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Administrative data

Description of key information

The test substance has no skin irritant properties in laboratory animals.
Studies on eye irritation in rabbits indicated irritant effects of the test substance.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is comparable to OECD Guideline 404 with acceptable restrictions (partly limited documentation, e.g. no scoring 48 h after exposure; ca. 1 mL test substance applied, exposure period 20 h and occlusive coverage conditions [worst case scenario]).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Skin irritation was tested using an internal method (BASF test) which is similar to OECD 404.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
- Purity: 99.9 %
No further details available.
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.35 kg (male), 2.63 kg (female)

No further details available.
Type of coverage:
occlusive
Preparation of test site:
other: no data (presumably shaved)
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: approximately 1 mL

The application site (dorsal skin) was covered with a cotton patch of 2.5 x 2.5 cm; the patch was soaked with the test substance and applied to the skin; no further data.
Duration of treatment / exposure:
1, 5, or 15 minutes (washing with Lutrol or 50 % aqueous Lutrol) or 20 h (unwashed)
Observation period:
Results were recorded each working day for up to 7 days (exceptions: see Table 2). The first scoring was conducted 24 h after initiation.
Number of animals:
2 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: After the reported exposure time the skin was washed (not after 20 h exposure).

SCORING SYSTEM:
BASF grading for redness and edema (see Table 1 below).
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 24-96 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 20 h exposure period; no edema detected; fine scaling in one rabbit at day 7
Irritant / corrosive response data:
In the female rabbit no effects were detected after 1-15 minutes exposure except a slight reddening on the day of exposure, and concerning 15 minutes exposure a slight reddening also at the day after exposure; in the male rabbit also no effects were detected except a questionable reddening 1-3 days after exposure for 1-15 minutes.

Data after 20 h exposure are presented in the Table 2 below.
No edema was seen in any test animal. At all time points for scoring not more than a questionable reddening was detected, which was reversible after 7 days. One rabbit showed a fine scaling 7 days after application.
Other effects:
Body weight was not altered in both animals.
No further effects were reported.

Table 2: Skin erythema in 2 rabbits after dermal exposure to the undiluted test substance for 20 h

Time after initiation of exposure

20 hours exposure; erythema in

Rabbit 1 (f)

Rabbit 2 (m)

24 h

1

1

48 h

no data

no data

72 h

1

1

4 days

1

1

 7 days  fine scales  0

- Evaluation transformed to OECD-Draize scoring; no edema reported.

Interpretation of results:
GHS criteria not met
Conclusions:
DMAC was no skin irritant in rabbit. A slight transient (questionable) reddening of the skin was noted.
Executive summary:

In a study according to a BASF internal standard method comparable to OECD 404, two rabbits were dermally exposed to undiluted liquid test substance (ca. 1 mL) for 1, 5, 15 minutes or for 20 h to the back skin. The coverage was occlusive; the skin was washed after exposure (not after the exposure period of 20 h). Skin reaction was scored 24, 72, 96 h and 7 days after initiation.

The test substance had only slight skin irritant properties after an exposure period of 20 h. Questionable to slight reddening was found after 1-15 minutes of exposure, effects were reversible 48-96 h after exposure. After the 20 h exposure period no edema was seen in any test animal. At all time points for scoring not more than a questionable reddening (OECD score 1) was detected, which was reversible after 7 days. One rabbit showed a fine scaling 7 days after application. Therefore, the test substance was considered to be no skin irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study with acceptable restrictions (partly limited documentation, only 0.05 mL applied).
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Eye irritation was tested using an internal method (BASF test) similar to OECD405.
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
- Purity: 99.9 %
No further details available.
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Body weight: 2.66 kg (male), 2.12 kg (female)

No further details available.
Vehicle:
unchanged (no vehicle)
Controls:
other: 1 drop of physiological saline was instilled into the other eye.
Amount / concentration applied:
TEST MATERIAL
- Amount applied:1 drop (corresponding to appr. 50 mm³)
Duration of treatment / exposure:
No washing
Observation period (in vivo):
10 minutes, 1, 3, 24, 48, 72 hours, 6, 8 days after instillation
Number of animals or in vitro replicates:
2 rabbits
Details on study design:
No washing of the test substance after 24 h (compare with OECD Guideline 405).

