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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1998-03-24 to 1998-04-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 406 with no deviation to the protocol.
Justification for type of information:
1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Ammonium paratungstate
Target: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR
Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
1999 guinea pig sensitisation study was available of good quality. Therefore, there is no need to conduct a LLNA study as the guinea pig sensitisation study scientifically fulfills the endpoint. The OECD 406 method provides sensitisation information likely to arise from exposure to test substance via intradermical injection and/or epidermical application to guinea pigs. The guinea pig sensitisation test detects chemicals with moderate to strong sensitisation potential, as well as those with relatively weak sensitisation potential. In such methods activity is measured as a function of challenge-induced dermal hypersensitivity reactions elicited in test animals compared with controls. In addition, guinea pigs have been the animal of choice for predictive sensitisation tests for several decades (way before the LLNA became the test of choice).
The existing guinea pig data submitted here is of good quality as clear results are presented in this robust summary and test methodology followed OECD 406 guidelines, and conducted under GLP. This study it is considered acceptable according to page 266 in ECHA's Chapter r7a on Guidance on Information Requirements and Chemical Safety Assessment.

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium wolframate
EC Number:
234-364-9
EC Name:
Ammonium wolframate
Cas Number:
11120-25-5
Molecular formula:
(NH4)10H2W12O42*4H2O
IUPAC Name:
Ammonium (para)tungstate
Constituent 2
Reference substance name:
Ammonium paratungstate
IUPAC Name:
Ammonium paratungstate
Details on test material:
- Name of test material (as cited in study report): Ammonium paratungstate (CAS# as cited in study: 12028-06-7)
- Physical state: White powder
- Analytical purity: >99.9%
- Storage condition of test material: Room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffs, UK.
- Age at study initiation: 4 to 7 weeks
- Weight at study initiation: 349 to 424 g
- Housing: Groups of 5 in suspended metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Harlan Teklad 9600 FD2 SQC ad libitum. Hay was given thrice weekly.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.5 to 23.5
- Humidity (%): 40 to 59
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 artificial light (0700 - 1900)

IN-LIFE DATES: From: 1998-03-24 To: 1998-04-24

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Alembicol D
Concentration / amount:
-Induction Intradermal: 10% w/v in Alembicol D.
-Induction topical application: 75% w/v in Alembicol D.
-Topical challenge: 75 and 37.5% w/v in Alembicol D.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Concentration / amount:
-Induction Intradermal: 10% w/v in Alembicol D.
-Induction topical application: 75% w/v in Alembicol D.
-Topical challenge: 75 and 37.5% w/v in Alembicol D.
No. of animals per dose:
ten test animals and 5 control
Details on study design:
RANGE FINDING TESTS: From preliminary investigations 75% w/v in Alembicol D was the maximum practical concentration and did not give rise to irritating effects.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: single
- Exposure period: 48 hrs
- Test groups: 2
- Control group: 1
- Site: interscapular area
- Frequency of applications: Once
- Concentrations: Intradermal - 10% w/v in Alembicol D
Topical - 75% w/v in Alembicol D

INDUCTION INTRADERMAL INJECTIONS:
A 40 x 60 mm area of dorsal skin on the scapular region of the test animal was clipped free of hair. Three pairs of intradermal injections were made into a 20 x 40 mm area within the clipped area. Injectables for the test animals were prepared as follows: 1) Freud's complete adjuvant was diluted with an equal volume of water for irrigation. 2) Ammonium paratungstate, 10% w/v Alembicol D. 3) Ammonium paratungstate 10% w/v in a 50:50 mixtureof Freund's complete adjuvant and Alembicol D.

INDUCTION TOPICAL APPLICATION:
Six day after the injections, the same 40 x 60 mm intrascapular area was clipped and shaved free of hair and the site was pre-treated by gentle rubbing with 0.5 mL per site of 10% w/v sodium lauryl sulphate in petroleum. Twenty-four hours later a 20 x 40 mm patch of Whatman No. 3 paper was saturated with approximately 0.4 mL of ammonium paratungstate, 75% w/v in Alembicol D. The patch was placed on the skin of test animals and covered by a length of impermeable plastic adhesive tape. This in turn was firmly secured by elastic adhesive bandage wound round the torso of the animal and fixed with "Sleek" impervious plastic adhesive tape. The dressing was left in place for 48 hours.

