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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
As with all inorganic salts, the significance for toxicity or environmental assessment is the presence of specific ions that will form when in solution or when in biological systems.In the case of Cr III salts, the counter ion will have an effect on solubility and this is itself dependant on the type of media being used and in particular the pH of that media. It is generally accepted that in the case of metal salts, testing with salts that are soluble in the respective test media will ensure maximum exposure of the metal ions. This will include chlorides and nitrates as being more soluble and will indeed have relevance when dissolved in acid media, such as if ingested.Read-across to other chromium III salts is therefore considered valid as long as the exposure in the test system is greater than wold be expected for the substance under review for registration.

Data source

Reference
Reference Type:
publication
Title:
Sensitization of guinea pigs to chromium salts
Author:
Gross, P.R. ; Katz, S.A.; Samitz, M.H.
Year:
1968
Bibliographic source:
J. Investigative Dermatology, 50(5), 424-427

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Maximised method
Principles of method if other than guideline:
The purpose of the study was to examine cross sensitisation between Cr(VI) and Cr(III). The test method was modiifeid to provide a consistently successful level of sensitisation.
GLP compliance:
no
Remarks:
Study predates GLP
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Existing data; further animal studies not justified

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: albino
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS- Weight at study initiation: 300-500 g

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: induction: Freund's complete adjuvant, elicitaiton: phsiological saline
Concentration / amount:
0.5 ml of 0.034 M CrCl3 = 5.34 g/l concetration
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
Route:
intradermal
Vehicle:
other: induction: Freund's complete adjuvant, elicitaiton: phsiological saline
Concentration / amount:
0.1 ml of 0.00042 M Cr Cl3 = 66 mg/l
Adequacy of challenge:
other: Based on known effects of Cr 6+
No. of animals per dose:
30
Details on study design:
Guinea pigs were sensitised by adminstering three subcutaneous injections of an emulsion containing 0.5 cc Freund's complete adjucant and 0,5 cc 3.4 x 10-2 M CrCl3 into the nape one week apart. Three weeks later, the animals were tested with intradermal injections in clipped or epilated skin. The eliciting dose was 4.2 x 10-4 M CrCl3. Animals sensitised with CrCl3 were also tested with a number of additional trivalent salts, and to conjugates of chromium linked with plasma proteins and skin extract proteins. The concentrations were determined as being the lowest concentrations causing positive effects with Chrome VI compounds.
Challenge controls:
The challenge dose produced no reaction in 30 control animals.

Results and discussion

In vivo (non-LLNA)

Results
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
66 mg/l
No. with + reactions:
0
Total no. in group:
30
Clinical observations:
No adverse effects
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

The eliciting dose produced at 48 hrs a well defined indurated erythematous papule at least 10 mm in diameter.

Ten out of 13 animals developed positive reactions (at least +1). four of these were read as +2. None developed +3 or +4 reactions. Eight out of 10 of these animals also reacted to KCr2O7 (Cr(VI). The differences in the level of reaction were not statistically significant.

Table II Skin test reactions to potassium dichromate and chromic chloride in guinea pigs sensitised to chromic chloride

Guinea pig number

Chromic chloride

Potassium dichromate

1

+1

+1

2

+2

+1

3

+1

+2

4

+1

+1

5

+1

+1

6

+2

+2

7

+1

-

8

+2

+1

9

+1

+1

10

+2

-

Note: (—)= noresponse; (±) =equivocal response, less than 10 mm diameter; (+1) = response of 10 mm diameter; (+2) = response of 15mm diameter; (+3) response of 20 mm diameter; (+4) response of 20 mm diameter with central necrosis.

Similar studies were also carried out with solutions of four other trivalent chromium salts. The highest concentrations  which were not irritating to control animals were determined by serial dilution and subsequently used for skin testing. These were: chromic acetate (2.5 x 10-3M), chromic nitrate (9.6 x 10-4M), chromic oxalate (2.5 x10-4M), chromic sulfate (2.4 X 10 M). Three animals sensitized to CrCl3 showed weaker cross-reactions to the same compounds.

TABLE IV Skin test reactions to chromium salts in guinea pigs which had been sensitized to chromic chloride

Guinea pig no

Chromic chloride

Potassium dichromate

Chromic acetate

Chromic nitrate

Chromic sulfate

Chromic oxalate

1

+1

+1

-

+1

+1

±

2

+2

+1

+1

+1

+1

±

3

+2

-

+1

+2

+1

-

 

Attempts to sensitize guinea pigs with the above trivalent salts, other than CrC13, were uniformly unsuccessful. Concentrations of 1.7 x 10-2 M to 5 x 10-2 M were used with Freund's complete adjuvant in a schedule identical to that which had been successfully used for potassium dichromate and chromic chloride.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Guinea pigs were sensitised to chromic chloride in a procedure designed to mazimise the sensitisation response. attempts to sensitise guinea pigs to other chromium (III) salts (chromic acetate, chomic nitrate, chromic oxalate and chromic sulfate were uniformly unsuccessful.
Executive summary:

Thirteen guinea-pigs were given chromium chloride hexahydrate by three subcutaneous injections in the nape 1 week apart. The sensitizing injections contained 0.5 ml of FCA with 0.5 ml of 3.4 × 10−2 M chromium chloride. Three weeks later, the animals were tested with an intradermal injection into clipped or epilated skin. The eliciting dose was 0.1 ml of 4.2 × 10−4 M chromium chloride. After 48 h, this produced moderate positive responses in 10 of the 13 animals, whereas the control animals (injected only with FCA) showed no reactions.

Of the 10 guinea-pigs sensitized to chromium chloride, 3 elicited weaker cross-reactions after intradermal injection of chromium acetate, chromium nitrate and chromium sulfate. Chromium oxalate did not elicit significant reactions. Using the same study method, the authors also attempted to sensitize guinea-pigs with chromium acetate, chromium nitrate, chromium sulfate and chromium oxalate, but without success.