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Description of key information

For this endpoint, two studies are available.The first consists in an animal experiment and the second concerns human results.

The maximization method of Magnusson and Kligman (Shell 1982) :

In a skin sensitization test (Shell, 1982), the potential of Heptanaltoinduce delayed contact hypersensitivity was evaluated in guinea pigs according to the maximization method of Magnusson and Kligman (1969). Thirty animals were allocated to 2 groups: a control group 1 (5 males/ 5 females) and a treated group 2 (10 males/ 10 females). The induction phase has been realized both by intradermal route on day 1 (1 %) and by cutaneous route one week later (undiluted). The challenge phase was realized two weeks after the topical induction by cutaneous application of undiluted test substance. Skin reactions were evaluated approximatively 24 and 48h after removal of the dressing. At the end of the study animals were killed without examination of internal organs (no necropsy). One test animal was found dead on the day the topical induction procedure was to be conducted (death was presumed to have been due to stress associated with treatment), and another test animal was killed for human reasons prior to being challenged (it had lost 27 % off its initial body weight). Therefore, only 18 test animals were subjected to the challenge procedure. Four out of the 18 test animals (22.22 %) showed positive responses at 24 h after the removal of the challenge patches and 3 animals still have a positive repsonse after 48 hours. All treated areas, with the exception of those on the positively responding animals, were clearly defined and appeared 'dry' after removal of the patches.Under these experimental conditions and according to the Magnusson and Kligman method, the test item (Heptanal) undiluted induced positive skin sensitization reactions in 4/18 guinea pigs (22.22 %) and is therfore considered as not sensitizing according to CE criteria.

Human data (Hoechst 1974):

To determine the contact-sensitizing potential of heptanal, 25 healthy adult volunteers were exposed to the material under occlusion for five alternate-day 48 hour periods (data reported in section 7.10.4). The patch sites were pre-treated for 24 hours with 5 % aqueous sodium lauryl sulfate under occlusion (Maximization test, RIFM-71 -4 -12). The challenge sites were read after removal of the patch and 24 hours thereafter. Under the conditions of this test, heptanal do not induce contact-sensitization in Human. All together these results suggest that heptanal is not a sensitizer.


Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 6 July 1981 To 7 August 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2c: Comparable to guideline study with acceptable restriction.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
LLNA method was not available at the time the guinea pig test was performed.
Species:
guinea pig
Strain:
other: 'P'
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The Shell Toxicology Laboratory (Tunstall) Breeding Unit.
- Age at study initiation: 9-12 weeks old
- Weight at study initiation: Males (508-779 g)/ Females (460-612 g)
- Housing: 2 and 3 per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: From: 6 July 1981 To: 7 August 1981
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 1 %
cutaneous induction: undiluted
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
cutaneous challenge: undiluted
No. of animals per dose:
Control group: 5 males and 5 females
Treated group: 10 males and 10 females
Details on study design:
RANGE FINDING TESTS:
Intradermal test: 0.05, 0.1, 0.5 or 1.0 %
Cutaneous test: 50, 75 or 100 %

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 intradermal route on day 1 (3 injections of 0.1ml ) and cutanaous route on day 8.
- Test groups: Heptanal in solvent (corn oil)
- Control group: FCA only
- Site: dorsal region between the shoulders
- Duration: 3 weeks
- Concentrations: intradermal injection 1 % (w/w) and cutaneous application undiluted

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: two weeks after the topical induction (probably day 22)
- Exposure period: 24h
- Test groups: Heptanal (undiluted)
- Control group: Heptanal (undiluted)
- Site: posterior right flank (left flank -vehicule control-)
- Concentrations: undiluted (0.1 ml of the test substance was applied on skin)
- Evaluation: 24 and 48h after challenge
Challenge controls:
none
Positive control substance(s):
not specified
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
undiluted
No. with + reactions:
4
Total no. in group:
18
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: undiluted. No with. + reactions: 4.0. Total no. in groups: 18.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
undiluted
No. with + reactions:
3
Total no. in group:
18
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: undiluted. No with. + reactions: 3.0. Total no. in groups: 18.0. Clinical observations: no data.
Reading:
other: positive control not specified in the report
Group:
positive control
Remarks on result:
other: not specified in the report

Table1: Sensitization challenge response data for each treated animal at 24 and 48h

Treated group
Sex Animal number Immediate 24h 48h
Male 5496 - - -
5497 - - -
5498 - - -
5499 (a)    
5500 tr + +
5505 - - -
5506 + + +
5507 - - -
5501 - - -
5502 tr tr -
Female 5478 - - -
5479 - - -
5480 - - -
5481 - - -
5482 - - -
5483 - - -
5484 - - -
5485 - - -
5486 - - -
5487 (b)    

(a) Animal killed for human reasons before the challenge procedure was conducted. This animal was lethargic and had marked loss of body weight.

(b) Animal was found dead on the day of, but prior to, the topical induction procedure. Death was presumed to have been due to stress associated with treatment.

Table 2:Sensitization challenge response data for each control animal at 24 and 48h

Control group
Sex Animal number Immediate 24h 48h
Male 5508 - - -
5509 - - -
5510 - - -
5503 - - -
5504 - - -
Female 5488 - - -
5489 - - -
5490 - - -
5491 - - -
5492 - - -

Four point scale:

- : No different from surrounding skin

tr (trace): Slight redness, edges not defined

+ : Pink/red square with defined edges

++ : Beet red square with well defined edges

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under these experimental conditions and according to the Magnusson and Kligman method, the test item (Heptanal) undiluted induced positive skin sensitization reactions in 4/18 guinea pigs (22.22 %) and is considered as not sensitizing according to CE criteria.
Executive summary:

In a skin sensitization test (Shell, 1982), the potential of Heptanal (batch No. SC810507) to induce delayed contact hypersensitivity was evaluated in guinea pigs according to the maximization method of Magnusson and Kligman (1969). Thirty animals were allocated to 2 groups: a control group 1 (5 males/ 5 females) and a treated group 2 (10 males/ 10 females). The induction phase has been realized both by intradermal route on day 1 (1 %) and by cutaneous route one week later (undiluted). The challenge phase was realized two weeks after the topical induction by cutaneous application of undiluted test substance. Skin reactions were evaluated approximatively 24 and 48h after removal of the dressing. At the end of the study animals were killed without examination of internal organs (no necropsy). One test animal was found dead on the day the topical induction procedure was to be conducted (death was presumed to have been due to stress associated with treatment), and another test animal was killed for human reasons prior to being challenged (it had lost 27 % off its initial body weight). Therefore, only 18 test animals were subjected to the challenge procedure. Four of the 18 test animals (22.22 %) showed positive responses at 24 h after the removal of the challenge patches and 3 continued to do so at 48 h. All treated areas, with the exception of those on the positively responding animals, were clearly defined and appeared 'dry' after removal of the patches.

Under the tested condition and according to the maximization method of Magnusson and Kligman, the test substanceHeptanal does not induce delayed contact hypersensitivity in guinea-pigs.

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

Justification for classification or non-classification

According to REGULATION (EC) No 1272 -2008:

Heptanoic acid is not a skin sensitizer according to the results obtained with a standardized method in guinea pigs (similar to OECD 406) and based on the human data in the maximization test.

Justification : Positive response obtained in <30% of the test animals (in OECD 406).

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