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Description of key information

No skin sensitisation reaction in an in vivo study on guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
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 original study report was written in the format of a memorandum to W.K. Lowen, dated December 2, 1955, and contained only the conclusions from a series of toxicity studies conducted with 4 chemicals, including the test substance. However, the original report did not contain the individual results of any of the studies. This supplement was written to add the procedures used and the data generated from the skin sensitisation study conducted with the test substance. This supplement to the report was completed March 2, 2010. This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Principles of method if other than guideline:
The study was conducted in guinea pigs to determine the potential for the test substance to elicit a dermal sensitisation reaction. A preliminary skin irritation test in 10 guinea pigs was conducted with a 10 %, 25 %, or 50 % solution of the test substance in water. Based on irritation results, the concentration of 50 % test substance was selected for the induction phase. For the induction phase, one group of 5 guinea pigs received intradermal injection of a 0.1 % solution of test substance in saline on test day 0, 2, 4, 7, 9 and 14. A second group of 5 guinea pigs received a topical application of 50 % test substance in water to an abraded skin site on test day 0, 2, 4, 7, 9, and 14. Evaluation of irritation on the treatment site was conducted at 1, 24 and 48 hours post dosing. On test day 29, animals were challenged with a topical application of 50 % test substance to intact or abraded skin sites. In addition, animals were also challenged with an intradermal injection of 0.1 % test substance in saline. Irritation was evaluated 1, 24, and 48 hours post dosing. Due to ambiguous results from the intradermal administration, the intradermal administration was repeated on test day 35.
GLP compliance:
no
Type of study:
other: skin sensitisation study
Justification for non-LLNA method:
The study was conducted 1955 before LLNA test method was in place (OECD TG 429 was adopted in 2002).
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
- Physical state: Liquid
- Purity: Purity of the test substance was not measured. However, based on the boiling point and density provided on the sample transmittal documents dated October 12, 1950 (165 ºC, and 0.9366 g/cm³ at 25ºC), the test substance appears to be consistent with technical grade (boiling point 164-166 ºC, and 0.94 g/cm³, respectively).

No further details available.
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No details available.
Route:
intradermal
Vehicle:
other: saline
Concentration / amount:
0.1%
Day(s)/duration:
0, 2, 4, 7, 9, 14
Route:
other: epicutaneous, abraded skin
Vehicle:
water
Concentration / amount:
50%
Day(s)/duration:
0, 2, 4, 7, 9, 14
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
other: Intradermal injection and topical administration (intact or abraded skin, 2 groups).
Vehicle:
other: saline (injection), water (topical)
Concentration / amount:
0.1% (injection), 50% (topical)
Day(s)/duration:
29
No.:
#2
Route:
intradermal
Vehicle:
other:
Concentration / amount:
Rechallenge: 0.1% in saline
Day(s)/duration:
35
No. of animals per dose:
- Induction: 5 animals (intradermal injection dosing method); 5 animals (scratch dosing method)
- Challenge: 7 animals (topical dosing method), 3 of these animals (scratch dosing method) and 4 animals (intradermal injection dosing method)*
* Loss of 3 animals to epidemic of dysentery.
Details on study design:
RANGE FINDING TESTS: A preliminary skin irritation test in 10 guinea pigs was conducted with a 10, 25, or 50 % solution of the test substance in water, applied topically to 3 separate locations on each guinea pig. Irritation was reported at all 3 concentrations 1 hour following application. At 24 hours, irritation was only observed on the sites treated with the 50 % solution. Based on the irritation results following topical application of 50 % test substance, this concentration was selected for the induction phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6
- Test groups: Intradermal injection (5 animals); scratch (5 animals)
- Frequency of applications: test days 0, 2, 4, 7, 9, 14
- Concentrations: 0.1 % solution of test substance in saline (intradermal); 50 % solution of test substance in water (scratch)

