Heptanoic anhydride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug 2002 to Feb 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

- exposure time 24 hrs instead of 4 hrs, few details in test description and reporting

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Heptanoic anhydride

EC Number:

210-940-5

EC Name:

Heptanoic anhydride

Cas Number:

626-27-7

Molecular formula:

C14H26O3

IUPAC Name:

heptanoyl heptanoate

Constituent 2

Reference substance name:

Heptanoic acid anhydride

IUPAC Name:

Heptanoic acid anhydride

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Tierzucht Schönwalde GmbH, Schönwalde, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 276-313 g (males), 188-193 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: >= 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23°C
- Humidity (%): 54-62 %
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated skin served as control

Amount / concentration applied:

0.64-0.67 mL / male animal or 0.40 -0.42 mL / female animal (= 2000 mg/kg bw)

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

Details on study design:

Skin areas were assessed 1, 24, 48 and 72 hours after the end of administration. Evaluation of skin reactions(reddening, scab formation and swelling of the skin) was done according to the system recommended in Directive 67/548/EEC.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.95

Max. score:

4

Reversibility:

fully reversible within: 11 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Very slight to slight skin reddening was noted in all animals treated with 2000 mg/kg bw. In addition, desquamation was observed in all female animals and in two male animals. The local intolerance reactions observed in rats were reversible within 11 days after administration. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0 for swelling and 0.95 for reddening and scab formation (see table 1).

Any other information on results incl. tables

Table 1: Mean values of findings relevant for classification.

Test compound ZK 56406 (2000 gm/kg)		Animal number and sex
Location (finding)	Time-point after end of exposure	10M	11M	12M	4F	5F	6F
Reddening and scab formation	1 hour*	0	0	2	2	2	2
	24/25 hours	1	0	1	2	2	2
	48 hours	1	0	1	2	1	1
	72 hours	0	0	1	1	1	0
Individual mean values:		0.67	0	1.0	1.67	1.33	1.0
Mean value of all animals:							0.95
Swellings	1 hour*	0	0	0	0	0	0
	24/48 hours	0	0	0	0	0	0
	48 hours	0	0	0	0	0	0
	72 hours	0	0	0	0	0	0
Individual mean values:		0	0	0	0	0	0
Mean values of all animals:							0

M = male

F = female

*         = not included in calculations of mean values

Applicant's summary and conclusion

Interpretation of results:

other: slight local intolerance reactions noted up to day 8.

Executive summary:

A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg (0.64-0.67 mL / male or 0.40 -0.42 mL / female) led to slight local intolerance reactions up to day 8 after administration. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0 for swelling and 0.95 for reddening and scab formation.