Suberic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-08-13 - 2018-05-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

Test was sponsored by supplier in India. Since no other data is available no new animal study was performed.

Test material

Test material information

Constituent 1

Reference substance name:

Suberic acid

EC Number:

208-010-9

EC Name:

Suberic acid

Cas Number:

505-48-6

Molecular formula:

C8H14O4

IUPAC Name:

octanedioic acid

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Molecular formula: C8H14O4
Molecular Mass:
174.20
Characteristics (Physical Appearance):
White Crystalline powder
CAS No.:
505-48-6
Batch Number:
308
Purity:
100%

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

Animal Species
and rationale for selection:
Guinea pig (Cavia porcellus); Guinea pig has been the animal of choice for predictive Sensitisation tests, and is the species preferred by the regulatory guidelines.
Strain
and rationale for selection:
English (Hartley); The strain has been selected due to its availability in requisite numbers.
Source:
Sri Raghavendra Enterprises, Bangalore, India
Age at the start of the study:
13 weeks
Sex:
Female; females were nulliparous and non-pregnant.
Body weight range (Day -1):
329 g to 496 g
Number of animals used:
Pilot Study - 2 animals;
Main study - 30 animals;
(Treatment group - 20 animals; Control group - 10 animals)
Veterinary Examination:
Prior to final assignment to the study, the animals were subjected to a veterinary examination to ensure that the selected guinea pigs were in a good state of health.
HOUSING AND FEEDING CONDITIONS Accommodation : Animals were housed in room number AR-04, in the experimental animal facility of INTOX PVT. LTD., maintained under appropriate barriers. Animals were housed singly in solid bottom polypropylene cages [size: 42 cm (L) x 29 cm (W) x 19 cm (H)] with stainless steel grill tops, facilities for food and water bottle, and bedding of clean and sterilized paddy husk. The cages were suspended on stainless steel racks.

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

other: analytical grade water with 0.2% Tween 80

Concentration / amount:

56% w/v of SUBERIC ACID

Day(s)/duration:

0,7,14

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: analytical grade water with 0.2% Tween 80

Concentration / amount:

56%

Day(s)/duration:

day 28

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20

Challenge controls:

analytical grade water with 0.2% Tween 80

Positive control substance(s):

yes

Remarks:

α-Hexylcinnamaldehyde

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

56%

No. with + reactions:

0

Total no. in group:

20

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

56%

No. with + reactions:

0

Total no. in group:

20

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Results 5

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Dose level:

10%

No. with + reactions:

5

Total no. in group:

10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The allergic contact sensitisation potential of SUBERIC ACID was assessed in guinea pigs as per the method described by Buehler E. V., in compliance with the Organization for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals, Section 4, No. 406 - Skin sensitisation, adopted by the council on 17 July 1992.
In this test, induction of sensitisation was attempted by exposing the guinea pigs to 56% w/v of SUBERIC ACID in analytical grade water with 0.2% Tween 80 on days 0, 7 and 14 by epidermal route on the clipped left flank area, there was no evidence of erythema and / or swelling at the site of application. After an induction period of 14 days, the animals were similarly subjected to a ‘challenge application’ with 56% w/v of SUBERIC ACID in analytical grade water with 0.2% Tween 80 on day 28 of the study, on their right flank.
In absence of a sensitisation response in any of the treated animals to challenge by the test item, SUBERIC ACID is classified as non sensitiser to guinea pigs as per the criteria of classification for the Buehler test (Kimber et. al., 1990).

Executive summary:

The skin sensitisation potential of SUBERIC ACID was assessed in guinea pigs as per the method described by Buehler E. V., in compliance with the Organization for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals, Section 4, No. 406 – Skin sensitisation, adopted by the council on 17 July 1992.

In this study, based on the results of a pilot study, induction of sensitisation was attempted by exposing the guinea pigs to 56% w/v of SUBERIC ACID in analytical grade water with 0.2% Tween 80 on days 0, 7 and 14 by epidermal route on the clipped left flank area. After an induction period of 14 days, the animals were similarly subjected to a ‘challenge application’ with 56% w/v of SUBERIC ACID in analytical grade water 0.2% Tween 80 on day 28 of the study, on their right flank. Treated group comprised of 20 animals and control group comprised of 10 animals.

Skin reaction was recorded at 24 and 48 hours after removal of each induction patch and was also evaluated at 24 and 48 hours after removal of the challenge patch. The guinea pigs were examined for survival and abnormal clinical signs daily during the study, and their body weights were recorded at start and termination of the experiment.

In this study all guinea pigs survived throughout the duration of the study. Clinical observations made periodically during the study revealed that, test item did not induce any signs of systemic toxicity in the exposed animals. There was no adverse effect of the treatment on the body weight gain by the exposed guinea pigs.

Skin Reaction Following Induction Applications

As revealed at 24 and 48 hours after removal of each induction patch for the induction applications made on days 0, 7 and 14, the test item did not induce any skin reaction on the site of application in the treated guinea pigs.

Skin Reaction Following Challenge Application

After challenge application made on day 28, as observed on days 29 and 30, there was no evidence of any acute dermal response at the site of application in the form of erythema and / or swelling in all animals from the control and the treatment groups.

Conclusion

In absence of a sensitisation response in any of the treated animals to challenge by the test item, SUBERIC ACID is classified as non sensitiser to guinea pigs as per the criteria of classification for the Buehler test (Kimber et. al.,1990).