Orthoboric acid, compound with 2,2',2''-nitrilotriethanol

Endpoint summary

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:

25th April 2017 to 25th May 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

LLNA frequently gives false positives for irritating substances therefore Buehler test was used. The testing will also be submitted to other regulatory agencies that do not accept LLNA testing.

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

Prior to use, all animals were acclimated for at least five days. Animals were individually housed
in wire mesh suspension cages. The animals were maintained on a 12-hour cycle light controlled
room, at a temperature of 64° - 79°F and a relative humidity of 30-70%. The animals were
maintained according to the recommendations contained in the National Academy Press 2011:
“Guide for the Care and Use of Laboratory Animals.” The animals were supplied Purina Guinea
Pig Chow and tap water ad libitum during both acclimation and test periods. Tox Monitor
Laboratories has daily access to feed analysis; water analysis from the city of Chicago is on file.
There were no contaminants in either the feed or the water that would be expected to affect the
outcome of this study.

Route:

epicutaneous, semiocclusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.4ml

Day(s)/duration:

6 hours

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#20

Route:

epicutaneous, semiocclusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.4ml

Day(s)/duration:

6 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20 test animals ( induction phase and challenge phase )

Details on study design:

The irritation screen phase was conduicted to determine the irritation potential of the test substance. The irritation potential of the test substance at levels of 100%, 75%, 50% and 25% were evaluated in one group of two animals. Four levels of test substance were evaluated per animal. Dilutions of the test substance were formulated w/w in deionized water . The position of the different concentrations of the test substance on the animals was varied to adjust for possible site-to-site variation in response. The day prior to test substance exposure, the hair was removed from each of the animal's backs using a small animal clipper. Closed patches were applied to the animals in the following manner. A 0.4 ml quantity of each test preparation was applied directly into a 25 mm Hilltop Chamber®. The animals were held gently, and the chambers were applied as quickly as possible to the clipped left shoulder. The chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed. Based upon the irritation screen results the test substance was dosed as 100% concentration for the induction phase of the study, and 100% concentration, the highest non-irritating concentration, for the challenge phase of the study.

Induction phase : The left shoulder of each test animal was clipped with a small animal clipper the day before exposure.The animals were held gently and the chambers were applied as previously described under the "Irritation Screening". Two additional induction doses were conducted following the same procedure, at weekly intervals After the last induction exposure, the animals were left untreated for two weeks (14 days) before primary challenge

Challenge phase: The same exposure procedure as for the "Induction Phase" was used, except the Hilltop Chambers were applied to a skin site that had not been previously exposed. Each animal received a single chamber of the test substance. The day following the primary challenge exposure all animals were scored as described under the “Observations” section.

Challenge controls:

10 animals - 6 was used as as controls and 4 were kept for a rechallenge if required.

Positive control substance(s):

yes

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1005 concnetration

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% concentration

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

Interpretation of results:

GHS criteria not met

Conclusions:

Following primary challenge test substance at 100% concentration, the incidence of grade 1 response or greater in the test group (0 of 20) was compared to that of the naive control group (0 of 6). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced. Therefore, in accordance with the criteria set forth in the CLP Guidance’s, the test substance will not be classified for skin sensitisation.

Executive summary:

Dermal sensitization potential of the test substatance was conducted utilizing a Buehler Technique Guinea Pig Sensitization Protocol. The test substance was evaluated for sensitization potential by applying 0.4 ml at a 100% concentration directly into Hilltop Chambers® and applying them to the clipped left shoulder of twenty albino guinea pigs in the following manner: The animals were held gently, and the chambers were applied as quickly as possible to the clipped left shoulder. The chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed. Two additional induction doses were conducted following the same procedure, at weekly intervals. Two weeks after the final application the animals received a topical primary challenge dose (6 hour contact) of test substance at 100% concentration, on a naive site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initiation of the primary challenge application. Ten guinea pigs served as a naive control group, and remained untreated through the induction phase. Six naive control animals received only the primary challenge dose, at a 100% concentration. The four remaining guinea pigs were designated for a re-challenge, if necessary.

Following primary challenge test substance at 100% concentration, the incidence of grade 1 response or greater in the test group (0 of 20) was compared to that of the naive control group (0 of 6). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced. Therefore, in accordance with the criteria set forth in the CLP Guidance’s, the test substance will not be classified for skin sensitisation.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Additional information:

The test substance was tested for dermal skin sensitization potential using a Buehler Technique Guinea Pig Sensitization Protocol. The test substance was evaluated for sensitization potential by applying 0.4 mL at a 100% concentration directly into Hilltop chambers and applying them to the clipped left shoulder of twenty albino guinea pigs. The animasl were held gently, and the chambers were applied as quickly as possible to the clipped left shoulder. The chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximatley six hours later, the tape and chambers were removed. Two additional induction doss were conducted following the same procedure at weekly intervals.

Two weeks after the final application the animals received a topical primary challenge dose (6 hours contact) of the test substance at 100% concentration, on a naive site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initation of the primary challenge application.

Ten guinea pigs served as a naive control group, and remained untreated through the induction phase. Six naive cotrols animals received only the primary challenge dose, at a 100% concentratiuon. The four remaining guinea pigs were designated for a re-challenge, if necessary.

Following primary challenge of the test susbtance at 100%, the grade 1 response or greater in the test group (0 of 20) was compared to that of the naive control group (0 of 6). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced.

Therefore, in accordance with the criteria set forth in the classification, labelling and packaging (CLP) guideline, the test substance will not be classified for skin sensitization.

An in vitro skin senstization study has not been conducted on this substance as a OECD, GLP compliant in vivo skin sensitization study was ava

Justification for classification or non-classification

Following primary challenge test substance at 100% concentration, the incidence of grade 1 response or greater in the test group (0 of 20) was compared to that of the naive control group (0 of 6). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced. Therefore, in accordance with the criteria set forth in the CLP Guidance’s, the test substance will not be classified for skin sensitisation.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.