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Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17/11/2004 - 20/01/2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
OECD, 2002
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
Source: Harlan Ntherlands
Age: 8-12 weeks
Body weight: 16-24 g
Identification: Each cage by unique cage card.
Randomization: Randomly selected by computer algorithm at time of delivery.
Acclimatization: Under test conditions after health examination. Only animals without any visible signs of illness were used for the study.
Housing:Individual in Makrolon type-2 cages with standard softwood bedding ("Ugnocel", Schill AG, CH-4132 Muttenz).
Diet : Pelleted standard Kliba 3433, batch no. 42104 mouse maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum. Results of
analyses for contaminants are archived at RCC. There was no contamination of the diet.
Water: Community tap water from FOllinsdorf, available ad libitum. Results of representative bacteriological, chemical and contaminant analyses are archived. There was no contamination of water.

ENVIRONMENTAL CONDITIONS:
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Air changes per hour: 10 - 15
Photoperiod: 12 hour fluorescent light / 12 hour dark cycle with at least 8 hours music during the light period.
Vehicle:
dimethylformamide
Concentration:
0,1% 0,25% 0,5% 0,9% 2% (w/v) in dimethylformamide
No. of animals per dose:
4 females
Details on study design:
TEST ITEM FORMULATION PREPARATION
The test item was placed into a volumetric flask on a tared Mettler balance and the vehicle (N,N-Dimethylformamide (DMF)) was quantitatively added. The weight/volume (w/v) dilutions were prepared individually using a magnetic stirrer as homogenizer.
Test item formulations were made freshly before each dosing occasion and no more than 4 hours prior to application to the ears.
Homogeneity of the test item in the vehicle was maintained during treatment with the magnetic stirrer.
The test item was assayed at five concentrations, which were selected based on information on the toxicity, irritation potential and results obtained for a lower purity sample of this chemical.
Concentrations were in terms of material as supplied.

TREATMENT APPLICATION
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 0.1 %, 0.25 %, 0.5 %, 0.9 % and 2.0 % (w/v) in N,N-Dimethylformamide (DMF). The application volume, 25 pi, was spread over the entire dorsal surface (0 - 8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals). A hair dryer was passed briefly over the ear's surface to prevent the loss of any of the test item applied.

Five days after the first topical application, all mice were administered with 250 pi of 80.77 pCi/ml 3HTdR (equal to 20.2 pCi 3HTdR) by intravenous injection via a tail vein.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
A statistical analysis was conducted for assessment of the dose-response relationship, and the EC3 value was calculated according to the equation
EC3 = (a-c) [(3-d)/(b-d)] + c
where EC3 is the estimated concentration of the test item required to produce a 3-fold increase in draining lymph node cell proliferative activity; (a, b) and (c, d) are respectively the co-ordinates of the two pair of data lying immediately below and above the S.1. value of 3 on the local lymph node assay dose response plot.
Positive control results:
STIMULATION INDICES
2.7 (test item concentration 5% w/v) *
3.4 (test item concentration 10% w/v) *
12.4 (test item concentration 25% w/v)

EC3= 7.1%(w/v)
A clear dose response relationship was obeserved
* This value was used in calculation of EC3
Key result
Parameter:
EC3
Value:
ca. 0.28
Remarks on result:
other: Indication of skin sensitsation
Parameter:
SI
Value:
ca. 2.7
Test group / Remarks:
test item concentration 0.1 % (w/v)
Key result
Parameter:
SI
Value:
ca. 2.6
Test group / Remarks:
test item concentration 0.25 % (w/v)
Key result
Parameter:
SI
Value:
ca. 6.1
Test group / Remarks:
test item concentration 0.5 % (w/v)
Parameter:
SI
Value:
ca. 7.6
Test group / Remarks:
test item concentration 0.9 % (w/v)
Parameter:
SI
Value:
ca. 13
Test group / Remarks:
test item concentration 2.0 % (w/v)
Cellular proliferation data / Observations:
DETAILS ON STIMULATION INDEX CALCULATION

(STIMULATION INDEX) (S.I.). Before DPMlnode values were determined, mean scintillation-background DPM was subtracted from test and control raw data.
(STIMULATION INDEX) (S.I.) is calculated according to the following formula:

S.1. = dpm/LN of treated group/dpm/LN of control group

A test item is regarded as a sensitizer in the LLNA if the following criteria are fulfilled:
- First, exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the STIMULATION INDEX (S.I.).
- Second, the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local
toxicity or immunological suppression.

EC3 CALCULATION
Ec3 = (a-c) [(3-d)/(b-d)] + c = 0.28 % (w/v)

CLINICAL OBSERVATIONS:
Mortality / Viability Twice daily from acclimatization start to the termination of in-life phase.
Body weights On the test day 1 (prior to the 151 application) and on the test day 6.
Clinical signs (local I systemic) Daily from acclimatization start to the termination of in-life phase. Particular attention was paid to the treatment sites

 Test item concentration %(w/v)  DPM measurement  Number of lymph nodes  SI
 0.1  4569  8  2.7
 0.25  4362  8  2.6**
 0.5  10424  8  6.1**
 0.9  13036  8*  7.6
 2.0  22187  8*  13.0

* the size of the draining lymph nodes of this group is larger than taht of the control group

** This value is used in calculation of EC3

Ec3 = (a-c) [(3-d)/(b-d)] + c = 0.28 % (w/v)

EC3 =. Estimated concentration for a STIMULATION INDEX (S.I.) of 3.

a,b,c,d = Co-ordinates of the two pair of data lying immediately below and above the S.I value of 3 on the LLNA dose response plot.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.).
In this study STIMULATION INDICES of 2.7, 2.6, 6.1, 7.6 and 13.0 were determined with the test item at concentrations of 0.1 %, 0.25 %, 0.5 %, 0.9 % and 2.0 % (W/v) , respectively, in N,N-Dimethylformamide (DMF).
Cysteamine HCL was therefore found to be a skin sensitizer and an EC3 value of 0.28 % (w/v) was derived.
Cysteamine HCL is classified as H317 ‘Category 1’ - May Cause an Allergic reaction" according to CLP Regulation (EC) No 1272/2008
Executive summary:

In order to study a possible contact allergenic potential of Cysteamine HCl, five groups each of four female mice were treated daily with the test item at concentrations of 0.1 %, 0.25 %, 0.5 %, 0.9 % and 2.0 % (w/v) in N,N-Dimethylformamide (DMF) by topical application to the

dorsum of each ear lobe (left and right) for three consecutive days. A control group of four mice was treated with the vehicle (N,N-Dimethylformamide (DMF)) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine eH-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group.

Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H_methyl thymidine measured in a /3-scintillation counter.

All treated animals survived the scheduled study period.

No clinical signs were observed.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification