Reaction mass of m-terphenyl and o-terphenyl

Endpoint summary

Description of key information

- Read across from biphenyl-2 -ol (CAS 92 -52 -4); Key study, Buehler Test (according to OECD 406), Bor:DHPW Pigs, 0.1 mL (5 %) intradermal induction; 40% epidermal occlusive for topical induction and challenge, negative

- Read across from biphenyl-2 -ol (CAS 90 -43 -7); Key study, Guinea pig maximisation test (according to Magnusson-Kligman, 1970), guinea pigs, 0.5 % intracutaneous induction, subsequently 25 % epicutaneous occlusive induction and 5 % epicutaneous occlusive challenge, negative

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied, based on the chemical structure of the potential analogues, their toxicokinetic behaviour and other available (eco-)toxicological data.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance Reaction mass of m-terphenyl and o-terphenyl and the source substance biphenyl -2-ol used in this study both belong to the group of closely related aromatic hydrocarbons. Also known as (di-)phenylbenzenes or bi-/tri-phenyls, they consist of a central benzene ring substituted with either two phenyl groups or one phenylgroup and a hydroxyl group. Moreover, all isomers have a common functional group(s) and are expected to have common breakdown product(s). Therefore both substances are expected to follow the same toxicokinetic pattern.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)

source substance:
biphenyl-2-ol ( or 1,1’-Biphenyl)
structural formula: C12H10
c1ccc(cc1)c2ccccc2
CAS 90-43-7
EC No 201-993-5
purity: analytical grade

target substance:
Reaction mass of m-terphenyl and o-terphenyl
structural formula: C18H14
The substance consists of two constituents, each with their own Smiles notation and structural formula:
o-terphenyl: c(c(c(cccc1)c1)ccc2)(c(cccc3)c3)c2
m-terphenyl: c(c(cccc1)c1)(cccc2c(cccc3)c3)c2
CAS -
EC No 904-797-4
purity: not specified

3. ANALOGUE APPROACH JUSTIFICATION
Reaction mass of m-terphenyl and o-terphenyl and biphenyl-2-ol belong to the group of closely related aromatic hydrocarbons. These (di-)phenylbenzenes or bi-/tri-phenyls, also known as diphenylbenzenes or triphenyls, consist of a central benzene ring substituted with two phenyl groups or one phenyl group and a hydroxylgroup. Both chemicals are expected to be metabolised similarly building similar metabolites (“common breakdown product").
The similar findings (refer to data matrix outlined below) for both substances support the conclusion that similar molecules will be formed from both substances when applied systemically, and these molecules. In consequence, biphenyl-2-ol may serve as read-across substance for Reaction mass of m-terphenyl and o-terphenyl. For the endpoint skin sensitisation this is also underlined by a profiling performed with the OECD QSAR Toolbox v4.2. Similar to the constituents of the target substance, m- and o-terphenyl, the source substance biphenyl -2-ol does not possess the ability to bind to proteins as profiled by the general mechanistic profiling method “Protein binding by OECD” and by “Protein binding by OASIS”. Additionally, all endpoint specific profiling methods related to skin sensitisation included into the OECD QSAR Toolbox do not indicate any sensitising mode of action. So, the available data on biphenyl-2-ol can be used to cover the skin sensitisation endpoint currently lacking from Reaction mass of m-terphenyl and o-terphenyl, making further testing obsolete.