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: test day 29
- Test groups: Topical (all 7 animals); intradermal (4 of the 7 animals); scratch (3 of the 7 animals)
- Concentrations: 50 % solution of test substance in water (topical); 0.1 % solution of test substance in saline (intradermal); 50 % solution of test substance in water (scratch)
- Evaluation (after challenge): 1, 24 and 48 hours post dosing

OTHER:
-Rechallenge: On test day 35, the animals previously challenged with an intradermal injection, received an additional injection as described above, and the injection sites were evaluated at 1, 24, and 48 hours post dosing. The second intradermal injection was conducted to clarify the results of the previous injection.
- Body weights were recorded initially and after induction and challenge phases.
Challenge controls:
No data
Positive control substance(s):
not specified
Positive control results:
No data
Reading:
1st reading
Hours after challenge:
1
Group:
other: Topical test group
Dose level:
50 % test substance solution
No. with + reactions:
7
Total no. in group:
7
Reading:
1st reading
Hours after challenge:
1
Group:
other: Topical test group w/Scratch application
Dose level:
50 % test substance solution
No. with + reactions:
3
Total no. in group:
3
Reading:
1st reading
Hours after challenge:
1
Group:
other: Topical test group w/Intradermal application
Dose level:
0.1 % test substance solution
No. with + reactions:
3
Total no. in group:
4
Reading:
2nd reading
Hours after challenge:
24
Group:
other: Topical test group
Dose level:
50 % test substance solution
No. with + reactions:
1
Total no. in group:
7
Reading:
2nd reading
Hours after challenge:
24
Group:
other: Topical test group w/Scratch application
Dose level:
50 % test substance solution
No. with + reactions:
1
Total no. in group:
3
Reading:
2nd reading
Hours after challenge:
24
Group:
other: Topical test group w/Intradermal application
Dose level:
0.1 % test substance solution
No. with + reactions:
4
Total no. in group:
4
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
other: Topical test group
Dose level:
50 % test substance solution
No. with + reactions:
0
Total no. in group:
7
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
other: Topical test group w/Scratch application
Dose level:
50 % test substance solution
No. with + reactions:
0
Total no. in group:
3
Reading:
other: 3rd reading
Hours after challenge:
48
Group:
other: Topical test group w/Intradermal application
Dose level:
0.1 % test substance solution
No. with + reactions:
0
Total no. in group:
4
Reading:
rechallenge
Hours after challenge:
1
Group:
other: Test group challenged with second Intradermal injection
Dose level:
0.1 % test substance solution
No. with + reactions:
3
Total no. in group:
4
Reading:
rechallenge
Hours after challenge:
24
Group:
other: Test group challenged with second Intradermal injection
Dose level:
0.1 % test substance solution
No. with + reactions:
0
Total no. in group:
4
Reading:
rechallenge
Hours after challenge:
48
Group:
other: Test group challenged with second Intradermal injection
Dose level:
0.1 % test substance solution
No. with + reactions:
0
Total no. in group:
4

Body weights measured after induction and challenge demonstrated that the animals were growing normally. For the induction phase, one group of 5 guinea pigs received an intradermal injection (0.1 mL) of a 0.1% solution of test substance in saline on test day 0, 2, 4, 7,9, and 14. A second group of 5 guinea pigs received a topical application of 50 % test substance in water to an abraded skin site on test day 0, 2, 4, 7, 9, and 14. Evaluation of irritation on the treatment site was conducted a 1, 24 and 48 hours post dosing. Irritation was observed at 1 and 24 hours following either intradermal injection of 0.1 % or topical application of 50 % test substance to an abraded skin site. Irritation was not observed at 48 hours post dosing. On test day 29, animals were challenged with a topical application of 50 % test substance to an intact or abraded skin site. In addition, animals were also challenged with an intradermal injection of 0.1 % test substance. Irritation was evaluated 1, 24, and 48 hours post dosing. Intradermal administration was repeated on test day 35. Irritation was observed following a topical challenge application to intact or abraded skin; and following the intradermal challenge application at 1 hour and 24 hours post dosing. No irritation was observed at 48 hours post dosing. Based on the similarity of the irritation response following induction applications, the irritation response observed following the challenge phase was not considered to be consistent with a sensitising response. The test substance was not considered to be a sensitizer. The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the test substance was not considered to be a skin sensitiser.
Executive summary:

A study was conducted in guinea pigs to determine the potential for the test substance to elicit a dermal sensitisation reaction.