SCORING SYSTEM: BASF scores. Scoring was converted to OECD Guideline 405 grading (see table 1).
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 10 minutes, 1, 3, 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: other time points score 0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 3 & 24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Remarks on result:
other: other time points score 1
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 3, 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: score 1 after 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: all time points up to day 6
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: score 1 after 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: other time points score 1
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8days
Remarks on result:
other: other time points score 1; still score 1 at termination
Irritant / corrosive response data:
No effects in control eye. Other effects: see Table1 below. The reddening reached max. score 2 in both rabbits and was not completely reversible in one rabbit after 8 days (score 1); chemosis reached also score 2 but was not evident for 24 h (related to observation period >= 24 h after application). Corneal opacity reached score 2 only for one time point (24 h, both rabbits), later evaluation resulted in score 1; the effects were not completely reversible in one rabbit after 8 days. However, effects were regressive with time in both rabbits.
Other effects:
There were no other effects.

Table 1: Eye irritation in rabbits after instillation of 0.05 mL undiluted test substance

Rabbit 1 (male) // Rabbit 2 (female)

Time after application

Erythema

Chemosis

Opacity of the cornea

Iritis

Remark

10 min

2//2

2//1

0//0

0//0

Increased secretion in rabbit 1 and 2

1 h

1//2

2//1

1//1

0//0

Increased secretion in rabbit 1 and 2

3 h

2//2

2//2

1//1

0//0

-

24 h

2//2

2//2

2//2

0//0

-

48 h

2//2

0//1

1//1

1//0

Bleeding of the mucous membrane in rabbit 2

72 h

2//2

0//1

1//1

0//0

Bleeding of the mucous membrane in rabbit 2

6 days

1//2

0//0

0//1

0//0

Bleeding of the mucous membrane in rabbit 2

8 days

0//1

0//0

0//1

0//0

-

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
DMAC was irritating to the rabbit eye.
Executive summary:

Two Vienna White rabbits received instillation of one drop (approx. 50 mm³) of the undiluted test substance into the conjunctival sac. The other eye was treated with physiological saline for control. Scoring was performed 10 minutes, 1, 3, 24, 48, 72 hours and 6 and 8 days after instillation. The reddening reached max. score 2 in both rabbits and was not completely reversible in one rabbit after 8 days (score 1); chemosis reached also score 2 but was not evident for 24 h (related to observation period >= 24 h after application). Corneal opacity reached score 2 only for one time point (24 h, both rabbits), later evaluation resulted in score 1; the effects were not completely reversible in one rabbit after 8 days. However, effects were regressive with time in both rabbits.

In conclusion, undiluted test substance was irritant to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the OECD SIDS document (2001; SIAM 13) on N,N-dimethylacetamide (DMAC) data were presented on this endpoint which were also documented in this report. However, further studies relevant for evaluation were found which were not included in the OECD SIDS (2001). This might be related to the fact that the initial version of the OECD SIDS document was prepared for SIAM3 (1995). Delegates of SIAM3 criticised lacking information and these comments could still not be resolved at the meeting of SIAM12.

A bright set of studies is available for the endpoint irritation/corrosion for DMAC. In this endpoint summary only relevant studies are mentioned.

Skin irritation

The test substance had only slight skin irritant properties after an exposure period of 20 h. This was shown in a study on two rabbits which were dermally exposed to undiluted liquid test substance (ca. 1 mL) for 1, 5, 15 minutes or for 20 h. The coverage was occlusive; the skin was washed after exposures of 1 - 15 min but not after the exposure period of 20 h. Skin reaction was scored 24, 72, 96 h and 7 days after initiation. Questionable to slight reddening was found after 1-15 minutes of exposure, effects were reversible 48-96 h after exposure. After the 20 h exposure period no edema was seen in any test animal. At all time points for scoring not more than a questionable reddening (OECD score 1) was detected, which was reversible after 7 days. One rabbit showed a fine scaling 7 days after application (1970, RL2).

The following studies gave supporting data.

