Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 May - 21 Jun 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted in July 1992)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(adopted in July 1996)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
(adopted in August 1998)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Republique Francaise, Premier Ministre, Groupe Interministeriel Des Produits Chimiques, Paris Cedex, France
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was initiated prior to the implementation of the LLNA method.

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
444-960-2
EC Name:
-
Cas Number:
39148-16-8
Molecular formula:
C2H6O3P.Na
IUPAC Name:
sodium ethyl phosphonate
Test material form:
solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Hartley Crl: (HA) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, L'Arbresle, France
- Age at study initiation: 1 - 2 months
- Weight at study initiation: 352 ± 27 g (males), 354 ± 20 g (females)
- Housing: individually in polycarbonate cages with stainless steel lid and autoclaved sawdust
- Diet: 106 pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water: filtered water (FG Millipore membrane (0.22 micron) , ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 17 May To: 21 June 2002

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
1%
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
40%
Day(s)/duration:
48 h
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
25%
Day(s)/duration:
On day 22 for 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
preliminary test: 2 (per sex, test group)
main study: 10 (per sex, test group), 5 (per sex, control)
Details on study design:
RANGE FINDING TESTS:
Intradermal:
24 hours before treatment, the dorsal region of the animals was clipped. Injections were performed in the interscapular region.
Test concentrations: 0.1, 1, 5, 10 and 25% (w/w)
Evaluation of cutaneous reactions: 24 and 48 h, 6 days after the injections

Epicutaneous:
24 hours before treatment, both flank regions of the animals were clipped and shaved. The filter paper of a chamber (Finn Chamber®) was fully-loaded with a dosage form preparation. The chamber was then applied to the clipped area of the skin (one concentration per flank). The chamber was held in place by means of an occlusive dressing for 24 hours.
Test concentrations: 25 and 40% (w/w, 40% (maximal practicable concentration))
Evaluation of cutaneous reactions: 24 and 48 h after treatment or removal of the dressings

Criteria for the selection of concentrations suitable for the main test
- the concentrations should be well-tolerated (systemically and locally)
- intradermal injections should cause moderate irritant effects (no necrosis or ulceration of the skin)
- cutaneous application for the induction should cause a weak to moderate skin reaction or be the maximal practicable concentration
- cutaneous application for the challenge phase should be the highest concentration which does not cause irritant effects.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline
Injection 2: test substance in physiological saline (1%, w/w)
Injection 3: test substance (1%, w/w) in a 1:1 mixture (v/v) FCA/physiological saline
Epicutaneous: 40% (w/w)
- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline
Injection 2: physiological saline
Injection 3: physiological saline (50%, w/v) in a 1:1 mixture FCA/physiological saline
Epicutaneous: physiological saline
- Site: interscapular region (clipped on Day -1 and 7; clipped and shaved on Day 21 (flanks))
- Frequency of applications: every 7 days
- Duration: Days 1 - 10 (including maintainance of the occlusive dressing for 48 h)
- Concentration: 1% (intradermal), 40% (epicutaneous)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 h
- Test groups: test substance (right flank) and vehicle only (left flank)
- Control group: test substance (right flank) and vehicle only (left flank)
- Site: posterior right flank
- Concentrations: 25% (w/w)
- Evaluation (hr after challenge): 48 h and 72 h

Additional information on cutaneous exposure
The animals were teated with 0.5 mL sodium lauryl sulfonate (10%, in vaseline) one day prior to epicutaneous induction, in order to induce local skin irritation as the test substance failed to induce skin irritation after cutaneous application in the range finding test.

Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole (June 2002; control: 5 animals, test group: 10 animals; induction: intradermal: 1% (w/w), epicutaneous: 20% (w/w); challenge: 20% (w/w)

Results and discussion

Positive control results:
Challenge with 20% mercaptobenzothiazole resulted in skin sensitisation in 10/10 test animals scored with grade 1-3 detected at the 24 and 48 h reading time point. In the control group, no cutaneous reactions were observed.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction intradermal: 1%, challenge: 25%
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:
negative control
Dose level:
induction: 0%, challenge: 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction intradermal: 1%, challenge: 25%
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:
positive control
Dose level:
induction intradermal: 1%, challenge: 20%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
weak, mild or moderate sensitisation in 1/10, 4/10 or 5/10 animals, respectively; oedema in 4/10 test animals and crusts in 2/10 animals; dryness of the skin in 5/10 animals
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
induction intradermal: 1%, challenge: 20%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
mild and moderate sensitisation in 4/10 or 6/10 animals, respectively; oedema in 8/10 animals, crusts in 1/10 animals; dryness of the skin in all animals
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Results of the range finding test

Intradermal injection of 0.1 - 25% (w/w) test substance induced cutaneous irritation 24 and 48 h after treatment in all animals. Injection of 25% test item solution resulted in necrosis in 1/2 animals detected 48 h after treatment. 6 days after treatment, necrosis was observed in both animals after injection of 5, 10 and 25% test item solution. 6 days after substance injection, crusts were observed in 2/2 animals after injection of 0.1 or 1% test item solution mixed with FCA. Challenge with 40% (w/w) test substance solution induced cutaneous reactions in 1/2 animals (grade 1) 24 h after treatment whereas challenge with 25% test substance solution failed to induce reactions on the skin. In accordance to the criteria for the selection of the concentrations suitable for the main study (please see above under "Details on study design"), concentrations of 1 and 40% (w/w) were chosen for intradermal and epicutaneous induction, respectively, and for challenge 25%.

Results of the main study

Mortality

No mortality or signs of clinical symptoms were recorded until the end of the observation period.

Body weight

Body weight gain was comparable between the test and control group.

Skin reactions

Important local reactions were recorded between Day 6 and Day 16 at the intradermal injection sites of 2 animals of the treated group. After challenge, no cutaneous reactions were observed in control animals. In test animals, a discrete erythema scored with grade 1 was observed on both flanks in 1/20 animals at the 24 hours reading time point. A similar cutaneous reaction was observed in one further animal at the 48 h reading time point on the left flank (vehicle-treated flank). As the cutaneous reactions were determined either on the control and test item treated flank or on the control flank only, the observations were not interpreted as sign of sensitisation. 3/20 test animals revealed dryness of the skin 48 h after patch removal. No other cutaneous reactions were recorded in the test group.

Positive control

Challenge with the positive control substance revealed positive sensitisation reactions in 10/10 test animals at both time points. 48 h after patch removal, weak, mild or moderate reactions were observed on the right flank treated with the positive control substance during induction and challenge in 1/10, 4/10 or 5/10 animals, respectively. In addition, weak or mild sensitisation was observed on the left flank treated with the vehicle during the induction phase in 1/10 and 2/10 animals, respectively. Moreover, oedema and crusts were observed on the right flank treated with the positive control substance during induction and challenge in 4/10 or 2/10 animals, respectively. Dryness of the skin was determined in 5/10 animals. At the later reading time point, mild and moderate skin sensitisation was observed in 4/10 or 6/10 animals, respectively. Weak or mild sensitisation was also observed on the left flank in 2/10 animals each. Moreover, the flank treated wih the positive control during induction and challenge revealed oedema and crusts in 8/10 or 1/10 animals, respectively. Dryness of the skin was observed in 9/10 animals at the second reading time point.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Under the conditions chosen, the test substance was not a skin sensitizer in guinea pigs.