Acetaldehyde oxime

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, according to OECD test guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Adopted May 12, 1981

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

September 1984

GLP compliance:

yes

Remarks:

US FDA (21 CFR 58) and US EPA (40 CFR 160 and 40 CFR 792)

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfield, FRG
- Age at study initiation: approximately 2 months
- Weight at study initiation: 361-510 g
- Housing: metal cages with wire-mesh floors
- Diet: standard guinea pig diet, including ascorbic acid (1600 mg/kg) obtained from Hope Farms, Woerden (LC 23-B, pellet diameter 4 mm), in addition hay was provided once a week
- Water: ad libitum
- A combined quarantine/acclimatisation period of 14 days was allowed (7 days for the animals of the primary irritation experiment)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 60-90
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route:

intradermal and epicutaneous

Vehicle:

other: physiological saline; physiological saline emulsified with an equal volume of Freunds Complete Adjuvant; Milli-RO water

Concentration / amount:

induction:
-intradermal injections: 0.5%
-epicutaneous application: 25%

challenge:
- first: 0, 10, 25, 50%
- second: 0, 10, 20, 40%

Route:

epicutaneous, occlusive

Vehicle:

other: physiological saline; physiological saline emulsified with an equal volume of Freunds Complete Adjuvant; Milli-RO water

Concentration / amount:

induction:
-intradermal injections: 0.5%
-epicutaneous application: 25%

challenge:
- first: 0, 10, 25, 50%
- second: 0, 10, 20, 40%

No. of animals per dose:

test group: 20
control: 10

Details on study design:

RANGE FINDING TESTS:
Primary irritation experiments included intracutaneous injections and
epicutaneous applications of several concentrations of the test
substance diluted in Milli-RO water (Millipore Corp., Bedford, Mass,.
USA). One animal received 4 x 0.1 mI intracutaneous injections of 5%
(w/w) test substance and the undiluted test substance epicutaneously
applied. This animaI was found dead the next day. An extra animaI
was added and received 4 x 0.1 mI intracutaneous injections of 1%
(w/w) test substance and 0.5 mI 50% (w/w) concentrations
epicutaneously applied. The intracutaneous injections caused redness.
The epicutaneous application caused slight redness and scaliness of
the skin. This animal showed Iethargy, a pale skin and diarree the
days after treatment. Because of this, the test substance
concentration for the first induction was decreased to 0.5% (w/w).

Af ter cancelling the first Guinea Pig Maximization Test on study day 8
(because of mortality and systemic toxicity) an extra preliminary test was performed. For controling the
dermal toxicity of the test substance a second extra animal was
added, which received 0.5 mI 50% (w/w) test substance in Milli-RO
water. Also this animal showed the same signs of toxicity as the
animal before, therefore the test substance concentration for the
second induction was decreased to 25% (w/w). Four other animals
received an epicutaneous application of the test substance at 100%,
50%, 25% and 5% (w/w) in an amount of 0.05 mI using Square chambers
(v.d. Bend, Brielle, the Netherlands).
No signs of systemic toxicity were observed in these four treated
animaIs, except a slight bodyweight loss of the first animal.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 48 h (epicutaneous application)
- Test groups:
intradermal injection: test substance (0.5% w/w in physiological saline); Freunds Complete Adjuvant (FCA) emulsified with an equal volume of distilled water; test substance (1.0% w/w in physiological saline) emulsified with an equal volume of FCA
epicutaneous application: test substance
- Control group:
intradermal injection: physiological saline; FCA; FCA emulsified with an equal volume of physiological saline
epicutaneous application: water
- Site: between the shoulders
- Concentrations:
intradermal injection: 0.5 and 1% w/w
epicutaneous application: 25% w/w

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 21, 28
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: left flank (day 21), right flank (day 28)
- Concentrations:
first challenge: 50, 25, 10, 0%
second challenge: 40, 20, 10, 0%
- Evaluation (hr after challenge): 24 and 48 h

Positive control substance(s):

yes

Remarks:

Formaldehyde solution

Positive control results:

A positive control experiment was carried out in September 1987 (NOTOX 0000/809) in order to validate the animals and the test procedure.
Test substance: formaldehyde solution 37% (p.a., art. 4003, Merck, Darmstadt, FRG)
Induction phase: 5% (V/V) in Milli-RO water (Millipore Corp., Bedford, Mass., USA).
Challenge phase: 5%, 3% and 0.5% (V/V) in Milli-RO water.
A sensitization rate of 100 per cent was obtained to the 5%, 3% and 0.5% concentrations.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0, 10, 25, 50%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0, 10, 25, 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0, 10, 25, 50%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0, 10, 25, 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

rechallenge

Hours after challenge:

24

Group:

negative control

Dose level:

0, 10, 20, 40%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0, 10, 20, 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

0, 10, 20, 40%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0, 10, 20, 40%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0, 10, 25%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0, 10, 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

1

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0, 10, 25, 50%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0, 10, 25, 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

0, 10, 20, 40%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0, 10, 20, 40%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

0, 10, 20, 40%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 0, 10, 20, 40%. No with. + reactions: 0.0. Total no. in groups: 20.0.

INDUCTION

Eleven experimental animals showed severe erythema to eschar formation on the treated skin after removal of the dressings from the second induction. This was mainly a combined result of the intracutaneous injection and the epicutaneous application.

CHALLENGE

The test substance was diluted in Milli-RO water to three concentrations (50%, 25% and 10%) and administered epicutaneously to guinea pigs in the challenge phase. This challenge treatment produced positive skin reactions (grade 2 or more) in one experimental animal in reaction to the 50% test substance concentration. Nine other

experimental animals and two control animals showed red spots in reaction to one or two concentrations tested. Therefore, a second challenge was performed 7 days later with the following test substance cocncentrations: 40%, 20% and 10% (w/w).

None of the experimental animals showed a positive response in reaction to the concentrations tested. Five experimental animals showed red spots in reaction to one or two of the concentrations tested.

No skin reactions were observed in the control animals to any of the application sites, except for one animal 48 h after

removal of the dressings. No consistent signs of systemic toxicity were observed in any of the animals during the study.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: other: 67/548/EEC

Conclusions:

The results lead to a sensitization rate of 0%. It is therefore improbable that the test substance has sensitizing properties.

Executive summary:

A sample of AAX/310588 was tested in the Guinea Pig Maximization

Test (Magnusson and Kligman) to determine its sensitizing

potential.

Adult female guinea pigs (Dunkin-Hartley strain) were induced by

intradermal injections of the test substance, 0.5% (w/w) in

physiological saline, followed by epicutaneous application of a

25% solution of the test compound in Milli-RO water. After being

challenged with three test substance concentrations in Milli-RO

water, 50%, 25% and 10% (w/w), one experimental anima1 showed a

positive response (grade 2) in reaction to the 50% concentration.

Nine other experimental animals and two control animals showed

red spots in reaction the one or two of the concentrations tested.

Due to this unclear reaction, a second challenge was

performed 7 days later, with the following concentrations: 40%,

20% and 10% (w/w). None of the experimental animals showed a

positive response in reaction to this second challenge treatment.

Five experimental animals and one control animal showed red spots

in reaction to one or two of the concentrations tested.

Thus, a sensitization rate of 0 per cent was obtained. Therefore

it is improbable that the test substance has sensitizing

properties.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation

 

Two studies were evaluated for skin sensitization, a guinea pig maximization test (Daamen 1988 (K1)) and a mouse ear swelling test (Koopmans 1989 (K2)).

 

In the key study (Daamen 1988), adult female guinea pigs (Dunkin-Hartley strain) were induced by intradermal injections of the test substance (0.5% (w/w) in physiological saline) followed by epicutaneous application (25% test compound solution in Milli-RQ water). Animals were challenged twice. The first time with 50, 25, 10 and 0% (w/w) and the second time with 40, 20, 10 and 0% (w/w) of the test compound.

After the first challenge, one animal out of 20 showed moderate but confluent redness. After the second challenge 7 days later, none of the animals showed redness.

 

In the supporting study (Koopmans 1989), AAO did not induce skin hypersensitivity in the mouse under the conditions of this test.

Migrated from Short description of key information:
AAO was found to be not sensitising to the skin.

Justification for selection of skin sensitisation endpoint:
K1 study.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sensitisation

The two evaluated studies, a guinea pig maximization and a mouse ear swelling test, concluded that AAO did not induce sensitisation under the test conditions. The guinea pig maximization test is one of the three recognized and officially accepted animal test methods for skin sensitisation defined by OECD test guidelines. According to CLP criteria, a test is considered positive when an adjuvant type test method results in a response of at least 30% of the animals. After the first challenge only one animal showed redness and after the second challenge none of the animals showed redness. As a consequence, AAO does not need to be classified as a skin sensitizer.

Respiratory sensitisation

No data available.