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Administrative data

Description of key information

A guinea pig maximisation study conducted according to OECD/EC guidelines (1981) and GLP principles is available (Klimisch 1). The test substance was found to have skin sensitising properties.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Guinea Pig Maximisation Test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16JUN1992 - 18JUL1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
date of inspection: 17 March 1992
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This guinea pig maximisation study was conducted in 1992, before LLNA was implemented.
Specific details on test material used for the study:
The test was performed with PEMP product, the registered substance.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, united Kingdom
- Age at study initiation: appr. 8-12 weeks old
- Weight at study initiation: 302-391g
- Housing: groups of up to three in solid-floor propylene cages
- Diet: Guinea Pig FD1 Diet (Special Diet Services Limited, Withamm, Essex, United Kingdom), ad libitum
- Water: tap water, ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 46-74
- Air changes (per hr): appr. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16JUN1992 To: 18JUL1992
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Remarks:
(or unchanged)
Concentration / amount:
Intradermal induction: 1% (w/v)
Topical induction: undiluted
Topical challenge: undiluted and 75% (w/v)
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Remarks:
(or unchanged)
Concentration / amount:
Intradermal induction: 1% (w/v)
Topical induction: undiluted
Topical challenge: undiluted and 75% (w/v)
No. of animals per dose:
20 (treated) and 10 (control)
Details on study design:
RANGE FINDING TESTS:
Intradermal application:
Two animals were intradermally injected with preparations of test material (1% or 5% in arachis oil B.P.). No local necrosis or systemic toxicity were seen after injection with 1% w/v. At 5% w/v, local necrosis was observed at 24 and 48 hours with eschar formation at 72 hours and 7 days (in absence of signs of systemic toxicity).

Topical application:
Two guinea pigs (intradermally injected with Freund's Complete Adjuvant nine days earlier) were occlusively exposed for 48 hours with the undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in arachis oil B.P.). No skin reactions were seen at 25% and 50% concentration. Exposure to 75% and 100% test substance resulted in scattered mild redness. At 100%, the skin reaction remained for up to and including 48 hours in both animals. At 75%, skin reaction was still visible after 48 hours in one animal, in the other all skin reactions resolved after 48 hours.
Furthermore, the flanks of two guinea pigs were treated occlusively for 24 hours with the undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in arachis oil B.P.). This resulted in skin reaction seen in both animals (scattered mild redness at 25% and 50%; moderate and diffuse redness at 75% and 100% ). The skin reactions had resolved after 24 hours.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: single intradermal and single topical exposure
- Exposure period: 48 hours (topical application)
- Site: area of appr. 40 mm x 60 mm on the shoulder region (clipped)
- Frequency of applications: single application
- Concentrations: 1% (w/v) (intradermal) and undiluted (topical)

B. CHALLENGE EXPOSURE
- No. of exposures: Single application
- Day of challenge: day 21
- Exposure period: 24 hours
- Site: right flank (undiluted sample), left flank (test substance at 75% (v/v))
- Evaluation (hr after challenge): 24 and 48 hours after challenge
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene
Positive control results:
In a study performed with 2,4-dinitrochlorobenzene (DNCB) following the same protocol between 29 November and 26 December, DNCB produced a 89% sensitisation rate.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
12
Total no. in group:
18
Clinical observations:
For all positive animals, reactions extended beyond treatment site
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
13
Total no. in group:
18
Clinical observations:
For all positive animals, reactions extended beyond treatment site
Remarks on result:
other: Clinical observations: For all positive animals, reactions extended beyond treatment site.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Scattered mild redness (score 1) limited to treatment site
Remarks on result:
other: Clinical observations: Scattered mild redness (score 1) limited to treatment site.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Scattered mild redness (score 1) limited to treatment site
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
4
Total no. in group:
18
Clinical observations:
For 5 animals, adverse reactions prevented accurate evaluation of the skin
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75%
No. with + reactions:
1
Total no. in group:
18
Clinical observations:
For 13 animals, adverse reactions prevented accurate evaluation of the skin
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Scattered mild redness (score 1) limited to treatment site
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

One test animal was found dead on day 1 with unknown cause of death. One test animal was killed for humane reasons on day 21 (no further details given).

Observations after topical induction:

One hour after removal of dressing, scattered mild redness was seen in 11/19 animals, and 7/19 had moderate and diffuse redness.

In one animal, the adverse reactions prevented accurate evaluation of the skin effects. Furthermore, 8/19 animals had scratched and bleeding test sites. after 24 hours, skin evaluation was not possible in 7/19 guinea pigs, related to dried blood and presence of hardened, dark-brown/ black-colored scabs. No skin reactions were seen in the control animals.

Observations after challenge:

Scattered mild redness and moderate and diffuse redness were elicited by the test material after challenge with 100% and 75% test substance after 24 hours. One animal (challenged with 75% test substance) was observed to have small superficial scattered scabs. In almost all challenged animals, the skin reactions extended beyond treatment site. At 48 hours, adverse reactions prevented accurate evaluation of the skin reactions. In these animals, desquamation was seen, accompanied by slight or well-defined oedema. For most animals, skin reactions extended beyond treatment site (these animals were regarded to give a positive reaction to the test substance).

No skin reactions were seen after treatment of induced animals with vehicle alone.

Body weight gains of the guinea pigs in the test group during the study were comparable to those observed in the control group.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Based on the results of a guinea pig maximisation study conducted according to OECD/EC guidelines (1981) and GLP principles, the test substance was found to have skin sensitising properties.
Executive summary:

A guinea pig maximisation study was conducted according to OECD/EC guidelines (1981) and GLP principles. Based on preliminary testing, the concentrations of test material were choosen as follows: 1% (w/v) in arachis oil B.P. (intradermal induction), undiluted (topical induction) and undiluted and 75% (topical challenge). One animal was found dead at day 1 (unknown cause) and one was killed in extremis on day 21. The test material gave a positive response in 12/18 (100%) and 13/18 (75%) animals after 24 hours. At 48 hours, adverse reactions (including desquamination and oedema) prevented accurate evaluation in many animals.

Based on the results of this study, the test substance was found to have skin sensitising properties.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A guinea pig maximisation study was conducted according to OECD/EC guidelines (1981) and GLP principles. Based on preliminary testing, the concentrations of test material were choosen as follows: 1% (w/v) in arachis oil B.P. (intradermal induction), undiluted (topical induction) and undiluted and 75% (topical challenge). One animal was found dead at day 1 (unknown cause) and one was killed in extremis on day 21. The test material gave a positive response in 12/18 (100%) and 13/18 (75%) animals after 24 hours. At 48 hours, adverse reactions (including desquamination and oedema) prevented accurate evaluation in many animals.

Based on the results of this study, the test substance was found to have skin sensitising properties.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, PEMP is classified for skin sensitization according to CLP Regulation (EC) No. 1272/2008.