Registration Dossier

Administrative data

Description of key information

Skin irritation: BASF AG 1952, non-GLP Study, comparable to guideline study, Albino rabbit, occlusive (patch), 20 h exposure: Not irritating

Eye Irritation: TSCATS: OTS 0516779, 1978, comparable to OECD TG 405, New Zealand White rabbits, 0.1 mL: Irritating

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:
comparable to guideline study with acceptable restrictions
Principles of method if other than guideline:
- Principle of test: BASF method.
- Short description of test conditions: A patch is soaked with DMF and applied onto the skin on the back of the rabbits and fixed with a bandage. The neat test substance (about 0.5 mL) was administered for 20 hours. After bandage removal the application site was examined. In case of symptoms, examination was performed further until the findings disappeared.
- Parameters analysed / observed: Application site (erythema and edema score)
GLP compliance:
no
Remarks:
The study was performed prior to the adoption of GLP compliance.
Species:
rabbit
Strain:
other: Albino
Details on test animals or test system and environmental conditions:
data not available
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): undiluted and as 50 % solution in water.
Duration of treatment / exposure:
20 hours
Observation period:
48 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: shaved back of albino rabbits.
- % coverage: 2.5 cm X 2.5 cm big patch
- Type of wrap if used: patch fixed with a bandage.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 20 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 24h, 24h/48
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.25
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 72 h data missing
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 72 h data missing
Irritant / corrosive response data:
Only one of the four animals showed faint redness on the first day after removal of the bandage.
Other effects:
no

Mean erythema score after 24 and 48 h (72 h data is missing); (animal 1/animal 2):

 Conc.  24 h  48 h  mean
 100%  1/0  0/0 0.5/0
 50%  1/0  0/0 0.5/0

Mean edema score after 24 and 48 h (72 h data is missing); (animal 1/animal 2):

 Conc.  24 h  48 h  mean
 100%  0/0  0/0 0/0
 50%  0/0  0/0 0/0
Interpretation of results:
other:
Remarks:
EU GHS criteria not met
Conclusions:
Only one animal showed faint redness on the first day after removal of the bandage. On the second day there were no more findings. The other animal was without any findings. Under the present test conditions DMF was not irritating.
Executive summary:

Study design

This non-GLP in vivo study was performed comparable with OECD guideline study. The neat substance (about 0.5 mL) was administered for 20 hours on the shaved back of 4 albino rabbits. For this purpose a 2.5 cm x 2.5 cm big patch was soaked with the test substance and applied onto the skin and fixed with a bandage. After removal of the bandage the application site was examined and in case of findings, observation continued until the findings disappeared.

Results

Only one animal showed faint redness on the first day after removal of the bandage. On the second day there were no more findings. The other animal was without any findings.

Conclusion

Under the present test conditions DMF was not irritating.

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:
comparable to guideline study with acceptable restrictions
Remarks:
No data on a OECD compliance
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
- Short description of test conditions: Instillation of 0.1 mL of neat test substance into one eye of 6 New Zealand rabbits without rinsing. The untreated eye served as control. Readings were done 1, 4, 24, 48, 72 hours and 4, 7, 10, and 13 days after application.
- Parameters analysed / observed: Scoring of ocular lesions was done according to Draize et.al. (1944).
GLP compliance:
no
Remarks:
The study was performed prior to the adoption of GLP compliance.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No information given
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
undiluted
Duration of treatment / exposure:
single dose
Observation period (in vivo):
13 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes were not rinsed after treatment.

SCORING SYSTEM: according to Draize et.al. (1944)
Irritation parameter:
other: primary irritation index
Basis:
mean
Time point:
other: 1h
Score:
50.8
Max. score:
110
Reversibility:
fully reversible within: 48 h
Irritation parameter:
other: primary irritation index
Basis:
mean
Time point:
72 h
Score:
35.8
Max. score:
110
Reversibility:
fully reversible within: 48 h
Irritation parameter:
other: primary irritation index
Basis:
mean
Time point:
other: day 4
Score:
35
Max. score:
110
Reversibility:
fully reversible within: 48 h
Irritation parameter:
other: primary irritation index
Basis:
mean
Time point:
other: day 13
Score:
3.3
Max. score:
110
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: no details given
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: no details given
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: no details given
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: no details given
Other effects:
Other observations: Primary irritation index was 50.8 after 1 h decreasing to 35.8 after 72 h and 35.0 on day 4 decreasing to 3.3 on day 13 (max. = 110). All animals in the present study showed large blisters on the inside of upper and lower lids at the 1 and 4 hour readings. Blisters decreased in size at the 24 hour reading and they were gone at 48 hours. According to the authors, the test substance was classified as severely irritating to the rabbit eyes when applied without rinsing.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Classification: irritating
Executive summary:

Study design

This non-GLP in vivo study was conducted comparable to OECD TG 405. In the present study neat DMF of 0.1 mL was instilled into one eye of 6 New Zealand white rabbits without rinsing. The untreated eye served as control. Readings were performed 1 h, 4 h, 24 h, 48 h, 72 h, 4 d, 7 d, 10 d and 13 d after application. Scoring of ocular lesions was done according to the method of Draize et al. (1944).

