubation period: 3 min)
Basis:
animal #1
Time point:
other: 48 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 3 animals were sacrificed after 24 hrs.
Irritation parameter:
erythema score
Remarks:
(incubation period: 1 hour)
Basis:
mean
Remarks:
of four animals
Time point:
other: 24 hours
Score:
3.75
Max. score:
4
Remarks on result:
other: animal #1: reddening, oedema; other animals: moist and blistering necroses
Irritation parameter:
erythema score
Remarks:
(incubation period: 1 hour)
Basis:
animal #1
Time point:
other: 48 hours
Score:
3
Max. score:
4
Remarks on result:
other: 3 animals were sacrificed after 24 hrs.
Irritation parameter:
erythema score
Remarks:
(incubation period: 1 hour)
Basis:
animal #1
Time point:
other: 8 days
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: necrosis
Irritation parameter:
edema score
Remarks:
(incubation period: 1 hour)
Basis:
mean
Remarks:
of four animals
Time point:
other: 24 hours
Score:
2.25
Max. score:
4
Remarks on result:
other: animal #1: reddening, oedema; other animals: moist and blistering necroses
Irritation parameter:
edema score
Remarks:
(incubation period: 1 hour)
Basis:
animal #1
Time point:
other: 48 hours
Score:
2
Max. score:
4
Remarks on result:
other: 3 animals were sacrificed after 24 hrs.
Irritation parameter:
edema score
Remarks:
(incubation period: 1 hour)
Basis:
animal #1
Time point:
other: 8 days
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: necrosis
Irritation parameter:
erythema score
Remarks:
(incubation period 4 hrs)
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 24 hours
Score:
4
Max. score:
4
Remarks on result:
other: moist and blistering necroses, oedema formation
Irritation parameter:
erythema score
Remarks:
(incubation period: 4 hours)
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 48 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: blistering necroses, animals were sacrificed due to severe skin corrosion
Irritation parameter:
edema score
Remarks:
(incubation period: 4 hours)
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 24 hours
Score:
3.5
Max. score:
4
Remarks on result:
other: moist and blistering necroses, oedema formation
Irritation parameter:
edema score
Remarks:
(incubation period 4 hours)
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 48 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: blistering necroses, animals were sacrificed due to severe skin corrosion
Irritant / corrosive response data:
3-minute exposure: Slight to intense reddening in all animals, oedema (marked) in two out of four animals 24 hours after application. Irritant effects were fully reversible after 48 hours. The animals were also exposed to a patch for 1 h. Three of the four animals had to be sacrificed after 24 hrs due to the corrosive effect caused by the 1 h skin exposure.
1-hour exposure: Severe to very severe reddening of the skin with oedema formation, moist and blistering necroses 24 hours after application. Three of the four animals had to be scarificed due to the corrosive effect after 24 hours. Surviving rabbit: Irritant effects were not reversible after 48 hours (necrosis).
4-hour exposure: Moist and blistering necroses and oedema formation 24 hours after application. 48 hours after application blistering necroses were visible. Both animals had to be sacrificed due to the corrosive effect.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Methoxyacetic acid exhibited a corrosive potential.
Executive summary:

In a primary dermal irritation study Vienna White Rabbits were dermally exposed to undiluted Methoxyacetic acid using cotton patches (2.5 x 2.5 cm) loaded with appr. 0.5 mL of Methoxyacetic acid. Applied occlusively, clipped dorsal skin was covered for 3 min, 1 hour or 4 hours. After removal of the patch remaining test substance was washed off. Exposed skin was evaluated 15 - 30 minutes afterwards and at 24 hours, 48 hours and 8 days after test substance application. Animals were then observed for 8 days. Irritation was scored by the method of Draize. Three-minute exposure resulted in intense reddening and marked oedema 24 hours after application. After 48 hours irritant effects were fully reversible. After 1 -hour exposure, severe to very severe reddening of the skin with oedema formation, moist and blistering necroses were noticed 24 hours after application. Three of the four animals had to be sacrificed due to the corrosive effect, after 48 hours irritant effects were not reversible in the surviving animal. In case of 4-hour exposure, moist and blistering necroses and oedema formation were noticed 24 hours after application. Furthermore, blistering necroses were visible 48 hours after application. Both animals had to be sacrificed due to the corrosive effect. Methoxyacetic acid exhibited a corrosive potential in this study.