Urea sulphate

Endpoint summary

Description of key information

Uronium hydrogen sulphate is not considered as irritant to the skin, but is severely irritant to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Target and source substances are highly similar, both structurally and chemically.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Granja San Bernardo, SL (Tulebras, Navarra)
- Age at study initiation: approximate age of 11-12 weeks
- Weight at study initiation: 2.8-3.2 kg
- Housing: the rabbits were housed individually in stainless steel cages (52.0 x 58.0 x 43.0 cm) placed on shelves and equipped with slatted floors.
- Diet: free access to a standard diet for rabbits Panlab 112
- Water: ad libitum
- Acclimation period: a minimum period of seven days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25 ºC
- Humidity: 30-65%
- Air changes: data not avaiable
- Photoperiod: 12 hours of light (7:00 to 19:00) and 12 hours of darkness every 24 hours

IN-LIFE DATES: data not available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: undiluted

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 animals

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: data not available
- Type of wrap if used: semi-occlusive patches used were fixed with a band or adhesive micro-porous hypoallergenic

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: after exposure with distilled water

SCORING SYSTEM: according to OECD guideline

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: mean value (24, 48, 72h)

Score:

1.22

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: mean value (24, 48, 72h)

Score:

0.22

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

It initially used a single animal (no. 1995), sequentially applying three dressings. The first dressing was removed after three minutes. After no serious skin reaction, it was applied a second dressing, which was retired after 1 hour. There was no serious skin reaction to either remove the second pack, so it was applied a third, which was removed at 4 hours d exposure.
At 60 minutes, at 24, 48 and 72 hours, 7 and 14 days after removal of patches exposed for 3 minutes and 1 hour respectively, there were no injuries in the area administered.
At 60 minutes after removing the patch exposed for four hours, it was observed well-defined erythema (grade 2) with slight edema (grade 2). At 24 hours after removal of the patch, there was very slight erythema (grade 1) accompanied by very slight edema (grade 1). At 48 and 72 hours after removal of the patch exposed for four hours the edema had complete remission, although there was again well-defined erythema (grade 2), which decreased to very slight edema (grade 1) during the observation at 7 days after removal of the patch. No skin changes were observed at 14 days after removing the patch in this animal, except slight scaling.
Subsequently it was applied to two animals (no. 2004 and 2005) a dressing with the test, it was was removed after 4 hours of exposure.
At 60 minutes after removing the patch, in one of these two animals (no. 2004) was recorded very slight erythema (grade 1) with very slight edema (grade 1). At 24, 48 and 72 hours in this animal was observed very slight erythema (grade 1). At 7 and 14 days after removing the patch, there were no skin lesions in this animal, although there was slight scaling during the observation at 7 days.
At 60 minutes after removing the patch, in the remaining animal (No. 2005) showed well defined erythema (grade 2) with slight edema (grade 2). At 24, 48 and 72 hours in this animal was recorded very slight erythema (grade 1), with very slight edema (grade 1) only in the reading performed at 24 hours. At 7 days after removing the patch, there were no skin lesions in this animal.
Mean ratings of erythema and edema at 24, 48 and 72 hours of the three animals after a 4-hour exposure were 1.22 (erythema) and 0.22 (edema).

Other effects:

The behavior and physical condition of the rabbits, and the evolution of body weight was normal during the study.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema	Edema
	Max. score: 4	Max. score: 2
60 min	2 / 1 / 2	2 / 1 / 2
24 h	1 / 1 / 1	1 / 0 / 1
48 h	2 / 1 / 1	0 / 0 / 0
72 h	2 / 1 / 1	0 / 0 / 0
Average 24h, 48h, 72h	1.7 / 1 / 1	0.3 / 0 / 0.3
7 days	1 / 0 / 0	0 / 0 / 0
14 days	0 / 0 / -	0 / 0 / -
Reversibility*)	yes	yes
Average time for reversion	14 days	48 hours

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Urea sulphate is not considered as irritant to the skin.

Executive summary:

In a primary dermal irritation study (OECD 404, GLP), young adult New Zealand White rabbits (3 animals) were dermally exposed to 0.5 mL of undiluted Lower-7/Acid Flow / Enquik (Uronium hydrogen sulphate) for 4 hours under semi-occlusive conditions. Animals then were observed for 14 days. Irritation was scored by the method cited in OECD guideline.

 

Mean ratings of erythema and edema at 24, 48 and 72 hours of the three animals after a 4-hour exposure were 1.22 (erythema) and 0.22 (edema).

 

In this study, Lower-7/Acid Flow / Enquik (uronium hydrogen sulphate) is not a dermal irritant. Classification is not required according to EU legislation (DSD or CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Target and source substances are highly similar, both structurally and chemically.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

This in vitro study was performed to assess the irritating or corrosive potential of the test item Aduct Urea-Sulfuric by means of the HET-CAM test. The test was carried out with fertilized and incubated chicken eggs. The aim was to evaluate the local irritating effects of Aduct Urea-Sulfuric on mucous membranes or eyes.

