Naphthenic acids, reaction products with diethylenetriamine

Endpoint summary

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:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

NA-DETA is a surfactant.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

- Semi barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: at least 10 x / hour
- Free access to autoclaved hay and to Altromin 3122 maintenance diet for guinea pigs (lot no. 0950), rich in crude fibre
- Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in Terluran - cages on Altromin saw fibre bedding (lot no. 261111)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Concentration / amount:

For the intradermal injection (induction - first stage), 1% of the test item was in PEG 400 and physiological saline 0.9% NaCl
For the topical application (induction – second stage), 25% of the test item in vaseline
For the topical application (challenge), 5% of the test item in vaseline

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Concentration / amount:

For the intradermal injection (induction - first stage), 1% of the test item was in PEG 400 and physiological saline 0.9% NaCl
For the topical application (induction – second stage), 25% of the test item in vaseline
For the topical application (challenge), 5% of the test item in vaseline

No. of animals per dose:

10 test animals, 5 control animals and 9 animals for preliminary study

Details on study design:

Induction: First Stage, Intradermal Injection
Three pairs of intradermal injections of 0.1 mL volume were given in the shoulder region which was cleared of hair by clipping so that one of each pair lies on each side of the midline.
Test Group: Day 0
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline 0.9% NaCl
Injection 2: a 1% concentration of the test item in PEG 400 physiological saline 0.9% NaCl
Injection 3: a 1% concentration of the test item formulated in a 1:1 mixture (v/v) FCA/physiological saline 0.9% NaCl
Control Group: Day 0
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline 0.9% NaCl
Injection 2: 100% PEG 400 and physiological saline 0.9% NaCl
Injection 3: a 50% (v/v) formulation of 0.9% NaCl in a 1:1 (v/v) mixture FCA/physiological saline 0.9% NaCl
Injections 1 and 2 were given close to each other and nearest to the head, while injection 3 was given toward the caudal part of the test area.

Induction: Second Stage, Topical Application
Test Group and Control Group: Day 6
Approximately twenty-four hours before the topical application the test area was painted with 0.5 g of 10% sodium lauryl sulphate
in vaseline after close clipping in order to create a local irritation.
Test Group: Day 7
The test item was dissolved in vaseline at a concentration of 25%. A patch was fully loaded with 0.5 g of the
prepared test item. Then it was applied to the test area and held in contact with the help of an occlusive dressing for 48 hours.
Control Group: Day 7
A patch was fully loaded with 0.5 g of vaseline. Then it was applied to the test area and held in contact with
the help of an occlusive dressing for 48 hours.

Challenge controls:

The flanks of treated and control animals were cleared of hair by close-clipping.
Test Group and Control Group: Day 20
The test item was suspended in vaselinel at a concentration of 5 %. A patch, loaded with 0.5 g
of the prepared test item was applied to the left flank of the animals and a patch loaded with 0.5 g of the vehicle to the right flank
(intraspecific control). The patches were held in contact with the help of an occlusive dressing for 24 hours.
The application area was not rinsed.

Observation
Test Group and Control Group
Approximately 20 hours after removing the patch, the challenge area was cleared of hair by the use of a depilatory cream.
Approximately 24 and 48 hours after removing the patch the skin reaction was observed and recorded according to the grades shown below.
Additionally all animals were observed for signs of toxicity at least once daily during the test period.

Positive control substance(s):

not required

Remarks:

performed periodically every 6 months

Positive control results:

The recent reliability check was performed in February 2011. The raw data of this study are kept in the BSL archives (BSL Project ID 120793).
The reliability checks are audited by the QA-unit periodically.
Positive-control substance: mercaptobenzothiazole, purity > 98%,
Fluka Chemica, Lot No. 41107195, expiry date: 20/01/2014
Concentrations: 2% induction I phase (in cottonseed oil)
25% induction II phase (in vaseline)
15% challenge (in Vaseline)
The sensitisation rate after application of the positive-control substance mercaptobenzothiazole (15% in vaseline)
was 90%, confirming the reliability of the test system.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1% Intradermal Induction; 25% Topical Induction; 5% Challenge

No. with + reactions:

10

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1% Intradermal Induction; 25% Topical Induction; 5% Challenge

No. with + reactions:

10

Total no. in group:

10

Table:  Challenge Exposure

Challenge Concentrations of Test Substance: 5%
	Number of Animals Showing Skin Reactions after
	24 hours	48 hours
Test Group	10	10
Negative-Control Group	0	0

Body Weight Development

The body weight development was within the biological range for all animals compared to historical data.

All animals of both groups survived throughout the test period.

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Remarks:

Migrated information

Conclusions:

NA-DETA should be classified as Xi;R43 according to DSD 67/548/EEC and as Warning, Category 1; H317 according to Regulation (EC) No 1272/2008.

Executive summary:

The skin sensitization potential of NA-DETA was tested according to the Guideline OECD 406.

10 out 10 animals treated with the test substance responded upon challenge. NA-DETA should be regarded as a skin sensitizer and should be classified as Xi;R43 according to DSD 67/548/EEC and as Warning, Category 1; H317 according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Migrated from Short description of key information:
The skin sensitizing potential of NA-DETA was investigated according to the Guideline OECD 406. NA-DETA should be regarded as a skin sensitizer.

Justification for selection of skin sensitisation endpoint:
Scientifically well-performed study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of NA-DETA was tested according to the Guideline OECD 406. 10 out 10 animals treated with the test substance responded upon challenge. NA-DETA should be regarded as a skin sensitizer and should be classified as Xi;R43 according to DSD 67/548/EEC and as Warning, Category 1; H317 according to Regulation (EC) No 1272/2008.