Six albino rabbits were treated with 0.5 mL of a test substance/water mixture (50:50). The applied skin was covered with cotton gauze pad and loosely wrapped with rubber sheeting (secured with adhesive tape). The animals were observed at 4 hours during initial removal of the test substance and then again at 24 and 48 hours after initial application. When tested and classified according to the regulations of the Department of Transportation, the test substance/water (50/50) formulation was not found to be corrosive to the skin of rabbits. The study and the conclusions which are drawn from it fulfill the quality criteria with regard to validity, reliability and repeatability (1977, RL2).

In the study of Smyth et al. (1962, RL2) five albino rabbits received uncovered dermal application of 0.01 mL undiluted test substance on the clipped skin. The exposure duration was 24 h. The authors observed least visible capillary injection within 24 h after application. It is concluded that the application of 0.01 mL undiluted test substance resulted in slight skin irritation. However, the study has some limitation (partly limited documentation; unusual evaluation system, no scoring later than 24 h).

Furthermore, a study comparable to OECD Guideline 430 (Oliver et al., 1988, RL2) was performed. This rat skin transcutaneous electrical resistance (TER) assay is able to reliably discriminate between known skin corrosives and non-corrosives. Skin corrosive effects lowering of the electrical resistance of an epidermal slice (rat skin) in vitro following chemical contact were studied 2 h after an exposure period of 30 minutes. The authors selected an electrical resistance value of 4 kΩ to discriminate between corrosive and non-corosive substances in this in vitro test, i.e. chemicals reducing electrical resistance below 4 kΩ skin disc in vitro would be predicted to induce a corrosive lesion in vivo using conventional animal protocols. Electrical resistance of the test substance in the rat skin transcutaneous electrical resistance assay was 4.9 ± 1.1 k Ω. Therefore, the test substance was categorized as non-corrosive in this in vitro assay (No data available after 1 and 4 h exposure. This in vitro assay can not be used to discriminate between irritating and non-irritating chemicals). However, before final evaluation the dye binding method should be used for verification of results. In conclusion, the electrical resistance in rat skin was not clearly reduced suggesting no corrosive properties of DMAC.

Data from an acute dermal toxicity study (Wiles et al., 1971, RL2) indicated no irritant effects in rabbits during the post exposure observation period of 14 days after dermal application of up to 1.5 mL per rabbit.

Eye irritation

Two Vienna White rabbits received instillation of one drop (approx. 50 mm³) of the undiluted test substance into the conjunctival sac. The other eye was treated with physiological saline for control. Scoring was performed 10 minutes, 1, 3, 24, 48, 72 hours and 6 and 8 days after instillation. The reddening reached max. score 2 in both rabbits and was not completely reversible in one rabbit after 8 days (score 1); chemosis reached also score 2 but was not evident for 24 h (related to observation period >= 24 h after application). Corneal opacity reached score 2 only for one time point (24 h, both rabbits), later evaluation resulted in score 1; the effects were not completely reversible in one rabbit after 8 days. However, effects were regressive with time in both rabbits.

In conclusion, undiluted test substance was irritant to the rabbit eye (1970, RL2).

Supporting evidence for irritant effects in the rabbit eye came from a second study report using both washing and non-washing procedure. Two rabbits were instilled each with 0.1 mL undiluted test substance (other eye remained untreated for control). In one rabbit the eye was washed after 1 minute exposure, no washing was performed in the other rabbit. The post exposure observation period was 14 days (no details about time points of evaluation; no scoring system data). More severe effects were detected in the washed eye: the cornea revealed marked injury with considerable edema at days 1-3; improvement with localized vascularization was seen at day 7 but superficial microscopic effects were noted even at day 14. The iris of this rabbit showed moderate iritis at days 1-3 and moderate redness, swelling and discharge of the conjuctivae through 2 days (no further details) with improving to mild swelling and redness at day 7 (no data about day 14). In summary, irritant effects in the rabbit eye were found but interestingly more severe effects in the washed eye as compared to the unwashed eye (1965, RL2).

Supportingly, irritating effects were observed in an in vitro test (1992, RL2). However, in this BCOP test corneas were incubated for 30 min with concentrations of 40 - 100%, instead of 10 min at 10 % according to the OECD TG 437.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified not for skin irritation, but for eye irritation Cat. 2 (H319: Causes serious eye irritation) under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

In the present entry in Annex VI to Regulation (EC) No 1272/2008, Dimethylacetamide is neither classified for skin irritation nor for eye irritation.