Registration Dossier

Administrative data

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:
Meets national standard methods with acceptable restrictions. Well documented and acceptable for assessment. Restriction: current test guidelines require skin contact periods of up to 4 hours. The 24-h, occlusive exposure is no more in line with current guidelines. It may be regarded as a "worst-case" situation. Given the weak skin reaction under worst-case conditions it may be assumed that the substance is not irritating when tested according to current guidelines.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979
Reference Type:
other company data
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
, occlusive dressing; skin contact period 24 hours
Principles of method if other than guideline:
Method: FR, Title 16, section 1500.41
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Test substance: Methylformiat
- Analytical purity: 98%.
- Impurity: methanol 2%.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.4 kg
- Housing: single cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40

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: 500 µL
Duration of treatment / exposure:
24 hour(s)
Observation period:
8 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2,5 x 2,5 cm
- Type of wrap if used: gauze, covered with impervious PVC sheeting, held in place by means of adhesive tape

SCORING SYSTEM:
- Scoring of skin reactions: according to the table "Grading of skin reaction" contained in OECD Guideline No. 404

EVALUATION
- primary dermal irritation index (PDII): the sum of the mean scores for erythema and edema seen in intact and scarified skin at 24 and 72 after beginning of the treatment were divided by 4.
- skin irritation according to 67/548/EC: only reactions of intact skin taken into consideration.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours after beginning of treatment
Score:
0.67
Max. score:
8
Reversibility:
not fully reversible within: 8 days

Any other information on results incl. tables

 

Skin reactions were read at 24, 48 (not reported), and 72 hours after beginning of the treatment, and after 8 days.

 

Evaluation according to FR, Title 16, section 1500.41:

The calculated primary irritation index was 0.67, i.e. the substance was slightly irritating according to the method used.

Evaluation according to 67/548/EC:

The intact skin reactions only were as tabulated below. The skin reaction scoring time schedule was not in full accordance with OECD Guideline No. 404.

Immediately after the 24-h occlusive patch removal a high score was seen in one animal. Scores were generally low, as were the overall means.

 

Table: evaluation of intact skin reactions

 

Time

(after start of treatment)

Animal No.

sum

Mean

(according to 67/548/EC)

 

1

2

3

 

 

Erythema

 

 

 

 

 

24 hours

0

0

0

0

 

72hours

0

0

0

0

 

8 days

0

0

0

 

 

Means (24+72 hours)

0

0

0

 

0

 

 

 

 

 

 

Edema

 

 

 

 

 

24 hours

3

0

0

3

 

72hours

1

0

0

1

 

8 days

0

1

2

 

 

Means (24+72 hours)

2

0

0

 

0.67

 

 

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

Conclusion:

 

Undiluted methylformate was examined according to the method described in the Federal Register (FR, Title 16, section 1500.41) in rabbits (3 rabbits, occlusive skin contact for 24 hours). At the end of the observation period edema was noted in 2 of 3 animals, and a primary irritation index of 0.67 was calculated, which indicated a weak potential for skin irritation (BASF AG, 1979; Fraunhofer-Gesellschaft, 1979).

However, current test guidelines require skin contact periods of up to 4 hours. The 24-h, occlusive exposure is no longer in line with current guidelines and it may be regarded as a "severe-case" situation. Given the weak skin reaction under such conditions it may be assumed that methylformate is not irritating when tested according to current guidelines.