A preliminary skin irritation test in 10 guinea pigs was conducted with a 10, 25, or 50 % solution of the test substance in water, applied topically to 3 separate locations on each guinea pig. Irritation was reported at all 3 concentrations 1 hour following application. At 24 hours, irritation was only observed on the sites treated with the 50 % solution. Based on the irritation results following topical application of 50 % test substance, this concentration was selected for the induction phase.

For the induction phase, one group of 5 guinea pigs received an intradermal injection (0.1 mL) of a 0.1% solution of test substance in saline on test day 0, 2, 4, 7,9, and 14. A second group of 5 guinea pigs received a topical application of 50 % test substance in water to an abraded skin site on test days 0, 2, 4, 7, 9, and 14. Evaluation of irritation on the treatment site was conducted a 1, 24 and 48 hours post dosing. Irritation was observed at 1 and 24 hours following either intradermal injection of 0.1 % or topical application of 50 % test substance to an abraded skin site. Irritation was not observed at 48 hours post dosing.

On test day 29, animals were challenged with a topical application of 50 % test substance to intact or abraded skin sites. In addition, animals were also challenged with an intradermal injection of 0.1 % test substance. Irritation was evaluated 1, 24, and 48 hours post dosing. Intradermal administration was repeated on test day 35. Irritation was observed following a topical challenge application to intact or abraded skin; and following the intradermal challenge application at 1 hour and 24 hours post dosing. No irritation was observed at 48 hours post dosing. Based on the similarity of the irritation response following induction applications, the irritation response observed following the challenge phase was not considered to be consistent with a sensitising response. Under the conditions of this study, the test substance was not considered to be a skin sensitiser.

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

The key-study (1955, RL2) was conducted in guinea pigs to determine the potential for the test substance to elicit a dermal sensitisation reaction. A preliminary skin irritation test in 10 guinea pigs was conducted with a 10, 25, or 50% solution of the test substance in water, applied topically to 3 separate locations on each guinea pig. Irritation was reported at all 3 concentrations 1 hour following application. At 24 hours, irritation was only observed on the sites treated with the 50% solution. Based on the irritation results following topical application of 50% test substance, this concentration was selected for the induction phase. For the induction phase, one group of 5 guinea pigs received an intradermal injection (0.1 mL) of a 0.1% solution of test substance in saline on test day 0, 2, 4, 7,9, and 14. A second group of 5 guinea pigs received a topical application of 50% test substance in water to an abraded skin site on test days 0, 2, 4, 7, 9, and 14. Evaluation of irritation on the treatment site was conducted a 1, 24 and 48 hours post dosing. Irritation was observed at 1 and 24 hours following either intradermal injection of 0.1% or topical application of 50% test substance to an abraded skin site. Irritation was not observed at 48 hours post dosing. On test day 29, animals were challenged with a topical application of 50 % test substance to intact or abraded skin sites. In addition, animals were also challenged with an intradermal injection of 0.1% test substance. Irritation was evaluated 1, 24, and 48 hours post dosing. Intradermal administration was repeated on test day 35. Irritation was observed following a topical challenge application to intact or abraded skin; and following the intradermal challenge application at 1 hour and 24 hours post dosing. No irritation was observed at 48 hours post dosing. Based on the similarity of the irritation response following induction applications, the irritation response observed following the challenge phase was not considered to be consistent with a sensitising response. Under the conditions of this study, the test substance was not considered to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

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 not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.