Registration Dossier

Administrative data

Description of key information

Tributyl borate is rapidly hydrolyzed to Boric acid and n-Butanol in the presence of water or moisture in the air (18.3 sec at 21°C). Reliable endpoint information of the hydrolysis products n-Butanol and Boric acid is used, which is entirely appropriate to draw conclusions on the skin sensitisation potential of Tributyl borate:

- Hydrolysis product n-Butanol: not sensitising [in vivo study; OECD 429; mouse local lymphnode assay (LLNA)];

- Hydrolysis product Boric acid: not sensitising [in vivo study; OECD 406; Buehler test).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: experimental study on hydrolysis product Boric acid
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP 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:
OECD Guideline 406 "Skin Sensitisation" method (Buehler test ) was performed before the LLNA was set as preferred test method.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson’s Mill Farms, South Brunswick, NJ
- Age at study initiation: Young adult
- Weight at study initiation: Males: 314 -411 g; females: 282-376 g
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 0.4 g 95 % w/w boric acid
Challenge: 95 % w/w boric acid
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 0.4 g 95 % w/w boric acid
Challenge: 95 % w/w boric acid
No. of animals per dose:
Test Group: 20 animals
Naive Control: 10 animals
Positive Control: 20 animals
Positive Naive Control: 10 animals
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Concentrations: 0.4 g 95 % w/w boric acid moistened with distilled water to enhance skin contact.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 28
- Exposure period: Test substance was wiped off with water after 6 h.
Challenge controls:
No data
Positive control substance(s):
yes
Remarks:
Dinitrochlorobenzene
Positive control results:
No data
Reading:
1st reading
Hours after challenge:
34
Group:
test chemical
Dose level:
0.4 g 95% w/w/boric acid
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Very faint erythema seen in one animal at induction stage and 2 animals at challenge stage and also in one naïve control. No other adverse effect observed
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 34.0. Group: test group. Dose level: 0.4 g 95% w/w/boric acid . No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Very faint erythema seen in one animal at induction stage and 2 animals at challenge stage and also in one naïve control. No other adverse effect observed.

Observations:

Treatments

Buehler test

Observations/Remarks

 

Day of treatment

 

Induction 1

day 0

Very faint erythema (0.5) observed at one test site at 24 hours after first induction dose. No other irritation observed

Induction 2

7

No irritation observed

Induction 3

14

No irritation observed

Challenge

28

No irritation observed

Scoring 1

29

Very faint erythema (0.5) observed at two test sites at 24 hours after  challenge dose. Irritation persisted at one site for 48 hours.  Very faint erythema (0.5) observed at one test site at 24 hours in one naive control.

Scoring 2

30

 

Results of skin sensitisation test:

 

Number of animals with signs of allergic reactions /
number of animals in group

 

Negative control

Test group

Positive control

scored after 24h

0 / 10

0 / 20

10/20

scored after 48h

0 / 10

0 / 20

7/20

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
OECD Guideline 406 "Skin Sensitisation" method (Buehler test ) was performed using 95 % w/w boric acid moistened with distilled water to enhance skin contact. Very faint erythema was observed in one animal at induction stage and 2 animals at challenge stage and also in one naïve control. No other adverse effects were observed therefore the test substance was considered a non-sensitiser.
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
other: experimental study on hydrolysis product n-Butanol
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA:J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Indianapolis, IN or Jackson Laboratories, Bar Harbor, ME
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 6-12 weeks
- Housing, diet, water: Animals used in the study were housed, fed, and handled in compliance with standards set forth by the U.S. Animal Welfare Act and recommendations in the National Institutes of Health‘‘Guide for the Care and Use of Laboratory Animals’’ and all procedures performed on animals were reviewedand approved by a veterinarian and the Institutional Animal Care and Use Committee.
Vehicle:
other: distilled water
Concentration:
5%, 10% and 20% (v/v) in distilled water
No. of animals per dose:
5
Details on study design:
- Groups of mice were treated 1x a day for 3 consecutive days on the dorsum of both ears with 25 µL of 1 of 3 concentrations of test material or with vehicle.
- 5 days after initial treatment, all mice were injected intravenously, via the tail vein, with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of 3H-methylthymidine (3H-TdR; specific activity 5.0 Ci/mmol).
- 5 h later, mice were euthanised and draining auricular lymph nodes were removed and pooled for each individual mouse.
- Single cell suspensions were prepared by gentle mechanical disaggregation through nylon mesh (100 µm pore size).
- Cell suspensions were washed 2x with an excess of PBS and precipitated with 5% trichloroacetic acid (TCA) and left at 4°C overnight.
- Samples were then centrifuged, resuspended in 1 mL 5% TCA and transferred to 10 mL of scintillation cocktail (Ecolume, ICN Radiochemicals, Irvine, CA).
- 3H-TdR incorporation was measured by ß-scintillation counting and expressed as disintegrations per min (dpm) per individual mouse.
- Stimulation indices (SI) for each experimental group were determined as the increase in 3H-TdR incorporation relative to concurrent vehicle treated control group. Positive: a 3-fold or greater increase in proliferation, compared with the concurrent vehicle control, obtained at one or more test concentrations.
Parameter:
SI
Value:
1
Test group / Remarks:
vehicle water
Key result
Parameter:
SI
Value:
1.6
Test group / Remarks:
5% (v/v)
Key result
Parameter:
SI
Value:
1.2
Test group / Remarks:
10% (v/v)
Key result
Parameter:
SI
Value:
1.4
Test group / Remarks:
20% (v/v)
Cellular proliferation data / Observations:
- vehicle water: 366 ± 44 mean dpm (± SEM)
- 5% (v/v) 1-butanol: 598 ± 157 mean dpm (± SEM)
- 10% (v/v) 1-butanol: 451 ± 17 mean dpm (± SEM)
- 20% (v/v) 1-butanol: 530 ± 91 mean dpm (± SEM)
Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
not sensitising (SI < 3 at all 3 concentrations tested)
Executive summary:

The skin sensitization potential of 18 chemicals representing a variety of chemical classes was tested in the murine local lymph node assay (LLNA), whereby human data was used as the refernce for comaprison of the LLNA results.

11 of the tested materials are known to cause skin sensitization and 7 of which are believed not to be associated with any significant evidence of allergic contact dermatitis in humans. The LLNA correctly classified 16 of the 18 materials.

One of the correctly identified chemicals is Butan-1-ol that did not stimulate a SI of greater than 3 at all 3 concentrations tested [5%, 10% and 20% (v/v) in distilled water]. Accordingly, it can be concluded that Butan-1 -ol does not have the potential to cause skin sensitization.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Tributyl borate is not classified as a skin sensitiser according to Regulation (EC) No 1272/2008, because there is no evidence for a skin sensitising mode of action on the related hydrolysis products n-Butanol and Boric acid.