Results

Primary irritation index was 50.8 after 1 h decreasing to 35.8 after 72 h and 35.0 on day 4 decreasing to 3.3 on day 13 (max. = 110). All animals in the present study showed large blisters on the inside of upper and lower lids at the 1 and 4 hour readings. Blisters decreased in size at the 24 hour reading and they were gone at 48 hours. According to the authors, the test substance was classified as severely irritating to the rabbit eyes when applied without rinsing.

Conclusion

Classification: irritating to eyes

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A non-GLP in vivo study was performed comparable with OECD guideline study to evaluate skin irritation (BASF AG, 1952). In the study, the neat substance (about 0.5 mL) was administered for 20 hours on the shaved back of 4 albino rabbits. For this purpose a 2.5 cm x 2.5 cm big patch was soaked with the test substance and applied onto the skin and fixed with a bandage. After removal of the bandage the application site was examined and in case of findings, observation continued until the findings disappeared. Only one animal showed faint redness on the first day after removal of the bandage. On the second day there were no more findings. The other animal was without any findings. Under the present test conditions DMF was not irritating.

In another acute dermal study (TSCATS: OTS 0516779, 1978), DMF was of low acute dermal toxicity in the rats. In the same study, the irritation potential of DMF was assessed during 14 day post observation period. DMF at dose level of 3160 mg/kg was applied on abraded skin of 2 male and 2 female Sprague-Dawley rats under occlusive conditions for 24 h. On days 2, 4, 8, 11 and 15 the exposure sites were examined and scored for erythema and edema on a graded scale of 0 to 4. Each animal was observed for mortality and toxic effects at 2 and 4 hours post-dosing and daily thereafter. In the post observation period, ¼ animals died (one male animal) on day 4 of the study, however, gross necropsy revealed no substance-related effect. Among the remaining animals, no signs of systemic toxicity or percutaneous absorption were observed. Under the test conditions, the substance is considered as not irritating.

Eye irritation

A non-GLP in vivo eye irritation study was conducted comparable to OECD TG 405 (TSCATS: OTS 0516779, 1978). In the study neat DMF of 0.1 mL was instilled into one eye of 6 New Zealand white rabbits without rinsing. The untreated eye served as control. Readings were performed 1 h, 4 h, 24 h, 48 h, 72 h, 4 d, 7 d, 10 d and 13 d after application. Scoring of ocular lesions was done according to the method of Draize et al. (1944).

Primary irritation index was 50.8 after 1 h decreasing to 35.8 after 72 h and 35.0 on day 4 decreasing to 3.3 on day 13 (max. = 110). All animals in the present study showed large blisters on the inside of upper and lower lids at the 1 and 4 hour readings. Blisters decreased in size at the 24 hour reading and they were gone at 48 hours. According to the authors, the test substance was classified as severely irritating to the rabbit eyes when applied without rinsing.

In another in vivo study, which is comparable to OECD TG 405 (BASF AG, 1952), DMF of 50 µl (undiluted, 50 % and 10 % solution) was applied to the conjunctival sac of one eye in 3 rabbits. After 10 minutes, 1, 3 and 24 hours the eyes were examined and in case of findings, observation was continued until the findings disappeared. The eyes were not washed out after 24 hours as specified in OECD TG 405. Marked redness and chemosis as well as purulent secretion were observed in both animals. In one animal, transient opacity of the cornea occurred two days after substance application. Both animals recovered and were without findings 6 and 7 days after treatment, respectively. Supporting the results of TSCATS: OTS 0516779, 1978, DMF is considered irritating to the eyes.


Justification for selection of skin irritation / corrosion endpoint:
The most documented study available.

Justification for selection of eye irritation endpoint:
The most documented study available.

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the data of skin irritation, the classification is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulations (EC) No 1272/2008.

Based on the findings of the key eye irritation study, the classification and labelling is warranted in accordance with the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulations (EC) No 1272/2008 as Eye irritation Cat 2. (H319 Causes serious eye irritation).