B. CHALLENGE EXPOSURE
- No. of exposures: Single
- Day(s) of challenge: 2 wks after the topical induction application
- Exposure period: 24 hrs
- Test groups: One group of 10 animals
- Control group: One grooup of 5 animals
- Site: Left flank of each animal
- Concentrations: 0.2 mL of ammonium paratungstate, 75% w/v in Alembicol D to an anterior site on the flank and 37.5% w/v in Alembicol D to a posterior site.
- Evaluation (hr after challenge): 24 and 48 hrs

INDUCTION CONTROLS
During the induction phase, the control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.
CHALLENGE:
The control and test animals were challenged topically two weeks after the topical induction application using ammonium paratungstate, 75 and 37.5% w/v Alembicol D. Hair was removed by clipping and then shaving from an area on the left flank of each test animal. A 20 x 20 mm patch of Whatman No. 3 paper was saturated with approximately 0.2 mL of ammonium paratungstate, 75% w/v in Alembicol D was applied to an anterior site on the flank.Ammonium paratungstate, 37.5% w/v Alembicol D was applied in a similar manner to a posterior site. The patches were sealed to the flank for 24 hours under strips of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".
Challenge controls:
Animals were challenged topically two weeks after the topical induction application using ammonium paratungstate, 75 and 37.5% w/v Alembicol D. Hair was removed by clipping and then shaving from an area on the left flank of each test animal. A 20 x 20 mm patch of Whatman No. 3 paper was saturated with approximately 0.2 mL of ammonium paratungstate, 75% w/v in Alembicol D was applied to an anterior site on the flank. Ammonium paratungstate, 37.5% w/v in Alembicol D was applied in a similar manner to a posterior site. The patches were sealed to the flank for 24 hours under strips of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".
Positive control substance(s):
yes
Remarks:
Hexy cinnamic aldehyde (HCA), Benzocaine and 2-mercaptobenzothiazole (MBT)

Results and discussion

Positive control results:
In this study HCA produced evidence of skin sensitization (delayed contact hypersensitivity) in all of the ten animals, thus confirming the sensitivity and reliability of the experimental technique.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
approximately 0.2 mL Alembicol
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No dermal reactions seen in any of the control animals
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
approximately 0.2 mL Alembicol
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No dermal reactions seen in any of the control animals
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 ml of 10% APT (w/v) in Alembicol D
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No dermal reactions seen in any of the test animals
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge with APT, 75% w/v in Alembicol
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 ml of 10% APT (w/v) in Alembicol D
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No dermal reactions seen in any of the test animals
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenged with APT, 75% w/v in Alembicol
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 ml of 10% APT (w/v) in a 50:50 mixture of Freund's complete adjuvant and Alembicol D
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No dermal reactions seen in any of the test animals
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenge with APT, 37.5% w/v in Alembicol
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 ml of 10% APT (w/v) in a 50:50 mixture of Freund's complete adjuvant and Alembicol D
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No dermal reactions seen in any of the test animals
Remarks on result:
no indication of skin sensitisation
Remarks:
Challenged with APT, 37.5% w/v in Alembicol
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
HCA, 10% v/v in Alembicol D
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Dermal reactions seen in all ten test animals. Dryness and sloughing of the epidermis.
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
HCA, 10% v/v in Alembicol D
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Localised dermal reactions (restricted to a small area of the challenge site), dryness and sloughing of the epidermis, thickening, dryness and sloughing of the epidermis
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

INDUCTION:

Dermal reactions seen following the induction applications were:

- Intradermal injections - necrosis was recorded at all sites receiving Freund's Complete Adjuvant in test and control animals.

- Slight to well-defined irritation was seen in test animals at sites receiving ammonium paratungstate, 10% w/v in Alembicol D and slight irritation was observed in control animals receiving Alembicol D.

Topical application - slight to well-defined erythema was observed in test animals following topical application with ammonium paratungstate, 75% w/v in Alembicol D.

- Slight erythema was seen in most of the control guinea-pigs.

CHALLENGE:

There were no dermal reactions seen in any of the test or control animals, therefore all ten test animals gave negative responses.

BODYWEIGHTS:

Bodyweight increases were recorded for all guinea-pigs over the period of the study.

CLINICAL SIGNS:

No signs of ill health or toxicity were recorded.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, Ammonium paratungstate did not produce evidence of skin sensitization (delayed contact hypersensitivity) in any of the ten test animals.
Executive summary:

No skin sensitiation data of sufficient quality were available specifically on ammonium metatungstate (target substance). However, skin sensitisation data are available on ammonium paratungstate (source substance), which are used for read-across. Due to similar water solubility for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate to estimate of potential toxicity for this endpoint. For more details, refer to the read-across category approach description in the Category section of this IUCLID submission or Annex 3 of the CSR.

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