4. DATA MATRIX
There is mainly physico-chemical data available on the toxicological properties of Reaction mass of m-terphenyl and o-terphenyl. Data on biphenyl-2-ol covers the skin sensitisation endpoint. The identification and discussion of common properties will be based on available data including toxicological and physicochemical data.
The physical state of the two substances is solid (Reaction Mass of m-terphenyl and o-terphenyl is a cream coloured solid block at room temperature; biphenyl-2-ol is a soft solid a room temperature, melting to a yellow liquid). Their melting point lies at 32 °c and 145 °C; their boiling point at 355°C and 343°C. Furthermore, their density is quite similar (1.11 x 10E3 kg/m3 at 20.0 ± 0.5 ºC and 1.041 x 10E3 kg/m3 at 80ºC/ 1.133 x 10E3 kg/m3 at 25 ºC) and the vapour pressure is also in the same range (1.8 x 10E-2 Pa at 25 °C corresponding to 1.7765 x 10E-7 atmosphere and 1.6x10E-5to 3.0x10E-14 atmosphere; the estimated vapour pressure of the o-, m- and p-terphenyls ranged from 4.3 x 10E-7to 8.0 x 10E-10 atmosphere).
The available data for the following physico-chemical properties, which are relevant for absorption into living organisms, are very similar. Both substances are medium sized molecules with a molecular weight of 230.3 (Reaction mass of m-terphenyl and o-terphenyl) resp. 170.21(biphenyl-2-ol), they are both slightly soluble in water ((Less than 1.0 x 10E-4 g/L of solution at 20.0 ± 0.5 °C (Reaction mass of m-terphenyl and o-terphenyl) and 0.7 g/L at 20°C (biphenyl-2-ol)) and have a rather high logPow (3.01 to 5.94 (reaction mass of m-terphenyl and o-terphenyl) and 3.18 at 22.5°C (biphenyl-2-ol)). Reaction mass of m-terphenyl and o-terphenyl is not readily biodegradable. In contrast biphenyl-2-ol is readily biodegradable. However, they are both not expected to be or known not to be hydrolysed due to lack of functional groups. For Reaction mass of m-terphenyl and o-terphenyl a QSAR calculation has been performed for the bioconcentration factor (BCF). For both - m-terphenyl and o-terphenyl - a BCF of 2041 L/kg wet-wt (3.31 log BCF) was predicted.

There is only data available for the target substance Reaction mass of m-terphenyl and o-terphenyl for the following toxicological endpoints: Repeated dose toxicity oral and Toxicity to reproduction (fertility / developmental toxicity).
Moreover, there is data available for the Read Across substance biphenyl-2-ol: Skin sensitisation.
The Read Across substance biphenyl-2-ol has been shown to be not sensitising to skin. For Reaction mass of m-terphenyl and o-terphenyl a NOAEL of 100 mg/kg bw was derived for the endpoint Repeated dose toxicity oral and for reproduction / developmental toxicity, based on effects around parturition at 300 mg/kg/day.

Reason / purpose for cross-reference:

read-across source

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5 %

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

5 %

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Group:

negative control

Remarks on result:

other: no details specified

Remarks:

.

Group:

positive control

Remarks on result:

other: no details specified

Remarks:

.

Interpretation of results:

not sensitising

Conclusions:

OPP has been shown to be not skin sensitising according to the results of the present investigation.
The target substance Reaction mass of m-terphenyl and o-terphenyl and the source substance biphenyl-2-ol used in this study belong to the group of closely related aromatic hydrocarbons. Also known as phenylbenzenes / diphenylbenzenes or biphenyls/ triphenyls, they consist of a central benzene ring substituted with one/ two phenyl groups.
Therefore both substances are expected to follow the same toxicokinetic pattern. For the detailed procedure of the read-across principle and justifications, please refer to the analogue approach justification depicted above.

Executive summary:

The sensitising potential of seven industrial antimicrobial agents (including biphenyl-2 -ol (OPP) and its sodium salt, SOPP) was evaluated using the guinea pig maximisation test. Out-bred female albino guinea pigs (350-450 g) were used for the test. Propylene glycol was used as a vehicle for OPP while SOPP was dissolved in water. Moderately irritant concentrations were assessed in an irritancy test on a maximum of 4 guinea pigs and used for the topical inductions. For the challenge a non-irritant concentration and dilutions thereof were used. The tests were done in series of up to five groups of 20 guinea pigs. Four compounds could be tested simultaneously, 20 animals were used as controls and treated with vehicle only. In the series where four biocides were tested simultaneously, the control animals were challenged with the four biocides in the highest non-irritant challenge concentration. OPP and SOPP were tested at two concentrations in a total of 80 animals. The concentrations in vehicle were 0.5% or 5% for the intradermal induction (day 0) and 25% for the topical induction (day 7), for both compounds. The challenge was done on day 21 with a 5% concentration. In one case, the challenge was repeated after 1-2 weeks. The right and left flanks were used alternately. Blind reading of challenge reactions was done at 48 and 72 h. The Magnusson-Kligman grading scale was used to evaluate the challenge reactions. A grade 1 reaction was not regarded as sensitisation. The overall classification is based on the day 21 reading. OPP has been shown to be not skin sensitising according to the results of the present investigation.

