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Administrative data

Description of key information

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: conforms to current guideline and GLP.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This Guinea pig maximization test was performed in 2001, i.e. before the LLNA became the standard test for assessment.
Specific details on test material used for the study:
- Name of test material (as cited in study report): TPP
- Physical state: White granular solid
- Lot/batch No.: F21022
- Storage condition of test material: room temperature in the dark
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: supplied by David Hall Limited UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 345 - 410 g
- Housing: singly or in pairs in solid floor polyproylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Free access to guinea pig FD1 diet
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 deg C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours/light


Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
intradermal induction: 5%
topical induction: 75 %
topical challenge: 75 % and 50 %
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
intradermal induction: 5%
topical induction: 75 %
topical challenge: 75 % and 50 %
No. of animals per dose:
10 test and 5 control
Details on study design:
1st application; intradermal induction:
Shortly before treatment the hair was removed from an area approx. 40 x 60 mm on the sholder region of each animal. A row of three injections was made:
a) Freud's Complete Adjuvant plus destilled water in a ration 1:1
b) 5 % w/w TPP in arachis oil
c) a 5% w/w formulation of TPP in a 1:1 preparation with Freud's Complete Adjuvant plus destiled water
Approx. 24 and 48 hours after intradermal induction the degree of erythema at the test material injection site was evaluated.

2nd application; topical induction:
On day 7 the same area was clipped again and treated with topical application of the test material (75 % w/w in arachis oil; occlusive epicutaneous)

3rd application topical Challenge:
On day 21 an area of approx. 50 x 70 mm on both flancs of each animal was ciplled free of hair and topicallytreated with 75 % and 50% w/w TPP in arachis oil (occlusive epicutaneous)
Positive control substance(s):
yes
Remarks:
2-Mercaptobenothiazole
Positive control substance(s):
mercaptobenzothiazole (CAS No 149-30-4)
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 and 75 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 and 75 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50 and 75 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 and 75 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Interpretation of results:
GHS criteria not met
Conclusions:
not sensitizing
Executive summary:

A study was performed to assess the contact sensitisation potential of TPP in guinea pigs according to OECD guidelines study 406. Ten test and five control animals were used for the study. Two phases were involved in the main study; an induction of a response by intradermal injection and topical application and a topical challenge of that response. Based on sighting tests, the concentrations of TPP for the induction and challenge phases were selected as:

Intradermal induction: 5%w/w in arachis oil; Topical Induction: 75%w/w in arachis oil; Topical challenge 75 and 50%w/w in arachis oil. The results showed that TPP produced a 0% (0/10) sensisitisation rate and classified as a non-sensitiser to guinea pig skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A study was performed to assess the contact sensitisation potential of triphenyl phosphate in guinea pigs according to OECD guideline study 406. Ten test and five control animals were used for the study. Two phases were involved in the main study; an induction of a response by intradermal injection and topical application and a topical challenge of that response. Based on sighting tests, the concentrations of triphenyl phosphate for the induction and challenge phases were selected as:

Intradermal induction: 5%w/w in arachis oil; Topical Induction: 75%w/w in arachis oil; Topical challenge 75 and 50%w/w in arachis oil. The results showed that triphenyl phosphate produced a 0% (0/10) sensisitisation rate and classified as a non-sensitiser to guinea pig skin.

The OECD Guideline 406 (1992) for the Guinea pig maximisation test (GPMT) requires treatment of the test site with SLS prior to topical induction with non-irritating test materials, based on the studies of Magnusson and Kligman (1969). Such a treatment induces an additional provokation of skin inflammation. Later assessments of scientific experts for skin sensitization (see ECETOC Report No. 29 of September 2000, pages 17-18, and Steiling et al., Food and Chemical Toxicology 39, 293-301, 2001) come to the conclusion that SLS should no longer be used as a pretreatment in the GPMT. The rational for this recommendation, besides animal welfare reasons, is given here in short (for further details see attached pages of the ECETOC Report):

• The skin is already inflamed by the use of Freud’s Complete Adjuvant (FCA).

• SLS facilitates percutaneous absorption of the test material in a non-adequate (non-physiologic) manner.

• Skin integrity may be compromised by SLS, resulting in hyperirritable skin.

• SLS may in some circumstances act itself as an allergen.

• Animals that are already aggressively treated by FCA may be traumatized by additional irritation via SLS that may compromise performance of the test.

Following this recommendation all inhouse GPMTs have been performed without SLS treatment since 2001. This deviation from guideline has no impact on the validity of the test and the reliability of the result.

Single human cases have been reported with allergic dermatitis from TPP through the years (Andersen, 1977; Berkhoff, 1938; Carlsen, 1986; Hjorth, 1964; Pegum, 1966; Spritig, 1995).

Among the 23192 patients patch tested from 1950 to 1962, positive reactions to cellulose acetate film containing 7 to 10% triphenyl phosphate and 3 to 4% phthalic esters occured in 15 (0.065%). The sensitivity to ceullose acetate film was analysed in only two cases, in both of which the sensitiser was found to be trihphenyl phosphate. In the others it may have been either triphenyl phosphate or phthalic ester (Hjorth, 1964).

In a retrospective evaluation of human patch tests, none of the 343 patients reacted to TPP (Tarvainen, 1995).

174 patients patch tested with a variety of plastic and glue allergens showed no allergic reaction towards TPP. One patient showed signs of irritation. This indicates TPP did not cause skin sensitisation (Kanerva, 1997). In a retrospective evaluation of human patch tests, 1 of 358 patients reacted positive to TPP at 5% between 1991 -1996. 3 out of 358 patients showed irritation (Kanerva, 1997).

The authors in this review of five references conclude that only scarce indication of contact sensitising potential from TPP (Kayser, 2001).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Triphenyl phosphate was tested negative in a Guinea pig maximization test (OECD 406). According to EU Regulation 1272/2008 triphenyl phosphate does not meet the requirements for classification as a skin sensitiser.