Registration Dossier

Administrative data

Description of key information

In conclusion, the test substance 6PPD was not skin irritating to rabbits skin (Monsanto Co. 1973, Randall and Bannister 1990). The even very low skin irritation potential is confirmed by an additional skin irritation studies (Monsanto Co. 1962). A rather slight and transient eye irritation potential is noted in two eye irritation studies (Monsanto Co. 1962, 1973).

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, data from summary without detailed documentation, acceptable for assessment
Principles of method if other than guideline:
Method: other skin irritation study
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
other: intact and abraded skin
Vehicle:
other: undiluted (warmed to 46°C to liquefy)
Controls:
not required
Amount / concentration applied:
Concentration: 0.5 other: ml (undiluted)
Duration of treatment / exposure:
24 hour(s)
Observation period:
7 d
Number of animals:
6
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 72 h
Score:
0
Max. score:
8
Reversibility:
other: no effects
Remarks on result:
other: no effects

RS-Freetext:
AVERAGE SCORE
0.0/8.0

Non irritating to rabbit skin

Interpretation of results:
not irritating
Remarks:
Migrated information
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, data from summary without detailed documentation, acceptable for assessment
Principles of method if other than guideline:
Method: other: in vivo eye irritation study
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
other: undiluted (warmed to 46°C)
Controls:
not required
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
24 h
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
6
Details on study design:
Comment: no data
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1.2
Max. score:
110
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: transient slight erythema, transient discharge and discomfort

RS-Freetext:
AVERAGE SCORE:
1.2/110

immediate: slight discomfort

1 h: slight erythema, capious discharge

24 h: slight erythema, moderate discharge

48 h: slight erythema

Interpretation of results:
slightly irritating
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

There are no studies according to the current OECD guideline; however, there are study reports which give sufficient information to evaluate this endpoint.

The skin irritation potential of the test substance 6PPD was evaluated in a skin irritation study with six New Zealand albino male and female rabbits (Monsanto Co. 1973, Randall and Bannister 1990). The warmed test substance (500 ml warmed to 46°C to liquefy) was applied under semi-occlusive dressings to clipped intact and abraded skin of 6 New Zealand albino rabbits for 24 hours. A 7-day observation period followed the test substance application. The test substance 6PPD was practically non-irritating to rabbit skin (mean irritation score: 0).

In an earlier study undiluted 6PPD (amount not given) was applied to the clipped, intact skin of 3 rabbits for 24 hours under a dressing of plastic strips. The compound was removed with soap and water. Within 4 hours 2/3 rabbits developed barely perceptible redness (average score 0.6/8 according to the method of Draize). At the 24 hour-reading slight to well defined erythema were reported as the maximal reaction (score 1.6) returning to barely perceptible redness within 72 hours (score 1.0) and complete reversibility within 120 hours (score 0.0). The compound was evaluated as a slight irritant (Monsanto Co. 1962).

In another limited documented skin irritation study groups of 6 rabbits were exposed to preparations of 6PPD in vaseline (0.5 g with 2.5 or 25 % 6PPD corresponding to 0.0125 and 0.125 g 6PPD) or olive oil (0.025 g 6PPD in 0.5 ml oil) according to the method of Draize (no information on occlusion). Exposure of the scarified or unscarified skin was for 24 hours, further readings were after 24 and 72 hours. Neither individual nor average scores for erythema / oedema or the time course of the reaction and the reversibility of effects were documented in the available publication. Test results were presented as primary cutaneous irritation indexes (PCII) of 0.6 and 1.0 calculated for the low and high concentration vaseline preparation of 6PPD, leading for both to a classification of low irritant potential (criteria not documented). In contrast for the oily preparation a PCII of 3.3 was reported which was evaluated as a medium irritating effect (Herve-Bazin et al., 1977). In view of possible vehicle effects and the limited documentation of this publication, the findings were not included in the risks assessment, which is in line with the recent OECD risk assessment on 6PPD (2005).

Eye

There are no studies according to the current OECD guideline but there are study reports which give sufficient information to evaluate this endpoint.

The eye irritating potential of the test substance 6PPD was evaluated in an eye irritation study with New Zealand albino rabbits (Monsanto Co. 1973). 100 ml of the test substance (warmed to 46°C to liquefy) was applied into the conjuntival sac of the rabbits. A 7-day observation period followed the application of the test substance. Eye response were scored in accordance with the Federal Hazardous substances Act (F.H.S.A.), 21 CFR, § 191.12 (1964).

The test substance was slightly irritating to the rabbit eye (irritation mean score at 24, 48, and 72 hours: 1.2/110.0). Effects on the conjunctivae were noted in all animals at 24 hours (mean score 24 h: 5.6/110) but were reversible within 72 hours. The test substance was not classified as an eye irritant according to F.H.S.A.

In another eye irritation study undiluted 6PPD (0.1 ml) was applied to the eyes of 3 rabbits for 24 hours followed by a 5 day post exposure period. After 1 hour slight edema and erythema, copious discharge and slight dullness of the corneal area were observed with an average score of 20.6/110 according to the method of Draize. Iris and cornea cleared somewhat in 24 hours and within 72 hours iris clarity was normal. Very slight redness and edema disappeared by the 5th day (Monsanto Co.1962).

Justification for classification or non-classification

No classification is required according to the classification criteria 67/548/EEC and regulation no. 1272/2008 (GHS).