Registration Dossier

Administrative data

Description of key information

Guanidine Thiocyanate has to be classified as skin corrosive category 1C based on the severe reactions observed in an OECD 404 guideline study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
1210.7339
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 3.03 kg
- Housing: The animal was individually housed in a suspended metal cage.
- Diet (e.g. ad libitum): (STANRAB SQC Rabbit Diet, Special Diets Services ltd, Witham, Essex, UK) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum
acclimatisation period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 21 °C
- Humidity (%): 49 - 60 %
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hour dark/light cycle

IN-LIFE DATES: From: To:
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
Test Material
- Amount(s) applied (volume or weight with unit): 0.5 g of the test material, moistened with 0.8 mL distilled water
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
1
Details on study design:
TEST SITE
Three suitable test sites were selected on the back of the rabbit.
At each test site a quantity of 0.5g of the test material, moistened with 0.8 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
Each patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm).
To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animal was returned to its cage for the duration of the exposure period.

One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by
gentle swabbing with cotton wool soaked in distilled water.


SCORING SYSTEM: Draize scoring
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
3-minute exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3-minute exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
1-hour exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
1-hour exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4-hour exposure
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: corrosive - adverse reactions from 48 hour reading onwarts prevented accurate evaluation of oedema
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4-hour exposure
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: corrosive -adverse reactions from 48 hour reading onwarts prevented accurate evaluation of erythema
Irritant / corrosive response data:
4-Hour Exposure Period:
Moderate to severe haemorrhage (attributed a Draize score of 3) and blanching of the skin were noted at the treated skin site one hour after patch removal and at the 24-hour observation. Loss of skin elasticity and flexibility were also noted at the treated skin site at the 24-hour observation. A hardened dark brown/black-coloured scab and well-defined erythema surrounding other skin reactions were noted at the treated skin site at the 48 and 72-hour observations with blanching of the skin also noted at the 48-hour observation. A sunken, hardened, dark brown/black coloured scab resembling a crater was noted at the treated skin site at the 7-day observation.
A sunken, hardened, dark brown/black coloured scab resembling a crater, lifting to reveal further deep scabbing, and scar tissue were noted at the treated skin site at the 14-day observation.
Moderate oedema was noted at the treated skin site one hour after patch removal and at the 24-hour observation.
The reactions noted at the 48-hour and subsequent observations precluded the evaluation of erythema and oedema.
The reactions noted at the treated skin site were indicative of dermal corrosion.

1-Hour Exposure Period:
No evidence of skin irritation was noted.

3-Minute Exposure Period:
No evidence of skin irritation was noted.
Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
Guanidine Thiocyanate has to be classified as skin corrosive category 1C based on the severe reactions observed in this OECD 404 guideline study.
Executive summary:

In a primary dermal irritation study according to OECD guideline 404, the single 4-hour, semi-occlusive exposure of Guanidine Thiocyanate to the intact skin of one rabbit produced moderate to severe erythema and moderate oedema. Haemorrhage of the dermal capillaries, blanching of the skin, loss of skin elasticity and flexibility, a hardened dark brown/black-coloured scab, a sunken, hardened, dark brown/black coloured scab resembling a crater, scab lifting to reveal further deep scabbing, scar tissue and well-defined erythema surrounding other skin reactions.

The reactions noted at the 48-hour and subsequent observations precluded the evaluation of erythema and oedema.

The reactions noted were indicative of dermal corrosion.

 

After single 1-hour or 3-minute exposure of Guanidine Thiocyanate to the intact skin of one rabbit under semi-occlusive conditions there was no evidence of skin irritation.

 

According to CLP, EU GHS (Regulation (EC) No 1272/2008), Guanidine Thiocyanate has to be classified as corrosive Cat. 1C and labeling with H 314 is required.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary dermal irritation study according to OECD guideline 404, the single 4-hour, semi-occlusive exposure of Guanidine Thiocyanate to the intact skin of one rabbit produced moderate to severe erythema and moderate oedema. Haemorrhage of the dermal capillaries, blanching of the skin, loss of skin elasticity and flexibility, a hardened dark brown/black-coloured scab, a sunken, hardened, dark brown/black coloured scab resembling a crater, scab lifting to reveal further deep scabbing, scar tissue and well-defined erythema surrounding other skin reactions. The reactions noted at the 48-hour and subsequent observations precluded the evaluation of erythema and oedema.

The observed effects were indicative of dermal corrosion. However, there was no evidence of skin irritation after single 1-hour or 3-minute exposure of Guanidine Thiocyanate to the intact skin of one rabbit under semi-occlusive conditions.

Based on these results Guanidine Thiocyanate has to be classified as corrosive to skin Cat. 1C and eye damage Cat. 1, thus further testing on eye irritation does not need to be conducted.

Justification for classification or non-classification

According to CLP, EU GHS (Regulation (EC) No 1272/2008), a substance has to be classified as corrosive on the basis of the results of animal testing a substance is classified as corrosive. A corrosive substance is a substance that produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to a 4 hour duration. Corrosive reactions are typified by ulcers, bleeding, bloody scabs and, by the end of observation at 14 days, by discoloration due to blanching of the skin, complete areas of alopecia and scars.

 

Based on the effects observed in one animal in a OECD 404 guideline study Guanidine Thiocyanate has to be classified as corrosive and one of the three subcategories provided within the corrosive category has to be allocated.

For Guanidine Thiocyanate subcategory 1C apply, as response was observed after an exposure period of 4 hours and observations up to 14 days.

 

According to CLP, EU GHS (Regulation (EC) No 1272/2008), a skin corrosive substance is considered to also cause serious eye damage which is indicated in the hazard statement for skin corrosion (H 314: Causes severe skin burns and eye damage). Thus, in this case both classifications (Skin Corr. 1 and Eye Dam. 1) are required but the hazard statement H318 ‘Causes serious eye damage’ is not indicated on the label because of redundancy.

 

For Guanidine Thiocyanate no studies via inhalation route are available.

Except from the low vapour pressure of Guanidine Thiocyanate, formation of particles or droplets of inhalable size cannot be entirely excluded. Due to the corrosive properties of the substance and applying precautionary principles a supplementary labelling with EUH071 was considered appropriate.