Registration Dossier

Administrative data

Description of key information

One Guinea Pig Sensitization (Maximization Test aggording to Magnusson-Kligman) was conducted. Based on the results, DPT is not regarded as a dermal sensitizer.

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:
2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximisation test (Magnusson-Klingman according to OECD TG No. 406) is available which was performed before 10 May 2017.According to Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a "In vivo skin sensitisation studies that were carried out or initiated before 10 May 2017, and that meet the requirements set out in Article 13(3), first subparagraph, and Article 13(4) shall be considered appropriate to address this standard information requirement."
This would not justify conducting an additional LLNA due to animal welfare.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm Hill Breeding Laboratories, Chelmsford, MA 01824 or any other USDA registered acceptable source.
-Gender: Male and female
-Identification: Ear tag and cage card.
- Age at study initiation: 4-5 weeks at start of dosing; records of dates of birth for animals used in this study will be retained in the Calvert archives.
- Weight at study initiation: Body Weight Range 307 - 440 grams (males and females) at the outset (Day 1) of the study.
- Housing:Animals were housed (individually) in compliance with USDA Guidelines. The room in which the animals were kept is documented in the study records. No other species were kept in the same room.
- Diet (e.g. ad libitum): All animals had access to Harlan Teklad Guinea Pig Diet (certified) ad libitum. No contaminants were known to be present in the certified diet at levels that would be expected to interfere with the results of this study.
- Water (e.g. ad libitum): Water was available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert SOP's. No contaminants were known to be present in the water at levels that would be expected to interfere with the results of this study.
- Acclimation period: Main study animals were acclimated to their housing for a minimum of 7 days prior to their first day of dosing. Dose range animals were acclimated to their housing for a minimum of 5 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 23°C
- Humidity (%): 20 to 71%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
-IN-LIFE Dates: From 9 Apr 2014 to 7 May 2014
Route:
intradermal
Vehicle:
soya oil
Concentration / amount:
test article concentration 5 % / volume 0,1 mL per site
Day(s)/duration:
Day 1
Adequacy of induction:
not specified
Route:
other: topical
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % of the test article / 0.3 mL
Day(s)/duration:
Day 8
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
other: topical
Vehicle:
soya oil
Concentration / amount:
100 % of the test article / 0.2 mL
Day(s)/duration:
Day 22/ 24 and 48-hour grade
Adequacy of challenge:
not specified
No. of animals per dose:
The main study was conducted with 10 animals/sex for the test article group, 5 animals/sex for the vehicle control group and 3 animals/sex for the positive control (1-chloro-2,4-dinitrobenzene [DNCB]) group.
Total Number: 4 for primary Irritation (Dose Range-finding)-lntradermal
4 for primary Irritation (Dose Range-finding)-Topical
20 in test Article Group
10 in vehicle Control Group
6 in positive Control Group
Details on study design:
The positive control group used six animals with induction exposures of 0.1% 1-chloro-2,4-dinitrobenzene (DNCB) in saline
(Hospira, lot#29-154-JT, exp. 1 May 2015, clear liquid, room temperature) (intradermal exposure) and in petrolatum (topical exposure).
A topical challenge exposure of 0.05% DNCB in petrolatum and petrolatum alone (Sigma, lot# 5LBB2440V, Exp. June 2016, clear ointment, room temperature).

RANGE FINDING TESTS:
Intradermal Dose Range: Prior to induction, the irritation potential of the test article was determined. Four naive animals were exposed to four different test article concentrations by the intradermal technique described in the site preparation and intradermal induction stage. In this test, both sides of the animal were clipped and exposed to concentrations of the test article (1, 2.5, 4 and 5%). The location of each of the concentrations of test article differed in each of the four animals to compensate for any site-to-site variations. Approximately twenty-four hours and twenty-eight minutes after dosing, the scores were recorded.


Topical Dose Range: Four na·lve guinea pigs were exposed to four different concentrations of the test article (1 0, 25, 50 and 1 00%). The procedure described in topical induction period was employed except that the wrapping was removed approximately twenty-two hours and 49
minutes after dosing (refer to deviation in Appendix II). Approximately twenty-one hours and thirty-six minutes after unwrap the sites were
depilated as described in the challenge section. Approximately three hours and thirty-five minutes later, the sites were examined for skin
reactions (24-hr grade). The location of each of the concentrations of test article differed in each of the four animals to compensate for any
site-to-site variations.

In consultation with the Sponsor, it was decided to proceed to the main study using a test article concentration of 5% intradermally and 100% topically.
Challenge controls:
Positive control: 0.05% DNCB in petrolatum and petrolatum alone (Sigma, lot# 5LBB2440V, Exp. June 2016, clear ointment, room temperature).
Vehicle control: Soybean Oil
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (DNCB)
Positive control results:
The positive control group exhibited the anticipated positive reaction to validate
the study.
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
All animals appeared normal throughout the course of the main study.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other:
Remarks:
One aninmal elicted a weak grade I hypersensitivity response at 24 h which is not regarded as signifikant according to the guidleine. The test article did not elicit a positive response in the test article treated animals at 48 hours following the challenge
Reading:
2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.05% ONCB in petrolatum
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
positive indication of skin sensitisation

Scoring-Main Study

Incidence of Dermal Irritation Scores at Challenge

   Group

 
 Challenge Treatment   

 

 
 Dermal Irritation Scores                     

 24 -hour Grade         

          48 -hours Grade

 0

 1

 2

 3

 0

 1

 2

 3

 Vehicle control

 

 

 DPT@100%

 10

 0

 0

 10

 0

 0

 0

 Soybean Oil

 10

 0

 0

 0

 10

 0

 0

 Test control

 

 

  DPT@100%

 19

 1

 0

 0

 20

 0

 0

 0

 Soybean Oil

 20

 0

 0

 0

 20

 0

 0

 0

Positiv Control

 

 

 0.05% DNCB in petrolatum

 0

 4

petrolatum

 6

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study and based on the results, an intradermal induction of 5% OPT Dipentylterephthalate in soybean oil and a topical induction of 100% OPT Dipentylterephthalate in soybean oil, followed by a topical
challenge at 100% to guinea pigs elicited a weak grade I dermal contact hypersensitivity response at 24 hours which Magnusson and Kligman do not regard as significant. The test article did not elicit a positive response in the test article treated animals at 48 hours following the challenge. However, this finding at 48 hours causes Dipentylterephthalate to be categorized as a weak grade I dermal sensitizer at 48 hours which Magnusson and Kligman do not regard as significant according to the Magnusson and Kligman method of grading sensitization.
Executive summary:

Scoring-Dose Range Study

In the intradermal dose range, no erythema to discrete or patchy erythema was observed in the four animals at 1%, 2.5%, 4%, and 5%. Grades of zero were observed in the four animals receiving the topical test article concentrations of 10%, 25%, 50%, 100% during the dose ranging finding study. In consultation with the Sponsor, it was decided to proceed to the main study using a test article concentration of 5% intradermally and 100% topically.

Mortality/Clinical Observations-Main Study

No mortality was observed and all animals appeared normal throughout the course of the main study.

Body Weights-Main Study

No biologically relevant differences in the final body weights of the animals in the main study occurred.

Endpoint conclusion
Additional information:

Under the conditions of the study and based on the results, an intradermal induction of 5% OPT Dipentylterephthalate in soybean oil and a topical induction of 100% OPT Dipentylterephthalate in soybean oil, followed by a topical challenge at 100% to guinea pigs elicited a weak grade I dermal contact hypersensitivity response at 24 hours which Magnusson and Kligman do not regard as significant. The test article did not elicit a positive response in the test article treated animals at 48 hours following the challenge. However, this finding at 48 hours causes OPT Dipentylterephthalate to be categorized as a weak grade I dermal sensitizer at 48 hours which Magnusson and Kligman do not regard as significant according to the Magnusson and Kligman method of grading sensitization.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available study, the test substance is not classified for sensitisation according to EC Regulation No. 1272/2008.