α,α'-propylenedinitrilodi-o-cresol

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating (bioassay, 2012)

Eye irritation:
in vivo study (BASF, 1959): not irritating
in vitro study (BASF, 2012): reconstructed human cornea): not irritating
in vitro study (BASF, 2012, OECD 437, Bovine Corneal Opacity and Permeability Test): not corrosive

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH
- Age at study initiation: 6-8 months
- Weight at study initiation: 3.94-4.79 kg
- Housing: single housing
- Diet (e.g. ad libitum): STANRAB (P) SQC
- Water. Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test patch (2.5 cm x 2.5 cm) was moistened with a dose of 0.5 mL of the undiluted liquid test item.
The test item was molten at 80 °C for approx. 1 hour and was administrated hand warm.

Duration of treatment / exposure:

4 hrs

Observation period:

72 hrs

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of the exposure period with Lutrol®** and Lutrol® / water (1 : 1).
- Time after start of exposure: 4 hrs

SCORING SYSTEM:
Erythema and eschar formation
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well- defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

Edema formation
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well- defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.53

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

In all animals very slight erythema (grade 1) was noticed immediately after removal of the patch and persisted in two of these animals up to hour 24. In the third animal very slight erythema was also noted at hour 1 but increased to well-defined erythema (grade 2) at the 24-hours reading. At hour 48 very slight erythema was observed in this animal. The cutaneous reactions were reversible in all animals within 72 hours after removal of the patch.

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described cutaneous reactions as well as the average score for irritation, alpha,alpha'-Propylenedinitrilodi-o-cresol does not show a skin irritating potential under the test conditions chosen.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1959

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

One drop of the test substance was applied to the rabbit's eye. The occular reactions were scored after 10 min, 1 h, 3 h and after 24 h and further on until effects were reversible.

GLP compliance:

no

Species:

rabbit

Strain:

other: white rabbit

Details on test animals or tissues and environmental conditions:

no data

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 drop of the test material

Duration of treatment / exposure:

1 drop was applied and not washed out

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Details on study design:

SCORING SYSTEM: comparable to the scoring system outlined in OECD 405 guideline

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.25

Reversibility:

fully reversible within: 2 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Alpha,alpha'-Propylenedinitrilodi-o-cresol does not show an eye irritating potential under the test conditions chosen.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The potential of the substance to cause acute dermal irritation or corrosion was assessed according to OECD Guideline 404 and GLP by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three White New Zealand rabbits (semi-occulsive dressing). The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch.

The following test item-related clinical observations were recorded during the course of the study:

· Very slight to well-defined erythema (grade 1 to 2)

The cutaneous reactions were reversible in all animals within 72 hours after removal of the patch. Mean scores over 24, 48 and 72 hours for each animal were 1.0, 0.3 and 0.3 for erythema and 0.0, 0.0 and 0.0 for edema.

Considering the described cutaneous reactions as well as the average score for irritation, the substance does not show a skin irritating potential under the test conditions chosen.

Eye irritation:

During an in vivo study comparable to OECD 405 guideline which was conducted with two rabbits by BASF (1959), one drop of the unchanged test substance was applied to the rabbit's eye while the untreated eye was used as control. The eyes were not washed and the occular reactions were scored after 10 min, 1 h, 3 h and after 24 h and further on until effects were reversible. Both animals showed a slighty reddened eye 3 hours after application of the test item which was fully reversible within 24 and 48 hours after test substance application, respectively. Mean redness score of both animals: 0.25 (24/48 h). The test substance was not irritating to the eye.

This result was confirmed by two in vitro studies (both BASF, 2012) conducted according to GLP. A study performed according to OECD TG 437 (Bovine Corneal Opacity and Permeability Test, BASF, 2012) showed that the test item did not exhibit a corrosive potential towards isolated bovine corneas and the second in vitro study using reconstructed human corneas (EpiOcular) confirmed that the test item did not show an eye irritation potential.

Justification for classification or non-classification

Based on the available data, the test substance is not classified with regard to skin and eye irritation according to Regulation (EC) No 1272/2008 (CLP).