GLP compliance:

yes

Species:

other: in-vitro test

Details on test animals or tissues and environmental conditions:

The HET-CAM test was carried out with Lohmann Selected Leghorn chicken eggs. The Lohmann Selected Leghorn chicken was selected for several reasons: the ability to hatch the eggs of this breed is very consistent and reproducible. There did not appear to be any hereditary defects in this breed.

Observation period (in vivo):

300 seconds

Number of animals or in vitro replicates:

three eggs

Details on study design:

In this HET-CAM assay the test item was tested pure. Three eggs were treated with the test item.
Each about 300 μL of the test item were applied directly to the membrane in order to cover at least 50% of the membrane. Each 300 μL of the positive and negative controls were applied to three eggs each. During the observation period for 300 seconds any lesions in close proximity to the covered membrane were monitored and recorded.
The membranes of the eggs were observed for 300 seconds. Lesions of the underlying blood vessels were monitored and noted. In particular three endpoints were observed and the time point at which an effect occurs was recorded. The three endpoints were:
• haemorrhage
• coagulation
• lysis of the blood vessel

Test Groups:
1. Negative Control: saline
2. Positive Control / Sodium dodecyl sulfate: 1% solution in deion. water
3. Positive Control / NaOH: 0.1 N
4. Test Item: pure

Evaluation of results:
CAM Mean Irritancy Index:
0 – 0.9: Not irritant
1 – 4.9: Slight irritant
5 – 8.9: Moderate irritant
9 - 21: Severe irritant

Irritation parameter:

in vitro irritation score

Value:

ca. 10.27

Remarks on result:

other: Severe irritating effects were observed during 5 min incubation with Aduct Urea-Sulfuric. The calculated mean irritancy index is 10.27. The positive controls induced a severe irritation on the blood vessels. The calculated mean irritancy indices are 9.95

Table 1: Results with Aduct Urea-Sulfuric, as well as negative and positive control

Test Group	Time until Haemorrhage [s]	Time until Lysis [s]	Time until Coagulation [s]	Irritancy Index	Mean Irritancy Index
Negative Control	301	301	301	0.00	0.00
Negative Control	301	301	301	0.00
Negative Control	301	301	301	0.00
Positive Control 0.1 N NaOH	9	61	24	18.78	18.87
Positive Control 0.1 N NaOH	9	50	19	19.18
Positive Control 0.1 N NaOH	10	66	24	18.64
Positive Control 1% SDS	18	76	301	9.97	9.95
Positive Control 1% SDS	17	80	301	9.89
Positive Control 1% SDS	23	71	301	10.00
Test Item	16	73	301	10.07	10.27
Test Item	12	60	301	10.44
Test Item	11	67	301	10.29

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

It can be stated that in this study and under the experimental conditions reported, the test item Aduct Urea-Sulfuric (Uronium hydrogen sulphate) possess an irritating potential.

Executive summary:

This in vitro study was performed to assess the irritating potential of Aduct Urea-Sulfuric (uronium hydrogen sulphate) by detection of damages in blood vessels under the chorioallantoic membrane of 9 day incubated chicken eggs (HET-CAM, GLP).

The test item was tested pure.

The observation time was 5 minutes at room temperature.

Physiological sodium chloride solution (0.9% (w/v)) was used as negative control.

The negative control showed no irritating effect on the blood vessels under the membrane.

An 1% solution of SDS and 0.1 N NaOH were used as positive controls.

The positive controls (SDS and NaOH) induced severe irritation on the blood vessels.

Severe irritating effects were observed during 5 min incubation with Aduct Urea-Sulfuric. The calculated mean irritancy index is 10.27. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item Aduct Urea-Sulfuric (uronium hydrogen sulphate) possess an irritating potential.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In a primary dermal irritation study in rabbit (OECD 404, GLP), urea sulphate was not considered as a skin irritant: mean ratings of erythema and edema at 24, 48 and 72 hours of the three animals after a 4-hour exposure were 1.22 (erythema) and 0.22 (edema).

Eye irritation:

As a corrosive effect was observed during the skin sensitisation test (see section 7.4.1), only an in-vitro eye irritation test (HETCAM) was performed. In this test, severe irritating effects were observed during 5 min incubation with urea sulfate. The calculated mean irritancy index is 10.27 and it was concluded that the test item possesses an irritating potential. As the test item is considered to be corrosive, no further in-vivo test is required.

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation:

Data are conclusive for skin irritation, but not sufficient for classification according to CLP criteria (Regulation (EC) No 1272/2008). No classification is proposed for skin irritation according to CLP.

 

Eye irritation:

Data are conclusive for eye irritation, and sufficient for classification according to CLP criteria (Regulation (EC) No 1272/2008). Uronium hydrogen sulphate is classified as Eye Damage category 1 (Causes serious eye irritation).