The target substance Reaction mass of m-terphenyl and o-terphenyl and the source substance biphenyl-2-ol used in this study belong to the group of closely related aromatic hydrocarbons. Also known as phenylbenzenes / diphenylbenzenes or biphenyls/ triphenyls, they consist of a central benzene ring substituted with one/ two phenyl groups.

Therefore both substances are expected to follow the same toxicokinetic pattern. For the detailed procedure of the read-across principle and justifications, please refer to the analogue approach justification depicted above.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no data available for the target substance. However, several reliable test results are available for structurally related read across substances. The results of these will be described in the following.

The key study for the read across substance biphenyl (CAS 92 -52 -4) is a Buehler test with Bor:DHPW guinea pigs (according to OECD 406). 20 female guinea pigs (286 - 352 g bw) received three intradermal injections on one line. The distance between the injections was 1-2 cm; the application volume was 0,1 mL. The treatment of the test animals was performed as follows: 1) cranial injection: FCA (Difco Lab.) 1:1 mixture with physiological saline (sterile); 2) medial injection: 5% diphenyl in 'Pastillen' mixed with polyethyleneglycol 400; 3) caudal injection: 5% diphenyl in 'Pastillen' mixed with polyethyleneglycol 400 and FCA in similar proportion. 2 times ten guinea pigs received the same injections, however, the injections mentioned above under 2) and 3) do not contain diphenyl but an appropriate quantity of polyethyleneglycol 400. Afterwarts, the topical induction was performed (1 week after the intradermal induction). One day before the treatment areas were shaved and a 10% sodium lauryl sulphate solution in paraffin oil was applied. Between the injection sites, hypoallergic plasters (2 x 4 cm) are applied, covered with aluminium foil and fixed to the skin with an adhesive tape. The plasters were treated as follows: a) test group: 0,5 mL diphenyl in 'Pastillen' 40%; b) control group: 0,5 mL polyethyleneglycol 400; At the end of the 48 hours exposure the substance is removed with physiological saline.

Guinea pigs were challenged three weeks after the last induction application.  The animals of the test group and the first control group are treated with a 40% test solution impregnated hypoallergic plaster at the left side for 24 hours which is fixed to the skin with self adhesive tape. At the right side, which serves as a control, only a plaster impregnated with polyethyleneglycol is applied and fixed. The application volume is 0.5 mL. At the end of the exposure, the substance is removed with sterile physiological saline and the skin is shaved around the treatment area.

The challenge application sites did not show any evidence of erythema in the animals, nor did any of the naïve animals have any signs of irritation. Diphenyl did not have skin sensitisation potential under the conditions of this maximization test in guinea pigs. As such, the test item biphenyl is considered to be not sensitising to the skin.

The second key study for the read across substance biphenyl-2 -ol (CAS 90-43-7) is a Guinea pig maximisation test (according to Magnusson Kligman, 1970). Out-bred female albino guinea pigs (350-450 g) were used for the test. Propylene glycol was used as a vehicle for biphenyl-2 -ol (OPP) while the sodium salt of biphenyl-2 -ol (SOPP) was dissolved in water. Moderately irritant concentrations were assessed in an irritancy test on a maximum of 4 guinea pigs and used for the topical inductions. For the challenge a non-irritant concentration and dilutions thereof were used. The tests were done in series of up to five groups of 20 guinea pigs. In total, in this test 7 industrial antimicrobial agents were investigated. Four compounds could be tested simultaneously, 20 animals were used as controls and treated with vehicle only. In the series where four biocides were tested simultaneously, the control animals were challenged with the four biocides in the highest non-irritant challenge concentration. OPP and SOPP were tested at two concentrations in a total of 80 animals. The concentrations in vehicle were 0.5 % or 5 % for the intradermal induction (day 0) and 25 % for the topical induction (day 7), for both compounds. The challenge was done on day 21 with a 5 % concentration. In one case, the challenge was repeated after 1-2 weeks. The right and left flanks were used alternately. Blind reading of challenge reactions was done at 48 and 72 h. The Magnusson-Kligman grading scale was used to evaluate the challenge reactions. A grade 1 reaction was not regarded as sensitisation. The overall classification is based on the day 21 reading. OPP has been shown to be not skin sensitising according to the results of the present investigation.

There was one additional study available describing the effects of a polyphenyl mixture (Haley et al. 1959), however the composition of the mixture is clearly different from the currently produced mixtures and therefore these results are not taken into account.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The classification is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No 1272/2008.